The Utility of Technetium-99m DTPA Inhalational Scans in Artificially Ventilated Patients

S. Patrick Butler, Philip 0. Alderson, Robin L. Greenspan, David G. Doctor, and Vincent J. DeFillipi

Division ofNuclear Medicine, Department ofRadiology, Columbia University, New York, New York

been less readily accepted. It generally has been felt that Technetium-99m diethylenetriaminepentaacetic acid the central deposition tendencies of radioaerosolsare ([@‘Tc]DTPA)radioaerosolscans performedon 21 con likely to be accentuated in this patient group. This did secutive artificially ventilated patients were compared to not seem the case in our clinical experience, however. 50 similarscansperformedon patientsbreathingwithout mechanical assistance. All patients were referred for eval In order to investigate this situation further, a retro uationof suspectedpulmonaryembolism.The comparison spective study was undertaken to evaluate the charac revealedincreasedextrathoracictrachealandmediastinal teristics and quality of radioaerosolinhalation studies tracheal deposition but less central bronchial deposition in in a group of artificially ventilated patients. the artificiallyventilatedpatients.Peripheralpenetrationin both groups of patients was excellent. Within the artificially ventilatedgroup,peripheralpenetrationof activityseemed MATERIALS AND METHODS equally good in patients receiving positive-end axpiratory pressure ventilation (n = 14) and those ventilated with All 387 aerosol inhalational scans performed at Columbia normal pressures (n = 7). The frequency of regions in Presbyterian Medical Center from October 1985 to January whichaerosolactivity(A) was presentin the same zone 1988 were reviewed. Twenty-one of these scans were per as a (P)defect was the same inthe controls and formed on 20 artificially ventilated patients. From the remain artificially ventilated patients (12% against 14%) but the ing 366 scans, 50 scans from 50 different patients were ran frequency of the reverse type of mismatch (i.e., P > A) domly selected to serve as a typical group of non-ventilator was significantlyhigherin the artificiallyventilatedgroup dependent patients whose aerosol deposition patterns after (42% against 14%, p < 0.001). The results suggest that inhalationduringtidal ventilationcouldbe comparedto those [@Tc]DTPAaerosolscansinartificiallyventilatedpatients are associatedwithgoodperipheralpenetrationof activity seen in artificially ventilated patients. The clinical character andfrequentlyyieldvaluableclinicalinformation. isticsof both the comparisongroup and the artificiallyventi lated group are given in Table 1. The medical conditions that J NucI Med I990;31:46-51 necessitated ventilatory support were varied: five patients were postcardiorespiratory arrest, five were postoperative and the remainder had respiratoryfailure (left ventricular failure in four patients, generalized sepsis in three patients, drug abuse in two patients and chronic obstructive airways disease in one patient). dioaerosols were introduced for ventilation scan For the routine aerosol inhalation scan, 1110 MBq (30 ning many years ago (1,2). Recently, technical improve mCi) of technetium-99m-labeleddiethylenetriaminepentaa @ ments in delivery systems have resulted in substantially cetic acid Inc., NJ) in a volume increased clinical utilization. In fact, radioaerosols cur of2 ml of0.9% saline was placed in either a Cadema(Cadema rently are considered comparable to radioactive gases Medical Products, Middletown, NY) or a Syntevent (Synaco as adjuncts to perfusion imaging in patients suspected Inc., Palo Alto, CA) nebulizerthat was aerated at 10 1per of (3,4). In the past, a major minute of 100% oxygen from a compressed air tank. The patient was placed in the supine position over the gamma criticism of radioaerosol inhalation scans has been ex camera and was instructed to inhale until a count rate of cessive central bronchial deposition and relatively poor 100,000cpm was reached (3 to 5 minutes). Typically,this peripheral penetration ofaerosol. With current delivery resulted in @—28MBq (750 @iCi)of activity being deposited in systems, this appears to be less of a problem. In artifi the patient's lungs (5). Six aerosol images (the anterior, pos cially ventilated patients, however, radioaerosolshave terior, left anterior oblique (LAO), right anterior oblique (RAO), left posterior oblique (LPO) and right posterior oblique (RPO) projections) then were acquired using the same AcceptedFeb. 13, 1989;revisionaccepted Aug.23, 1989. Forreprintscontact: Philip0. Alderson,MD,Dept.of Radiology,Div.of conventionallargefield-of-viewgamma camera(PickerDyna ,622 West 168th St., New York, NY 10032. Camera 4, Picker Inc., Northford, CT). Each image contained

46 The Journalof Nudear Medicine•Vol. 31 •No. 1 •January1990 TABLE 1 osition patterns in patients being artificially ventilated and ClinicalArtificiallyTidalArtificialrespirationventilationgroupgroupMale:Details of Tidal Respiration Group those breathing normally. Ventilated Patientsand All scans were graded for extrathoracic tracheal activity, mediastinal tracheal activity, central bronchial deposition and peripheral penetration by using four-part scales. In each case, if the feature in question was absent, the image was graded “0―.Conversely, if the feature was present, it was subjectively :33:1Agefemale ratio 1 yrRange(mean) 57 yr61 graded as 1+ to 3+ positive. The 3+ grade was used when the yrPrincipal 31—93yr31—82 intensity of the feature in question exceeded that of general lung activity itself; 2+ was used when activity was about equal diagnosis to that of the lung; 1+ was used when activity was definitely presentbut lessthan that in the lungs.Peripheralpenetration Carcinoma86Coronary was determined by visually comparing the ventilation scan to 56Chronic artery disease the perfusion scan and estimating the limitation of penetra 51Postopairwaysdisease 50Pneumoniaminorsurgery tion, using the outermost edges ofthe perfusion scan (exclud 42Postop ing local defects) to define the lung borders. Penetration of 30SLEorthopaedic activitywasgradedas “excellent―when the aerosolscan and 20Pulmonary perfusionscanweresuperimposable;as“good―whentheouter 20Deep embolism margins of the aerosol scans were equal to perfusion scans in 20Peripheralvenous thrombosis distance from the hila, but were more faint; as “fair―when 21Drugabusevasculardisease there was only faint activity in the peripheral third ofthe lung; 02Other and “poor―when penetration was markedly decreased. In 62No addition,comparisonwith the perfusionscan was utilizedto diagnosisavailable 60 note the occurrenceof regionaldiscrepanciesin aerosol-per fusion activity. When aerosol activity was visualizedin the —100,000counts and required 2 to 3 mm of imagingtime. region ofa perfusion defect, it was described as a conventional aerosol-perfusiondefect(A-Pmismatch).When peifusionac Perfusion imaging then was performed in the same six projec tivity was seen in a region without or with substantially tions after injection of 148 MBq (4 mCi) of[@mTcJmacroag reduced aerosol activity, it was defined as a reverse A-P gregated albumin (MAA)(Mallinckrodt, St. Louis, MO). Each perfusionviewcontained 500,000counts with a count rate mismatch. Afterall scansweregraded,the grade 1-2 abnormalitiesin exceeding by at least four times that obtained during inhala each category were grouped and considered “mild―with the tion scanning alone. grade 3-4 abnormalities also being grouped and considered All ventilatory support was provided by the same type of volume-cycledventilator(Bennett VentilationModel MA-l, “marked―.These two groups were compared using a chi square analysis to determine if there were any significant Puritan Bennett Corp., Los Angeles, CA) with a tidal volume of between700 to 900 ml. Positiveend expiratorypressures differencesbetweenthe twogroupswithrespectto the param (PEEP) up to 12 mm water (mean 4 mm water) were used in eters mentioned above. some patients (see below). The aerosol apparatus was con nected “inseries―with the ventilator during the study in the RESULTS manner recommended by the manufacturers. The nebulizer All 21 scans ofthe artificially ventilated patients were is placedin the ventilatorcircuit and is not aerated until the of sufficient quality for diagnostic interpretation. The entire circuit is closed. In this way, the possibility of contam scan of one of the tidal ventilation patients had to be ination of the area with radioaerosol is minimized. Similarly, at the conclusionof the inhalation of the radioaerosol,the excluded from the analysis of local A-P concordance generation of radioaerosol is stopped before the nebulizer is because of poor peripheral penetration of activity but removedfrom the respiratorycircuitso that the possibilityof was included in the other comparisons. The statistical radioaerosolcontaminationis minimized.Removingthe neb analysis demonstrated significantly more extrathoracic ulizer from the circuit takes 10—20sec. At all times the tracheal (p < 0.01) and mediastinal tracheal deposition nebulizer unit is adequately shielded. The ventilator's param (p < 0.001) in the artificially ventilated group but eters were not changed (including PEEP) and no additional significantly less (p < 0.001) central bronchial (i.e., endotracheal suctioning was performed on these patients prior perihilar) deposition than in controls (Table 2). Periph to scanning. A respiratory care technologist was present eral penetration was excellent in both groups of patients. throughout the inhalation of radioaerosol—evenfor scans Only 10% of the artificially ventilated patients had done on emergencies on off-hours shifts—andcontrolled the moderate decreases in peripheral penetration and none patient's ventilation. For the purposes of review,scans were randomized and had severe limitations. then analyzedbytwoexperiencednuclearmedicinephysicians In the artificially ventilated patient group, the count who wereunawareof whetherthe scan was that of an artifi rate over the thorax in the first image ofthe ventilation cially ventilated patient. Disagreements were resolved by con scan was 2.30k cts/sec with an s.d. of 1.16k cts/sec. In sensus. The review was designed to determine if there were the last image, the count rate was 2.43k cts/sec with an any significant, reproducible differences between aerosol dep s.d. of 0.99k cts/sec. In addition, the count rates in

Precisionof RegionalBoneMineral•LaBlancat al 47 TABLE 2 or other causes was found after being suggested by the Radioaerosol Deposition PatternsandTidalin Tidal Ventil radioaerosol findings in two of these nine patients even ArtificiallyVentilatedPatientsation though it was unsuspected clinically. Artif.Finding One such patient was a 70-yr-old man who under Grade ventValue(n=50)(%) vent (%)p went a cholecystectomy. Postoperatively, the patient (n=21)Tracheal developedfeverand upperabdominal pain and surgical deposition 010%1 6% re-exploration revealed a perforated small bowel. Dur 142 50 ing anaesthetic induction for the second operation, the 293 30 patient started vomiting vigorously and intubation was 47<0.01Mediastinal 14 difficult. The patient was artificially ventilated postop eratively and, 48 hr following surgery, rapid atrial fi deposition 029%1 42% brillation/flutter occurred. An aerosol-perfusion lung 52 30 scan was performed to exclude pulmonary embolism. 243 22 The chest radiograph(Fig. 1A) showed a largeinfiltrate 42<0.001Central 6 at the right lung base with an accompanying smaller infiltrate at the left lung base. In the aerosol-perfusion 57%sitionbronchialdepo- 0 20% study (Fig. lB, C, D, E) radioaerosol activity in the 3421 36 tracheobronchial tree revealed an inappropriate prox 93 32 imity between the carina (arrow) and lung bases, i.e., it 0<0.001Peripheral 12 suggested that the bases were symmetrically hypoven tilated. In addition, the perfusion study demonstrated penetration 76%GoodExc 48% relatively preserved perfusion at the left and right bases. 14Fair 24 Thus, there were significant reverse aerosol-perfusion 10Poor 12 mismatches involving both left and right lung bases, 0=0.50Mismatches 6 with the left being larger than the right. Bronchoscopy revealed copious secretions throughout the bronchial 14%=0.45Reverse 12% tree. The secretions were removed and intensive chest mismatches 14% 42%<0.001 physiotherapy with repeated tracheobronchial suction ing was initiated. Prior to the bronchoscopy, the arterial gases were pH 7.41, p02 86 mmHg, pCO2 35 mmHg those patients on PEEP were not significantly lower in on an inspired oxygen concentration of 75%. Thirty the last image as compared to the first image (2.22k cts six hours after bronchial cleansing, the patient was ±0.91; 2.78k cts ±0.87). extubated with arterial gases of pH 7.40, p02 100 Two-thirds of the artificially ventilated patients (n = mmHg and pCO2 37 mmHg on a face mask of 50% 14) were on PEEP. Some differences were noted be oxygen. tween the radioaerosol deposition patterns in this group and the remainder of the artificially ventilated group. Tracheal deposition was more common (p < 0.05) in patients on PEEP, but centralbronchial deposition was TABLE 3 less common (p < 0.05) as shown in Table 3. Peripheral Effectof PEEP on RadioaerosolinPEEPDeposition Pa Artificially Ventilated Patientsttarns penetration was equally good in patients with or with NoPEEP out PEEP.The frequencyof A-P discordanceof either (n=7)Mild(n=14) the conventional or reverse type was not significantly different in artificially ventilated patients receiving or ValueTrachealdeposition Marked Mild Markedp not receiving PEEP. 4<0.05Mediastinal 2 12 3 Conventional A-P mismatch occurred in 14% of artificially ventilated patients and 12% of the tidal ventilation group, but reverse A-P mismatch occurred 3N.S.Centraldeposition 5 9 4 in 43% ofthe artificially ventilated patients and in only 14% of the tidal ventilation patients (p < 0.001). The bronchial 14 0 5 2 chest radiographs of those patients with reverse mis deposftion<0.05Peripheral match were reviewed; at the site of reverse mismatch, four patients (44%) had an infiltrate, one (11%) had 1N.S.. penetration 12 2 6 atelectasis plus an infiltrate, one (11%) pulmonary oli gemia, one pleural effusion (1 1%) and two (22%) had a clear radiograph. Bronchial obstruction from mucus Not significant.

48 TheJournalof NudearMedicine•Vol.31 •No. 1 •January1990 FIGURE 1 70-yr-oldmanwasartificiallyventilated A following abdominal exploration with suddenonset of atrial fibrillation/flutter and hypoxia48 hr after surgery.A: An

‘ AP chest radiograph demonstrating findings includinga large right basilar infiltratewitha smallerleftbasilarinfil trate. B: Posterior [@‘Tc]MAAperfu sionscan with accompanying[@Tc1 DTPAradioaerosolscan(C).LPOpro jections of same scans (D) and (E). In the inhalationstudy, radioaerosolactiv @ityin the tracheobronchial tree revealed B D aninappropriateproximitybetweenthe ‘Oar • canna (arrow) and lung bases, i.e., it suggested that the bases were sym metrically hypoventilated. In addition, the perfusion study demonstrated rel atively preservedperfusion at the left and right bases. Thus there were sig nificant reverse ventilation perfusion mismatchesinvolvingbothleftandright lung bases, with the left being larger I thanthe right.Clinicalimprovementfol E lowedbronchialdeansingbilaterally.

DISCUSSION sive central deposition. A slow inflow rate should result in less turbulent flow, and thus less bronchial deposi Potential problems with radioaerosol inhalation stud tion. Second, the tidal volume is relatively large (700— ies in patients receiving mechanical ventilation include 900 ml), which permits greater lung expansion and difficulties with radioaerosol administration, poor pe could aid aerosol penetration. In addition, in two-thirds ripheral penetration of radioaerosol activity, and image of our patients the scans were performed while the artifacts that might be associated with radioaerosol in patients were on PEEP, which is designed to force air halation by a patient on a ventilator. into the lungs and keep the lungs expanded between With respect to radioaerosol administration, the “ininspiration and expiration. This, too, should assist ra series―placement of the nebulizer unit into the breath dioaerosol penetration. ing circuit allows the ventilator to drive the aerosol into The results of the current study suggest that changes the patient's lungs. There are several theoretical reasons in radioaerosol distribution patterns related to the pres why a radioaerosol propelled into the lungs by a venti ence of mechanical ventilation are predictable. Signifi lator might work well. First, the respiratory rate of the cantly increased extrathoracic tracheal and mediastinal ventilator is slow (12—14breaths per mm) and this tracheal deposition is likely to be seen. This probably is permits a slow regular input of radioaerosol into the the result of adherence of the radioaerosol to the inner lung. Central bronchial deposition has been attributed surface of the endotracheal tubing, and may be facili to turbulent flow in the large airways resulting in exces tated by the presence there of bronchial mucous secre

Precisionof RegionalBone Mineral •LeBlanc et al 49 tions. Central bronchial deposition was not significant lower resistance ofthe non-ventilated lung. Thus, PEEP and peripheral penetration was excellent; no patient could result in, or contribute to, a worsening of systemic had a major limitation in penetration and only 10% oxygenation by causingan increasedblood flow to a had moderate limitation. In all the artificially ventilated nonventilated lung. Such a tendency toward increased patients, scans were of such quality that all perfusion reverseA-P mismatchwasnot seenin the PEEPsubset defects could be correlated with regional ventilation to of our population, however. assess whether the perfusion defect was matched or not. The present study has demonstrated that inhalational Other studies (6) of radioaerosol inhalation in pa radioaerosol lung scanning in artificially ventilated pa tients on artificial ventilation have recommended the tients results in scans of an excellent quality. The “in use of insoluble tracers rather than [99mTc]DTpA The series―set-up is easy. The nebulizer units are commer potentially rapid clearance of [99mTcJdiethylenetri@ cially availableand can easilybe adaptedbeforebeing aminepentaacetic acid (DTPA) in certain lung disorders installed into the ventilator circuit. In addition, signifi was cited as a reason for this choice. Our experiences cant pathophysiological events can be demonstrated with DTPA were excellent, however. Technetium-99m with such scans and can lead to important changes in DTPA deposited in the lung is absorbed across the patient management. The findings suggest that inhala alveolar epithelium and excreted through the kidneys. tional lung scanning in artificially ventilated patients is In normal patients, the halfclearance time ofthis tracer not only feasible,but valuable. varies from 60—90mm (7). The theoretically rapid clearance that may be seen in some patients has not been a problem in our experience. Our patients inhale REFERENCES radioaerosol while under the gamma camera and im aging is commenced as soon as an acceptable count rate is obtained. The entire procedure time for the routine I. Taplin GV, Poe ND. A dual lung scanning technique for evaluation of pulmonary function. Radiology 1965;85:364— six views (each of 100,000 cts) is 15—20mm. In our 368. artificially ventilated group, the count ratesobtained in 2. Taplin GV, PoeND, GreenbergA. Lungscanningfollowing the sixth image were not significantly prolonged from radioaerosolinhalation. J NuciMed l966;7:77—87. those in the first image. Accordingly, we believe that 3. Alderson P0, Biello DR. Gottshalk A, et al. Comparison of E99mTc]DTPAis an adequate radioaerosol for evalua Tc-99m DTPA aerosol and radioactive gases as adjuncts to perfusion in patients with suspected pulmonary tion of most artificially ventilated patients. scintigraphy.Radiologyl984;l53:515—521. The high frequency (42%) of reverse A-P mismatch 4. Ramanna L, Alderson P0, Berman D, et al. Regional corn in the artificially ventilated group in the current study parison of Tc-99m DTPA aerosol and radioactive gas venti is interesting. Such discordance has been seen in venti lation studies in patients with suspected pulmonary embo lation-perfusion studies (8—11)and has been attributed lism.JNuclMed l986;27:l39l—l396. 5. Alderson P0, Martin EC. Pulmonary embolism: diagnosis to a failure of hypoxic vasoconstriction in the affected with multiple imaging modalities. Radiology l987;l64:297— lung segment. It has been shown experimentally (12) 312. that alveolar hypoxia results in significant vasoconstric 6. VezinaW, ChamberlainM, Vinitski 5, et al. Radioaerosol tion ofthe regional pulmonary vasculature in a normal ventilation imaging in ventilator dependent patients. C/in lung. For unknown reasons (13) this normal autoreg Nuc/Med l985;lO:759—766. 7. Coates G, O'Brodovich H. 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50 The Journalof Nudear Medicine•Vol. 31 •No. 1 •January1990 non-ventilated lung: failure of hypoxic vasoconstriction. Am 17. Carvalho P. Lavender JP. Incidence and aetiology of the JRoenzgeno/1983;l41:151—156. reverse(V/Q) mismatch defect. Nuc/Med Comm 1988;9:167. 16. Benumofii, WahrenbrockEA. Bluntedhypoxicpulmonary 18. Enjeti 5, O'Neill JT, Terry PB, et al. Effectsof positive end vasoconstrictionby increased lung vascular pressures.J App/ expiratory pressure on shunt flow in atelectasis. Resp Physio/ Physiol 1975;38:846—850. l982;48:243—254.

JANUARY1960 thermal rearrangement of l-napthionic RadlosulfurLabeldCongo acid sulfate,the latter material containing RedDye the S325isotope. [email protected]@ Selected manuscriptsfrom DonaldR. Kotst the issuesof the Journalof ThelabeledCongoreddyedistribu NuclearMedicinepublished tion then was studied in normal rats. 15 and 30 years ago. Congo red,anoiganicdyewithanaffini Editedby F.F.Mand Plasmaclearancetestsusing12mgofla ty for amyloid tissue, has been used to beled dye seemed to parallel liver func diagnose amyloidosisby photometric dyeusedin thetest,by incorporatinga tion, and attempts to block the removalof determination of plasma clearance. The radioactive label in the molecule. the Congo red by saturating the reticuloen dose oforganic dye used has been known Congo red dye containing35Swas dothelialsystemwithbromsulphaleinre to produce serious side effects and sen prepared by the coupling of tetrazotized suIted in increased retention of the Con sitivity in patients. An attempt has been benizidine with sodium naphthionate. go red as compared with normal subjects. made to appreciably reducethe amountof Naphthiomcacid was preparedby the U

JANUARY 1975 ClinicalExperiencewith[““TcJvirtuallynoundesirableurinaryexcretion. evaluated for renal imaging in the past DMSA:A NewRenalImaging Sixty-fivepatientswerestudiedusing decade, no one compound has been Ibund [@“Tc1DMSAand a gamma scintillation to be ideal. It seems clear that @9'ccorn Agent camera. In all but three patients, the im pounds havedecided advantagesbecause Hirsch Handmaker, Bradford W. Young,JeroldM. Lowensteln ages obtained were ofsufficient quality to oftheir physical characteristics. Difficul satisfythe clinicalquestionasked. ties havearisen as a result ofthe chemical A varietyofradiopharmaceuticalshave Ithasbeensuggestedthattheuseofra formsofthesecompoundswithregardto been proposed to improve the quality of dionuclide scintigraphy may be valuable availability,difficultyin preparation, high renal imagespresentlybeing recorded in the evaluation of acute and chronic soft-tissuebackground,urinary excretion, with radiomercurial compounds. pyelonephritis,andin fivepatientswith or poorhandlinginp atientswithaltered Technetium-99m-dimercaptosuccinic this disease cortical defects and scars renal function. Many ofthese difficulties acid (DMSA) is an agent that provides clearly were seen. have been reduced oreliminated with the superiorimagesofrenalparenchymawith As indicated by the variety of agents use of [@“Tc]DMSA. U •••S I S •S •S S •••••••I ••S •••S •••S ••S •I ••••S •S ••S ••••• JANUARY 1990 Half-Life Working with H. Saul Winchell, “Whilesome things change, others Hirsch Handmakr Handmaker and other researchers were staythesame:'Handmakernoted.“There exploring a wide variety of unique was a great deal ofenthusiasm and scien “Thatwasadifferenttime,averydif radiopharmaceuticals when they were tificzeal, but there wasalso the FDA, and ferent time:' Hirsch Handmaker remem made aware ofthe “leap―OfT.S. Lin. Lin, theywereascautiousandslow-movingas hers, when prompted to recallthe clinical whowasfamiliarwiththeuseofDMSA they are today regarding radiopharma environment from which his paper for the treatment of renal complications ceuticals. Though we had what we be emerged. resulting from the use ofantimony in the lievedto be more than enough evidenceto “Itwasatimewhenpessimismabout treatment ofa serious schistosomiasis in convince our clinical colleagues of its medical practice and the survivability of festation in China, extrapolated that safety and efficacy, the FDA was very slow nuyclearmedicinedid not exist.A time DMSAmight be used for imagingthe to act to approve the agent:' whentherewasstillagreatdealofexcite renal cortex whenlabeled appropriately. Fifteenyearslater,Handmakerhas the ment about the tracer principle, about Handmaker and his associates then satisfaction of knowing that linking well suited isotopes to chemical compiled compelling clinical data for the [99mTc]DMSAremains an important compoundsto permitimagingof oipns use of [“mlc]DMSA.But there were radiopharmaceutical for the evaluationof and functions previously inaccessible.― problems,familiarproblems. renal cortical function and integrity. U

Precisionof Regional Bone Mineral •LeBlanc et al 51