The Influence of Various Factors on the Accuracy of Gaffium-67 Imaging for Occult Infection
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The Influence of Various Factors on the Accuracy of Gaffium-67 Imaging for Occult Infection EufronioG. Maderazo,NancyB.Hickingbotham,CharlesL. Woronick, and John J. Sziklas The Medical Research Laboratory, Department ofMedicine, and the Nuclear Medicine Laboratory, Department ofPa:hology, Hartford Hospital, Hartford; and Departments of Medicine, Pathology, Laboratory Medicine and Nuclear Medicine, University of Connecticut School ofMedicine, Farmington, Connecticut To examine whether the results and interpretation of gallium-67citrate imagingmay be adversely influenced by factors present in compromised patients, we reviewed our 1-year expenence in 69 patients in intensive care units, renal transplants, and those on hemodialysis. Our results indicate that it is an inappropriate diagnostic procedure for acute pancreatitis since seven of nine had false-negative results. Using loglinear modeling and chi-square analysis we found that treatment with antiinflammatory steroids, severe liver disease, end stage renal disease, and renal transplantation with immunosuppressive therapy did not interferewithgallium-67uptake.Increasedrate oftrue-negativeresultsinpatientswithend stage renal disease was due to a greater and earl*r use of the test in the febrile transplant patient and in hemodialysis patients with infections not amenable to diagnosis with gallium-67 scan (transient bacteremia and bactenuria). We conclude that gallium-67 imaging is a useful diagnostic tool that, with the exception of acute pancreatitis, has very few false-negative results. J Nuci Med 29:608-615, 1988 he search for occult infections continues to be a infections and abscesses, and some neoplasms (1-3). common and important activity, and a vexing problem Because of these characteristics, it has been used as a in the case of the critically ill or compromised patient. convenient imaging procedure to help in the evaluation At present, there are several competing technologies of cases of fever of unknown origin. Its chief drawback that are available for this purpose. These include com is that localization of abdominal infection is hampered puted tomography (CT) scan, ultrasound and nuclear by normal bowel excretion. This has led many to re @ magnetic resonance imaging which provide primarily place 67(j@with [‘‘In]PMNimaging particularly for structural information, and gallium-67 (67Ga) scan and occult infection within the abdomen. This procedure, indium-labeled leukocyte imaging ([‘1‘InJPMN)which however, is more labor intensive and has not in our detect mainly pathophysiologic changes. The 67Gaand hands demonstrated sufficient superiority to warrant [1 I ‘In]PMN imaging procedures are particularly useful total replacement on cost-effective or logistical grounds. as a whole-body search procedure when localizing We continue to rely mainly on gallium and reserve symptoms or signs are lacking, and may serve to direct labeled leukocytes for selected patients. the attention of CT or ultrasound to certain areas. Although our experience with 67Ga supports its cm Since 1971, the [670a]citrate scan has been used as ical usefulness and parallels the experience reported by screening procedure to detect areas of inflammation or others (4—6),we have observed a few of our own infection (1). Although it lacks specificity, its sensitivity (anecdotal) cases suggesting that certain factors, such as is high in detecting inflammatory lesions, including immunosuppressive therapy, especially with glucocor ticoids, and renal and hepatic failure may be more Received May 26, 1987;revision accepted Nov. 12, 1987. likely to result in a false-negative result. For reprints contact: E. 0. Maderazo, MD, Medical Research To determine whether these assumptions might have Laboratory, Hartford Hospital, Hartford, CT 06115. some basis in fact, we retrospectively reviewed our 608 Maderazo,Hickingbotham,Woronicketal The Journal of Nuclear Medicine gallium scan experience in these selected groups of Statistics patients. In order to determine the effects of third variables on the outcome ofthe gallium scan in infected/inflamed versus non infected/noninflamed patients, the data were subjected to MATERIALS AND METhODS logiinear modeling (8). The data were arranged in the form of three-dimensional 2 x 2 x 2 contingency tables, in which the Patient Population third dimension is the presence or absence of the third van Since our primary interest was to study the factors that able, such as steroid treatment. A set of hierarchical models might influence the frequency offalse-negative scans, selection wasconstructedbasedupon thegeneralloglinearmodel (Table ofthe stratafor review was carriedout to include all critically 1), and the best model was selected using the likelihood-ratio ill patients in intensive care units, all patients on hemodialysis, test statistic (02) to test the goodness of fit. 02 is defined as: and all renal transplants with gallium scans between July 1984—June1985. We found and reviewed the medical records Iobservedvalue of 69 patients in whom gallium scans were ordered to search 2 @(observedvalue) x ln I for foci of infection. There were 32 females and 37 males, LexPected value with an age range of 1mo to 91 yr at the time oftesting. Forty where the summation is over all the cells in the table. For of the 69 patients were seriously ill in an intensive care unit sufficiently large samples, G2 and x2 have approximately the at the time of the study. Two patients were studied twice same distributions, so that p-values for significance may be during two different hospital admissions within a 6-mo time obtained from a chi-square table. Because the overall validity period. The ability of the gallium scan study to predict the of the gallium scan is not in question, the infection-gallium presenceorabsenceoffocalinfectionwasthenjudgedbased scan result (IG) interaction is included in every model, cx upon a combination of criteria that include clinical findings cepting for Model 1which we included only for completeness. and the results of cultures, CT scans, ultrasound, aspiration, (see Appendix for a more detailed explanation). drainage or exploratory procedures, and response to antibiotic. For most, the presence of infection was eventually obvious as a resultof the drainageof purulent material,positive cultures, RESULTS or by postmortem examination. In others, particularly for respiratory and abdominal lesions, the clinical differentiation There were 84 gallium scan procedures for 102 target of true infections from noninfectious inflammatory lesions is body sites performed on 69 patients. Target body site not always obvious. is defined as the site specified by the requesting physi cian, and other concomitant nonspecified but clinically Gallium Scan Procedure evident sites of infection/inflammation. If the site was The adult dose of[67Ga]citrate was 5 mCi (185 Mbq) given intravenously. Imaging was carried out using a large field-of not specified and/or not clinically evident prior to the viewcameraequippedwitha triplepeakanalyzercenteredon scan, the whole body was considered as one target site the lower three 67Gaphotopeaks and a medium-energy colli unless prior clinical findings allow separation of multi mator. For routine survey studies, imaging was usually carried plc involved areas of infection/inflammation. Unex out at 1 and 3 days postinjection. The Day 1 study was rarely plaineduptakeswerealsoconsideredtargetsites(unex definitive and served as a baseline to help distinguish physio plainedpositives). logic bowel activity in abdominal scans (which tends to move) Of the 102 target sites, there were 61 true-positive from pathologic (fixed) activity. Enema or suppository-in uptakes, five false- (unexplained) positive uptakes, 25 duced evacuation was frequently employed prior to repeat true-negative results, and 11 false-negative results. imaging. Sometimes repeat imaging was carried out as late as Thus, the sensitivity (100 x 61/72) was 85%, the spec 7 or 8 days postinjection. Similarly, for the kidneys, images at ificity ( 100 x 25/30) was 83%, the false-negative rate 24 hr, and 48 or 72 hr as well as comparison of uptake in both kidneys help distinguish normal urinary activity from (100 x 11/72) was 15%, the false-positive rate (100 x abnormal residual (usually focal) activity. 5/30) was 17%, and the accuracy (100 X 86/102) was The Day 1 images also serve as scout films and may direct 84%. attention to a specific organ such as liver, spleen, or kidneys. The unexplained (false) positive uptakes were noted In order to provide more precise anatomic localization and as follows: two individuals had unexplained uptake in better lesion contrast, we may then elect to perform a tech the thigh, one in the buttock, one in the kidney, and netium-99m (99mTc)/670asubtraction study utilizing a dual one in the right lung. radionucide simultaneous acquisition subtraction technique. Ofthe 11false-negative results, seven were in patients This has been previously described (7) and may be performed with acute pancreatitis in whom the pancreas failed to for any organ where there is a @mTcorgan-specific imaging show excess uptake. One of these seven patients with agent available, such as liver, spleen, kidneys, bone, or even pancreatitis had an abdominal fistula with a small blood pool. Images were obtained in at least two and prefer ably three projections. The simultaneous acquisition dual abdominal abscess, which also failed to accumulate channel technique avoids misregistration problems due to excess