CLINICAL APPLICATIONS OF COMPUTER-ASSISTED RENOGRAPHY R. H. Secker-Walker,E. P.Shepherd,and K. J. Cassell University College Hospital, London, England Radioisotopes were first used to assess kidney overall renal function is obtained and furthermore function by external scintillation counting in 1955. the shape of the mediastinal clearance curve can be After preliminary observations in rabbits which compared to the renogram tracings to give an mdi looked promising, Taplin and his colleagues tried cation of what is happening to Hippuran in a poorly 1311-Urokon in man (1) . They were initially dis functioning kidney. For instance, if the renogram heartened by the “monotonous,noncharacteristic curve falls less rapidly than the mediastinal clear records regardless of renal status―that they ob ance curve, Hippuran is accumulating in the kidney. tamed (2) . lodopyracet (Diodrast) was much more Several investigators have used ‘811-iodinatedhu successful, but it was another 5 years before Tubis man serum albumin (1311-IHSA) to measure renal and Nordyke introduced radioactive orthoiodohip and extra-renal vascular background activity (7,8) purate or ‘311-Hippuranin 1960 (3). and in 1966 Hall and Monks described a method Since then 1311-Hippuran has become the tracer of correcting renogram tracings for this blood back @ of choice for renography. It is handled much like ground activity by giving 1311-IHSAbefore the para-amino hippuric acid and is almost exclusively Hippuran (9). Britton and Brown adapted this and very rapidly excreted by the kidneys so that method by using a digital computer to subtract the 92% of unbound 1311-Hippuran is cleared from the blood background activity—a technique called plasma in a single passage through the normal kid Computer-Assisted Blood Background Subtraction ney (4,5). Renography (CABBS Renography) (10) . The tech After intravenous injection 1311-Hippuran, which nique employed at University College Hospital is is partially protein bound (6), spreads throughout based on the method developed by Britton and the vascular space, starts to exchange with the extra Brown. This paper describes our experience with vascular space, and is removed from the circulation, computer-assisted renography in more than 100 pa partly by glomerular filtration but mostly by tubular tients, indicates its relation to other tests of renal secretion. After traversing the renal tubules, collect function, and outlines areas in which it is clinically ing ducts, and renal pelvis, the ‘311-Hippuranpasses useful. down the ureters to the bladder. The renogram is a composite trace of the changing quantity of radio METHODS activity in the nephrons, in the renal pelvis, in the The majority of patients in this study were referred blood within the kidney, and also in the tissues for radioisotopic assessment of individual kidney around the kidney that are viewed by the external function during the investigation of either hyper detector. The activity in the blood and tissues around tension, chronic pyelonephritis, or an obstructive the kidney makes up a considerable part of a reno uropathy. With the exception of a few patients with gram and as the function of a kidney becomes im a history of allergy to contrast media, each patient paired, this blood and tissue background activity had an intravenous pyelogram. Arteriograms and accounts for an even larger proportion of the trac ing so that interpretation becomes increasingly dif ficult. Received March 8, 1971; revision accepted Oct. 28, 1971. If blood clearance is monitored by a third detector For reprints contact: R. H. Secker-Walker, Dept. of Nu clear Medicine, The Mallinckrodt Institute of Radiology, placed over the upper mediastinum, an indication of 510 South Kingshighway, St. Louis, Mo. 63110. Volume 13, Number 4 235 SECKER-WALKER, SHEPHERD, AND CASSELL 1311-HIPPURAN RENOGRAM CORRECTIONFORBLOOD BACKGROUND FIND RATIO OF HEART COUNTS TO KIDNEY COUNTS WITH 1311-H.S.A. RATIO'(HSA.K— BGK)/(HSA-H- BG-H) O z SUBTRACT THE BLOOD DISAPPEARANCE CURVE. 0 MULTIPUED BY THIS RATIO, FROM THE RENOGRAM U) KIDNEY TRACE-(HIPP.K —HSA-K)-@(IIIPN4-HSA-H) Ui 0. * RATIO) U)I.-. z D 0 U TIME FIG. 1. Methodofcorrectingfor‘bloodbackground.―Tracingssent counts due to radioactive human serum albumin; and HIPP-H from mediastinal detector and one kidney detector are shown. BG-H and HIPP-K represent counts due to 1―l-Hippuran over mediastinum and BG.K represent background counts; HSA-H and HSA-K repre (-H) and kidney (-K), respectively. retrograde pyelograms were performed when clini 13114HSA intravenously and the counts from each cally indicated. detector recorded for 6 mm; this is followed by 1311.. Radioisotope renography and kidney scanning Hippuran ( 1 pCi/7 kg) and the renogram recorded were undertaken on the same day, or within 48 hr for 16—20mm. This whole procedure takes up to of each other in all but one patient, and were always 30 mm. The data tape is then processedon the Uni performed within 6 hr in the patients with acute versity of London Atlas Computer. obstruction to the outflow of urine, if they had both In addition to renography, most of the patients studies. studied (90/109) had kidney scans following 197Hg The patient lies supine on a couch with a perspex chlormerodrin ( 1 pCi/kg body weight) as described window beneath the renal areas. Matched detectors previously (11 ) . The scans were made on either a [Nuclear Enterprises 1¾-in. Na(Tl) crystals with 3-in. or 5-in. Picker Magnascanner. With the scans wide-angled collimators] viewed each kidney from performed on the 3-in. scanner, the relative amount beneath the perspex window and a third detector of radioactivity within each kidney was determined is placed anteriorly over the upper mediastinum. either by counting the dots on the color scans or The kidneys are located from an injection of 2—4 else using a slit collimator, and expressing the counts @Ciof 197Hg-chlormerodrin given 45 mm or more in one kidney as a percentage of the total counts beforehand. in both kidneys. Fifteen patients also had renograms The pulses from the detectors after suitable ampli repeated while seated in front of a gamma camera fication and pulse-height analysis are fed into rate (Nuclear Enterprises, Mark III) . The kidneys were meters and scalers (Harwell 2000 series) . The rate located from the 197Hg-chlormerodrin given for meters drive a Honeywell chart recorder, while the scanning, and then each patient was given up to 150 scalers are read every 10 sec and reset to zero by a pCi1311-Hippuran and pictures were taken every 2½ Data Dynamics high-speed punch producing paper mm for 15—20mm. tape. Estimations of blood urea and 24-hr creatinine For the renogram, background counts are recorded clearance were carried out by Technicon Autoana for at least 100 sec. The patient is then given 5 pCi lyzers in the hospital's biochemistry laboratory. 236 JOURNAL OF NUCLEAR MEDICINE COMPUTER-ASSISTED RENOGRAPHY Outline of computer program. The data tape con the corresponding 1311-Hippuran plus ‘311-IHSA sists of background counts, 1311-IHSA counts and array to give the activity-time curve of 1311-Hippuran 1311-Hippuran plus 1311-IHSA counts from the three alone as seen by each detector. channels (right kidney, left kidney, and mediastinum) For the blood and tissue background correction accumulated at 10-sec intervals. After reading in each point of the mediastinal clearance curve is mul the data and storing the 1311-IHSA counts •and 1311.. tiplied by the ratio for each kidney and subtracted Hippuran plus 1311-IHSA counts from each channel from the corresponding point of the renogram to in separate arrays, the mean background counts per give the computer-corrected renogram or kidney 10 sec are determined for each channel and sub trace (Fig. 1) . Although 1311-Hippuran is almost tracted from the corresponding 1311-IHSA and 131J. exclusively and rapidly excreted by the kidneys, the Hippuran plus ‘311-IHSAarrays. Smoothing of the blood clearance curve represents both the removal counts is carried out by a running average over 30- of Hippuran by the kidneys and in addition its spread sec intervals, preserving the peak of the mediastinal into the extravascular space. In contrast the clear clearance curve. ance curve recorded by the mediastinal detector rep The last 2 mm of the 1311-IHSA counts in each resents the blood clearance curve modified by the channel are used to determine the ratio of the counts extravascular spread of ‘311-Hippuranthat takes over the mediastinum to those over each kidney so place into the tissues in the field of view of this that for any given level of activity within the blood detector. We have assumed that this “mediastinal stream in the mediastinum, the level of activity in clearance―curve more accurately reflects the rate at the blood stream within the field of view of each which Hippuran enters the kidneys than the blood kidney detector can be determined. clearance curve. The mean 1311-IHSA counts per 10 sec in each In order to determine the outflow of ‘311-Hippuran channel over this same 2 mm are subtracted from from each kidney the integral of the mediastinal DERIVATION OF 1311HIPPURAN FLOW FROM EACH KIDNEY INTEGRATED BLOOD CLEARANCE CURVEADJUSTEDTOMATCH THE I-3MINUTE SEGMENT OF THE KIDNEY TRACE I- > I- TIME FIG.2. Methodofcorrectingforinitialdilutionof1'@l-Hippurancurve is dashed lines. Center panel shows integrated mediastinal throughout vascular compartment and calculating outflow of “I- clearance curve and kidney trace. Integrated clearance curve is Hippuran. In left panel 1―l-Hippuran mediastinal clearance curve adjusted to match 1—3-mmsegment of kidney trace by multiplying has been superimposed over the ‘°I-IHSAcurve for first 6 mm after this part of curve by factor which gives best fit determined by least injection.