Wednesday, June 2!, 1967 9:00—10:30 A.M. Spanish Ballroom

SESSION A. BRAIN AND CEREBRAL BLOOD FLOW Session Chairman: WILLIAM H. OuENDoiw, Los Angeles

A-i “Comparisonof Indiam 113-rn Chelates and Technetium-99m Pertechnetate as Brain Scanning Agents.― H@i@Y N WAGNER JR., HOWARD S. Si'i@'.m'iAND DAVID A. GOODWIN, (Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, Baltmore, Md.) A major factor in the improved accuracy and better quality of brain scans over the past few years has been the greater yield of emitted photons resulting from the use of multi millicurie doses of the short-lived radionuclide, technetium-99m. Disadvantages of 99mTc @ pertechnetate are : ( 1 ) the short half-life of the parent nuclide, which must be obtained at weekly intervals; (2) the high blood level at the time of the scan may obscure lesions in highly vascular areas; and ( 3 ) the tumor-brain concentration ratios are not as high as we would like. Therefore, it seemed desirable to search for a better agent. Indium-113m can be less obtained from the parent nuclide, @3Sn,which has a half-life of 118 days and therefore needs to be purchased only at six- to eight-month intervals. We pre pared and screened several complexes of indium and found that indium chelates, such as diethyltriamine-pentaacetic acid (DTPA), gave tumor: brain concentration ratios of about 30: 1 in experimental tumors in mice. Indium chelates ( EDTA and DTPA) readily diffuse into the extracellular fluid and are also rapidly excreted by the kidney. The blood clearance half-time of indium chelates in man is about 70 minutes, with over 50 per cent of the admin istered dose appearing in the urine in approximately two hours. The physical characteristics of Indium-113m (1.7 hour half-life, no beta emission) allow millicurie doses to be given without danger of excessive patient radiation. The higher energy of ll3mIn (390 keV) requires collimators with thicker septa than those used with Technetium-99m. To achieve equal sensitivity, it was therefore necessary to use collimators with less spatial resolution. We compared 99mTc pertechnetate and ll3mln DTPA in paired studies of a series of a series of patients with a variety of brain tumors and other mass lesions. Accumulation of radioactivity in the mucous glands of the face, the frontal sinuses, salivary glands and choroid plexus noted with O9mTc pertechnetate were not seen with 113mJ@DTPA. Consequently, it was not necessary to administer atropine and perchlorate (as we do in the case of pertechnetate) to remove these normal areas of concentration that occasionally lead to problems in interpretation. Tumors and other lesions were visualized equaly well with both agents. At this time, it appears that ll3mIn is as good as O9mTc as a brain scanning agent.

A-2 “AComparison of In-113 and Tc-99m as Agents for Cerebral Scanning.― ROBERT O'M@u1A,GOPAL SUBRAMANIAN, AND JoHN G. MCA1@, (Department of Nuclear Medicine, Upstate Medical Center, State University of New York, Syracuse, New York.) Like Tc-99m, In-113m is a short-lived daughter radionuclide available from a radioiso tope generator system (physical half-life—104 minutes: gamma emission—.393 MeV). It is eluted from a column of hydrous zirconium oxide containing the parent Sn-i 13 with .05 N HC1 or HNO1. The eluant contains no radiochemical impurities and the leakage of parent Sn-i 13 activity is only i0@ to 106 times the activity of radioindium. The long half-life of the parent nuclide of 118 days offers an economic advantage over the 99mTc generator system. However, a higher fraction of the gamma photons of In-i 13m undergo internal conversion than for Technetium-99m. Consequently, the tissue radiation dose from In-il3m is higher. Because indium is a trivalent cation, it can be easily complexed with various chelating agents, including amino acids. Preliminary screening of 13 different complexes of radioindium 261 262 ABSTRACTS in mice indicated its potential value as an agent for cerebral scanning. A comparison of the tissue distribution was made between In-1i3—DTPA, In-il3m—tryptophane and Tc-99m pertechnetate in C 57 mice with transplantable ependymoblastoma. In-113m—DTPA produced higher tumor-to-brain concentration ratio and a more rapid blood clearance than other agents. The subcellular distribution of these radioactive agents was studied by zonal centrifugation. Preliminary trials of In-i 13m—DTPA compared with 99mTc pertechnetate indicate that the former agent has superior biological characteristics. No concentration is seen in the choroid plexus or in the salivary glands. The rapid blood clearance allows scanning to begin almost immediately after injection and the vascular structures appear less prominent. Because of the higher energy of its gamma omission, however, the resolution obtained with In-i 13m is somewhat inferior to Tc-99m. Brain scans comparing the two compounds will be shown.

A-3 “Rapid Sequential Cranial Scintiphotography for the Vascular Characteriza tion of Brain Lesions.― M@rrii@ws B FISH, MYRON POLLYCOVE, SEAN O'REILLY AND ARCHIE KHENTIGAN, (Niicli@Medicine Section, Clinical Laboratories, San Francisco General Hospital, Division of Clinical Path ology and Laboratory Medicine, Department of Pathology, University of California School of Medicine, San Francisco, California) The ready availability of near-ideal nuclides for clinical use such as D9mTc and the development of the Anger-type scintillation camera has made possible the imaging of a number of vascular structures and organs. Utilizing this approach, a procedure involving rapid serial scintiphotography of a vascular isotope bolus as it transverses these structures was devised. Rapid safe assessment of the vascular nature of intracranial lesions is accomplished employing an antecubital intravenous bolus injection of 9DmTc@pertechnetate ion, 10 mC, and an Anger type scintillation camera with standard manual photographic attachment. Rapid sequential studies obtained in over 20 subjects without demonstrable intracranial lesions exhibited the following vascular phases on anterior view : Aorta—early carotid arteries, mean of 5.3 sec. after injection; carotid and cerebral arteries, 7.9 sec.; cerebral arteries—capil laries, 9.5 sec.; early venous, 10.5 sec.; and late venous, 12.5 sec. The routine procedure which has evolved from these studies involves sequential scintiphotography at 1.5 sec. intervals after bolus injection followed by conventional multiple view cranial scintipho tography at i-5 minutes (vascular equilibration) and 60-80 minutes (extracellular fluid equilibration). Such studies have been performed in over 80 patients with suspected intra cranial pathology. The vascular nature of all demonstrated lesions was easily established. Primary neoplasms including malignant glioma and meningioma as well as vascular malfor mations exhibited increased vascularity. Cerebral infarcts and subdural hematomata demon strated decreased vascularity. In summary, this technique affords a simple, rapid, safe procedure for routine assessment of cerebral vascular disease and vascular characterization of intracranial lesions. These favor able features allow its use in outpatients, as a means of screening patients for cerebral arteriog raphy, as well as in patients in which cerebral arteriography is contraindicated.

A-4 “KineticStudies in Brain Scintiphotography.― MARsIIAu S MILLER, AND Gu@ H. SIMMONS,(Departments of Radiology and M@di@ine,University of Cin cinnati College of Medicine and Training and Manpower Development Program, National Center for Radiological Health, U.S. Public Health Service, Cincinnati, Ohio) Kinetic studies on 20 individuals undergoing brain scintiphotography with intravenous pertechnetate demonstrate the necessity for a 30-minute interval between injection and start of examination. Count rates registered by the gamma camera were recorded continuously on a strip chart from the time of injection until at least one hour later and correlated with serial scintiphotos and blood levels. The patients remained motionless throughout the pro cedure. An initial peak brain count rate at 17 seconds is associated with high concentration in large vessels. As pertechnetate disseminates into tissues, the count rate falls by 35% to a minimum at 49 seconds and pictorial detail becomes poor. As 99mTc collects in venous struc FOURTEENTH ANNUAL MEETING 263 tures, the count rate again rises. Maximum concentrations in antecubital and finger blood are found at about one minute, then begin a decline well described by a power function. Brain count rate continues to rise to a second maximum at five minutes and persists six mm utes before gradual decline. When pictures are taken with facial structures ( salivary glands, etc. ) shielded from the view of the crystal, there is little or no effect on the kinetic phenomena described. Photographic detail is improved by use of a newly available 4000-hole collimator. It would seem desirable to obtain scmntiphotos when the camera brain count/antecubital blood count ratio is maximum. This point is seldom reached before 30 minutes. Patients pre-treated with perchlorate maintain a lower brain/blood count ratio than the same patients studied without perchiorate. Cases are presented to show the possibility of missing lesions by examin ing a patient too soon, even though count rates over brain are higher at earlier times. This consideration is especially important in scmntiphotography compared to rectilinear scanning because of the swiftness with which all views are begun and taken on the gamma camera.

A-5 “Correlationof Cerebral Blood Flow Dynamics with Time Lapse Scinti photography Using the Gamma Camera with Multichannel Analyzer.― KENNETH 0 HENDRICKS, JAMES T. LAMBETH, AND ALEXANDER GorrsciIAu, (ArgonneCancerResearchHospitalandthe Universityof Chicago,Chi cago, Illinois)

Using an Anger Camera, modified 70 mm roll film magazine, and a RIDL 1600 channel analyzer, dynamic studies of cerebral blood flow have been performed on over thirty patients. Ten mC of 9OmTc pertechnetate were injected via an antecubital vein with the subject posi tioned beneath the camera in a half-axial projection similar to that used in carotid arteriog raphy. Coincident with the injection, 70 mm time lapse scintiphotographs were made from the camera cathod ray tube, while storage with rapid print-out of the digital information from a region-of-interest including the skull above the center of the orbits was performed simultaneously with the multichannel analyzer. Camera exposures of 1.5 sec per frame ( in cluding film advance ) and analyzer storage of .6 sec with print-out times less than one second were utilized to provide approximate correlation of scmntiphotographs and digital readout. Following the dynamic study, the midline of the cerebrum was identified by the position of the sagittal sinus on the analyzer display and the region-of-interest divided to compare right and left hemispheres. Counts in the range of 500-800 were usually obtained over each half of the brain during peak intervals. Eleven patients with bilaterally symmetric activity and no organic illness, on the basis of limited follow-up, have shown an average appearance time of ii seconds with a 5-second interval to the inflexion point of the initial slope. This point coin cides with the pre-venous phase of the bolus, as the sagittal sinus appears on subsequent frames of the scmntiphotographs. Asymmetric flow curves and delayed appearance with slow peaking have been seen in a variety of pathologic conditions such as cerebral tumor, vascular occlusion and subdural hematoma. Examples of these studies will be illustrated. Although still developmental, this technique provides a correlation of structure and function not available with other methods of evaluating cerebral blood flow.

A-fl “BloodFlow Studies with the Scintillation Camera.―Gi@iw@BURKE,AND ARLENE HALKO, (Radioisotope Laboratory, Michael Reese Hospital and Medical Center, Chicago, Illinois) The scintillation camera has been used for dynamic studies of renal and cerebral blood flow with technetium-99m pertechnetate. Renal blood flow studies have been performed in conjunction with scintillation camera 1311 hippuran renography. These coordinate isotopic renal function studies have been of particular value in the differentiation of compromised renal blood flow from obstructive uropathy, both of which may result in prolonged renal hippuran transit time. The visualization of the abdominal aorta achieved with technetium com pares favorably with that obtained on conventional aortography. This method has also been used to demonstrate blood flow through the brain and affords ready visualization of the caro tids and major cerebral arteries. The use of electronic crystal splitting and dual chart re corders permits the simultaneous quantitative estimation of blood flow thorugh each cerebral 264 ABSTRACTS hemisphere. This technique has been found to be of value in the diagnosis of occlusion of major cerebral arteries, arterio-venous malformations and subdural hematoma. Blood flow visualization and measurement with the scintillation camera is without hazard or discomfort to the patient and appears to be of significant value as a diagnostic procedure in a variety of renal and neurologic disorders.

A-7 “Measurements of Cerebral Blood Flow Using Xenon-133 and the Scintilla tion Camera.― [email protected] LOKEN, ARTHuR KLASSEN, ROBERT Pwi@cE, JOSEPH P. RESCH, (WiUiihe techiii@Iissistance of Stephen Bostrom ), ( Nuclear Medicine Clinic, University of Minnesota Hospitals, Minneapolis, Minne sota) During the past 20 years considerable attention has been focused on measurements of cerebral blood flow. Most of this work has been based on the nitrous oxide method introduced by Kety and Schmidt in 1945, which requires repeated or continuous sampling of blood from the jugular bulb and a peripheral artery. Our work, initiated two years ago, has been aimed at developing a simple, atraumatic and reproducible test for measuring cerebral blood flow. We are using xenon 133-gas, which may be administered by inhalation from a spirometer system or dissolved in saline and administered by selective injection into an internal carotid artery. Considerable time has been spent in developing a technique for handling xenon, particularly when administered in saline solution. A dual scintillation probe system and a scintillation (Anger) camera are being used in these studies. Both units employ strip chart recorders to obtain tracings of uptake and clearance of the inhaled xenon from cerebral tissues. In addition, serial scintiphotograms of the distribution of the radioactivity in the brain are being obtained with the scintillation camera. Computer techniques are employed in evaluating the data obtained from these studies. In a group of normal subjects studied to date using our dual scintillation probe system, data were obtained on cerebral clearance of inhaled xenon which are in good agreement with published figures of other investigators (Mallet and Veall, Obrist). We find that the clearance curve has at least two components with a rapid phase showing a half-time of about one minute and a slower component with a half-time of about eight minutes. These results are now being compared to those obtained with the scintillation camera and also clearance curves obtained following the injection of xenon in saline into an internal carotid artery.

Wednesday, June 21, 1967 11:OO—12:30 P.M. Spanish Ballroom

SESSION B. a) BRAIN SCAN EVALUATION b) CEREBROSPINAL FLUID CIRCULATION Session Chairman: WIL B. NE@, Seattle

B-i “AngerCamera Studes of Cerebral Blood Flow.―JAMESS. Aiir@ou, (Kansas City General Hospitaland Medical Center,Universityof MissouriSchool of Medicine, Kansas City) In the routine performance of 80 brain scans, the passage of the bolus through the cerebral vessels has been recorded in a series of 2-3 second exposures, using an Anger gamma camera. From 2-5 mC of 99mTc is administered intravenously with camera over the occipital area or over one side of the head. The bolus is first detected in the carotid and vertebral arteries which can be clearly separated only in the lateral views. The next picture records a diffuse activity throughout the cerebrum, corresponding to the bolus passing into the cerebral capillaries. The third picture reveals the bolus spilling over into the superior, lateral, venous sinuses. Subsequent pictures reveal the progressive build-up of activity in the venous sinuses as larger portions of the bolus are swept through the cerebral circulation. Reduced FOURTEENTH ANNUAL MEETING 265 blood flow in internal carotid arteries are frequently demonstrated in patients with cerebral infarcts. Defects in the capillary filling of areas of the cerebrum are demonstrable in large cerebral infarcts, but are not demonstrable in small ones. Greater activity concentration occurs over tumors even in the capillary phase. This finding suggests that increased blood flow to tumor areas may play a significant part in the concentration which results.

B-2 “Correlationof Brain Scanning with Other Neurological Diagnostic Pro cedures. J A AQUINO, R. M. CUNNINGHAM, J. F. Fi@ER, V. S. SAXENA, AND G. Sii@nni, (Department of Therapeutic Radiology and Nuclear Medicine, Victoria General Hospital and Daihousie Medical School, Halifax, Nova Scotia) A review of our experience in brain scanning covering a two year period from June 1964 to June 1966 will be presented. An attempt is made to correlate our findings along with other neurological diagnostic procedures. During this period, there were two hundred and forty-three patients who had brain scans. Fifty-four of these patients had brain tumors and, of these, fifty were considered to have positive brain scans. The four false negative scans consisted of pituitary tumor, thalamic tumor, tumor involving the third ventricle and metastases from a sympathecoblastoma. The efficiency of other neurologic diagnostic pro cedures are correlated with brain scanning. It will be shown that brain scanning has the highest rate of accuracy followed by arteriograms, air studies, electroencephalograms and plain skull x-rays. In a group of thirty-five patients with cerebrovascular lesions, the rate of detectability is low by all diagnostic procedures. Again, it will be shown that brain scanning has the highest rate. In this group of two hundred and forty-three patients, one hundred and fifty-four were subsequently discharged from the hospital as not having brain tumors of cerebrovascular lesions. All of these one hundred and fifty-four patients had brain scans. One hundred and thirty-six of them were considered to be normal outright. There were eighteen who were considered to be suspicious and further diagnostic procedures were done, which subsequently confirmed the absence of brain tumor or cerebrovascular lesions. It may be considered that there was a tendency to overinterpret the films, but this is justified by the simplicity. In the false positive scans, uptake by the choroid plexus was the most pre dominant cause of concern. The use of perchlorate before the injection of the technetium 99m has eliminated this concern.

B-3 “Passageof Subarachnoid Blood into Systemic Circulation in Primates.― JoHN C. KENNADY,With the technical assistance of Jamshid Ehtesham zadeh, (NeuroisotopeResearch Laboratory,Harbor General Hospital, Torrance, California, and the Laboratory of Nuclear Medicine and Radia tion Biology, UCLA School of Medicine) This study was carried out to determine if blood passes from the subarachnoid space into the systemic circulation in primates. Earlier studies in the dog showed that chromium-Si labeled blood cells appeared in the circulating blood intact and in concentrations related to volume and rate of injection. Fourteen monkeys, 8-9 kgs, had a catheter placed in the inferior vena cava and a #18 LP needle inserted in the cisterna magna. Two external monitoring detectors placed beneath the head and over the thigh registered the level of radioactivity in the cranial subarachnoid space and its first appearance in the systemic circulation. Blood samples were taken at fre quent intervals and assayed in a deep well counter. Autogenous 51Cr labeled blood was injected at the same rate to three groups of animals after the removal of 2-4 ml cerebrospinal fluid to reduce subarachnoid pressure. Four monkeys had 2 ml, four had S ml and six were given S ml plus an additional 4 ml 51Cr tagged blood thirty minutes after the initial injection. With 2 and 5 ml injections, radioactivity appeared in the cell fraction (RBC's) of the blood in 15 and 0.5 minutes, respectively. In 3-3.5 days, peak 51Cr blood levels were reached in all three groups (10%, 12% and 27%), decreased slightly (1-2%) the next four days and approximately halved in 30 days (4%, 5% and 13%). The 51Cr in the systemic blood re mained in the RBC's, a trace in plasma and in the WBC's. 266 ABSTRACTS

In primates, the tagged erythrocytes leave the subarachnoid space intact and in pro portion to the initial volume and pressure. The rate of appearance and concentration in the systemic circulation would indicate a direct “pore―or “tubule―type communication between the subarachnoid space and the venous sinuses of the central nervous system. The signifi cance of these results as related to subarachnoid hemorrhage in man will be discussed.

B-4 “FactorsComplicating isotope Measurements of Brain Extracellular Space.― WILLIAM H OLDENDORF, (Veterans Administration Center, Los Angeles, California) The volume of brain extracellular space ( ECS ) is of considerable interest in under standing the kinetics of various labels used in tumor localization and in studies of cerebro spinal fluid physiology. In the usual method of measuring ECS, a suitable label is maintained at a fixed plasma concentration until it is assumed the concentrations in the extracellular fluid and plasma are the same. The mean tissue concentration relative to plasma allows the easy computation of the volume of the ECS. In the brain this simple technique leads to unrealistically low values due to a mechanism which prevents the label concentration in ECS from rising as high as the plasma label. The very low permeability of brain capillaries retards the passage of all suitable ECS labels causing a delayed equilibrium. The label which does enter ECS is apparently lost to cerebrospinal fluid which acts as a “sink―for solutes in extracellular fluid. The label is then returned to blood by bulk flow and does not appear in the final tissue analysis. In addition, some labels will be transported out by active membrane transport. Animal experimental work supporting this “sink-action―of cerebrospinal fluid on brain ECS will be presented. Using 14C-sucrose rabbit brain, ECS was measured introducing the label into only the blood and both blood and a ventriculo-cisternal perfusion. When the “sink-action―of CSF was prevented by this latter maneuver, the apparent ECS rose from about 2% (with label only in blood) to nine per cent.

B-5 “IsotopeCisterno-and Ventriculo-Graphy.― GIovANNI DI CHIRO, WILLIAM L ASHBURN, (Section on Neuroradiology, National Institute of Neuro. logical Diseases and Blindness, and the Diagnostic Radioisotope Service, Department of Nuclear Medicine Clinical Center, National Institutes of Health, Bethesda, Maryland)

Isotope-cisternography and isotope-ventriculography are brain scanning techniques to study the normal and pathologic endocranial cerebrospinal fluid (CSF) cavities and CSF circulation. Tracers (RISA, Tc albumin) are injected generally by the lumbar route, rarely by suboccipital puncture, for isotope-cisternography. In the method of isotope-ventricul ography radiopharmaceuticals (Tc pertechnetate, RISA, Tc albumin) are introduced directly into the ventricular system through a ventnculographic burr hole. After the introduction of the isotope, external scintillation scans of the head are performed at various intervals. The labelled compound, injected intraventricularly, begins to flow into the basal cisterns within a few minutes and from here proceeds towards the convexity of the brain. At 12-24 hours, most, and sometimes all, of the activity is detectable in the superior longitudinal sinus. The tracer, when injected in the lumbar area, is detected in the basal cisterns in about one hour and from here it follows the same pattern as above. Isotope-cisternography and ventriculography have proven useful, in many instances indispensable, for the accurate diagnosis of: 1) cerebrospinal fluid rhinorrhea and otorrhea, 2) leptomeningoal cysts, 3) subarachnoid blocks due to arachacitis, bleedings, or other causes, 4) obstructive hydrocephalus, 5) intraventncular tumors, 6) porencephaly, 7) spon taneous ventriculostomy, 8) potency evaluation of neurosurgical shunts. The technical aspects of isotope-cisternography and ventriculography, with particular emphasis on the choice and the characteristics of the tracers to be used and the time sequency of the serial scans, will be discussed. Typical examples of normal and pathologic cisterno- and ventriculo-grams drawn from a material of hundreds of cases will be shown. Stress will be put on the informa tion which cannot be obtained by other neuroradiologic methods (pneuxoencephalography, FOURTEENTH ANNUAL MEETING 267 cerebral angiography, conventional brain scanning ) . Brain scanning today includes as neces sary adjuncts the methods of isotope-cisternography and isotope-ventriculography.

B-6 “Diagnosisof Low Pressure Hydrocephalus by CSF Iodine-131 RJSA Scan ning.―DAVID H. PATrEN AND D. FRANK BENSON, (Veterans Administration Hospital, Boston, Mass.)

Recent work by DiChiro concerning cerebrospinal fluid circulation has suggested that the technique of scanning after the intrathecal injection of 1311 RISA could be of value in the study of hydrocephalus, particularly in the recently emphasized entity of low pressure hydrocephalus. This latter condition is produced by an abnormality in the circulation of the CSF caused by an obstruction in the cerebral subarachnoid space, which prohibits normal escape of CSF through the Pacchinian viii. This obstruction of the normal flow of CSF produces massive hydrocephalus, clinically causing frontal dementia and gait disturbance, incontinence, disorientation, and amnesia. This entity is difficult but important to diagnose because treatment affords marked relief of symptoms. In the past the diagnosis has been dependent upon the pneumoencephalogram, a procedure which is both difficult and hazardous in this condition and gives results which are often inconclusive. We have found that the 1311 RISA scan is technically simpler, in nocuous and accurate in diagnosing low pressure hydrocephalus. Intrathecal injection of 100 ,@Cof @IRISA is followed by interval scanning up to three days. In low pressure hydro cephalus, there is a marked delay in the clearance of 1311 RISA from the cerebrospinal fluid with a notable lack of radioactivity in the sagittal region after 24 hours. We will demonstrate the scan features of low pressure hydrocephalus and compare them to both normals and to other varieties of hydrocephalus.

B-7 “Assessmentof the Cerebral Microcirculation― (Basic and Clinical Studies). JOHNC.KENNADY,LEONARDSWANSON,ANDGEORGEV.TAPLIN,(Laboratory of Nuclear Medicine and Radiation Biology, UCLA School of Medicine)

Accurate and clinically feasible tests for the adequacy of the cerebral microcirculation are not available. A need exists for a procedure which can detect regional vascular dis turbances in the macrocirculation of the cerebral cortex. Clinical application of brain hemi sphere scanning with 1311 labeled macroaggregates of albumin (RAMA) has been deferred for three-and-one-half years pending extensive evaluation of its cerebral toxicity in primates (40) and the development of RAMA suspension of narrow size range (iS-40@@)and high specific activity (1-2 mc/mg). Results from serial histological examination of brain sections in the acute cerebral toxicity studies are surprising, considering the number and size of aggregates injected, together with the calculated number of cerebral arterioles. One in 14 arterioles were estimated to be blocked longer than two hours in six monkeys, yet no evidence of microinfarction was observed. By comparison, when 80,000 solid inert plastic microspheres of similar size were injected, one in 250 arterioles were permanently blocked, but only 1800 microinfarcts (> 1S0@i)were found. These results indicate that efficient shunting of blood flow must occur around the arteriolar blockade at the pial and precapilary levels. The absence of microinfarction from RAMA suspensions containing soft, loosely-bound particles of similar size, but in much larger numbers, is best explained on temporary arteriolar blockade. The shunting of blood in the microcirculation increases the margin of safety when using RAMA as the test agent. The estimated margin of safety for normal man is at least 500 fold. The first ten patients studied had primary or secondary brain tumors. They were selected because they had a short life expectancy and the scanning procedure could provide supplementary infor mation regarding blood flow at the tumor site and the adjacent areas. The scanning results will be correlated with findings from cerebral angiography and electroencephalography and compared with conventional brain scans. The feasibility of extending the application of hemi sphcre scanning to patients with cerebrovascular disease will be discussed. 268 ABSTRACTS

Wednesday, June 2i, i967 9:00—10:30 A.M. Spanish Lounge SESSION C. CALCIUM AND BONE METABOLISM Session Chairman: WILLIAM H. BL@um, Los Angeles

C-i “Measurementof Total Body Calcium (Skeletal Mass) in Man by in Vivo Neutron Activation Analysis and Total Body Counting.― H. E. PALMER, W B Nw,R. MURANO,ANDC. R. Bicii, (University of Washington, Seat tliand Battelle Northwest Laboratories, Richland, Washington) Investigations have been instituted to examine the effect of disease on the calcium con tent of the human skeleton by quantitating total body calcium (98% is in bone) by in vivo neutron activation analysis. By exposing human phantoms and cadavers to a low level fast neutron flux from the University of Washington cyclotron, irradiation was found to be uni form throughout the body within ± five per cent. Immediately following irradiation, total body counting of the induced 49Ca was performed. The counter consists of a circle of six 4―x 9%―NaI crystals through which the cadaver is transported at an exponentially decreasing speed to compensate for the 8.8 minute half-life calcium-49. The 3.1 MeV 49Ca photopeak was readily identified and separated from the photopeaks of induced 24Na and chlorine-38. With a neutron dose of 0. 1 rad ( total body dose 1 rem or less ), 49Ca activity was counted with a precision of ±one per cent. Eighteen minutes is required for a single measurement, a 15-second neutron exposure and a 12.5-minute whole body count. It is concluded that in vivo total body neutron activation analysis can be safely performed and that precise measurement of induced 49Ca is possible. Using comparator calcium standards irradiated simultaneously with the subject, it is estimated that total body calcium can be quantitated with an accuracy of ±five per cent. Since geometric body differences are elim inated in serial studies of the same individual, changes in skeletal mass of 1.5% should be detected. Final quantitative calibration of the counting system is being done by chemical analysis of total calcium in the ash of cadavers previously irradiated and counted with the comparator standards. The possibility of measuring other body elements will be discussed.

C-2 “AReliable Measurement of Bone Mineral Content In Vivo.― JoHN R CAMERON, AND JAMES A. SoRKNsow, (Department of Radiology, University of Wisconsin, Madison, Wisconsin) A technique for measuring bone mineral content in vivo, which is accurate and repro ducible at the 2% level, has been developed. The technique yields an absolute measurement of bone mineral mass per unit length of bone at the measuring site. The determination is accomplished by measuring the transmission by the bone of a monochromatic photon beam from a radioactive source (1251, 27.3 keV). A scintillation detector is used. The effects of soft tissue are taken into account. We are presently able to measure any of the bones of the forearm and hand, and the os calcis. Devices are being built for measurements on the long bones of the leg, including the femoral neck. The accuracy of the technique was demon strated by comparative ashing studies on cadaver bones. The reproducibility was demonstrated by repeated measurements on several normal subjects over a period of several months. It has been used to demonstrate bone mineral changes in a number of clinically interesting subjects, including a 6% decrease in six months of the mineral content of the midshaft of the radius of a lactating female. The technique is useful for detecting small changes in bone mineral caused by diet, exercise, medication, disease, etc.

C-3 “TurnoverStudies with Calcium 45 in Pregnant and Lactating Animal&― JEAN-MARc LEGARE, BERNARD MARcu., AND JOSEPH STERNBERG, (University of Montreal, Montreal, Canada) @ Calcium 45 (20 @C,1 stable calcium) was injected intravenously into pregnant and lactating rats and the kinetics of plasma and bone calcium was determined by a completed FOURTEENTh ANNUAL MEETING 269

Bauer-Carlsson-Lindquist procedure. Fetal accretion was determined by neglecting the re sorption rate in 24 hours from fetal bones, as well as by subtracting the backflow of the isotope from the fetus to the mother. In adult control females, the plasma disappearance rate of 45Ca has the well-known multi-exponential shape, with the following equation:

0.30 t 0.045 t

@ — 2.3 15.4 y = K + 4.8― + 2.7e (t in hours) Pregnancy provokes a marked acceleration of the disappearance rate, especially in the second term of the equation: the half-value is shortened to 8.25 hours, instead of 15.4 hours in controls. The same values are noted in early (8-10 days) or late pregnancy ( 19-20 days). Lactation induces a considerable shortening of the half-value, an average of 5.3 hours (3@ of the control value ) . This phenomenon concerns only the newly introduced calcium-45, for the plasma level of stable calcium remains remarkably constant in each of the examined groups (88.3—94.2 @g/ml). Accretion rate in tibia averaged 7.2 mg/day for the controls and the exchangeable calcium averaged 3.15% of the total pool. Pregnancy induces a moderate increase of both the accretion rate (8.7 mg/day) and the exchangeable pool ( 5.82%); there is a concurrent increase of the resorption rate, so that in the given dietary conditions of the experiment, the bone growth was practically nonexistent. On the other hand, in lactating animals, the accretion rate is con siderably increased ( 15.94 mg/day), but it is dominated by an even higher resorption rate ( 16.46 mg/day), leading to a net deficit of 0.52 mg/day. This phenomenon is reflected in a significant decalcffication of the bone, whose Ca content diminishes from 71.6 mg/g in control to 63.7 mg/g during pregnancy and 52.7 mg/g during lactation. In late gestation, fetal uptake averaged 8.5 mg/day/litter, or the equivalent of the cal cium accreted in one maternal tibia; the accretion rate in the sucklings was in the same range. In lactating animals, a considerable proportion of the injected 45Ca was transferred to the progeny through the milk (33.2—45.6%of the injected 45Ca in 24 hours). These results suggest that during pregnancy and lactation, the hormonal constellation contrives to maintain plasma calcium within the normal level, but requires important readjust ments in the other compartments, especially at the bone accretion and resorption. It is difficult to affirm whether these changes are related to corresponding shifts in the parathormone thyrocalcitonin system, or rather to a combined effect of other factors acting on calcium homeostasy. It is also suggested that the bone resorption found in lactating animals is sec ondary to the rapid exchange of plasma calcium with the mammary gland.

C-4 “Autoradiographic Localization Studies of Fluorine-18 in Bone.―1DAVID H WOODBURY, (Department of Internal Medicine [Nuclear Medicine], th@ University of Michigan, Medical Center, Ann Arbor, Michigan) Fluorine-18 concentration in bone tumors has been demonstrated by photoscanning and well counting. If concentration occurred predominantly in bone tumor cells, therapeutic use of fluorine-18 might be considered because of its 0.696 MeV positron emission. Autoradio graphic demonstration of the locus of fluorine-18 localization in bone has been difficult be cause of its short half-life of 112 minutes and the difficult preparation of undercalcified bone for histologic studies. The development of a successful autoradiographic technique requiring only about two-and-one-half hours from excisional biopsy to exposure to photographic emul sion is reported here. Anesthetized immature and adult dogs and humans with bone tumors are injected with 3-5 mC of carrier free fluorine-18 about one hour before excisional biopsy. Bone specimens. in dogs have been excised from tibia, rib, mandible and vertebra. The alcohol-fixed specimen is embedded in Castolite heat-activated plastic and cut into sections approximately 50-60 microns in thickness on the Hamco-Gillings rotary saw. Representative sections are fixed to slides with Harleco synthetic resin solution, exposed to Kodak stripping film for 24 hours in a light tight box, developed, stained with hematoxylin and analyzed under the light microscope.

‘Thiswork was supported by the American Cancer Society Grant T-389. 270 ABSTRACTS

To date, autoradiographs have been obtained on ten normal dog bone specimens and one human osteogenic sarcoma with adjacent normal bone. These preliminary observations indicate that at one hour after the tracer dose in normal bone, fluorine-18 is found in highest concentrations in the periosteum and, to a lesser extent, in the vessels of trabecular bone and in the bone cells of the harversian system. Concentration has been found immediately around osteoclasts. This technique is now being applied to studies of the repair of fractured bone in dogs and bone tumors in humans.

C-5 “BodyRetention of Radiocalcium Determined by Whole-Body Counting.―' VENARD R KINNEY, AND W. NEWLON TAUXE, with the technical assistance of Mrs. D. Jenkins, ( Mayo Clinic, Rochester, Minn.) Whole-body counting was done on seven patients to determine if radiocalcium is lost from the body by a route other than urinary and fecal excretion. Total body radioactivity was measured 10 minutes after intravenous administration of 1 to 2.5 @@Ciof calcium-47 chloride and then daily thereafter. Study periods ranged from 7 to 21 days. The whole-body counter consisted of a chamber 6.5 by 7.5 by 8 feet made of 6-inch steel lined with lead 3@inch thick. Eight detectors were arranged in two banks, four above and four below the patient. Each detector consisted of an 18 by 18 by 6-inch NE-102 plastic scintillator viewed by four EMI 9530B photomultiplier tubes. Twenty-four-hour specimens of urine and individual stool specimens were collected throughout the study period. Radiocalcium content of each of these specimens was determined with a S by 4-inch sodium iodide (thallium) scintillation crystal. The difference between the body retention of radiocalcium as determined by whole-body counting and that predicted by the measurement of urinary and fecal excretion ranged from 0.2 to 4.0% of dose in the seven patients studied (mean, 2.1%). We conclude that there is no significant loss of radiocalcium from the body by routes other than fecal and urinary excretion. The study also demonstrates the feasibility of determining radiocalcium retention without collecting excreta. Measurement of radiocalcium absorption after administration of an oral tracer is similarly practical by means of whole body counting after allowance for gastrointestinal transit of unabsorbed tracer (S to 6 days); absorption could then be calculated from whole-body retention and cumulative urinary excretion of the radiotracer.

iThis investigation was supported in part by Research Grant AM-6908 from the National Institutes of Health, Public Health Service.

C-fl “Evaluation of an Oral Isotopic Measurement of Calcium Absorption.― GEORGE J MACID, (Metabolic Section, Veterans Administration Hospital, Livermore, California, and Metabolic Section, Santa Clara Valley Medical Center, San Jose, California) Many of the factors affecting calcium absorption by the human gut in health and disease states are incompletely understood. Metabolic balance procedures attempting to study this aspect of calcium metabolism are difficult, frequently inaccurate and usually require a minimum of two to three weeks of careful balance studies. In addition, net calcium absorption or the difference between the mean daily ingested calcium and the amount occurring in the stool, does not assess that part of the calcium derived from its secretion into the gastro intestinal tract, which may represent a considerable fraction in some cases. Radioactive calcium-47 and calcium-45 have been used to measure gastrointestinal ab sorption and secretion by a number of investigators and the results have varied with each method. A simplified four-hour procedure using plasma and urine radioactivity following an oral dose has been used recently, with apparently reliable and reproducible results. We have used this procedure in 13 normal subjects ages 21 to 38, one patient with a parathyroid ade noma before and after surgery, and in a mother and son with familial hypophosphatemia. FOURTEENTH ANNUAL MEETING 271

After baseline serum measurements, 30 @Cof Ca4TCl9 ( S.A. greater than 150 @@C/mg) mixed with 20 mg stable CaCl2 was given orally. Heparinized blood was collected at 30', 60', 90', 120', 180' and 240' and measured for radioactivity. Urine was collected in two-hour periods following the oral dose. All studies were performed in the post absorptive state. Results were as follows:

1. Plasma % ADMINISTERED DOSE PER LITER

Normals (13) Parathyroid Adenoma Familial Hypophosphatemia Time Range Pre-Op Post -OP Mother Son

30' 0.8—4.1 2.2 3.6 4.6 2.46 1.27 60' 1.0—5.8 2.7 5.9 5.7 3.35 1.53 90' 1.4—5.8 2.8 5.9 5.2 3.17 1.49 120' 1.5—5.1 2.6 5.4 5.1 3.08 1.46 180' 0.9—4.9 23 4.6 4.5 2.59 1.25 240' 0.8—4.2 2.1 4.2 4.1 2.29 1.09

2. Urine % ADMINISTERED DOSE

Normals (13) Parathyroid Adenoma Familial Hypophosphateinia Time Range Pre-Op Post-Op Mother Son lst2Hrs. 0.04—0.41 0.17 0.47 0.04 0.280 0.266 2nd2Hrs. 0.02—0.25 0.18 0.31 0.02 0.057 0.118

4Hr.Total 0.07—0.59 0.26 0.78 0.06 0.337 0.384

Correlationwith seven-daystoolradioactivitywillbe performedin selectednormal subjects and in patients with disease states affecting calcium and phosphorous metabolism. It appears that this method does provide a rapid and reliable means of evaluating the comparativeabsorptionof calciumby thegut in normaland abnormalsubjects.

C-7 “KineticsofRadionuclidesUsed forBone Studies,―DAVID A WErn@, ERNEST J. GREENBERG,ALEXANDRADIMIcH,PETERJ. KENNY,W. P. LAUWM@us, AND JOHN S. LAUGHLIN, (Division of Biophysics and Medical Research, Sloan-Kettering Institute for Cancer Research, New York, New York)

A comparisonof the kineticsof intravenouslyadministereddosesof 47Ca (chloride), 85Sr (chloride), STmSr (chloride, @8F(sodium fluoride) and 68Ga (citrate) is presented. The resultsof serialserum and externalpointcountmeasurementsare describedforeach of the fiveradionuclides.The levelsof externalpointcountdataexpressedas per centof adminis tereddose are illustratedat sequentialtimesafterinjectionforboth normal and lesionin volved bone. Quantitative computer-analyzed scan data illustrate in vivo distribution char@ acteristics for each radionucide. Radiation dose to the patient, detector sensitivity, and effectivehalf-lifeareevaluatedwithrespectto theobservedexternalpointcountsand serum kinetics for establishing base-line criteria of nuclide selection for particular diagnostic problemsinbone. 272 ABSTRACTS

Wednesday, June 21, 1967 11:00—12:30 P.M. Spanish Lounge

SESSION D: SKELETAL AND JOINT DISEASE Session Chairman: R@[email protected]. PETERSON, Iowa City

D-1 “TheEarly Detection of Bone Metastasis in Patients with Stage II Carci noma of the Breast at Time of Radical Surgery.― DAVID M. SKi..uioi@, AND N DAVID Ciwuu@s, (the Departments of Nuclear Medicine of the Albert Einstein Medical Center and Temple University Health Science Center, Philadelphia, Pennsylvania) Inasmuch as there has been liftle, if any, change in the five-year survival rate in mam mary carcinoma since the introduction of radical mastectomy, the possibility exists that bone metatasis may have already occurred at the time of initial operation, unsuspected by con ventional means of examination. We have initiated a program of bone scanning with strontium 85 on patients with carcinoma of the breast at the time of surgery and have found that ap proximately 17% of the patients with Stage II carcinoma of the breast have abnormal bone scans at the time of radical mastectomy without observable roentgenographic changes, a finding which supports the above hypothesis. Although we and others have found that strontium bone scanning is not specific for cancer, it would be extremely unlikely that other diseases which are known to produce abnormal bone scans, such as fracture and osteomyelitis, Paget's dis ease and so forth, could be implicated in these cases, inasmuch as these patients were asympto matic and the roentgenograms were negative. Prior experience has led us to believe that these changes are almost certain to be metastastic cancer.

D-2 “Evaluationof Compression of Vertebral Bodies Employing Use of Stron tium.85.― MARSHALL F HALL, ROBERT C. Fui'ss., AND ALBERT J. Gu.soN, (Division of Nucliar Medicine, Orthopaedic Surgery, University of Miami School of Medicine, Miami, Florida) The authorsare presentingtwenty-fivepatientswith x-rayevidenceof compressionof vertebraes, who subsequently had strontium uptake for evaluation of time lapse from injury. All compression fractures secondary to cancer have been eliminated. A number of these cases have been followed for a period of two years or until the radioactive uptake has returned to normal status. The scanograms performed have been on a qualitative basis, rather than a quan titative basis. The clinical orthopaedist is always faced with the problem of wedged vertebrae of the back subsequent to trauma. The x-ray evidence of injury is obvious; however, we find numer ous instances of thoracic and lumbar vertebrae which are wedged with no previous history of trauma or significant clinical findings. In reviewing this series of cases, we have shown that the strontium-85 uptake shows osteoblastic activity compatable with recent trauma. The study also showed that, with time, some scanograms over the compression fracture site reverted to normal within six months and others took twenty-four months to return to normal value. It is interesting to note that delayed symptomatology of back pain with compression fractures isnotatalluncommon. In a number of thesecases,ithas been daysor weeks beforeenough symptomatologyin the back occurredthatthe clinicianorderedx-rays.Afterx-rays,the questionarosewhetherthewedged vertebraseenwas due to a previousinjuryor the recent accident. A severe compression fracture of the back, with breaking and bony changes, is easily diagnosed by x-ray. However, minimal injuries are difficult to ascertain. We are hopefulthatthisseriesof caseswillstimulatethe evaluationof thisprocedure foran added tooltotheclinicalorthopaedicsurgeon.I considerthattheuse of strontiumby theorthopaedistcomparesin valueto theuse of the sedimentationrateby the internist.In creased strontium uptake is indicative of bony reaction. FOURTEENTH ANNUAL MEETING 273

D.3 “TheUse of Strontium-87m for Bone Scanning.― Msiu.& K. LOKEN, AND JAMESD MACGIBBON,(Nuclear Medicine Clinic, University of Minnesota Hospitals, Minneapolis, Minnesota) Autopsy studies show that metastases to bone from carcinoma occur much more frequently than demonstrated by clinical evaluation or by radiography. It has also been shown pre viously that the strontium-85 photoscan can demonstrate bony metastases before they can be detected clinically or on radiographs. Strontium-85 is of limited value in bone scintiphotography because only a relatively small amount of the isotope may be administered if the radiation dose to the patient is to be maintained within reasonable limits. This procedure necessitates using a slow scanning speed and waiting from one to several days after injection of the strontium-85 for body background to drop before beginning the scan. In strontium-87m we have an isotope with a short physical half-life, enabling us to administer a larger dose and thus attain a fast scanning speed. In addition, the scan can be started within one hour after injection. We have studied patients with various malignant diseases using strontium-87m and will discuss our method and results. Among these patients are some who have been studied with both strontium-87m and strontium-85. A comparison and evaluation of the results using the two isotopes will be presented.

D-4 “Pattern of Distribution of SR-85 in Osteoarthritis of the knee.― DAVID G. ANDERSON, GöRAN C H BAUER, AND EDWARD M. SMITH, (Hospital for Special Surgery, Department ofSurgery (Orthopaedics ), Cornell Univer sity Medical College, New York, New York) Earlier measurements of 47Ca and 85Sr uptake in the spine and the hip in man have demonstrated that osteoarthritis is associated with an increased rate of bone tissue turnover. The present study was aimed at correlation of the uptake of 85Sr, as influenced by osteo arthritis, to radiologically visible anatomic details. Forty-seven human subjects were studied; the majority of the knees were afflicted with primary osteoarthritis of the medial type. Two weeks following parenteral injection of 85Sr, the distribution of tracer in the knee region was determined by external counting. A focused collimator permitted significant measurements in 3@―square areas superimposed on the radiograms. It was found that the uptake of 85Sr was higher than normal in those areas of the osteoarthritic knee where osteosclerosis was a pre dominant radiographic feature; medially in genu valgum and laterally in genu valgus. Some observations suggest that alterations in the uptake pattern of 855r may precede radiographic abnormality. The model studied demonstates the unique possibilities offered by the skeleton as regards topologicdefinitionand itwillbe shown how the relativevaluesfor855ruptakereported heremay be translatedinabsoluteterms.

D-5 “ThreeYears Experience with Joint Scanning.― WILLIAM S [email protected], THOMAS E. WEISS, PAUL J. MURISON, AND JOHN D. WATSON, JR., (Ochsner Clinic, New Orleans, Louisiana) For the past three years, tagged albumin joint scans have been used to evaluate patients with arthritic disease. Initially 1311H5A was used as the tracer, but more recenfly 99mTc al bumin and ‘311-Iodipa.midehave been employed. These latter tracers with short effective half lives deliver a lower radiation dose and permit rescanning in one or two days. Joint scanning has been useful in the initial evaluation of a patient with joint complaints, as the scan may aid in establishingan organicor functionaletiologyfor the symptoms.Once a diagnosisof organic disease has been established, the joint scan is an objective method for following the course of the patient's disease to progression or remission. Cases illustrating the use of joint scanning technique under these circumstances will be presented.

D-6 “TheUse of Intra-Articular Radioactive Gold in Patients with Rheumatoid Arthritis.― RALPH JACOX, PAUL A Fuuu@ii, ROBERT FINE, COLIN POULTER, Pmur RUBIN, ANDFREDERICKZucK, (Departments of Radiology, Medicine 274 ABSTRACTS

and Surgery, University of Rochester School of Medicine and Dentistry, Rochester, New York) Persistent or recurrent synovial effusions resemble malignant serous effusions in that fluid collects in a closed cavity lined by an endothelial membrane. Repeated aspiration is frequently necessary to alleviate symptoms caused by the accumulation of fluid. Whereas surgical synovectomy is useful, it is sometimes ineffective in curing persistent effusions and recurrences are common. Furthermore, surgery may be contra-indicated in poor-risk patients. It has been shown that in the presence of a moderate-sized effusion, the introduction of colloidal radiogold ( Au-198) into the knee joint is followed by diffusion of the material throughout the joint cavity and subsequently by its adsorption and localization on the synovial membrane-surface. Although the radiosensitivity of diseased synovial tissue is un predictable, overproduction of fluid may be reduced in those patients in whom the thickness of the lining cells does not exceed the average depth of beta-particle penetration ( 1mm). The present study was designed to evaluate the use of colloidal 198Au in the treatment of persistent or recurrent knee effusion refractory to orthodox modalities of treatment. Patients were selected on the basis of active chronic or progressive rheumatoid synovitis of the knee joint(s), involvement of the joint having been present for a period of at least six months pre-therapy, during which conservative measures had failed to control symptoms. A constant intra-articular dose of 10 mC 198Au ( in 10 cc total volume was used in every instance and following the injection the knee was moved actively and passively for a half hour in order to ensure distribution of the material throughout the entire joint. To define the spatial distribution and movement of the radiocolloid in the body, serial external counts were taken over a number of areas that included the injected knee, regional lymph nodes, and the liver at periods ranging from one-hour to 24-hours post-injection. Joint scans were obtained at six-hour and 24-hours and scintillation scans were also made of the regional and more distant lymph nodes as well as of the liver during the course of the first 24 hours. The urinary excretion of 198Au and serial blood radioactivity were also measured. The pattern and extent of synovial proliferation as well as the shape and size of the knee cavity are well-defined on the scans of the joints. Radioactive material is absorbed from the synovial membrane since detectable levels of radioactivity are consistently present in blood and in urine excreted in the first 24 hours; however, the concentrations and total quantities of 198Au involved are small in relation to the dose. Localization of radioactive material in regional and more distant lymph nodes as well as in the liver is a consistent findingin allpatients;illustrationsof thesewillbe demonstrated.The clinicalresponseto intra-articularcolloidal198Au therapyin the first6 to 12 months of follow-upand the correlationwith chemical,cytologicaland immunologicaltestsof the synovialfluidand with synovialbiopsywillbe presentedfordiscussion.

D-7 “ColloidalChromic Phosphate P.32 for Treatment of Chronic Synovial Ef fusions.― P M JOHNSON, AND C. C. CInusm4N, (Columbia University Col lege of Physicians & Surgeons, New York, N. Y.) Chronicjointeffusionsare usuallyrefractoryto conservativemanagement and require periodicaspirationto relievepainfuldistentionof the jointcapsuleby synovialfluid.Both externalradiotherapyand surgicalsynovectomyhave been employedas therapeuticmeasures. In 1963,Makin and associatesreportedconsiderablesuccessin treatmentof chronic synovialeffusionsby intra-articularadministrationof colloidalgold,gold-198.Similarresults were later obtained by Gynning et at, who also used gold-198. In the past two years we have performed 12 intra-articular administrations of colloidal chromicphosphateP-32insixpatientssufferingfrom chroniceffusionsof theknee jointsdue to rheumatoidarthritis.In certainpatients,effusionin the contra-lateralknee servedas a controlto judgethe effectof treatment.The resultsin thissmallseriesof patientsindicate that the treatment is beneficial for large effusions where little joint destruction has occurred. However, effusionsassociatedwith moderateor severejointdestructionapparentlydo not benefit significantly from instillation of phosphorous-32. To our knowledge colloidal chromic phosphate P-32 has not previously been employed for this purpose. FOURTEENTH ANNUAL MEETING 275

Wednesday, June 21, 1967 9:00—11:00 A.M. Georgian Room

SESSION E. THE CARDIOVASCULAR SYSTEM Session Chairman: ROBERT A. BRUCE, Seattle

E-1 “EarlyObservations on the Correlation of Myocardial Scans and Coronary Arteriograms.― Ricauw A Ws@rz@, WILLIAM J. WILSON, AND CH@uuss A. DOBRY, (Department of Rad1@l@@University of Virginia, School of Medi cine, Charlottesville, Virginia) The technique of myocardial scanning after the intravenous administration of an agent such as Radioiodinated Fatty Acid ( 1311) or Cesium chloride ( l3lCs) has been reported to demonstrate acute myocardial infarcts, as an area of decreased activity, but the scan representation, if any, of other types of myocardial disease is not well-documented. In a pilot project, we have performed myocardial scans with lSlCsCl on all patients referred for selective coronary arteriography to determine if there is any correlation between the arteriographic and scan findings. These patients constituted a group in which coronary artery disease was a consideration, but in whom history, physical findings, ECG, laboratory studies and other diagnostic measures were inconclusive. The early results are encouraging. A correlation appears to exist between “cold―areas on the scan and arteriographic evidence of significantly compromised coronary blood flow even in the absence of other findings suggestive of acute myocardial infarction. In some patients, with chest pain suggestive of atypical angina, normal myocardial scans and normal coronary arteriographic findings coincided. We have found that we cannot differentiate between acute myocardial infarcts and areas of decreased 131CsCl concentration secondary to impaired coronary blood flow or areas where the myocardium is signfficantly thinned or replaced by fibrous tissue following old healed myocardial infarctions. The results to date suggest this technique may serve as a useful screening procedure prior to coronary arteriography and as an aid in the diagnosis of coronary artery disease. A report of progress to date and representative cases will be presented.

E-2 “Measurement of the Distribution of Cardiac Output With Radioactive Particles.― PRILH D R VAN HEERDEN, Toimu MIGITA, ROBERT NORTHCUrr, VINCENT L0PEz-MAJAN0, DONALD E. Tow, AND HENRY N. WAGNER, JR., (Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland) In Sapirstein's method, the distribution of cardiac output can be measured after intra venous injection of ionic 42K or rubidium-86. The percentage of the dose in each organ is related to the percentage of the cardiac output reaching the organ. These methods have the disadvantage that they require measurements within 60 seconds after injection. If labeled particles are injected into the left heart, their distribution in various organs should be similar to the distribution of the cardiac output if the particles are uniform in size, large enough to be extracted from the blood during the first circulation, are well mixed after injection and are not metabolizedbeforethe measurementsare made. Immediatesacrificeof the animalsis notrequiredand particleslabeledwithdifferentnuclidesmake possibleserialmeasurementsin the same animal. In initial studies, we injected ‘311-labeledmacroaggregates of albumin into the left heart of dogs and measured their distribution in various organs. The macroaggregates are non uniform in size and break down very easily. Labeled carbon microspheres (15 ±S micra in diameter) were found to be more satisfactory for studies of the systemic circulation in experi mental animals. Microspheres labeled with 169yb, 85Sr or 46Sc were used and their distribu tion was similar. 276 ABSTRACTS

The results that we obtained for the distribution of the cardiac output to various organs were: brain, 4.9%;liver, 6.5%;kidney, 8.8%;spleen, 3.9%; pancreas, 0.9%; stomach, 1.8%; duo denum, 1.2%; small intestine, 7.4% and the colon, 3.4%. These findings were similar to the reported results of Sapirstein's method.

E-3 “Correlationof Computer-Derived Cardiac Output Measurements with Di rect Determinations.―1 MuiIAriMAD A RAzz@uc, ROBERT E. Borrl, AND W. J. MACINTYRE, (Department of Medicine, Western Reserve University, Cleve. land, Ohio) The determination of cardiac output by focusing an external detector on the precordium has been complicated by two factors. The first of these factors is the accurate calculation of the extrapolated portion of the dilution curve following recirculation and the second is the time involved in processing the obtained data from the strip chart recorder in order to calculate the total integration of area. While automatic cardiac output calculators have been devised for the single peak dilu tion curves of non-radioactive dyes, such instrumentation has not been applied to the double peaked curve of radioisotopic external precordial measurements. In the present study a computer program was written to integrate the primary portion of the dilution curve, determine the point before which recirculation occurs and calculate the extrapolated area. The program then sums the two areas and divides the total into the amount of injected radioisotope to solve the well-known Stewart-Hamilton equation for cardiac output determination. The measurement in this series of 62 patients was paralleled by a system of direct recording in which a scaler is used to integrate continuously the dilution curve. In the mean time, another scaler is used to obtain a differential count rate of the curve at increments of one second. The count rate of the trailing edge of the curve is plotted to yield the parameters necessary to calculate the extrapolated area. This latter system has enabled determination of the cardiac output to be calculated in 15 minutes and has yielded an average deviation of 3.9% ±2.4% (Mean ±1 5. D.) from the computervalues.Itisexpectedthatsuch a simple,accurateand fasttechniquewillenable cardiacoutputdeterminationtobe extendedintoroutineclinicaluse of assessmentof cardiac patients rather than beign of academic interest.

iSupported by Grant HE 06304 from the National Heart Institute, National Institutes of Health,U.S.PublicHealthService.

E-4 “RealTime Dynamic Function Studies with the Gamma Ray Scintillation Camera.― R E PETERSON, R. F. CECH, AND E. V. WEINER, (Radioisotope Service,VA Hospitaland Nuclear Medicine Division,UniversityHospital, Iowa City, Iowa) The use of a storage oscilloscope with a scintillation camera has permitted taking movies of dynamic physiologic events in real time (rather than lapse time or serial time exposures) with the ordinary range of OOmTcdoses used for conventional scanning. A special storage oscilloscopeservesas an intermediateintegratingdevice by providinga phosphor of variablepersistencewith sufficientlightoutputto permitphotographyin the undarkened room. The effect of variations of erase rate, intensity and contrast controls of a storage oscil loscope on the photographic imaging of radioactive sources moving at various rates have been systematically studied. The optimum adjustment of the storage oscilloscope for photog raphy varies considerably between the extremes of sources moving several meters per minute to essentially fixed sources. The optimum conditions have been ascertained for photographing respiratory excursions of the liver and demonstrate the effect of such movement on the delineation of liver lesions. The delineation of normal and abnormal blood flow through the cardiopulmonarytreewillbe demonstratedwithmovies. FOURTEENTH ANNUAL MEETING 277

E-5 “GammaScntillation Camera—Cinephotographic Studies.― BERTRAMJ. L. SAUEBBRUNN, BERGENE KAWIN, AND JAMES SENECAL, ( Radioisotope Labora tory, Veterans Administration Hospital, Washington, D. C.) The use of the gamma scintillation camera for the study of blood circulation within organs is receiving increasing attention. In order to explore this technique more completely, we have utilized time lapse photography to help evaluate normal and abnormal blood flow. The visual representation of the sequence of vascular flow into and through organs dis played on the oscilloscope output of a gamma scintillation camera was recorded on 16mm motion picture film following intravascular injection of radioactive pertechnetate ion ( Na 99mTcO ) into patients. The kinetic distribution and diffusion of the bolus of radioactivity within i@e vascular channels was filmed at frame exposure times that ranged upward from 3@second per exposure. When recorded by this cinephotographic technique, the dynamic sequence of early circulatory events emphasized the versatility of the scintillation camera presentation and increased its diagnostic value. Patterns of flow were evaluated in normal and diseased states of the heart, brain, and kidney.

E-6 “Xenon-133Measurements of Muscle Blood Flow in Hemiplegic Patients.― RALPH J GORTEN, (Division of Nuclear Medicine, Department of Radiol ogy, Duke University Medical Center and the Veterans Administration Hospital, Durham, N. C.) The effects of paralysis on muscle blood flow are not known with certainty. Previous reports indicate that flow may be increased, decreased, or unchanged. The confficting nature of the results available in the literature is in part caused by past limitations in methodology. These can now be overcome by the use of xenon-133 as the indicator for measurements of tissue clearance. This radioactive, volatile, inert gas is lipophiic and has a low muscle:bbood partition coefficient, causing its rapid diffusion across cell membranes and clearance by the local blood supply. The gamma emission makes it possible to monitor externally its rate of disappearance the slope of which can be used to calculate muscle blood flow. Paired wafer scintillation crystal detectors count rate meters, and logarithmic chart recorders were used to monitor xenon-133 clearance after simultaneous intramuscular injec tions of 70 @Cof dissolved indicator in both arms or both legs of 16 hemiplegic patients. In over three fourths of the measurements at rest, values for small vessel blood flow were significantly higher for the paralyzed limbs as compared to respective contralateral normally innervated limbs. Subsequent paired determinations during reactive hyperemia after 10 minutes of arterial occlusion revealed no significant differences between the two sides. It is concluded that muscle inactivity caused by central loss of motor innervation is usually associated with increased small vessel blood flow during resting conditions. This phenomenon is most likely caused by a loss of sympathetic control of vasomotor tone causing arteriolar dilatation or by constant muscle fibrillatory activity causing an increased need for nutrient blood supply. Both of these factors may follow loss of normal muscle innervation. During reactive hyperemia, however, the need for oxygen by the deprived tissues predomi nates over the above factors and no differences in local blood flow can be detected between the paralyzed and the normal limbs.

E-7 “Detection of Venous Obstruction in the Legs with 99m-Tc Albumin.― DoN ALD E Tow, HENRY N. WAGNER, JR., AND WENDY A. NORTH, (Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland) Obstruction of the venous blood flow from the legs can be demonstrated by contrast venography, but the method is difficult. We have devised a method based on measurement by means of externalradiationdetectorsof the rateand completenessof outflowof 99m-Tc labelledalbuminfrom thevascularspaceof the legs.The method isas follows:the patient lieson a tilttablebeneathwhich two crystalscintillationdetectorsaremounted,one under 278 ABSTRACTS each leg. One milicurie of 99m-Tc albumin is injected into an arm vein and 15 minutes are allowed for the material to become mixed in the vascular compartment. The radioactivity of the mid calves, knees and thighs is monitored continuously during separate head down tilts. The resultant decrease in radioactivity is linear during the first 10 seconds, gradually slows and reaches a plateau within 30 seconds. The rate and completeness of emptying are related to the degree of tilt. In six adult subjects without known venous disease, the decrease in radioactivity in the calf 30 seconds after 15 degress tilting was 24 ±7.6% (mean ±S.D.) of the original volume; 29.6 ±11% after a 30 degrees' tilt and 43.7 ±9.5% after a 45 degrees' tilt. The difference in rate of emptying between the two legs in the same individual averaged five per cent for all degrees of tilting. In five patients with unilateral thrombophlebitis, the differences between the two legs averaged 15 per cent. Consistent differences between the two legs could be demonstrated in normal subjects if an external pressure of 60 mm Hg or more was applied to one leg. The method may be useful in the early detection of occult venous occlusion.

E-8 “Evaluation of the Peripheral Circulation in Diabetes.― M A RAZZAK, A. M. HASSABALLA, AND H. ABOU-KHATWA, (Department of Medicine, Faculty of Medicine, Cairo University, U.A.R.) Following the intravenous injection of 30 @Cof radio-iodinated human serum albumin (RISA), the radioactivity build-up curves of both feet were recorded, using a pair of identical scintillation detectors attached to a dual counting rate meter and a strip chart recorder. When the uptake curve reached its plateau, the same procedure was repeated using an equal amount of RISA three minutes after the intravenous injection of 10 mgm Tolazoline hyrochloride ( Priscol ). The areas under the curves obtained before and after the application of Priscol were either measured by a planimeter or calculated according to the following equation: Area Level of radioactivity at 10 mm ( 10 —T1/ 0.69) The difference between these two areas is expressed as percentage of the original curve. In 30 normal individuals, the results obtained ranged between 27 and 90% with a mean of 56 ±17 ( Mean ±1 S.D. ). Therefore, values less than the lower extreme of this normal groupand beyond two standarddeviationsfrom the averagewere consideredabnormal. Using thistestto studythe peripheralcirculationin 48 diabetics,an abnormalresult denoting the presence of peripheral vascular insufficiency was observed in 16 patients without any sexpredilection.Thisperipheralvascularaffectionwas of bilateraldistributionin eight patients, whereas the remaining eight diabetics had an abnormal response in one leg only. Furthermore, there was no correlation between the presence of peripheral vascular affection and the durationor severityof diabetes.However,the incidencewas significantlyhigherin those above 50 years of age and in patients suffering from diabetic peripheral neuritis. These findings point to an etiological relationship between the occurrence of peripheral vascular affection, elderly age and neuropathy in diabetic patients.

E-9 “DifferentialDiagnosis of Edema Using 1-131 HSA and Na22 Cl.―E.A. NOVAK, AND J. J. MATOOLE, (Special Laboratory of Nuclear Medicine & Biol@y, Veterans Administration Hospital, Omaha, Nebraska) A method to differentiateedema caused by venous obstructionfrom that due to lymphatic obstruction was investigated. The technique is based upon the half-time of clearance of radioactivelylabeledcolloidand electrolytesuspensionsinjectedsubcutaneouslyin the calf. 1-131 HSA and Na22 Cl were utilized in this study to evaluate lymphatic and venous patency, respectively. Two microcuries of each substance in a volume of 0.1 ml. were em ployed and the activity from each isotope was separated by pulse height analysis. Clearance half-times in normal individuals were 20 hours for 1-131 HSA and 20 minutes for Na22 Cl. The precision and sensitivity of the procedure was evaluated by artificially inducing various degrees of venous obstruction by means of a blood pressure cuff. A series of patients with FOURTEENTH ANNUAL MEETING 279 unilateral edema of the lower extremities were tested and the results were compared with standard technics of x-ray lymphangiography and venography. The results of the study are presented and the clinical usefulness of this procedure is discussed.

E-1O “Redistributionof Blood Flow Within an Extremity During Reactive Hy peremia.― PHILIP A B@uwERLD,AND HENRY N. WAGNER, JR., (Division of Nuclear Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland) Recently, Ballard, Fielding and Hyman reported that there is a shift of blood flow to the capillary circulation during reactive hyperemia. Their conclusions were derived from observations on the clearance of radioiodide from cat skeletal muscle after release of an arterial occlusion. The particle distribution technique of measuring the distribution of periph eral blood flow is based upon the intra-arterial administration of radioactive particles, the distribution of which is determined by scintillation scanning. The particles have an average size of 15 micra and lodge in the arterioles and capillaries of the first vascular bed they en counter; after lodging in the capillary bed, the particles break down several hours after injec tion. In this study, 400 microcuries of radioiodinated microaggregated albumen were injected into the femoral artery. Reactive hyperemia was produced by inflating a plastic boot that covered the lower extremity up to the level of the mid-thigh and maintaining a pressure above mean arterial pressure for five minutes; twenty seconds after releasing the cuff, the particles were injected. After injection of the particles, the total counts from foot to mid-thigh were determined by scanning the posterior aspect of the extremity with an 8-inch thalium activated Nal crystal scintillation detector. Six normal subjects were tested in a resting state and 12 normal individuals were studied during reactive hyperemia. After correction for variations in the injected dose, the total counts, in the leg of the group without hyperemia, averaged 114.469 ±47.200 ( 1 S.D. ). In the patients with reactive hyperemia, the total counts averaged 218.007 ±79.200 ( 1 S.D. ). A “t―test was performed and the “p―value was found to be 0.01. The data indicate that the group with reactive hyperemia had a significant increase in the number of trapped particles. This finding con sistent with the hypothesis that there is a shift of blood flow to the nutritive pathways during reactive hyperemia. The redistribution of flow to the capillary circulation in hyperemic muscle may be a consequence of the closing of functional arteriovenous anastomosis or the opening of additional capillaries.

E-11 “Useof Albumin-I― Macroaggregates in the Scanning Study of the Re gional Arterial Blood-Flow of the Limbs.― A CUAR6N, G. FL0RE5-IzQuIEIwo, M. GuEluumo, D. CoBos, AND H. TREvI (H@j@iital General del Centro Medico Nacional and Comisión Nacional de EnergIa Nuclear, Mexico City, Mexico) The injectionof macroaggregatedalbumin-131!(MAA) intothelumen of a distribution artery, followed by the scanning of the corresponding limb, makes possible the demonstration ofan imageofitsarterialblood-flow. Normally,the image shows a higherconcentrationof MAA withinthe musclebulk of the limb, due to the greater capillary bed of this region as compared to those regions without muscle.The necessaryconditionforobtainingthe image isthatthe whole arterialvascular supplytributaryto theinjectedvesselispatentdown to the capillarybed. Any obstacleto the transportationof MAA throughoutthe arterialtreedistalto the site of injection is depicted either by a striking decrease or by complete absence of radio activity in the region representing the distribution of the vessel involved. Inflammatory processes, on the contrary, show an increase of local radioactivity due to hyperemia. Typical cases of peripheral vascular diseases are shown, in which the scan images are correlated with data obtained by different procedures employed by physical diagnosis, such as selective arteriography, plethismography, etc. 280 ABSTRACTS

The usefulness of this method as a control of the results of surgical revascularization are shown. Microautoradiographic studies of muscle tissue obtained after the administration of MAA to an experimental animal show the tissue location of the particles. A hypothesis is postulated in order to explain the permanence of MAA within the muscle tissues during a span of time which allows the scanning of the region, as well as the reason why the method can be considered as harmless to the patient.

Thursday, June 22, 1967 9:00—10:30 A.M. Spanish Ballroom

SESSION F. THE KIDNEY Session Chairman: BELTON A. Bumiows, Boston

F-i “ClinicalStudies with ‘1C-Creatinine.―1ROBERT E CuiDunra, JOHN J. GAR REYr, AND FRANCIS K. HERBIG, ( The Section of Nuclear Medicine, Depart ment of Internal Medicine, Saint Louis University School of Medicine, Saint Louis, Missouri) The measurements of plasma and urine creatinine have been widely used as parameters of renal function and, specifically, for the determination of glomerular filtration rate. The generally accepted chemical methods for determination of plasma creatinine allow an analytical error of ten per cent. To avoid these errors in chemical procedures, a single in jection of 25-SO @C14C-creatinine is administered and serial blood samples are obtained. The plasma disappearance curve is determined by liquid scintillation counting. From the volume of distributionand theslopeof the disappearancecurve,the renalclearanceof the traceris determined.The method has been correlatedwith the chemicallydeterminedendogenous creatinine clearance and the glomerular filtration rate as measured by 131I-sodium iothalamate. The calculated volume of distribution has been compared with measurements of total body water.Thismethod doesnot requirelengthyor accuratelytimedcollectionsof urineand in patients with renal failure, a single injection provides blood levels that are measurable for several days. The removal of 14C-creatinine by peritoneal dialysis and extracorporeal hemodialysis in chronic uremic patients has been used as an index of the adequacy of dialysis and as a measure of pre-dialysis and post-dialysis renal function.

‘Supportedin part by USPHS Grant GM124S.

F-2 “Measurement of Renal Plasma Flow with o9mTc(V).Citrate Complex.― SAMUEL L Kou@rz, SHIN-HWA YE!!, JEFFREY WooD, JOSEPH P. KRIS5, AND ROY COHN, (Departments of Surgery, Radiology and Medicine, Stanford University School of Medicine, Palo Alto, California) Although PAH and 1311-Hippuran are good substances for the measurement of effective renal plasma flow, these substances have limitations when serial measurements are desired in thepresenceof poor renalfunction.PAH requiresconstantinfusionand urinecollection, making serial determinations tedious and time-consuming. Iodine-131 has a relatively long half-life (8.1 days), which allows a large background accumulation in the presence of poor renal function, preventing accurate serial measurements of renal plasma flow. These prob lems would be avoided by using a short-lived aamTc( V)-citrate complex. Comparative studies of the 99mTc( V )-citrate complex and 1311-Hippuran have been made in dogs with normal kidneys. Effective renal plasma flow (ERPF) measured by the plasma disappearance of a single intravenous injection of the complex agrees within ±eight per cent to FOURTEENTH ANNUAL MEETING 281 simultaneous ERPF measurements by the single intravenous injection of 1311-Hippuran. There were no toxic effects observed. The 99mTc(V)..citrate complex was distributed in total body water and was excreted in the urine as the intact complex. The favorable physical character istics and the physiological behavior of the citrate complex permit serial measurements of ERPF in poorly functioning kidneys. It has been helpful in the evaluation of renal transplants. In addition, serial scintiphotography allows a pictorial visualization of the kidney. Further application of this complex to pathological renal condition will be discussed.

F-3 “Determination of Renal Blood Flow by External Monitoring of Radiohip puran Disappearance.―1 MUHAMMAD A RAZZAK, ROBERT E. Born, WIL LIAM J. MAcbmmr, AND WALTER H. PiirrcHuw, (Department of Medicine, Western Reserve University School of Medicine, Cleveland, Ohio) Earlier methods for determination of renal blood flow ( RBF ) using chemical clearance techniques have yielded considerable important data. In these methods, however, a con stant infusion of the test agent and bladder washes are necessary. In addition, the results are liable to sampling errors encountered during the collection of blood and urine samples and during their subsequent analysis. To obviate these difficulties, Saperstein et al used a single injection rather than continuous infusion of PAH. Later, Tubis et at introduced the radio actively tagged 1311sodium iodohippurate for evaluation of renal function. Taking advantage of these findings, Gott at at introduced a method for determination of RBF by measuring 1311-Hippuran clearances following the single injection technique using serial blood samples from which space and disappearance slopes could be calculated. The validity of this method has been established by various groups of workers, both in experimental animals and in human beings. Using this technique in normal individuals, the RBF was found to be 1059 ± 120 ml/min./1.73 m2, a figure that agrees very well with reports of previous workers using dif ferent techniques. In the present work, the disappearance of radiohippuran from the circulation was mea sured by serial blood sampling and was compared to values obtained simultaneously from a detector placed over the manubrium sterni at the level of the second ribs in a group of 43 individuals (15 normals and 28 patients). The results obtained by both methods showed ex cellent agreement, the average deviation being 4.3% ±3.3 (Mean ±1 5. D.) over a range of RBF of 212 to 1245 ml/min./1.73 m2. The advantagesof thistechniqueincludethe increasedaccuracydue to the availability of more points for the calculation of the disappearance half-time of radiohippuran together with much less discomfort to the patient. Having these advantages in mind, the presented technique can be applied for the determination of RBF in most patients irrespective of their general condition.

1Supported by Grant HE 06304 from the National Heart Institute, National Institutes of Health, U. S. Public Health Service.

F-4 “TheMetabolism of Hydroxyproline in Osteopathy of Chronic Renal Fail ure.―C. CONSTANTINIDES, P. KO5TAMIS, D. KTOROS, AND B MALAMOS, (De partment of Clinical Therapeutics, School of Medicine, University of Athens, “Alexandra―Hospital, Athens, Greece) Advanced chronic renal failure is known to be accompanied by increased serum phos phorus and usually decreased serum calcium. The rise in serum inorganic phosphorus, which occurs when the glomerular filtration rate is reduced to 20 per cent of normal or less, the accompanying drop in serum calcium, or both, presumably increase the parathyroid activity. At the autopsy of such nephritic patients, occasional diffuse enlargement of the parathyroid glands has been described. Except for these two biochemical disorders in serum phosphorus and calcium, skeletal lesions are developed during the course of chronic renal failure of the type of rickets or osteomalakia and osteitis fibrosa. 282 ABSTRACTS

Urinary hydroxyproline, which is considered to be an index of collagen metabolism, was determined in normal subjects and patients with chronic renal failure in order to find the degree of osteopathy which accompanies this disease. In seventeen cases with chronic renal failure the urinary hydroxyproline was markedly decreased, as compared to the values of fifteen normal subjects. Because this diminution of urinary hydroxyproline is partially related to the decreased glomerular filtration rate, the purpose of this study was to determine the clearance of radio active proline, labelled with ‘4C,which will discriminate the degree of diminution of urinary hydroxyproline due to osteopathy of chronic renal failure from the degree of diminution of the same substance due to decreased glomerular filtration rate. The results are discussed in de tail.

F-5 “DifferentialKidney Function Assessment (The Role of Rapid Sequential Scanning). MICHAEL HAYES, LEONARD A. SWANSON, AND GEORGE V. TAP LIN, (Laboratory of Nuclear Medicine and Radiation Biology, UCLA School of Medicine, Los Angeles, California, and the Los Angeles County Harbor General Hospital, Torrance, California) Scans of diagnostic quality were obtained of both kidneys simultaneously using a multi probe scanner following 500-800 @iCinjections of either ‘311-orthoiodohippurate (OIH) or ‘311-iothalamate.The field of view encompasses both kidneys even in large adults. An ade quate renal scan can be obtained in less than two minutes. Rapid sequence scans provide information of functional and anatomic significance. The first scans in a normal rapid sequence study show activity mostly within the renal cortex, which demonstrate the functional size of the kidneys. Later, tracer activity moves into the calyces and pelvis. When OIH is injected rapidly in a small bolus, there is a transient nephrographic effect corresponding to the renogram peak. This effect is more distinct than that seen on an intravenous pyelogram (IVP ) because OIH is cleared approximately four times as rapidly as the commonly used urographic agents. Rapid sequence kidney scanning offers supplemental functional information to the IVP and renogram and can serve as an IVP substitute in patients allergic to urographic agents. This method of visualizing the kinetics of kidney specific agents is a useful research tool in kidney physiology and clinically can help distinguish the renal ischemia of vascular origin from upper urinary obstruction.

F-6 “Comparison of Methods for Renogram Evaluation.― ROBERT C MEADE, J@uw?sD. HORGAN,ANDJOSEPH A. MADDEN, (Radioisotoj@iService, Veterans Administration Center, and Marquette University, Milwaukee, Wisconsin)

This study was devised to gain information as to the relative merits of previously pro posed methods for evaluation of the renogram. From a prior study done to determine the normal range of the renogram, (Urology 86:163-170, 1961), the renograms from sixty-nine normal individuals, with no evidence of renal disease, were digitalized for evaluation by the IBM 7040 computer. Each renogram was evaluated for time and height of isotope appearance; time and height to peak; blood flow rise; time to return to appearance height; time to return to 75% and 50% of peak; height S minutes and 20 minutes after injection; height 5, 15 and 20 minutes after peak, secretory angle; excretory angle; accumulation rate; excretion rate; ratio of 20 minute to 5 minute height; and renogram index. In addition, the R/L and L/R kidney ratio and the maximum ratio difference was determined for each of the above parameters as well as for 20 minutes after the first peak. In general, the results of evaluation of our normal renograms were in good agreement with the same parametersreportedby otherlaboratories.Thisfactwas especiallytruewhen the patientpreparationand isotopedosewere comparableand seemed to indicatethatthereare several significant and reproducible methods of evaluation. To obtain further information as to the relative ability of each of the above parameters to distinguish the abnormal renogram, renograms from 100 patients, with renal disease proven by other function studies, were evaluated in the same way. The relative ability of individual and combined parameters to separate the normal and abnormal renogram were compared. FOURTEENTH ANNUAL MEETING 283

F-7 “KidneyScans for the Evaluation of Renal Trauma in Children.― L D SAMUELS, AND J. P. SMITH, (The Children's Hospital and Ohio State Uni versity, Columbus, Ohio)

Blunt trauma to the flank and abdomen is a common occurrence in children of school age. Automobile accidents, playground body contact and home accidents account for most of the kidney injuries seen at our hospital. Typically these children present with pain, either in flank or abdomen, with hematuria and sometimes with evidence of acute blood loss or shock. Kidney scans with 50-100 microcuries of 197Hg chiormerodrin have been performed on children entering Children's Hospital with a diagnosis of suspected renal trauma. Scans were done with an Ohio Nuclear scanner, equipped with a S-inch under-the-table crystal and a medium focus collimator capable of 3i-inch resolution. Typical results will be shown. It is possible to ascertain devitalized segments of kidney with great precision and also to locate any intrinsic or extrinsic masses, such as a subcapsular hematoma. By monitoring the rate meter visually, the relative functioning capacity, right to left, can be ascertained. In addition, the relative function of the different segments of a single kidney can be studied. Extravasation of blood and/or urine can be readily evaluated, with multiple follow-up scans in patients where continued leakage is suspected. Preoperative estimation of salvageable renal parenchyma has been possible in most cases with greater precision than with the IVP. The relative merits of ‘97Hgchlormerodrin, 203Hg chlormerodrin and IM 1311 Hippuran for kidney scans have been evaluated. All three of these materials can be used in sequence in a single patient with more information derived than from any single test. It is suggested that the kidney scan should be part of the routine work-up of children with hematuria after abdominal injury.

Thursday, June 22, 1967 11:00—12:30 P.M. Spanish Ballroom

SESSION G. SCANNING I, DATA EVALUATION Session Chairman: C. CRAIG HARRIS, Durham

Gd “Aninformation Transfer Function for Evaluation of Scanning Procedures.― PAUL V HAlipER, TOBY D. COHEN, AND ROBERT N. BECK, (Argonne Cancer ResearcliHospital[operatedby the Universityof Chicago forthe United States Atomic Energy Commission], and the Department of Surgery, Uni versity of Chicago, Chicago, Illinois)

The clinically useful message to be transmitted from the patient to the record in almost all scanning procedures is the pattern of radioactivity. Available information theory analyses indicate that there is an optimal compromise between sensitivity and resolution in the trans mission process, but the location of the compromise depends on arbitrary assumptions and its relevance to pattern is limited. Since any two-dimensional pattern can be resolved by Fourier analysis into its component space frequenéies, an optimization in these terms would appear to be general. This process may be accomplished by defining a resolution area as a square cell encompassing one wave length of the space frequency in question. It thus contains high and low countregionscorrespondingto themaximum and minimum of thisparticularspace frequency. The difference in counts between these regions depends on the total counts col lected in the cell and on the modulation transfer function. This difference, with its statistical variations, constitutes the received message, the transmitted message being the same differ ence in terms of true mean count rates. If each resolution area in the object scanned is thought of as being connected by an information channel to the corresponding region in the final record, then the transmitted information per channel in Shannon's terminology is equal to the entropy of the received message, minus the entropy of the received message when the transmitted message is known. This formulation gives a maximum information density per 284 ABSTRACTS area of scan which corresponds nicely with the highest space frequency that can be seen clearly in a scan of the sine wave sunburst pattern. It thus appears to provide an intuitively correct, experimentally verifiable criterion of merit, which aids in the judgment to be made of the optimal collimator configuration for a given object or radiation source, and gives ex plicit insight into the effects of contrast enhancement, pulse height analysis, and spatial filter ing upon the final image.

G-2 “QuantitativeAssessment of Scanning System Parameters.― A G SCiiuzz, L. KOHLENSTEIN,L. G. KNOWLES,W. A. YATES,ANDR. F. MUCCI, (Depart ment of Radiological Science, Johns Hopkins University, Baltimore, Mary land and Applied Physics Laboratory, Johns Hopkins University, Silver Spring, Maryland) A program has been initiated to study scanning system design parameters based on quantitative assessment of system performance as measured by observed thresholds of detec tion of lesions and by observer estimates of the character of lesions. The studies use a scan ning research system incorporating all real elements of the scanning system problem, includ ing the scan object, the detector, the data processing system, and the image system. In addi tion, the system can simulate in digital form a three-dimensional scanning problem, the re sponse functions of the detector collimator system and the interactions of both. The simula tion allows the size and location of the lesion and the specific activities of the lesion, organ, and background together with statistical noise to be rapidly varied; thus, we can explore the effects on system performance of parameter variation anywhere in the system. The data from clinical scanners recorded on magnetic tape permits comparison of the results from the digi tally simulated scan detector mode of the system with scans of phantoms and patients. An on-line Univac 1206 computer provides a means for varying data processing and image parameters and for exploring the advantages of auxiliary computations and displays concern ing the image. The image system incorporates its own 40,000—word storage for portraying a given picture while the observer is making his assessment. The system is used to study the detection and characterization of lesions in organs such as the kidney, as a function of lesion size, activity level, detector parameters and data processing parameters.

G-3 “ModulationTransfer and Scintillation Limitations in Gamma-Ray imag ing.―ELDON L KELLER, AND JOHN W. COLTMAN, (Westinghouse Research Laboratories, Pittsburgh, Pennsylvania) The sensitivityand resolutioncapabilityof gamma-ray imagingsystemsare inherently limited by the overall detection efficiency, the modulation transfer function of the entire system,and the effectof statisticalfluctuationson the processof visualperception.These factors have been combined in an analytical formulation useful in specifying the limiting performance of such systems. A system is optimized when its performance approaches its limiting performance as closely as is practicable. Performance is scintillation limited because a maximum amount of information is sought, consistent with the minimum radiation dose to the patient. Consequently, the system readout is essentially a “coarsegrained― image comprised of individual scintillations or dots. Under these conditions, the amount of discernible detail (resolution) is limited by the dot popula tion and the contrast in the image. That is, the minimum areal population required to resolve a spatialfrequencyf atan image contrastc isproportionalto (f/c)2.The collimatordesign affectsboth the modulationtransferfunctionand the populationof recordedscintillations; as the ultimateresolutionis increased,the acceptancediminishes.These factorsare com bined to specify the system performance as a plot of the highest spatial frequency resolvable versus the product of organ activity and integration time. By considering optimized collima tors with different limiting resolutions and geometric acceptances, a family of performance curves is obtained for which the envelope gives the limiting performance. This analysis has been applied to several gamma-ray imaging systems for a few of the more frequently scanned organs. For example, even though scintillation cameras of the FOURTEENTH ANNUAL MEETING 285

Anger type have the highest sensitivity of the systems considered, its low resolution capability is shown to severely limit its capability to utilize the high photon yields from isotopes such as Technetium-99m. Other comparisons will be discussed.

G-4 “Experience with Quantitative Scanning.― JOHN S LAUGHLIN, DAVID A. WERER,PETERJ. KENNY,ANDERNESTJ. GREENBERG,(Division of Biophysics, Sloan-Kettering Institute for Cancer Research, New York, New York) A variety of metabolic and other studies have been carried out with quantitative scan ning during the past nine years with different radionuclides and their labelled compounds. These studies have demonstrated the significance and scope of specific features of quantitative scanning and have regularly included such displays as digital scans, photo-scans and computer analyzed scans. Features investigated have included: 1. The ability to determine the statistical significance of uptake variation in adjacent or distant regions of a given scan; 2. The possibility of differential diagnosis on the basis of absolute activity patterns; 3. Sequential studies over periods ranging from hours up to years for metabolic investi gations; 4. The utility of computer-analyzed presentations; 5. The diagnostic use of activity profiles as a function of time for normal and diseased states; 6. The greatly increased dynamic range of the digital readout relative to the variation of activity over any part of the body; 7. The instantaneous display feature of digital scanning and controlled variation of dif ferent parameters in the computer-analyzed scans, etc. Additional features of the scanning system in use have been the capability of total body scanning for total body retention determination independent of redistribution of activity in the body, as well as the ability to handle high energy gamma-ray emitting nuclides. The conclusions are based on approximately 600 case investigations carried out during the past nine years for different disease states. These investigations have usually involved sequential scans with all three display methods over various periods of time. These are to be distinguished from routine quantitative scanning procedures which are carried out at the rate of about 1200 cases per year, primarily for bone, brain, liver, heart, kidney, etc., exclusive of thyroid studies. Specific clinical applications with such radionuclides as calcium-47, strontium 85, fluorine-18, iodine-131, selenium-75, zinc-6S, etc., and their labelled compounds are presented to illustrate these features.

G-5 “QuantitativeOrgan Scanning.―1B CASSEN, AND N. POE, (Laboratory of Nuclear Medicine and Radiation Biology of the Department of Biophysics and Nuclear Medicine, School of Medicine, University of California at Los Angeles)

The principles and theory of quantitative organ scanning are examined in order to establish the practical possibilities and limitations of various procedures. When self-absorption of the gamma radiation in the organ can be neglected (e.g., as it can in pulmonary blood flow studies with 131J macroaggregated albumin), a single stationary collimator channel view ing a point source at sufficient distance will respond with a counting rate inversely propor tional to the square of the distance. A suitable scanning motion can be designed so that the point source, when further away, can be seen for a longer time, thus exactly compensating for the inverse square loss with distance and enabling the total counts to be proportional to the activity. However, the scanning line spacing must be carefully controlled. For a continuously distributed source of activity with no small hot spots or abrupt changes within the field view of a collimator channel, except at organ boundaries, the further away a thin slab of activity, the larger the area of the slab seen through the collimator will be. Thereby, exact compen

‘These studies were supported by Contract AT (04-1) GEN-12 between the Atomic Energy Commission and the University of California. 286 ABSTRACTS sation for distance is obtained for the counting rate without a scanning motion. Either with or without a suitably scanning motion, a multiplicity of collimators can be used to increase sen sitivity and obtain adequate field coverage. The collimating channels can be parallel or, with some precaution, be in a focused array. A conventional focused collimator as routinely used in organ scanning at any instant views activity in a double cone-shaped field. Unless the scanning motion causes this double cone-shaped field of view to uniformly sample the whole region of activity, the data obtained will not be truly quantitative. A scintillation camera could be used with a parallel collimator grid if a sufficiently large field of view can be obtained. Edge effects can be neglected with sufficiently fine grained collimation. Self-absorption and spatially variable intervening absorption, except in small organs, complicate the quantitation. Methods of minimizing absorption effects are analyzed. Some experimental illustrations and verifications are presented here.

G-6 “Improvementof Image Quality of Photoscans by Spatial Filtering.― R.N. BECK, P. V. HARPER, D. B. CHARLESTON, AND N. J. YAsiu.o,( Argonne Cancer Research Hospital [operated by the University of Chicago for the United States Atomic Energy Commission] Chicago, illinois) The introduction of the modulation transfer function [MTF (v)}, or spatial frequency response, as a generalized measure of spatial resolution has recently been seen as a signi ficant advance in the analysis of imaging systems in optics, photography, and diagnostic radiology. In all such analyses, a very fruitful analogy can be drawn between the MTF (v) and the temporal frequency response of a sound reproducing system. When applied to radio isotope imaging systems, the MTF( v ) concept suggests promising new techniques for the analysis and manipulation of images produced by these systems. In particular, an optical device can be used to filter the spatial frequency components in a photoscan : 1. ) to smooth out unwanted fine details; 2. ) to sharpen the edges of low contrast structures; 3. ) to erase background without the danger of losing detail; 4.) to eliminate the line artifact produced by the scanning raster; or 5. ) to provide combinations of the above manipulations. In pm ciple, it should be possible to construct a filter with a spatial frequency response that is the inverse of the detector MTF ( v ). This filter would provide uniform overall frequency me sponse, or potentially “perfect―spatial resolution over the bandpass of the detector, much as an equalization filter compensates for distortion incurred in recording sound on tape, etc. With such a filter, image quality would be limited only by statistical fluctuations in the num ber of counts recorded per unit area. The spatial filtering device described utilizes simple, plano-convex lenses and an inexpensive HeNe laser as a source of coherent, monochromatic light, which is required for this technique. Despite the simplicity of the apparatus, results obtained with sharp cut-off filters are most encouraging. Similar results can be achieved by electronic filtering, using a flying spot scanner with an isotropic scan master.

G-7 “Filteringof Radioisotope Scan Data Using the System-Response Function.― ALLEN SPRAU, DONALD W. CHAAPEL, AND W NEWLON TAUXE, (Mayo Clinic and Mayo Foundation, Rochester, Minnesota) The purpose of this paper is to report the results of our work in filtering scan data by digital computer. The system-response function of the scanning system to a point source was found and stored in computer-compatible form. The procedure was carried out for each col limator in different geometric situations. This function was then used to filter subsequent computer-processed digitized scans. Examples of clinical and phantom scans are to be included in the report comparing computer-processed scans that were not filtered, computer-processed scans filtered with the system-response function and simultaneously recorded conventional photoscans. The filtering technique has been applied to many phantoms and more than 2,000 clinical scans and has been shown in all cases to be very effective in improving display quality and resolution. It has added to the quantification and to the objectivity of scan interpretation. The improvement is apparent on all types of printer displays and is especially evident on the com puter-generated isocount lines made by an x, y plotter to the point that 20 count-rate-intensity levels may easily be represented on a single computer-generated plot. FOURTEENTH ANNUAL MEETING 287

Thursday, June 22, 1967 2:00—3:30 P.M. Spanish Ballroom

SESSION H. SCANNING II, DATA PROCESSING AND COMPUTERS Session Chairman: PAUL V. HARPER, Chicago

H-i “AUniversal Computer Interface for a Multicrystal Rectilinear Scanner.― @ M SMITH, LOUIS KATCHIS, JR., AND RAYMOND DESCRENES, (Divi sion of Nuclear Medicine, University of Miami School of Medicine and Computer Center, University of Miami, Miami, Flordia) A computer interface has been developed which allows the digital scan data from a multicrystal rectilinear scanner ( Dynapix) to be analyzed by any computer which can be programmed to accept binary data. The interface converts the serialized binary data stored in the three eight-bit data registers of the scanner into four lines of parallel data. These lines of data are recorded on a seven channel, half-inch, incremental magnetic tape recorder at a rate in excess of two milliseconds per six-bit line. The packing density is 556 lines per inch with odd or even parity as required. In addition to the basic data transformation, the interface organizes the data so that a computer program can test that a complete picture element has been placed on tape. A pic ture element consists of four data lines and a reference line. The data contained in a picture element includes the spacial coordinates, anatomical landmark, and the number of counts. A complete scan may contain up to 40,000 picture elements, each representing an area 0.15 cm by 0.20 cm. Preceding the scan data, one may record on the magnetic tape whatever patient identifi cation information and technical factors relating to the scan are required. The interface auto matically generates any necessary record gaps or file marks. At present, an intensive program is under way to utilize the digital scan data. These areas include area integration, contour mapping and data averaging utilizing the line spread functionas the weightingfactor.Clinically,pulmonary,renaland hepaticdynamic function studies are being evaluated using the digital output from the Dynapix.

H-2 “The100-Level Smoothed Digital Computer Processed and Produced Scinti. scan.―W NEWLONTAUXE, (Mayo Clinic and Mayo Foundation, Rochester, Minnesota)

The use of data-blending by computer of digitized scan matrices to accord with col limator response characteristics has resulted in a superior scan representation so that up to 20 levels can be easily shown on a single print-out. That 20 levels, each representing 5% of maximal radioactivity, may not always be enough has been suggested by the findings of defects on one slice of a 20-level plot, but not on otherswhere the levelisshiftedslightly,or on conventionalphotoscans. We have therefore undertaken to produce scans with representation of a greater number of levels. While 20-level plots do not trouble the eye in our current scan format, plots con taining more than 20 are difficult to read. By shifting the symbols representing the 20 levels, each 1% from 1 to 4% of peak activity, one is able to represent 100 levels of activity in five print-outs of 20 levels each. The purpose of this paper is to relate the method and to present examples and clinical evaluation of such scan formats. The basic method for data processing involves the collection of all the data contained ina radioisotopescanon an eight-channeldigitalincrementaltaperecorder,processingitby a high-speeddigitalcomputerand readingitoutby a high-speedtypingdeviceor x-yplotter. Data from the scanner's multiple pulse-height analyzers, x and y addresses, body landmarks and identifyinginformationaretaped. 288 ABSTRACTS

The computer is programmed to seek the highest counting increment in the scan matrix, to divide it into 100 increments and to group these increments to be represented by various typed symbols or by x-y plotter. This method gives promise of great clinical usefulness with advantages of speed, high resolution accuracy, and low cost.

H-3 “MedicalRadioisotope Scanning i. Optimum Data Processing Considera tions in Two Dimensions.―' R. W. HABT, AND R A FARRELL, (Applied Physics Laboratory, The Johns Hopkins University, Silver Spring, Mary. land) One of the objectives of concern to radioisotope scanning is imaging the distribution of radioactivity within the human body. The attainment of this objective is referred to here as the “fidelityproblem.― Various errors are inherent in the scanning technique, especially errors arising from statistical fluctuations in the instantaneous rate of ‘y-rayemission, and “smearing―due to imperfect collimator resolution. This paper is concerned with the applica tion of certain techniques of statistical communications theory to determine an optimum method of data processing designed to minimize the effects of these errors on the fidelity of measurement of the activity distribution. In the present study, the analysis is applied to the two-dimensional case and is concerned primarily with how well ideal ( theoretical ) scanning systems could perform, rather than with the performance of existing, real systems. Fidelity is measured by how well, ( on the average), the output image matches the activity distribu tion in the “bestleast squares fit―sense and the analysis is concerned primarily with pre scribing that linear, homogeneous data processor which leads to maximum fidelity in the above sense. The analysis leads to an explicit expression for the optimum data processor, ( i.e. “filter―) and for the expected mean square error in terms of the autocorrelation function of the activity distribution, the collimator point response function and the expected total number of detected photons. Application of the theory is illustrated by several numerical examples, including a comparison between optimum filters and gaussian filters. This latter comparison shows that optimum data processing can result in a saving of a factorof 10 or more in the countratenecessaryto producea givenfidelityrelativeto the countratenecessarytoproducethesame fidelityusingthe bestgaussiandataprocessor.

‘Thiswork supportedinpartby NIH ResearchGrantGM 10548(04),and in partby the Bureau of Naval Weapons, Department of the U.S. Navy, under Contract NOw 62-0604-c.

H-4 “Computer Representation of Three-Dimensional Radioisotope Scanning Data.―' WILLIAM J MACINTYRE,JAMES H. Cimis@ru@'.,ANDGRETCHEN S. CUR TIS, (Department of Medicine, Western Reserve University and Euclid Clinic Research Foundation, Cleveland, Ohio) Although the identification of the presence or absence of an abnormality is sufficient for most clinical radioisotope scanning problems, recent interest has been centered more and more in the full range representation of radioactive deposition. Early attempts to demonstrate three-dimensional views were made by photographing a composite set of longitudinal profiles. Other methods designed to accomplish the same effect include multiple cut-offs, variable levelplaybackof photoscans,colorscanning,contourlinesand constructionof three dimentionalsolidmodels. In the present investigation, the scan data are arranged in a 40 x 40 matrix with each elementcorrespondingtothecountsreceivedina squareareawithdimensionsof %2 inchto ‘Ainch per side. If any element deviates more than the mean of the eight surrounding ele ments plus or minus the standard deviation, it is replaced by the mean ± 1 5. D. The recalculatedelementsare then averagedin sub-matricesof nine elementswith the center valuegivena weightingfactoroftwo.

‘Supportedby GrantHE-06304 from theNationalHeartInstitute,NationalInstitutesof Health, U.S. Public Health Service. FOURTEENTH ANNUAL MEETING 289

The final values are further rounded off to an arbitrary number of levels, twenty being sufficient for the distribution portrayed at this time. Analysis time on an IBM 1620 for the above procedure is approximately 15-20 minutes. The selected level values are then plotted out, using a Cal-Comp 565 as a series of profiles along the x-axis. To achieve an isometric effect, a straight line with a slope of plus or minus one half is added to the function. Similar profiles along the y-axis are superimposed with profile increments progressing along the x-axis. In order to prevent high amplitude profiles on one side of the distribution from obscuring small variations on the other side, four different projections are made of the corn bined profile. This operation takes 10 minutes per projection. Three-dimensional scans with this method have been made of the thyroid, brain and liver. While abnormalities with the distribution are readily apparent, it is believed that the ultimate use of this technique would be to show variations in deposition due to a non homogenous blood flow to a region.

11-5 “Digital Data Recording and image Enhancement Techniques in Recti linear Scanning.― Jom@ S CLIFTON, AND E. JAMES POTCHEN, ( Washington University School of Medicine ) A digital data acquisition system which provides for the direct recording of two channels of pulse information plus coordinates of position of the detector and serial time information has been constructed. The data is recorded directly, using an incremental magnetic tape system in format directly compatible with an IBM 360/50 computer. Programs have been written to manipulate this data which permit: ( 1 ) correction of count rates with respect to time for half-life of the isotope, ( 2 ) dual isotope scan measurements with simultaneous re cording of two scans, ( 3 ) background subtraction, ( 4 ) investigation of image enhancement by use of a transform functions, ( 5 ) direct quantitation in terms of iso-count contours, and ( 6 ) analysis of change of count rate in terms of statistical significance.

H-6 “Modifyingand Rearranging Scan Data Under Direct Observation Using a Magnetic Storage Drum, High-Speed Digital Circuitry, and CRT Dis play.―' DAvID E KUHL, AND ROY Q. EDWARDS, (Department of Radiology of the School of Medicine and the Hospital of the University of Pennsyl vania and the William H. Dormer Center for Radiology, Philadelphia, Pennsylvania) Our processor for scan data is designed to provide for a wide and flexible range of secondary data operations, direct picture display on a CRT screen and full operator control of both processing and display operations at the time of viewing. The instrument does not require the user to learn complicated programming schemes. The operator is expected to be a physician who will control the parameters of interest by punching preset buttons on a keyboard while observing changes displayed on a CRT screen. The instrument is intended to serve as a central processor and reader for data from several scanning units. At the time of scanning, counts detected during each predetermined spatial interval of detector displacement are recorded in six bit binary code on standard eight column perforated paper tape, along with position codes. After the scan is completed, the tape is read with a bidirectional tape reader and loaded onto a magnetic storage dnim2 in unidirec tional scan lines. Loading time is approximately one minute. The data from an entire scan raster is distributed on the drum circumference in eight parallel tracks-six for count content and two for position command codes. The drum has a packing density of twelve thousand bits per track, sufficient for the counting and positional data for over ten thousand picture elements.Operatingat eighteenhundred revolutionsper minute,an entirescan rasteris

1Supported by USAEC Contract No. AT(30-1)-3175, USPHS Research Grant No. C4456, and USPHS Research Career Program Award Ca-14,020 from the National Cancer Institute. NYO-3175-32. 2VermontResearchCorporation.Model 104A (floatinghead). 290 ABSTRACTS recycled thirty times per second, presented repetitively to the oscilloscope, and read out as a persistent display similar to the image on a television screen. Contrast and other picture parameters are under direct control of the physician at the time of viewing. Twelve complete scans can be stored in different sections of the drum simultaneously and all are available for immediate display by pushing a selector button. Additional data processing is accomplished in an arithmetic unit associated with the drum. This contains a twenty bit accumulator with facilities for eight bits parallel addition or subtraction at two megacycle clock rate. Some operations require the technician to pre process original data and prepare a perforated tape of secondary data. The system is designed to function primarily as an investigative tool for studying per ception of scan information and ways of making this information more meaningful. But we have akeady used the instrument successfully with clinical scan data as a workaday tool for adjusting contrast, smoothing random fluctuation ( data bounding and spatial averaging), generating isocount lines, and converting transverse section scan data to rectilinear coordinates.

H-7 “RecentDevelopments in Digital Computer Analysis of the Radionuclide Scan.―1D S GROOME, D. W. BROWN, A. C. SPRAU, AND D. W. CHAAPEL, (Division of Nuclear Medicine, University of Colorado Medical Center, Denver, Colorado and The Advanced Systems Development Division, IBM Corporation, Rochester, Minnesota) The amount of data accumulated during radioisotope scanning procedures is so large that utilization of a digital computer is mandatory if one wishes to apply modern statistical methods to their analysis. Pulses from the pulse height analyzer of the scanner enter an accumulator and as the crystal traverses preset increments of distance the accumulated count is trans ferred through an intercoupler to an incremental magnetic tape recorder for processing later by an IBM 7044 or into an on-line IBM 1800 for real time processing. The computer con verts the data to an array and then performs a statistical “filtering―.This filtering is accom plished by applying a three dimensional weighting function characteristic of the particular collimator and isotope used to successive areas of the array. The goal of this statistical processing is to determine the probability that an apparent decrease or increase in radio activity represents a significant deviation from normal. This is based in part on comparison to a library of previously performed scans. The computer can also be used to provide quanti tative analysis of the radiation per unit area per unit time over entire organs or arbitrary parts of organs. In addition, organs such as lungs can be compared to each other or serial changes such as tumor growth or regression can be quantitated. Either the computer's printer,a pairof typewriters,or an X-Y plottercan be used foroutput.The typewriters and plotter are on-line and located next to a remote console in the same room as the scanner. The printer and typewriters use characters of increasing density to denote areas of increased radioactivity. The computer is also used to rotate the scan into various three dimensional projections providing a better view of the profile of radioactivity within the organ. New photographic methods of output display have also been developed.

iThis work was supported by AEC Contract AT(1 1-1)-1472.

Thursday, June 22, 1967 9:00—10:30A.M. Spanish Lounge

SESSION I. BLOOD CELL METABOLISM AND SURVIVAL Session Chairman: ROBERT B. CHODOS,Syracuse

I-i “incorporaton of 75Se-Selenomethionine in Human Lymphocytes as an in FOURTEENTH ANNUAL MEETING 291

vitro Test of Globulin-Synthesizing Capacity.―1 H F CHENG, R. E. PEmi@ SON, AND T. C. EVANS, (Department of Radiology [Nuclear Medicine], and Radiation Research Laboratory, University of Iowa, Iowa City, Iowa) It is known that circulating lymphocytes in short-term culture can be stimulated to synthesis globulin protein, RNA and DNA by incubation with phytohemagglutinin. Quanti tation of such syntheses may serve as an assay of this capacity. This report describes such an assay in which globulin synthesis is measured by the incorporation of @5Se-selenomethionine into this protein. Leukocytes were obtained from plasma of heparinized human blood with dextran after sedimentation for two hours at 37°C. After one hour in a vial at 37°C, the granulocytes became attached to the glass surface and the lymphocyte suspension was transferred for concentration by centrifugation. Lymphocytes were resuspended in autologous plasma mixed with Medium 199 ( 1.5 X 10@ moles methionine/ml) containing 75Se-selenomethionine (0.5 x 10—smoles/ml). Duplicate cultures were set up in sterile tubes with and without phytohemagglutinin and were incubated for 24 hours at 37° C. In addition, there were duplicate cultures for Mero-time controls. All cultures were terminated by adding sodium sul fate to make a concentration of 18% for the precipitation of globulin protein. The precipitate was washed three times with 16% sodium sulfate. The radioactivity of the globulin was mea sured in a gamma well scintillation spectrometer. Results were expressed as millimicromoles of selenomethionine incorporated per million lymphocytes. Blood cells from 20 normal individuals have been tested. Mean values ( zero-time cor rected ) were 3 ±1 and 8 ±2 millimicromoles of selenomethionine per million lymphocytes in 24 hours without and with phytohemagglutinin, respectively. This would give an index of stimulation of 8/3 or 2.7 for the well individuals. This index of protein synthesis stimulation may be of interest and value in diagnosis and treatment of suitable patients.

1Supported by a grant from Iowa Division, American Cancer Society.

1-2 “TheRBC Potassium-42 influx, Malignancy and Hemolytic Anemia.―How ARD J DWOBKIN, AND MARY C@uuio@i, ( Department of Nuclear Medicine, Princess Margaret Hospital and University of Toronto, Toronto, Canada) Routinehematologicaland biochemicaltestingoftenofferlittlesupportforthe diagnosis of hemolyticdiseasein the presenceof malignancybecauseof livermetastases,marrow invasion and/or marrow suppressive therapy. The radiochromium red cell survival test offers a definitive diagnosis, but unfortunately may require many days for its performance. There fore, the increased potassium (K) influx into red blood cells (RBC) associated with hemo lyric disease was investigated as a possible rapid supplemental diagnostic aid in patients with hemolytic disease and malignancy For each subject, six 5 ml aliquots of heparinized whole blood were incubated with 42K in tracer amounts for up to two hours (at 37°C with agitation) and the rate of dis appearance of @2Kfrom the plasma measured. Using the slope of the linear semi-log relation ship found, one may calculate (using the hematocrit and the plasma K concentration) the RBC-K influx. Sixteen RBC-K influx determinations on ten normal subjects gave a range of 1.71 to 2.33 mM/L.RBC/hr. The patient's own plasma was used as the incubation medium to preserve steady-state conditions. At the end of the two-hour incubation period, the plasma glucose was never found to be below 50 mg/100 ml. Intentional alteration of the hematocrit in the incubation vial failed to effect K influx significantly. Seven patients with a malignancy and definite manifestations of hemolytic anemia gave RBC-K influx values which ranged from 2.49 to 4.44. Seven other patients with malignancy and anemia without evidence of hemolysis gave K influx values of 1.54 to 2.26. A variation of thissimpleand rapidtechniquemay offera new method forthe detectionof the hemolytic process.The contributionsof damaged red cellmembranes and an increasein the number of immaturered cellsto theproductionof an elevatedRBC-K influxwillbe discussed. 292 ABSTRACTS

1-3 “MercuryBinding to Erythrocytes.― E A AZEN, AND B. KRATOCHVIL,( Uni versity of Wisconsin) Trace concentrations of mercury ( around 106 M ) in the presence of 0.144 M NaCl or NaBr l)ind to erythrocytes to a limited degree, whereas mercury in the presence of iodide under similar conditions is completely bound by erythrocytes. The limited binding of mercury to erythrocytes in the presence of bromides or chlorides was unexpected, since excess thiol groups available for binding were present in the erythrocytes. When erythrocytes are in cubated with 0.144 M sodium halide solution, substances that bind mercury are found in the incubation fluid. Little of the mercury in iodide solution is bound by these extracellular substances, whereas most of the mercury in bromide and chloride solution is bound to these substances. The erythrocyte membrane appears to function like a dialysis membrane by per mitting the unbound fraction ( small mercury-halide complexes ) to enter the erythrocytes for intracellular binding while excluding the bound fraction of mercury (large molecules). The high concentration of binding substances in the erythrocytes results in binding of mercury that would not bind to dilute extracellular substances. Cellulose dialysis tubing mimics most of the properties of the erythrocyte system because of the presence of binding sites for mercury on the tubing. The data are best explained by the increasing affinity of chloride, bromide, and iodide ions for mercury and the reciprocally related ease with which halides can be displaced from mercury halide complexes to form “active―positively charged mercury ions for binding to extracellular substances or dialysis sacs. The factors involved in the binding of trace con centrations of mercury to erythrocytes may be as relevant to cell distribution of metals in the whole organism as they are with in vitro labeling experiments.

1-4 “inVivo Studies of RBC Lifespan Distribution Using Endogenous “CO Production.― STEPHEN ARTHUR LANDAW, AND H. SAUL WINCHELL, ( Dormer Laboratory, University of California, Berkeley, California) RBC lifespan studies were performed in animals by analysis of the endogenous produc tion of ‘@COin the breath, following injection of glycine-2-'4C. This isotope is incorporated into the alpha methene bridge carbon atom of RBC heme, and is quantitatively and rapidly excreted as ‘@COwhen the cells are destroyed. RBC destruction can thus be studied without venesection. Buffalo rats were given 50 @iCand LAF, mice 10 @zCof the labeled glycine by intravenous injection. ‘@COproduction rate was then measured in individual buffalo rats and in groups of five LAF, mice, for periods up to 200 days after injection of the isotope. The curves of ‘4C0production vs. time were fitted to a modified Pearl-Verhulst function using a CDC 6600 digital computer, with corrections for random heme catabolism and non instantaneous appearance of the label in circulating RBC (Shemin-Rittenberg correction). Fractionation of random heme catabolism into components due to random hemolysis and catabolism of non-hemoglobin heme (liver catalase, etc.) was estimated in separate experi ments. Mean potential RBC lifespans of 66.0 ±1.5 days for the buffalo rat, and 52.6 days for the LAF, mouse were obtained. Standard deviations for the distribution of RBC life spans about these means were 7.3 ±1.1 days for the rat and 9.1 days for the mouse. Com ponents of random hernolysis averaged 0.64 per cent per day in both species, while the mean overall RBC lifespan, which takes into account, both random destruction and time-dependent death, was estimated as 60 days in the rat and 48 days in the mouse. Because the model used to interpret these results is generally applicable, it should also be of use for similar studies in man.

1-5 “AnalogueComputer Analysis of Human Chromium-51 RBC Survival and Whole-Body Retention Data.―P E E BERGNER, C. C. LUSHBAUGH, W. D. GIBBS, AND W. FRANZ, (Medicil Division, Oak Ridge Institute of Nuclear Studies, an operating unit of Oak Ridge Associated Universities, Inc., Oak Ridge, Tennessee, under contract with the United States Atomic Energy Commission) Simultaneous measurement of whole-blood and whole-body radioactivity, after intravenous 51Cr-labeled RBC, offers an opportunity to study previously indescribable functional aspects FOURTEENTH ANNUAL MEETING 293 of RBC-destruction mechanisms. Contrary to the common hypothesis that a significant “elution―of label occurs, we have assumed that the peculiar behavior of 51Cr-labeled RBC is due to some RBC being “damaged―by the labeling procedure. On the basis of this hypo thesis and our previous theory for RBC destruction, a kinetic model has been constructed and solved by analogue computer. The model contains parameters related to senescence, to random destruction due to disease, and to different functions of the reticuloendothelial system and has been used successfully to analyze 51Cr-RBC survival data from 20 human subjects, five without disease and 15 with hematological diseases. Each was observed for 120 days or longer. The results suggest that the physiologic significances given a priori to the different parameters are reasonable; that is, the model describes not merely the life span of circulating 51Cr-RBC without resort to use of “elutiontheory,―but also different functions of the RE-system. The parameters of the model show a clear correlation with RBC disease, and appear more informative than the more familiar t0 value commonly used in hematologic diagnosis.

1-6 “Aninvestigation of Chromium-51 Metabolism in Normal individuals.―1 J W TYSON,JAMESH. Mi@E,JR.,GLENNV. DALBYMPLE,ANDH. N. MABvi!@, (Departments of Anatomy, Biometry, Physiology and Radiology of the University of Arkansas Medical Center; and the Radiology Service, Little Rock Veteran's Administration Hospital, Little Rock, Arkansas) A group of twenty-five healthy young adult volunteers, twenty-three men and two women, with age range twenty-one to forty-three years were studied. After screening for possible hematologic disorders, each person received an intravenous dose of sixty micro curies of 51Cr (as an RBC label). During the post-injection observation period, all mdi viduals had frequent blood sampling and the whole body counting performed. In addition to the blood and whole body measurements, ten individuals had measurements of retained radioactivitymade by externalcountingover the heart,liverand spleen.These measure ments coincided with the periods of blood sampling. Subtraction of the intravascular 5Cr component from the total body counts indicated a biphasic reticuloendothelial retention curve. The external counts over the liver and spleen substantiated this finding.

‘Supported by Atomic Energy Commission Contract AT-(40-1)-2681, NASA GR-04-001- 014 and NIH FR 00208-01.

1-7 “PlateletSurvival Measurements in Thrombokinetics.― LAURENCEHARKER, (University of Washington School of Medicine, Division of Hematology, Seattle, Washington) A systematicapproachto plateletdisordersrequiresreliablemeasurementsof platelet survival. Vital information relating to each category of the following functional classifications can be derivedfrom plateletsurvivalstudiesusingCr5-taggedplatelets,labeledin acid citrateplasma(pH 6.5). 1. ProductionDisorders 2. Disorders of Circulating Platelets a. Dysfunction b. SplenicPooling 3. IncreasedDestructionorLossofPlatelets a. Intravascular coagulation b. Immune Destruction c. Dilution The survival data differentiates increased destruction from other functional defects. Splenicpoolingisestimatedfrom recoverydeterminationsand indirectproductionestimates are derived from the relationship of the survival measurements and accurate peripheral platelet counts. Data will be shown to illustrate the usefulness of platelet survival measure ments in functionally defining platelet disorders. In addition, direct marrow examination docu mented the accuracy of platelet production estimates according to survival measurement. 294 ABSTRACTS

Thursday, June 22, 1967 11:00—12:30 P.M. Spanish Lounge

SESSION J. RETICULOENDOTHELIAL SYSTEM Session Chairman: MYRON POLLYCOVE, San Francisco

J-1 “Differencesin Distribution of Hematopoietic and Reticuloendothelial Mar row in Hematologic Disease.― DONALD VAN Dm@, DAvm C PRICE, CAROL SHKURKIN, AND HAL 0. ANGER, ( Dormer Laboratory, University of Cali fornia, Berkeley, California) Technetium-99m in the form of a sulfur colloid is being used increasingly as a tracer for bone marrow scanning. Although its physical and biological properties are well suited for scanning the reticuloendothelial component of marrow, this distribution will not necessarily coincide with the distribution of the other marrow functions, particularly in pathological or changing marrow states. In the present study, 100-150 @Cof iron-52 as ferrous citrate has been used to label the erythropoietic component of marrow in man. This use permits good marrow scans with the Mark II total body scanner followed by detailed scintiphotos with the scintillation camera 16-20 hours after slow intravenous injection. At the completion of such an erythropoietic marrow survey, 2.5-3.0 mC technetium-99m-sulfur-colloid is injected intravenously for a scan and scintiphotos of the reticuloendothelial marrow distribution, the two isotopes being readily separated by positron discrimination. Marrow distributions using these two tracers have been compared in over 20 patients with various hematologic diseases. In most instances, the marrow patterns are very similar or identical. However, several patients with varying degrees of dissimilarity have been found. One patient with congenital red cell aplasia demonstrated a normal 99mTc@sulfur@colloid distribution, but absent 52Fe-labeled erythropoietic marrow. Two patients with Hodgkmns dis ease previously treated with local radiotherapy had a patchy distribution of 52Fe uptake not reflected in the uniform O9mTc labeling pattern. Additional patients showed less marked variations between reticuloendothelial and erythropoietic marrow distributions. Masking of central marrow distribution by the predominant hepatic and splenic uptake of radiocolloid also proved in several cases to be a problem not encountered with 52Fe labeling. It is concluded that although 9OmTc@sulfur@colloiddoes adequately reflect hematopoietic marrow distribution in many instances, some pathologic states occur in which radioiron and radiocolloid patterns are not identical. Consequently, in any given patient, the reticuloendo thelialmarrow patternseenwithradiocolloidcannotbe assumedto representthe distribution oferythropoiesisand othermarrow functions.

J-2 “TheQuantitative Distribution of the Erythron and the RE Cell in the Bone Marrow Organ of Man.―WILL B N@p, AND RAE ELLEN Bowi@ii, (Univer sity of Washington School of Medicine, Seattle, Washington) In man, bone marrow scanning with radiocolloids suggests that the spatial distribution of colloid in the RE cell is similar to that of the active erythropoietic marrow (the erythron). Studies of the total skeleton of animals with normal and increased erythropoiesis indicated a nearly identical distribution of the RES and the erythron. In order to elucidate this relationship in man, the following studies were done in a hematologically normal 52-year-old male who had had surgical removal of the total pelvis and lower extremities (hemicorpectomy) for carcinoma of the rectum. Twenty-four hours prior to surgery, the patient received an intravenous in jection of colloidal gold-198 and transferrin bound iron-59. Following surgery, the distribution of ‘98Auand 59Fe in the resected skeleton was analyzed in detail. The skeleton contained 32% of the administered 59Fe (functioning erythron) and 3.2% of the injected colloid. In each bone unit, as well as in multiple small sections of each bone, the relative distribution of FOURTEENTH ANNUAL MEETING 295

‘98Auand 59Fe in the marrow was essentially identical. Of the total isotope recovered in the skeleton, the per cent distribution of erythron and RES ( 59Fe/l98Au) was; ilium 43.5/41.5, sacrum 17.8/18.5, pubis 8.5/8, ischium 6.5/6.0, femurs 23.5/24.0, remainder 0.5/2.0. It is concluded that in normal man, the spatial distribution of radiocolloids as depicted by bone marrow photoscanning portrays the relative distribution of active erythropoietic marrow.

J-3. “Temporary Dissociation of RES and Erythron Activity in the Marrow Fol lowing irradiation.― Wni. B. N@, S M LABso@r, R. E. Bow@, AND L. D. GROUSE, (University of Washington School of Medicine, Seattle, Wash ington) Various animal models have been designed to examine factors altering the functional relationship of the RES and the erythron in the bone marrow in order to provide a basis for interpreting radiocolloid marrow scans. The immediate and long term effect of x-irradiation on the marrow of the rabbit tibio-fibula was studied after acute exposure to doses of 250 to 5,000 r. From one to 60 days after irradiation, rabbits were sacrificed immediately following the plasma clearance of intravenously injected 59Fe and [email protected] per cent of RES or erythron function in the irradiated marrow was determined by comparing its total 59Fe and 99mTc activity to that in the marrow of the opposite non-irradiated tibio-fibula. Twenty-four and forty-eight hours after irradiation, erythropoietic function decreased 60 to 90% in a dose dependent fashion while RE cell activity remained normaL During the next six days erythropoietic function recovered toward normal and then began a secondary decline coincident with a progressive linear decline in RES function. Thereafter, both the RES and the erythron showed progressive loss of function of similar degree with doses of greater than 1,000 roentgens. With smaller doses, they both showed a parallel pattern toward recovery. Sixty days after exposure to 1,000 r or greater, RES and erythron function was reduced to approximately 18% of normal. Analysis of the patterns of impairment of erythron and RES function in conjunction with the histologic changes in the marrow suggest that the ultimate irradiation damage is related in time to the loss of RE cell integrity and the structural framework of the marrow organ. The implications of these observations in relation to radiocolloid bone marrow scanning will be discussed.

J-4 “ADouble isotope Method for Measurement of the Phagocytic and Cata bolic Rates of the Human Reticuloendothelial System (RES).―' DONALD W BROWN, DABwIN L. PALMER, AND DAVID RIFKIND, (Department of Radiology and Medicine, University of Colorado Medical Center, Denver, Colorado, and the Department of Medicine, VA Hospital, Albuquerque, New Mexico) Iodine-131-labeled heat-aggregated human serum albumin (MICRO-AA) plus Na125I isinjectedintravenouslyinhumans.Serialserum samplesarecollectedforperiodsup tothree hours. These samples are fractionated using Sephadex gel filtration and are counted by dual isotope techniques. From this, three sets of data points are obtained: the disappearance of MICRO-AA, the disappearance of 1251—,and the appearance of catabolic products of MICRO AA, mostly in the form of 1311—.Using a digital computer and non-linear least squares fitting, the first two curves can be described by sums of two exponents with constant coefficients. The first curve provides a measure of the phagocytic rate of the RES. Initial rates are the same in all subjects tested, but immunosuppressed patients have a slower rate at two hours suggesting impaired phagocytosis of the smaller of the MICRO-AA particles. The second curve characterizes the distribution of “free―iodide and is used to correct the third curve. Using this corrected curve and a simulation program, the total amount of MICRO-AA in the RES at any time is determined and the rate of release of its metabolites measured. This rate in creases during the first hour and then remains essentially constant. Data from patients with normal RES's will be compared to that from renal transplant recipients and patients with hematopoietic malignancies. iThis work was supported by U. S. Public Health Service Research Grant No. HE 09112and U. S.PublicHealthServiceFellowshipNo. 1-F2-A1-24,212-01. 296 ABSTRACTS

J-5 “Measurementof the Phagocytic Capacity of Aggregated Albumin and the Removal Capacity of BSP from the Liver.― U. U@A, M. ho, H YAMADA, K. KITANI,S. TAKASE,ANDH. KAMEDA,( University of Tokyo, Japan) In a previous report, we have presented data indicating that the phagocytic capacity of the RES can be obtained safely by measuring the rate of disappearance of various doses of labeled aggregated albumin particle. Our results (ho & Wagner) demonstrated that the mechanism of removal of aggregated albumin followed the mathematical model suggested by Michaelis and Menten in the enzyme-substrate systems. In patients with infectious disease and in patients with certain viral infections, an increase and a decrease in the ability of RES to remove this particulate matter were respectively observed. In the present study, we have utilized a further improved system to measure human @ RES capacity combined with a labeled BSP system to measure polygonal cell removal capacity quantitatively. Since clearance of BSP was also found to follow the Michaelis and Menten model, a similar method and mathematical analysis was performed to measure maximal removal capacity of BSP. By the present system, maximal phagocytic capacity of control cases was calculated as 0.340 mg/kg/mm. Contrary to the previous viral infections studied, cases with viral hepatitis showed marked increase ( in some cases more than twofold ) in this capacity. Cases with liver cirrhosis did not show any significant change in RES capacity. Maximal removal rate of BSP was calculated as 0.88 mg/kg/mm in normal subjects. Decreased value was observed in cases with hepatitis, while in a case with Dubin-Johnson syndrome, this value remained within the normal range.

J-6 “Specificityof reticuloendothelial blockade by colloidal particles.― LYNN R Wmn@iisPooN, RUSSELL C. BRIGGS, AND DONALD R. KORST, ( Departments of Radiology and Medicine, Section of Nuclear Medicine, University of Wis consin, Madison, Wisconsin) Previous studies indicate that the extent of blockade is greater and recovery of the reticuloendothelial system ( RES ) from colloidal blockade is more prolonged when measured by radioactive homologous colloid than when measured by radioactive heterologous colloid. This study was designed to further explore the specificity of RES blockade in the rat. Varying intravenous doses of non-radioactive colloidal gold (Au) or microaggregated human serum albumin (AA) were followed in fifteen minutes by uniform test doses of either the homologous (Au + ‘98Auor AA + AA —1311) or heterologous (Au + AA —1311 or AA + ‘98Au)radioactive colloid. Fifteen minutes following the radioactive test dose the animals were sacrificed and radioactivity in blood, liver, spleen, and femur was measured. The blocking dose of non-radioactive colloid was increased until the tissues assayed were refractory to a homologous test dose, with more of the injected test dose remaining in the blood. The ratio of activity/gm tissue to activity/gm blood was plotted against the mg/kg blocking colloid. When increasing doses of blocking colloid were followed by test doses of homologous colloid, a rapid decline in the tissue/blood ratios was observed for all three tissues. Similar curves were obtained for Au + 198Au and AA + A_A — 1311. When, however, the blocking colloid was followed by heterologous colloid, the decline in the ratios was much less pronounced and the curves could not be depressed to the level observed with homologous colloid, even with massive doses of heterologous blocking colloid. Tissue activity/tissue ac tivity ratios were also calculated from the above data. Information obtained suggests that the mechanism of RES blockade involves at least two components: 1) a mass action effect seen when blockade is measured by heterologous colloid and, 2) a specific block seen when blockade is measured by homologous colloid.

J-7 “LymphNode Scanning with Radioactive Gold.―EDDY C. K. TONG, AND Sm NEY RUBENFELD, (New York University Medical Center, New York, N. Y.) One hundred scans of nodes in the cervical, axillary, parametrial, inguinal and retroperi toneal chains were performed on patients with cancers or lymphomas in the head and neck, FOURTEENTh ANNUAL MEETING 297 breast and cervix, using radioactive gold, whose chemical and physiological features make this radiopharmaceutical an ideal agent for this type of study. This experience has led to elaboration of satisfactory techniques in scanning, dose levels, sites of injection, determination of effective half lives, absorbed dose at the site of infection, and other significant factors, all of which will be presented. Lymph node scans in the anatomic sites mentioned above in normal and pathological states will be shown and the potential usefulness of such scans emphasized.

Thursday, June 22, 1967 2:00—3:30 P.M. Spanish Lounge

SESSION K. IRON, COPPER, ZINC AND MANGANESE METABOLISM Session Chairman: CLEMENT A. FINCH, Seattle

K-i “Theinfluence of the Rate and Dose of Oral iron Administration on the Rapid and Slow Phases of iron Absorption.― R A FAWWAZ, H. S. WIN CHELL, M. POLLYCOVE, T. SARGENT, AND J. H. LAWRENCE, ( Dormer Labora tory, Berkeley, California) Iron absorption from the gastrointestinal tract occurs in two phases : 1 ) a rapid phase occurring within the first few hours and associated with the passage of intraluminal iron through the proximal small bowel, and 2 ) a slow phase occurring during subsequent days associated with the presence of iron retained in the upper small intestinal tract subsequent to the passage of the iron containing bolus. The purpose of this communication is to demonstrate that with an increase in the rate of administration and dose of ingested iron, there is an increase in the ratio of the amount of iron absorbed during the rapid phase to that absorbed during the slow phase. Intestinal iron absorption was studied, using three isotopes of iron. Iron-52 and 59Fe were administered orally to normal fasting subjects. Concurrent with the ingestion of the above isotopes, 55Fe was administered intravenously. The per cent of orally administered 59Fe ab sorbedand retainedin the body overa two week periodwas measured,utilizingthe whole body counter. The rate of absorption into the plasma of orally administered 52Fe was calcu lated, utilizing Hallberg's method. The visualization of the distribution in the body of orally administered 52Fe was achieved, utilizing the Anger Positron Camera. With increasing doses of orally administered carrier iron there was an increase in the total amount of iron absorbed into the body, although the fraction of the administered dose which was absorbed decreased and an increase in the fraction of iron absorbed during the rapid phase as opposed to the slow phase. When the relative absorption of iron is compared between a constant quantity of carrier iron given as a constant intragastric infusion and a single oral dose, there was an increase in the total amount of iron absorbed; and an increase in the fraction of iron absorbed during the slow phase in association with increased retention of orally administered 52Fe in the proximal small bowel. These results suggest that the processes responsible for the slow phase of iron absorption are more readily saturated than those responsible for the rapid phase.

K-2 “Thevariation of Plasma iron-59 Clearance T½ with Plasma iron Concen tration.―M A QUAIFE,ANDL. T. ODI@iir, (Special Laboratory of Nuclear Medicine and Biology, Omaha, Nebraska, and USAF Radiological Health Laboratory, Wright-Patterson Air Force Base, Ohio) The application of iron metabolism studies, particularly those of plasma radioiron clearance rate to the measurement of the effects of ionizing radiation upon humans and ex perimental animals, has been documented. Factors other than the depression of hematopoietic function which prolong the plasma radioiron clearance rate thus become important in the evaluation of results. It has been suggested that information on the status of erythropoiesis 298 ABSTRACTS

‘ based on clearance rate is so dependent upon the iron level that it has little meaning unless the serum iron levels are measured concomitantly. This suggestion of a direct interrelationshi@, coupled with a report of hyperferremia post-irradiation in experimental animals prompted the investigation of the relationships between plasma iron content and the plasma 59Fe clearance half-time under normal or basal conditions. The study was carried out in 22 sexually mature beagle dogs ( 11 males and 11 females). The mean plasma iron level was 163.1 ug% ±27 ug% with a SE of ±5.8 ug%. The mean plasma 59Fe clearance half-time was 85 mm ± 14 mm with a SE of ±3 mm. The values of individual triplicate determinations of the foregoing were analyzed for interrelationship. The correlation coefficient was .29, which indicated poor correlation, and a nonparametric paired sign test indicated a random distribution. Complete studies of the peripheral hemato logic picture conducted concomitantly with the foregoing indicated normalcy of hematopoiesis in the experimental subjects.

K-3 “ironAbsorption in Hemochromatosis Before and After Therapy.―T SAR @ ANDH. S.WINCHELL,(DormerLaboratory,Universityof California, Berkeley, California) In patients with endogenous hemochromatosis, prior to phlebotomy when serum iron concentration is elevated, intestinal iron absorption is usually within normal limits. To demon strate that such patients have an intrinsic, abnormally high iron absorption at times when their storage iron depots and serum iron concentration are at normal levels, six patients with endo genous hemochromatosis were studied before and after phlebotomy therapy. The fasting subjects were given 2 to 4 @Cof 59Fe orally with 4 mg FeSO4. The 59Fe retained two weeks later, as measured with a whole body counter, was taken as the per cent of the dose absorbed. The results were compared with the normal range previously defined by a regression func tion relating absorption to reticulocyte count. All six patients had absorption within or below the normal range prior to therapy. Four months to one year after completion of phlebotomy therapy, at a time when serum iron concentration was normal and the patient was normochro mic and normocytic, iron absorption was found to be markedly increased above the normal range. Subsequently, three of these patients had a gradual increase in serum iron without further phlebotomy, indicating a partial repletion of iron stores. A repeat iron absorption test showed that absorption was again within the normal range when serum iron was ele vated and tolerance to subsequent phlebotomy confirmed that iron stores had indeed been increased at this time. These results demonstrate a definite abnormality in iron absorption in endogenous hemochromatosis, ruling out the possibility that the disease is due solely to excessive iron intake.

K-4 “Ferrokinetics iron-59 of Copper-Calcium Deficiency Anemia in Mice.―1 R B CHODOS, D. A. RICHERT, R. WEU.s, JR., W. H. STORY AND W. W. WESTERFELD (Nuclear Medicine Service, Veterans Administration Hos pital, Syracuse and the Departments of Medicine and Biochemistry, State University of New York Upstate Medical Center, Syracuse, New York) Young mice maintained on an exclusive meat diet develop a severe macrocytic anemia witha megaloblasticbone marrow.Thisanemiamay be preventedor treatedsuccessfullyby copper or calcium (Guggenheim et a!), but is unresponsive to iron and other hemopoietic factors. Studies were undertaken to determine if a synthetic casein-base copper and calcium deficient diet would produce a similar anemia in mice and whether the anemia could be treated successfully by copper or calcium. Radioiron tracer methods were utilized to define the effect of copper (and calcium) upon erythropoiesis and iron metabolism in deficient and treated anemic mice. The deficient diet produced an anemia that was prevented by copper or calcium and was successfully treated by both agents. The response to copper was more rapid and com plete.

‘Researchsupported in part by Ronnie Greenhouse Fund. FOURTEENTH ANNUAL MEETING 299

Ferrokinetic ( 59Fe ) studies in copper-calcium deficient anemic mice revealed a striking increase of radioiron in the liver and a marked decrease of radioiron incorporation into hemo globin. Hepatic radioiron decreased significantly and hemoglobin radioiron increased when copper or calcium was administered to deficient, anemic mice. The response again was more rapid with copper than with calcium. Corresponding hematologic data revealed an increase in reticulocytes with a proportionately greater increase initially in the hematocrit than in hemoglobin levels, producing a decrease in mean corpuscular hemoglobin concentration ( MCHC ). As hemoglobin synthesis increased, radioiron was released from the liver and the MCHC returned toward normal. These data suggest the anemia resulting from a copper-calcium deficient diet is due to a maturation arrest of erythropoiesis and a decrease in heme synthesis. It is associated with a striking increase in hepatic iron. Copper and calcium would appear first to produce matura tion of erythropoietic elements and then an increase in hemoglobin synthesis.

K-S “Zinc-65Metabolism in Cirrhotic Rats.― ARTHUR M. KAHN, PANCHITA B. THOMAS, AND JAMES G. R@R, ( Surgical and Radioisotope Services, Wads worth Hospital, Veterans Administration Center, Los Angeles, and the Department of Surgery, UCLA School of Medicine, Los Angeles, Cali fornia)

Patients with alcoholic cirrhosis have been found to have a decreased concentration of zinc in both liver and serum, as well as hyperzincuria. Rats with carbon tetrachloride induced cirrhosis also have significantly decreased levels of liver and serum zinc. The purpose of this report is to further delineate the pathogenesis of the zinc deficiency associated with cirrhosis of the liver. The gastrointestinal absorption of zinc was determined in fifteen normal and nine cir rhotic rats following the intragastric administration of zinc-65. The degree of radioactivity was measured daily by whole body counting of each animal until the initial unabsorbed 65Zn had been excreted. The control group absorbed and retained 14.4 per cent of the administered dose compared to 15.6 per cent for the cirrhotic group. This difference was not statistically significant. The uptake of 65Zn was measured in the serum, liver, and spleen of twenty-nine normal and ten cirrhotic rats. Three hours following the subcutaneous injection of the 65Zn, the animals were sacrificed and the amount of radioactivity was measured in the serum, liver, and spleen of each animal. The uptake of 65Zn in cirrhotic livers was significantly greater than normals. Contrariwise, the serum and spleen of the cirrhotic animals took up signifi cantly less of the 65@ than the control group. Increaseduptakeofparenterallyadministered65Znby thecirrhoticliverand normalgas trointestinal absorption suggest that the zinc deficiency in the serum and liver of cirrhotic rats may be due to other causes. These causes include increased excretory losses, altered transport mechanisms, or dietary deficiency. These possibilities are now being investigated.

K-6 “Zinc-BindingCapacity of Serum.―1WnLLtM H STRAIN,CHARLESG. ROB, WALTER J. PomEs, JohN A. HENNESSEN, WESLEY BARKER, AND JoHN MON TOYA, (School of Medicine and Dentistry, University of Rochester, Roch ester, New York, and USAF Hospital, Wright-Patterson AFB, Ohio) A method ‘hasbeen developed for measuring the zinc-binding capacity (ZnBC) of serum. The test is conducted in plastic containers with 0.1 @Cof buffered carrier free 65Zn and a cationic resin sponge or powder. The procedure is similar to the well-known T-3 and iron binding tests. We have used the zinc content of head hair in the past to estimate zinc deficiency and

iThis research was supported in part by grants HE-10213 and RH-00042, USPHS; by the Horatio H. Burtt Research Fund of the University of Rochester; and by a grant from the Aerospace Medical Division, under approval of the Surgeon General, U.S.A.F. 300 ABSTRACTS

sufficiency in man. We found the male Egyptian dwarfs studied by Prasad et a! to have a mean hair zinc level of 54 ppm before zinc therapy and 123 ppm after treatment for some months with oral zinc sulfate USP [Strain et a! J. Lab. Gun. Med. 68:244 ( 1966)]. Similarly, 25 male patients with proven atherosclerosis had a mean hair zinc level of 62 ppm before treatment with zinc sulfate. Hair analysis has a definite place in zinc therapy, but is cumber some. The ZnBC test has been applied to a variety of problems. Zinc deficiency has been de fined by measurements on sera from zinc deficient and sufficient mini-pigs. Sera from normal young males have been studied to determine normal distribution range, seasonal variations and correlation with total zinc as measured by atomic absorption. These normal values are contrasted with similar measurements made on sera from patients with zinc deficiency.

K-7 “TheMetabolism of Manganese in Chronic Manganese Poisoning.―ISMAEL MENA, SERGIO FUENZALIDA, GEORGE C. Co@rzi@s, ( Department of h@li@i@ Medicine, Catholic University, Santiago, Chile, Brookhaven National Lab oratories, Upton, New York)

Chronic manganese poisoning occurs among miners due to inhalation of ore dust. The clinical picture is characterized by a period of psychomotor excitement and, later on, by an ir reversible phase of neurological damage due mainly to extrapyramidal involvement. Ninety per cent of the patients have features very similar to Parkinson's disease. Furthermore, the severity of these symptoms makes it a crippling and irreversible process. The striking similarity of chronic manganese poisoning and Parkinson's disease suggest the convenience of evaluation of the metabolism of this trace metal. Determinationof the metabolismof manganese was made by means of studyingthe fate of 54Mn carrier free injected intravenously into three different populations, mainly manganic patients, healthy manganese miners, and healthy hospital personnel in the city of Santiago. Whole blood and plasma clearance were studied by means of continuous blood sampling at frequent intervals during the first day and daily thereafter, during a period of 30 days. Whole body counts and regional counts over liver, brain and thigh were performed daily during a 30-day period. Results can be seen in Table I and Table II. These findings suggest that manganese dissapears from the blood in 95-99% of cases with a rapidity compatible with single passage clearance and that the whole blood and liver manganese clearance are rapid as compared with other pools, namely the brain and thigh. However, there is a distinct difference among the three populations observed: the healthyworkingminersexposedto manganese dusthave fasterturnoversthan the chronic patients and normal controls, thus indicating that rapid clearance of manganese coexists with exposure to manganese dust, but not necessarily with disease.

TABLE I

BloodA) GroupT3/@ PlasmaT@ Whole

@ mm.B)Normals (19)1.34 0.3 mm.1.28 0.2

@ mm.C)Miners(20)2.03 0.7 mm.2.19 0.4

@ mm.SignificantChronicPoisoning(18)1.44 0.2 mm.1.33 0.2

versusB: versusB: DifferencesA 0.01 < P <0.02A 0.001 < P < P0.01 FOURTEENTH ANNUAL MEETING 301

TABLE II

Whole Body Liver Head Thigh (days)A) GroupT3/@ (days)T@ (days)T@/@ (days)T3/2

@ 11B)Normals (19)37.5 7.5 d24.6 * 754 * 557 *

*337*1539*19C)Miners(20)15 *2 d13

Chronic16SignificantPoisoning (18)28.3 * 8 d26 * 762 * 648 *

versusB: versusB: P <0.001 P <0.001 DifferencesA B versus C: B versus C: 0.001

Thursday, June 22, 1967 9:00—10:30 A.M. Georgian Room

SESSION L. RADIOPHARMACEUTICALS I Session Chakman: WILLIAM G. MYERS, Columbus

L-1 “ComparativeEvaluation of Technetium-99m, Cakium-68 and indium-113m for Liver, Lung, Kidney, and Brain Visualization.― KATHERINE A LATHROP, PAUL V. HARPER, ALEXANDER GOTTSCHALK, ROBERT N. BECK, GARVAS M. HINN, PEGGY FINSTON, AND TOBY D. COHEN, ( Argonne Cancer Research Hospital [operated by the University of Chicago for the United States Atomic Energy Commission], and the Departments of Surgery and Radiol ogy, University of Chicago, Chicago, Illinois) Three short-lived radioisotopes U9mTc, 68Ca and ll3mIn, currently available from gen erators as daughters of long-lived parents, may be manipulated chemically so that they can be used for liver, lung, kidney and brain visualization. Various considerations in their use have been investigated, including cost, convenience, radiation dose to patient and personnel, ease of preparation, FDA acceptability, and scan quality, using a rectilinear scanner and a scintillation camera with positron attachment. Localization studies in animals, phantom studies, clinical scans, measurements of modulation transfer functions and detector sensitivities have been made under a variety of conditions in an attempt to compare these agents quanti tatively. Physical comparison includes detectability of similar lesions under conditions of con stant radiation dose to the patient and constant observed count rate. Economic comparison is based on cost, time for preparation and investment in ancillary chemical equipment. An at tempt is made to arrive at the circumstances under which each agent, for each machine, for each procedure, could be used most favorably. Preliminary conclusions indicate that where the clinical volume is large, O9mTc is the favored single agent in most categories and that, in some cases, simultaneous double or multiple isotope studies with the other agents may in crease the information yield.

L-2 “Distribution and Scintiphotography Studies of a New Bone-Marrow Scan ning Agent: Technetium-99m-iron Colloid.― SHIN-HWA Yllhl, JOEL OHL5EN, 302 ABSTRACTS

SAMUEL L. KOUNTZ, AND JOSEPH P. KRISS, ( Division of Nuclear Medicine, Stanford University School of Medicine, Palo Alto, California) A DDmTc..Fe colloid has been synthesized as follows: 99mTc(VII) was reduced with ascorbic acid in the presence of thiocyanate and the colloid was formed by neutralizing the reduced material with the alkali-modified stabilizers Dextran and gelatin in the presence of ferric chloride and then heated to form a stable, clear, brown solution. The formation of the colloid is rapid and almost complete. The product can be identified by radiochroma tography in 85% methanol and its colloidal character verified by microscopy and filtration through the millipore filters. The tissue distribution of the OOmTc..Fecolloid was performed in the rabbit. When the colloid was injected intravenously, most of it was rapidly excreted in the urine with a half-time of less than five minutes. The remainder was slowly cleared from the circulation as well as fixed in the bone marrow and the kidney. On sacrifice at 1.5 hours after injection, 2 to 4% was recovered in the skeleton including the marrow. No significant radioactivity was noted in the liver, stomach, spleen and intestine. Scintiphotographic studies using an Anger-type scintillation camera fitted with a multi channel collimator were performed in rabbits. After intravenous injection of approximately 200,@C/kg of the 9OmTc..Fe colloid, the bone marrow in the spine and pelvis was clearly vis ualized. The scintiphotos of the kidneys and cardiac blood pool were also obtained. No image of the liver was demonstrated. It is necessary to empty the urinary bladder before pelvic marrow scanning, because the kidney excretes much of the injected dose. The simplicity of preparing the colloid, the physiologic behavior of the compound and the favorable physical characteristics of 99mTc indicate potential clinical usefulness of this agent for bone-marrow visualization by scintillography.

L-3 “Factorsinfluencing the Distribution of Labeled Hydrous Ferric Oxide Col laid.―R L HAYES, J. E. CARLTON, B. L. B@iw, @iJ. J R@vr@n, (Medical Division, Oak Ridge Institute of Nuclear Studies, an operating unit of Oak Ridge Associated Universities, Inc., Oak Ridge, Termessee, under contract with the United States Atomic Energy Commission) Stable colloids of hydrous ferric oxide are readily prepared by the hydrolysis of dilute solutions of ferric salts. This colloid can be used as a scanning agent when labeled with an appropriate radionuclide. The particle size of the colloid may be varied by control of the rate of hydrolysis through alterations in ferric salt concentration and heating rate. The factorsthatinfluencethe distributionof 68Ga-labeledhydrousferricoxidecolloidsare being investigated in detail with emphasis on attainment of enhanced deposition in bone marrow. Results should also apply to ferric oxide colloids labeled with other radionuclides. The blood clearance of intravenously administered colloids is profoundly affected by the total number of particles administered. Studies have shown that the number of particles ad ministered in turn has quite a dramatic effect on the early deposition of this colloid in bone marrow. Ratios of bone-marrow concentration to liver concentration as high as 5:1 one hour after administration have been achieved by control of this factor. The type and amount of lyophilic stabilizer used in the preparation of °8Ga-labeled hydrous fernc oxide colloids also appears to have an effect, though less dramatic, on the deposition of this material in the bone marrow. Investigation of the effect of particle size on distribution will require a knowl edge of the particle size distribution so that the number of particles administered can be held constant.

L-4 “Technetium-99m Labeled Compounds for Possible Pancreatic Scanning.―' MANUEL Turns, WILLIAM H. BI.AIw, AND JOHN S. ENDow, (Radioisotope Research Laboratory, Veterans Administration Center, Los Angeles, Cali fornia, and the Departments of Radiology and Medicine, UCLA Center for the Health Sciences, Los Angeles, California)

iSupported in part by a grant 549141-40559 from the American Cancer Society. FOURTEENTH ANNUAL MEETING 303

Studies will be reported of the progress of labeling with vamTc of the pancreatrophic amino acids cysteine, cystine and methionine, as well as the gastrointestinal hormones pancreozymin, secretin and a secretin-like synthetic polypeptide. The advantages of the radionuclide 99―Tc label and the use of the above non-toxic compounds are obvious. Results to date show that a labeled cystine or methionine compound of adequate specific activity can be prepared rapidly. Cysteine has been shown to reduce pertechnetate to 99mTc of lower valence states, and simultaneously becomes oxidized and binds the 9OmTc. The iron-oxidized ascorbic acid-technetium complex does not bind to cystine and methionine as it does to albumin, but rather makes the vvmTc unavailable for incorporation into the amino acids. Modifications of the methods of preparation of these labeled compounds are being investigated so as to increase their specific activity by the use of traces of carrier metals and other means. Experimental details will be presented for the preparation and characterization of these compounds, as well as the results of organ distribution studies.

L-5 “RadioalhuminSuspensions of Higher Specific Activity and More Uniform Size.― GEORGE V TAPLIN, MARY LER GiuswoLD, Ju.@rnm Huiuwrr, AND DELORES E. JOHNSON, ( From the Laboratory of Nuclear Medicine and Radiation Biology, UCLA School of Medicine, Los Angeles, California, and the Los Angeles County Harbor General Hospital, Torrance, California) A need exists for improved radioalbumin suspension in lung, liver and spleen scanning and for estimating liver blood flow by the colloid blood disappearance method by Dobson. Colloidal radiogold is composed of particles ( 5-30m@) too small to permit accurate estimation of liver blood flow and is inadequate for satisfactory visualization of the normal spleen by scanning. Currently available radioalbumin macroaggregates contain 10-20% unaggregated albumin, some colloidal size aggregates and as much as 5% free radioiodine. These Un desirable properties should be eliminated because they contribute to the radiation exposure of the patient unnecessarily and detract from the efficiency of lung scanning. Macroaggre gated radioalbumin suspensions of higher specffic activity (1-2 mC per mg) and narrower size range (1S-40/L) are needed for lung scanning and are mandatory for cerebral cortical blood flow assessment by scanning in man. Four new techniques were employed during the past year to produce radioalbumin suspensions of more uniform size. These include a standard microwave oven (Tappan) to obtain more uniform distribution of energy absorption during the heating process; an ultra sonic agitator which selectivity disrupts large aggregates and permits elimination of exces sively large particles from the suspension; and reheating of the samples by immersion in boiling water to increase the size of small aggregates in the suspension. Finally, simultaneous ultrasonic agitation and hot water immersion shows great promise as a possible single pro cedure for producing suspensions of any desired size range. Microaggregated albumin suspensions (1-SAL) are more efficiently extracted from the blood by the liver and spleen and are removed from these organs 3-4 times more slowly than small colloidal (5-30m @)suspensions. They can be prepared quickly and efficiently by microwave heating and ultrasonic agitation. Microwave exposure for 15-20 seconds con @ verts albumin solutions into 1-20 size aggregates. Ultrasonic agitation for 10-15 minutes breaks down the larger aggregates selectively and produces suspensions of more uniform size (1-5/h). Splenic accumulation of the 1-5/h aggregates is much greater than from small colloidal suspensions of albumin or gold and permits adequate visualization of this organ in normal subjects. Photomicrographs of microradioalbumin and macroradioalbumin suspensions prepared by these new techniques will be presented to demonstrate the improvements attained. In addition, results of clinical and experimental applications of the improved test agents will be presentedtoshow theiradvantages. 304 ABSTRACTS

L-6 “Colloidal indium-113m for Liver, Spleen and Bone Marrow Scanning.― DAVID A GOoDwIN, How@uw S. STERN, AND HENRY W. WAGNER, JR., ( Divi sion of Nuclear Medicine, The Johns Hopkins Medical Institutions, Balti more, Maryland) Liver, spleen and bone marrow scanning may be performed with a variety of radio colloids which are phagocytized to the reticuloendothelial system after intravenous injection. Carrier-free ilamIn, obtained from lIaSn@llamIn generator, can be easily made into a colloid which is taken up by the RES. Gelatin ( USP ) is added to a column eluate of lI3mIn and the solution adjusted to pH 7-8 with dilute sodium hydroxide. The final gelatin concentration approached two per cent ( 20 mg/mI ). In mice, after intravenous administration, the liver concentration approaches 80 per cent; the spleen approaches 10 per cent and the rest ap pears in the bone marrow ( four per cent per gram ) and other RES sites. Preliminary calculations indicate an approximate radiation dose to the liver of 0.5 rad per millicurie, with a lesser amount to the spleen and bone marrow. For liver, spleen and bone marrow scanning we have used 1-2, 3 and 5-8 millicuries, respectively. Visualization of these tissues is excellent and comparable to scans obtained with 99mTc@sulphur colloid. One distinct advantage of lismIn colloid—in addition to decreased scattering because of the 390 KeV photon—is the absence of radioactivity in the gastrointestinal tract and bladder. The latter problem has been associated with preparations of DDmTc@sulphurcolloid containing free pertechnetate ( 99@'TcO4-) ion and in those patients receiving 99@'Tcpertechnetate for a brain scan 24 hours prior to the liver, spleen or bone marrow scan.

L-7 “TheUse of Stannous Hydroxide Precipitates as a Radioisotope Carrier in Perfusion Scanning.― ROBERTO MAASS, AND JORGE ALVAREZ, (Dirección de Medicina Nuclear, Comisión Nacional de EnergIa Nuclear and Centro Hospitalario 20 de Noviembre, Mexico City) In 1963, when Taplin published his first paper on the use of macroaggregates of radio albumin ‘@‘Iin determining the pattern of pulmonary blood flow, he was actually initiating an originalmethod which could be appliedto perfusionstudiesof multipleorgansor systems. The ever growing interest in studies using Taplin's technique has brought with it a search for new isotope carriers and improvements in the procedures. There is a trend towards the development of more uniform vehicles and of radioactive particles better suited for the specific scanning problem under study, as well as for the increased safety of the patient. Several authors hoping to take advantage of the benefits of vDmTc, have proposed methods for the preparation of macroaggregates of radioalbumin labeled with this isotope. However, eluting 99@'Tcfrom the generator and subsequently labeling albumin with it and precipitating macroaggregates, is a rather time-consuming procedure. Therefore, there is evidently a need for a fast and reliable method for obtaining scanning agents labeled with technetium-99m. A new approach has been proposed by Stern et a! using ll3mJn, which is coprecipitated with ferric chloride to form homogeneous particles similar to albumin macro aggregates of a size suitable to be trapped in pulmonary arterioles for a period of several days and which are used as carriers for the radioactive isotope. In this paper we are setting forth the first published experiences in humans with stannous hydroxide, which we have found to be an excellent carrier for vvmTc and with which we have developed a rapid and reliable method to produce uniform precipitates of convenient size. The scanningstudieswhich we are presentingwere accomplishedusing thisnew product.We aLsopresentour findingswith regardto the sizeof precipitatesand their biologic behavior in pulmonary tissue. We have also established the capability of these precipitates in serving as carriers for other radioisotopes. The advantages inherent in the use of this product are considered. FOURTEENTH ANNUAL MEETING 305

Thursday, June 22, 1967 11:00—12:30 P.M. Georgian Room

SESSION M. RADIOPHARMACEUTICALS II Session Chairman: H. DAVIS BRUNER, Washington, D. C.

M-l “Radiocarbon-il for Scanning.―' WILu@tM G MYERS, AND WILLIAM W. HUNTER, Ja., (The Ohio State University HeaUhCiii@r, Columbus, Ohio) Scintillation cameras and fast mechanical scanners make feasible applications of short lived (half-life = less than one hour ) ‘y-isotopesfor “inside-out―fluoroscopy. The 20.5-minute +@-isotope, carbon-il, consequently becomes of major significance for nuclear medicine because of its potential as a label for much of the 18% of carbon in us. The two 511-keV “back-to-back―annihilation photons emitted incidental to “Cdecay are available for in vivo studies of 11C-labeled metabolites and pharmaceuticals. Localizations may be by directionalized detectors coupled either to single or high-resolution coincidence, or time-of-flight circuitry. The short physical half-life of 1IC produces low radiation exposures. Among the many 11C-labeled compounds synthesized in this laboratory during the last @ decade, 1‘CO2and IC carbonates are most readily prepared and initial applications of them for scanning are now under study. Carbonate normally constitutes several per cent of bone and a labile exchange occurs between this carbonate and blood bicarbonate. A basic isotonic solution of ‘ @@o2was in jected intravenously into several dogs with primary osteogenic sarcomata. Marked tumor target/nontarget accumulations were apparent on scans within 10-20 minutes after injection. Pancreatic juice is high in bicarbonate, especially during secretin stimulation. Accumula tion of IIC in the pancreas region was faintly discernible on some of the scans. Studies designed to stimulate pancreatic secretion of 1‘C-bicarbonate are in progress to optimize the pancreas/nontarget ratio for scanning. Tomography with the Anger positron scintillation camera should be especially useful for such studies. Intravenousinjectionoftemporarilyinsoluble11C carbonatesof calciumand/orstrontium (labeledalternativelywith8TrnSror 85m5rprovide“y-raycarrier―particlesforscanninglungs and otherorgans. ‘Supported by the Julius Stone Fund for Research in Medical Biophysics and by funds appropriated for cancer research by The Ohio Legislature.

M-2 “NewMedical RadionuclidePreparationsfrom ORNL isotopesDevelopment Center.―'H B HUPF, H. A. O'Bun@N,JR., AND R. E. LEwIS, (Isotope De. velopmeniCenter, Oak Ridge National Laboratory, Oak Ridge, Tennessee) One of the functionsof the IsotopesDevelopmentCenterof ORNL is to study the production and chemical separation technology for commercially unavailable radionuclides which may have value in nuclear medicine. Medical and biological researchers desiring these uncommon nuclidesforevaluationareinvitedto participateincooperativeprogramswiththe Center.In theseprograms,both productiontechnologyand medical usefulnesscan be evaluated for reactor-produced and cyclotron-produced radionuclides. We studiedtheproductionof la4mCsand ‘29Cswhich have been proposedas medical @ tools for following blood flow to organs. Currently, (T1 = 9.7 d, 30-keV x ray) is being used for locating myocardial infarcts, but has limited usefulness for deep-seated organs becauseofthelow energyemission. Cesium-134m (T1 = 2.9 hr, 0.130-MeV gamma) is an ideal radionuclide for measuring blood flow; however, production by the l33Cs(n,.y)Is4mCsreaction is complicated because of the concurrent production of ‘34Cs(T1 = 2.1 y) by neutron capture and by decay of the isomericstate.Yieldsforthree-hourirradiationsof CsNO5 targetsin thermalneutronposi 1Research sponsored by the U. S. Atomic Energy Commission under contract with the Union Carbide Corporation. 306 ABSTRACTS

tions of the ORR averaged 44.4 mCi Ia4mCs per mg target and 0.120 mC 134Cs per mg target. The presence of long-lived ‘34Csmay be a limitation to the medical usefulness of cesium-134m. Of the cesium nuclides investigated, ‘29Cs(T1 33 h ) has probably the best potential as a medical radiodiagnostic agent. It decays by electron capture (no beta particles) and emits several gamma rays near 0.4 MeV. Yields of approximately 50 /LC I29Cs per mg 130Ba were obtained by bombarding isotopically enriched ‘3OBa(N03)2contained in a thin-walled aluminum tube for two hours in the proton beam of the ORNL 86-inch Cyclotron. The separated product was radiochemically pure, except for a trace of l3ICs, and the target was recovered for reuse. Cooperative programs involving radionuclides such as 1231, 69mZn, 83Rb, ‘88Re,47Sc, and 3@Phave also been established for medical and biological evaluation.

M-3 “Lungand Liver Scans with Chromium-Si Labeled Dextran.― ALBERTE JoHNSoN, AND FRANK Gou@, (Veterans Administration Hospital and Uni versity of Miami School of Medicine, Coral Gables, Florida) Dextran, a polysaccharide of about 200,000 glucose units, with a molecular weight of ap proximately 40 million, can be converted by hydrolysis to polysaccharides of any desired range of molecular weights. These glucose polymers of less than 10,000 to two million molec ular weight ranges were tagged with chromium-Si by an autoxidation technique and injected intravenously into rats. The distribution and excretion of the labelled dextrans was followed by scanning the intact live animal, by measuring the clearance times of the labelled dextran by whole body counting, and by quantitative assay of individual organs. The lower the molec ular weight of dextran, the more it concentrated in heart and lung tissue and the faster it was cleared by the kidneys; the higher the molecular weight the more it concentrated in the liver. Thus, a soluble dextran polymer of two million molecular weight concentrated in the liver in sufficient quantity to permit scanning with good resolution. Since this material clears the various tissues at a uniform rate, it is possible to use a single low dose of this pure gamma emitting 51Cr dextran for serial scanning of the liver over a prolonged period of time. High molecularweightdextranintheformofSephadexparticlesoflessthanfourmicraindiameter, aretakenup by the liverin lessthan 10 minutes,whereashigh molecularweightdextran beads of 10-40 micra are retained in the pulmonary circulation. Because of stable and uniform particle size the lung scans are of excellent quality. The labeling of glucose polymers with a pure gamma emitting isotope points to the great potential of such radioactive organic com pounds for external monitoring in experimental clinical applications.

M.4 “Assaysof Radioactive MateriaLs for Use in Patients—A Five Year Study.― PATRICIA A. CuccErr, AND JOSEPH M. BROWN, JR., (Radiation Safety Sec tion, National Institutes of Health, Bethesda, Maryland) For the past 13 years, the Radiation Safety Office staff of the National Institutes of Health has been responsible for the radioisotope assay and isotope purity vertification of all radioactive materials used in patients at the Clinical Center. A statistical study of the results obtained over the past five years is presented along with the methods employed in rapidly assaying radionuclides to a ± 10% value. The percentage of the total number of assays per year having discrepancies greater than ±10% has been determined and the frequency of gross error, i.e., exceeding ±50%,is discussed. Specific examples of discrepancies are given and the predominant causes of supplier error are examined.

M-5 “Useof a Clinical Whole-Body Counter for Radiopharmaceutical Dosim etry.―H N WELLMAN, J. KERKUJCEs, M. PETTUS, AND E. L. SAENGER, (Na tional Center for Radiological Health, Public Health Service, U. S. De partment of Health, Education, and Welfare, and the Radioisotope Lab oratory, University of Cincinnati) There is a continualneed for accuratebiologicaldata on radiopharmaceuticalsfor FOURTEENTH ANNUAL MEETING 307 dosimetry calculation. This need is especially applicable to new radiopharmaceuticals as they are introduced to the field of nuclear medicine. A program is described for continued collection of data on presently used radiopharmaceuticals, utilizing a whole-body counting room equipped with an 8―x 4―sodium iodide (Ti ) crystal and smaller collimated sodium iodide (Ti ) crystal systems for localized counting. Techniques to reduce geometrical effects and approximate “scanning data― are described. Results are reported in 47 patients studied for extended periods, usually greater than three months, after administration of a wide variety of radiopharmaceuticals, including 198Au, 4TCa, 60and 5TCo vitamin B,.,, 51Cr labelled red blood cells, 51Cr human albumin, 59Fe, 197and203Hg chlormerodrin, 1@197Hg@2@hyroxypropane,1311 sodium iodipamide, ‘@@Irose bengal, 1311 human albumin, 1311 thyroxine, T5Se selenomethionine, and technetium-99m pertechnetate. Where possible whole-body data are supplemented by “organ―counts. Similar data have been previously reported in children and an additional six children are herein described after administration of Na131I. Dose calculations are given based on these biological data. Future methods for obtaining more exacting dosimetry measurements are discussed.

M-6 “APreliminary Survey of the Medical Uses of Radioactive Materials.― KENNETH D WILLIAMS, AND JEROME H@u@nm@, (U. S. Public Health Ser vice, National Center for Radiological Health) In 1958, the Office of Isotopes Development of the U.S. Atomic Energy Commission contracted with the Stanford Research Institute ( SRI) to conduct a national survey to determine the current position of radioisotope use in the clinical practice of medicine. The SRI report estimated, at that time, that there were 400,000 administrations of radiopharmaceu ticals to humans. Since that time, researchers and clinicians have developed a wide variety of techniques devoted to the practical application of radioisotopes in medicine. The in creasing uses of radiopharmaceuticals has thus prompted the Society of Nuclear Medicine to investigate the scope and trends in nuclear medicine in the U.S.A. In 1966, the National Center for Radiological Health of the U. S. Public Health Service in cooperation with the Society of Nuclear Medicine contracted with the Stanford Research Institute to conduct a national survey of the medical use of radiosotopes and to plan, prepare, and implement a continuing census system. The present two-year study consists of three parts: 1) a general questionnaire sent to all medical users of radioactive materials, 2) a detailed questionnaire survey of a carefully selected sample from Part I, and, 3) the development of a continuing census system. The findingsfromthequestionnaireswillbe presented.

M-7 “Abstract:Radiation Exposure from the Use of a Molybdenum-99—Tech netium-99m Generator.― W MARION JORDAN, AND JOHN A. BURDINE, JR., (Nuclear Medicine Division, Department of Radiology, Baylor University College of Medicine, Houston, Texas) Radionuclide generators allow the Nuclear Medicine Laboratory to elute and use short livedisotopeswhich resultin lowerradiationdosagesto the patientsreceivingthem. Con sequently, it is possible to be lulled into a false sense of security if one is not aware that the radiationexposureto the laboratorypersonnelmay be much higherthan thatreceivedin dealingwithmore conventionalisotopes.The patient,to be sure,receivesa relativelyshort exposure because of the rapid decay of the radionuclide, but the technician is continually in contact with fresh isotope which in the larger doses employed emits a greater photon flux during the period of handling. Not only is exposure obtained during administration, but the isotope must be milked from the generator usually on a daily basis. In addition, the tech nician may have fairly intimate contact with the material for a considerable period of time, whiletheisotopeistaggedtovariouscarriers. When dealingwith isotopessuch as technetium-99m,in which the gamma energyis relativelysoft,theradiationdosageabsorbedby the hands ishigherin relationto the body 308 ABSTRACTS

dose than that found when using more energetic radionucides. Because of this, a film badge worn on the lapel or at the belt may not indicate the true exposure to which the body is subjected. The purpose of this communication is to present data which we have recorded over a consecutive six-month period during which we have eluted, calibrated and used the eluate from a 100 millicurie molybdenum-99-technetium-99m generator on a daily basis. Ring badges were worn by personnel involved in the milking and calibration process and a separate set by those who injected the isotope. Data was accumulated independently from these two groups, so that the comparative exposure could be determined. In addition, all personnel wore routine lapel or belt film badges and pocket dosimeters to record total exposure. This exposure record is presented along with a series of dosimeter readings made at varying distances from the isotope generator and injection sources.

Thursday, June 22, 1967 2:00—3:30 P.M. Georgian Room

SESSION N. THE LIVER Session Chairman: EUGENE L. SAENGER, Cincinnati

N-i “TheEffect of Biliary Obstruction on the Uptake and Secretion of Car bon-14-Labeled Cholesterol by the Isolated Perfused Rat Liver.― ROBERT M Fsiurns, HERBERTP. JACOBI,AND ANTHONYJ. B@uu@x,( Omaha Veterans Administration, Special Laboratory of Nuclear Medicine and Biology, and the University of Nebraska College of Medicine, Department of Biochem istry, Omaha, Nebraska) Biliary obstruction was produced for 48 hours in the adult male rats by ligation of their common bile ducts. These animals were then utilized as blood and liver donors for study with an isolated perfused rat liver. The perfusate consisted of blood diluted with an equal volume of Tyrode's solution. Carbon-14-labeled acetate added directly to the perfusate served as the percursor for the biosynthesis of C'4-labeled cholesterol in these livers. The accumulation of the synthesized C'4-labeled cholesterol in the perfusate was then measured. When livers and perfusate obtained from biliary obstructed rats were studied, a marked increase in the accumulation of C14-labeled free cholesterol was noted in the perfusate. The accumulation of C'4-labeled esterified cholesterol was not altered. In other experiments designed to study the uptake of C14-labeled lipoprotein cholesterol from the perfusate by liver, mevalonic-2-C14-acid as the dibenzylethylenediamine salt was injected intraperitoneally into either biliary obstructed or normal rats two hours before they were used as blood donors. Normal or blood from obstructed rats was then utilized as the perfusate from which the uptake of C14-labeled lipoprotein cholesterol by normal or ob structed livers, respectively, was followed. No marked differences were observed in the up take of C'4-labeled lipoprotein cholesterol in the two sets of experiments. Since the total concentration of cholesterol in “biliaryobstrutced― perfusate was greatly elevated, the actual rate of uptake of lipoprotein cholesterol from this medium by biliary obstructed livers must have been considerably greater than the uptake of lipoprotein cholesterol from normal livers. Although these data would indicate that in biliary obstruction there is an increased rate of uptake of cholesterol from blood by liver, the rate of secretion of cholesterol by liver into blood must be relatively greater in order to account for the net accumulation of choles terol in blood. Since the activity of C14-labeled cholesterol in normal and obstructed livers was the same after perfusion, even though the rate of cholesterol secretion by the latter livers was elevated, it follows that a higher rate of cholesterol biosynthesis occurred in the obstructed livers. The increased rate of secretion of cholesterol would appear to stem from an increased rate of cholesterol biosynthesis. FOURTEENTH ANNUAL MEETING 309

N-2 “Pulmonary Excretion of Selenium 75 and its Relationship to Liver Func tion.―JOSEPH STERNBERG, JULES BRODEUR, AND ARMAND MERCwiu, ( Univer sity of Montreal, Montreal, Canada) Administration of SeT5O3Na., to rat by oral or parenteral route is followed by a rapid exhalation of Se75, as volatile Se@( CH,, @2•When the amount of stable selenium ranges from 10 to 30 ug/animal ( 50-150 ug/kg), the exhaled isotope averages 12-14% of the total amount. After intravenous injection, the excretion is more accentuated at the beginning ( 30-35%/hour for the first 15 minutes ), then slows down and usually stops in 30-40 minutes. The conversion of selenite into dimethyl-selenide occurs chiefly in the microsomes of the liver, and part of the general transmethylation process. For doses between 20-100 ug selenium, an amount of 1-3 ug CH, is readily available for conversion into dimethyl selenide; large doses in the toxic range ( 2,000-2,500 ug/kg ) considerably increase the rate of excretion as well as the amount of eliminated methyl groups ( 16-18% of the total, and 22-25 ug per animal). Func tional diminution obtained by sub-total hepatectomy is followed by a marked slowing down of the excretion rate, suggesting that the readily available CH, groups are diminished. Addi tion of methyl donors ( methionine, vitamin B,2 ) does not increase the excretion rate; on the other hand, inhibition of the enzymic processes of the liver by the compound SKF-525, or by acute or chronic administration of ethionine remains without effect on the lung elimination of selenium-75. Stimulation of the overall enzymic processes of the liver by sub-acute treatment with phenobarbital induces a significant increase of the excretion rate, especially the phase of readily available methyl groups. Selenium-75-methionine in trace or larger doses is not excreted through the lungs, a fact of importance for the clinician and the health physicist. This phenomenon could be applied for clinical diagnosis of the functional state of the liver, in cases where the lipotropic function is investigated.

N-3 “LiverRegeneration Following Hepatectomy, Evaluated by Scintillation Scanning.―J K SIEMSEN,AND J J. P@uuEEiu,( The University of Southern California School of Medicine and the Los Angeles County General Hospital)

The great regenerative capacity of the liver after partial removal is well known from animal studies and from limited observation in humans. Serial scintillation scanning lends itself uniquely to the study of rate and extent of regeneration. In addition, postoperative follow-up scans obviate the need for second-look laparotomies in liver cancer. Scintigraphic and metabolic data on seven patients are presented. Three underwent re moval of seventy to eighty per cent of the liver because of trauma. Regeneration was so rapid that normal liver mass was reformed in four to eight weeks. In two patients the shape of the regenerated liver was normal; in the third, a “mirror image― of the normal liver was formed. Functional recovery, measured by multiple tests, was even more rapid than morphologic reconstitution, with the exception of protein synthesis. The other four patients underwent left hepatic lobectomy only, two because of trauma, two because of cancer. Regeneration of the part removed was much more sluggish and in complete. This observation supports the impression gained from animal experiments that the amount of tissue removed is the controlling stimulus for speed and extent of regeneration.

N-4 “The‘Quantitative' Gold-198 Liver Scan in Diffuse Hepatic Parenchymal Disease.―PAUL A FARlunI, and RICIE/uwMCLUIEN, with the Technical As sistance [email protected] Carlin, Kathryn Stolar, and Maryann Crandall, (Divi sion of Radiation Therapy and Radioisotopes, Department of Radiology, University of Rochester School of Medicine and Dentistry, Rochester, New York)

The radioisotope liver scan provides a visual image of the liver as a functioning organ, especially regarding size, shape, position and presence of space-occupying masses. The pri mary use of scanning in clinical diagnosis is in the detection of space-occupying lesions where 310 ABSTRACTS

the diagnostic and localizing accuracy of the technique is quite high. On the other hand, the value of the scan is less clearly established in the investigation of diffuse hepatic parenchy mal disease. In performing 198Au hepatic photoscans we have been impressed by the charac teristic scan-pattern obtained in patients with clinically and biopsy-proven cirrhosis of the liver, namely, reduced and non-uniform distribution of intrahepatic 198Au radioactivity in as sociation with increased splenic and bone marrow uptake of radiocolloid. Furthermore, there is a general trend toward further reduced and less uniform hepatic uptake and even more 198Auuptake in the spleen and vertebral bone marrow in patients with clinical signs of hepatic decompensation, portal systemic collateral circulation and presumably portal hypertension. This observation has prompted us to “quantify―the hepatic photoscan data from pa tients in terms of (i) max. cpm in liver, (ii) max. cpm in spleen, and (iii) objective intrepre tation of the visualized relative uptakes (and patterns of distribution) of 19SAU in liver, spleen and vertebral bone marrow. In addition, external scintillation counts were taken over @ the liver and sacrum using a diverging collimator and the results expressed as the ratio.

In most patients in vivo combined 1311 Rose-Bengal and 198Au blood clearance studies were performed, since these provided semiquantitative information concerning hemodynamic and parenchymal functional changes in liver disease. The results of these findings and their correlation with the histopathology and extent of liver involvement and with other param eters of liver function and perfusion will be presented.

N-5 “CeliacArterial Perfusion Scanning.― P M JOHNSON, I. E. KANTOR, A. J. SCHWARTZ, AND G. S. FREEDMAN, ( Co1iiii@bia University College of Physi cians and Surgeons, New York, N. Y.) Catheterization of the cellac axis for selective arteriography provides a convenient route for administration of a particulate radiopharmaceutical to diineate the sinusoidal or capillary beds of the upper abdominal viscera, particularly of the liver. The authors have employed this method to administer macroaggregated albumin labelled with 131J to patients who were then studied by area photoscanning and serial external scintillation counting. Conventional hepatic photoscans had previously been obtained in these patients. There was no adverse reaction to intra-arterial administration of the radiopharmaceutical. The distribution of activity in the upper abdomen varied with the position of the catheter tip at injection. In some patients hepatic radioactivity predominated, while in others splenic or gastric radioactivity was conspicuous. Comparison of perfusion and conventional scans of the liver is instructive. In the normal subject these scans are often nearly identical. However, in various diseases of the liver, in teresting differences in distribution of radioactivity are noted. In one patient with hemangioma of the liver, transhepatic shunting of the radiopharmaceutical was demonstrable. Selected samples of upper abdominal perfusion scans are shown and are compared with conventionalhepaticphotoscans.Data relevanttotheintrahepaticeffectivehalflifeof macro aggregated albumin are presented. An evaluation of the clinical usefulness of celiac arterial perfusion scanning is given.

N-6 “Gold-198Liver Scanning in Hepatic Amebic Disease.― EPHRAIM OTERO, (In stituto Nacional de Cancerologia, Bogota, Columbia)

Forty-six patients with the diagnosis of amebic (E. histolytica) disease of the liver have been studied by scintiscanning with colloidal radioactive gold, gold-198. Thirty-three exhibited space-occupying lesions which were anatomically confirmed as amebic abscesses, ranging in di ameter from 2.5 to 12 centimeters. Thirteen patients with a history of intestinal amebiasis, who complained of pain in the right hypochondrium and had signs of hepatic amebic involve ment, gave scan pictures of normal livers. Of these, two were anatomically confirmed as nor mal; seven had been medically treated and probably corresponded to cases of “amebic hepatitis― without the formation of abscess and four had had previous drainage of abscesses, the scans being useful to rule out the possibility of recurrence. FOURTEENTH ANNUAL MEETING 311

Of the 33 patients with space-occupying lesions corresponding to amebic abscesses, in 30 ( 91 per cent ) they were located in the upper, central or lower right lobe; only three abscesses were located in the left lobe of the liver. A linear correlation could also be ob tamed between the diameter of the space-occupying lesions, in the AP or lateral scans and the pus contents of the abscesses as reported by the surgeons. Scintiscanning has also proved useful for the following-up of patients receiving medical and/or surgical treatment for amebic abscesses : the space-occupying lesion persists, in our experience, for up to six months after the patient has been considered as clinically cured. The time of persistence seems also to depend on the initial size of the lesion.

N-7 “Allocation of the Amoebic Abscess According to the Distribution of the intrahepatic Branches of the Portal Vein.―A CUAR@N, B. SEPu@JLVEDA,G. Tiwjo, ANDH. Tnnvu@o, (Hospital General del Centro Medico Nacional y Comisión Nacional de EnergIa Nuclear, Mexico City, Mexico)

Hepatic scanning studies were performed in 671 patients with one or more amoebic abscesses of the liver. A total of 722 abscesses were demonstrated. The distribution of these 722 abscesses was analyzed according to the scheme of Healey and Schroy, who divided the liver into ten vascular segments. 94.3% of the patients had only one abscess; 4.2% presented simultaneously two abscesses and only 1.5% suffered more than two simultaneous abscesses. Out of the total of cases, 78.3% were located at the right lobe and 21.7% at the left one. The most affected regions were those whose vascular supply came from the anterior and posterior segmental branches of the right lobar trunk of the portal vein. The possible ways of entrance of the amoebae towards the different hepatic segments are discussed, as well as the anatomic characteristics of the intra-hepatic branches of the portal vein explaining the peculiar distribution of the lesions. The anterior scan image was able to ltcalize 89.8% of the abscesses within the right lobe and 100% of those localized within the left lobe. The right lateral scan image was unable to depict a single abscess of the left lobe, but accurately showed the location of 95.2% of those of the right one. The combination of both anterior and right lateral scan images allowed the localization of 100% of the left lobe abscesses and 99.8% of those within the right one.

Friday, June 23, 1967 9:00—10:30 AM. Spanish Ballroom

SESSION 0. SCANNING Ill, SPECIAL TECHNIQUES ON DATA EVALUATION Session Chairman: GERALD J. HINE, Vienna

0-1 “ParathyroidScanning: The Problem of Organ Delineation in the Chang ing Blood Background.― E JAMES POTCHEN, AND JOHN S. CLIFrON, (Wash ington University School of Medicii@) It has been shown by Potchen, et a! (1965) that while the parathyroid gland exhibits specificivity for selenomethionine the rate of accumulation and excretion are both rapid and the peak uptake occurrs within forty minutes of injection of the material into the blood stream. Consequently, localization of this specffic uptake is complicated and often prevented by the presence of a continuously changing blood background of the same radioactive ma terial. Using a series of photo scans recorded sequentially in time, it has been shown that a simple form of background subtraction is possible by optical integration of these scans. By utilizing a dual isotope technique, direct digital data acquistion and computer analysis of the data, a method has been devised for the subtraction of the changing blood background with consequent enhancement of specific uptake within the gland. 312 ABSTRACTS

0-2 “The1600 Channel Analizer-Gamma Camera Combination for Evaluation of Organ Configuration and Function.― ROBERT E Pou@, JAMES T. LAM BETH, KENNETH 0. HENDRICKS, AND ALEXANDER GOTTSCHALK, ( Argonne Can cer Research Hospital and the Section of Nuclear Medicine, University of Chicago Hospitals, Chicago, Illinois) The analogue and digital read-out modes provided by parallel circuitry of the 1600 channel analizer have been adapted to the assessment of organ configuration and function. In pancreas scanning with dual nuclide technique ( technetium-99m sulfur colloid and selenomethionine ), technetium uptake by the liver has been stored in the subtract mode and subtracted from the liver-pancreas image to provide a clearer view of pancreatic structure. The analizer-camera combination has been used to provide the required assessments of size and activity in the use of delayed renal scanning for the estimate of renal plasma flow. Difference in renal size is measured from the count of renal channels, holding analizer threshold constant for both determinations. This direct measure of renal size is a distinct simplification in comparison with methods previously used. Undesired sources of activity are eliminated by appropriate choice of the region of interest; erasure of background in the field of interest and correction for detector non-uniformity are accomplished, using data derived from a uniform sheet source phantom. Study of the variation in pulmonary perfusion with marcroaggregated albumin ( upper lower lung ratios ) has been begun, using digital read-out of the 1600 channel analizer. Techniques and problems related to these studies will be described and examples will be shown.

0-3 “AreaScanning for Quantitative Measurement of Radioactivity in internal Organs.― NOBORU ARIMIZU, AND A. C. Moiuus, JR., ( Medical Division, Oak Ridge Institute ofNiic1@ Studies, an operating unit of Oak Ridge Asso ciated Industries, Inc., Oak Ridge, Tennessee) Area scanning can supply additional information toward the quantitative measurement of radionuclides deposited in internal organs. This fact was demonstrated by more than 300 experiments on plexiglass phantoms containing solutions of radionuclides when subjected to scanning. The radioactivity demonstrated was measured by counting the dots on the scan. Counting responses to plane, thin-circular and cylindrical shapes of different sizes were measured in air and in water to see how the response changed according to the size, position, nuclide, and energy range of the activity. If a selected portion of the scan record is quantized and appropriate corrections are made, the response to a source of uniform activity is dependent on its depth, but not upon its size. This study suggests that by using radioisotope scanning it is possible to quantitate the activity of organs, in addition to the thyroid gland, when the scan counts are summed over a selected area and corrections are applied for nearby activity.

‘Under contract with the United States Atomic Energy Commission.

0-4 “TheSimulation of Data from Scan Detector Systems.― L C KOMLENSTEIN, A. G. SCHULZ,R. F. MUCCI,ANDL. G. KNOWLES,(Applied Physics Labóth@ tory, Johns Hopkins University, Silver Spring, Maryland and Depart ment of Radiological Sciences, Johns Hopkins University, Baltimore, Mary land) Quantitative assessment of scanning system parameters requires the capability to re peatedly scan, with a variety of collimators, a scan object whose properties can be quantita tively controlled and readily varied. We have developed a computer program which simulates the output of a radiation detector as it scans an organ phantom and which makes it possible to vary comprehensively the parameters of the target object and its surroundings. An organ phantom, various lesions and a collimator point source response function are described in three dimensions to an IBM 7094 computer. The simulated scan of the organ and the lesions are computed independently and are then combined under operator control FOURTEENTH ANNUAL MEETING 313 in a Univac 1206 computer; actual values are selected for the various parameters ( specific activities, detector efficiency, time required for scan, etc. ) and statistical fluctuations cor responding to radioactive decay are simulated. The simulation has the following characteristics: 1 ) One or two lesions of any size can be placed anywhere within an organ. 2 ) The specific activity of the organ, lesions, and surrounding body can be mdc pendently and continuously varied. 3 ) Any collimator can be used whose response function can be measured or calculated. 4 ) The collimator-detector efficiency and the time taken for the scan can be varied. 5 ) The attenuation of gamma rays is considered in every case. 6 ) The effects of scattering are included by using the response function measured in a phantom. The simulation has been used to “scan―a kidney and eight lesions with a 253-hole focusing collimator and families of scans relating various parameters have been generated.

0-5 “PositiveScintigraphy of Tumor by Means of intra-Arterial injection of Radio-iodinated MAA (Macroaggregated Albumin)― MASOA KANEKO, TsuNEo SASAKI,ANDCHolCimio, (Department of Radiology, Aichi Cancer Center Hospital, Chikusa-ku, Nagoya, Japan) Selective arterial catheterization by Seldinger's technique was performed in 52 cases, beside three cases of carotid artery puncture. Iodine-131- or 125I@MAAwas injected in doses of 250-500 @C(1-5 mC of higher specific activity) into the arteries through the catheter or needle. Immediatly after injection, the distribution of MAA was examined by linear and area scanning. Scanning was repeated daily until the tumor was positively delineated or for at least two weeks if this phenomenon did not occur. After injection, non-radioactive iodine was given to saturate the thyroid gland. In the operated cases, the specimen was examined for the distribution of the radioactive materials and activity in normal and tumor tissues was compared. In most of the cases of tumor, a positive scintigram was obtained. Non-neoplastic cases were negative. Surgically removed specimen contained higher radioactivity in the neoplastic tissue than that in normal or non-neoplastic tissues.

0-6 “ADigital Diagnostic Coding System for Clinical Nuclear Medicine.― Rus sw@ C Biuccs, AND DONALD R. KORST, (Departments of Radiology and Medicine, Section of Nuclear Medicine, University of Wisconsin, Madison, Wisconsin)

The growth in number and variety of clinical nuclear medicine procedures has resulted in accumulation of large quantities of potentially useful data. This potential cannot be realized without a rapid, flexible system of data retrieval. To this end, the authors have devised a 36-digit code for use with an IBM data processor, which is capable of readily presenting information on age, sex, radionuclides, pharmaceuticals, procedures, system studied and pathology defined. Additional complementary information is also coded. The program parallels the format currently recommended by the American College of Radiology for use in roentgenologic diagnosis. The method utilizes a table of 60 potentially useful radionuclides. Procedures coded are general rather than specific and the total of 35 includes studies such as activation analysis, dosimetry, whole body counting, and emission, transmission, and profile scanning. Each of nine different body systems contains a potential of ten anatomic and/or functional sub divisions. For any given case, the above information may be combined with a diagnostic normal code or one of eight general codes for pathology. In turn, each code for pathology may be sub-divided for more precise classification according to the body system being studied. Consideration is given to inclusion of the Standard Nomenclature of Diseases. The digital method provides information readily adaptable to computer analysis. Cur rent results and the possible role in inter-institutional information exchange are discussed. 314 ABSTRACTS

0-7 “Applicationof Sequential Sampling Analysis to Radioisotope Scanning.―' H S KArZENSTEIN,( Solid State Radiations, Inc., 2261 South Carmelina Avenue, Los Angeles, California) For a given set of conditions, radioisotope scanning rates are limited by the lowest activity areas of interest. If the scanning speed is programmed responsive to the observed counting rate, it should be possible to greatly reduce the required time for scanning, with no sacrifice in the image quality. The problem has been examined from the point of view that each resolution element scanned represents the testing of a multiple hypothesis con cerning the activity level of that element. A given element is observed for the minimum period of time necessary to obtain the desired degree of statistical confirmation. This pro cedure is derived from the sequential sampling analysis of Wald and has been shown to be optimum. A clinical scanner has been modified by the replacement of the scan motor with a stepping motor capable of being programmed for variable scan speed. Counts are processed by a hybrid digital-analogue computer to provide scan programming signals and a dot intensity readout. Results on simulated clinical scans are presented.

‘Supported by the Division of Biology and Medicine of the U. S. Atomic Energy Com mission under contract #AT(04-3)627.

Friday, June 23, 1967 11:00—12:30 P.M. Spanish Ballroom

SESSION P. SCANNING IV, NEW INSTRUMENTATION Session Chairman: Mnuin.L A. BENDER, Buffalo

P-i “Transverse-Section Tomography with the Scintillation Camera.― H 0 ANGER, D. C. PRICE, AND P. E. Yos@r, (Donner Laboratory, Universft)Tof California, Berkeley) By rotating a patient in front of a modified Nuclear-Chicago scintillation camera, transverse section views are obtained similar to those produced by the transverse-section scanner of KuhI. For section views of the brain, the patient sits in a chair and the camera views his head from a horizontal direction. The chair rotates slowly about a vertical axis through the center of the patient's head. A special semifocused collimator having channels that are parallel if seen from the top and focused if seen from the side, is used. With this special collimator, the camera views a single horizontal slice of tissue two to three centi meters in vertical thickness that extends through the patient's head. Storage and readout of the images is by means of a modified oscilloscope camera, although a computer memory system could be used. Photographic readout is accomplished by rotating the film in the scope camera in synchronism with the patient, while each detected gama-ray is displayed as a vertical line on the film. The dots appearing in the cathode-ray tube are changed into vertical lines simply by placing an array of glass rods before the scope camera lens. After one or more complete rotations of the patient and the film, a transverse section view composed of intersecting lines is obtained. Even though the camera is viewing the patient's head from a horizontal direction at all times, the resulting view is from the top of the patient's head. It is similar to a vertex view, except that overlying and underlying activity is eliminated. Compared to Kuhi's method, which uses dual scanning probes, the new system has two advantages. First, the patient can be rotated continuously, instead of through 7.5° intervals, thus eliminating certain minor artifacts in the images. Second, the mechanical motions are relatively simple. No electronic modifications to the scintillation camera are necessary and, FOURTEENTH ANNUAL MEETING 315 of course, the same equipment can be used in unmodified form for conventional static and dynamic studies. The calculated sensitivity and resolution of the two methods is approximately equal. The same technique is applicable to other organs. For the liver, the same semi-focused collimator can be used to provide an image of a single transverse plane, or a conventional parallel hole multichannel collimator can be used with a multiple-section oscilloscope camera that provides transverse section images of six different planes through the liver simultaneously. Computer memory system can also provide simultaneous images of several different planes.

P-2 “initialClinical Results with a New Technique for Radioisotope Tomog raphy.― DAVID C PRICE, AND HAL 0. ANGER, (Donner Laboratory, Univer sity of California, Berkeley, California) A variety of radioisotopic tracers and imaging devices have been used for brain scan ning. The recent availability of aamtechnetium pertechnetate, particularly in conjunction with the scintillation camera, has greatly facilitated tumor localization by permitting multiple views of the head in short scanning times. Nevertheless, there still remains a need for better methods of tumor delineation as a guide for surgical intervention. A new modification of the scintillation camera is being developed to permit tomographic cross sections of radioisotope distribution through any horizontal level of the head. The instrumentation will be presented in detail separately. In brief, both the patient and the recording polaroid camera are rotated simultaneouly through 360°, while each dot on the oscilloscope is converted into a vertical line by a Maddox rod lens. The height of the region studied is limited either by the use of a special semi-focusing technetium collimator, or by masking out the upper and lower 90% of the oscilloscope face. The latter method is feasible because the standard technetium collimator has an infinite depth of focus. Using this system, a focus of activity in one portion of the field seen by the scintillation camera gives a series of lines on rotation which overlies each other at the location of the lesion as visualized in cross section from above. A number of patients have been scanned to date by coordinated hand rotation of the patient and the recording camera, using 3-5 mCi Damtechnetium pertechnetate as the scanning agent. Scintiphotos will be shown illustrating the normal cranial structures visualized by the technique, in particular, the vault of the skull at various levels, the base of the skull, and the parotid glands which stand out sharply. Examples of positive brain lesions will give a measure of its usefulness in pathologic scans. The technique may also prove useful for the localization of other lesions or organs, such as the kidneys.

P-3 “Experimentaland Theoretical Performance of a Digital Positron Camera.―' PETER J K1@N@, JohN W. Bi@rrw, AND JOHN S. LAUGHLIN, (Division of Biophysics, Sloan-Kettering Institute for Cancer Research, New York, New York) Experimental measurements on the following parameters of two digital Anger Cameras incorporating 13%―diameter crystals will be presented: linearity, spectral resolution, and inherent spatial resolution as a function of gamma ray energy (0.14 MeV to 0.66 MeV) channel width, photomultiplier tube type (regular Sli and bi-alkali) and arrangement, and light pipe thickness. Experimental measurements on the following parameters of the two units used in coincidence as a positron camera will be presented: (1) Singles to coincident count rate ratio for various source arrangements as a function of coincidence gate width and energy channel width. (2) Transverse resolution for normally incident gamma rays of 0.51 MeV. These experimental determinations are compared with theoretical computations which take into account the effect of photocathode sensitivity, the input data rate and its statistical distribution in time and the distribution of geometrical efficiency between the two detectors. On the basis of these determinations, the capability of the instrument for three-dimensional localization after final interfacting with the IBM 1800 computer will be described.

‘Supported in part by AEC Contract AT(30-1)-910 and by NCI Grant CA-08748. 316 ABSTRACTS

P4 “ANew Device of y Camera.―S. M@uuNo, S KURIHARA,S. MIYASHIRO,M. KUMANO, H. UEDA, M. 110, Y. SASAKI, AND H. KAMEDA, ( Tokyo Shibaura Electric Co., and the University of Tokyo, Tokyo, Japan) As stationary devices for Rlscanning, several systems were reported by Anger, Bender, Blau, TerPoggosian and Kellershon. Some of them are now used successfully for clinical studies. In this report a new device based on the multistage image tube (s) system is introduced. This device is designed for the detection of spacial distribution of y nuclides with wide range energy, and can be fabricated without complicated electronic circuit. Since multistage image tube-M7074A (Toshiba) is extremely sensitive to the dim photon image, various optical coupling of the input photosensitive surface with either fluorescent plate or scintillation crystal can be designed. A zinc sulfate fluorescent plate ( 300 x 300 x @ 0.5mm ) and a single sodium iodide crystal ( 300 x 10mm) were used for low ‘yand for medium energy ‘yrays respectively. Different multi-hole collimator systems projects a gamma ray image of the subject on a fluorescent plate or scintillator. Through an optical lens system, an image on fluorescent plate or scintillator is focused on the input surface of the multi stage image tube. After the intensification of input dim photon up to 105 times ( maximum light flux gain of one tube) or 3 10 x 10@ times (arbitrary gain of dual tube system), a dim image can be converted to the bright picture on the output phosphor screen, which was recorded photographically with quite short time intervals. Sensitivity and resolution of this new imaging device were found to be quite satisfactory. Data of fundamental experimental analysis and animal as well as clinical data is presented.

P-5 “Furtherimprovements on the Catheter-Type i-N Junction Detector and its Application to Hemodynamic Studies.― S TAKAYANAGI, T. SUGITA, T. KOBAYASHI, H. UEDA, Y. SASAKI, K. MACHIDA, I. ITo, AND M. 110, ( Central Research Laboratory, Tokyo Shibaura Electric Company, Ltd., Kawasaki, Japan, and the University of Tokyo, Tokyo, Japan) At the last meeting, the development of a catheter-type p-n junction semiconductor detector was reported by our group. The basic characteristics of the device and its usefulness in experimental circulation studies were shown. During the past year, we have made further improvements both on the detector and its associated electronic circuits. The probe is made of a disc-type silicon p-n junction detector attached to one end of a coaxial signal cable. The outer diameter of the probe has been reduced to 3 mm, which will allow the probe to be inserted into human vessels. In order to solve the possible difficulty arising from an unisotropic response of the disc (end window) type arrangements,a coaxial-typep-n junctiondetectorhas alsobeen developed. This new design has two advantages; (1) the sensitivity of the detector can be increased several times without increasing the outer diameter of the probe, and (2) the sensitivity becomes nearly isotropic, allowing the more precise measurement of dilution process in the vessels. A completely transistorized low-noise charge-sensitive preamplifier was developed to eliminate microphonic noise. The whole electronic system was also transistorized to reduce the circuit voltage to ensure further safety. Cardiac shunt detection was proved to be possible by canine experiments, in which artificial left to right shunt was produced between the carotid artery and the jugular vein. Continuous measurement of canine cardiac output was made with the detector inserted into the right ventricle and 85Kr saline solution infused from the femoral vein with a constant rate.The effectsof drugs such as epinephrineand methoxamine on cardiacoutputwere studied with this continuous cardiac output monitoring system. To summarize, a catheter-type p-n junction detector with high sensitiveness, nearly isotropic sensitivity and more smaller size, was developed. This detector has proved to be useful for the detailed analysis of hemodynamic change. Its application to human beings will be presented.

Abstracts continued in the May 1967 issue of JNM