Scintigraphic Findings Beyond Ejection Fraction on Hepatobiliary Scintigraphy Are They Correlated With Chronic Gallbladder Disease? Chad T. Christensen, DO,* Justin G. Peacock, MD, PhD,* Penny J. Vroman, MD,*† and Kevin P. Banks, MD*† Objective: To determine if classically reported findings associated with chronic cholecystitis on hepatobiliary scintigraphy (HBS), such as delayed small bowel (SB) transit, slow gallbladder (GB) filling, and reversal of the normal GB and SB transit, are associated with a depressed GB ejection frac- tion (GBEF). The secondary objectives were to determine whether GBEF is correlated with the time of GB filling, time of SB transit, or reversal of nor- mal GB/SB filling sequence. We hypothesize that an association between a depressed GBEF and these classical HBS findings could validate them as surrogate markers for chronic GB disease. Patients and Methods: We reviewed all HBS exams over a retrospective 16-month period. Data from 221 patients (mean age, 45.3 ± 15.2 years; 152 female and 69 male subjects) who underwent HBS with GBEF determi- nation for evaluation of chronic symptoms concerning for biliary etiology met inclusion criteria. Classically reported findings for cholecystitis were recorded for each patient. Comparisons were made using t test and Fisher test analysis. Results: Comparing exams with normal and abnormal GBEF values, there were no significant differences based on age, sex, GB fill time, normal versus delayed SB transit, and reversal of normal GB/SB filling sequence. Additionally, we did not see a correlation between the measured GBEF and GB fill time, SB transit time, or reversal of normal GB/SB filling sequence. Conclusions: Delayed SB transit, slow GB filling time, and reversal of the normal GB and SB filling sequence on HBS imaging are not associated with the measured GBEF and not predictive of chronic GB disease. Key Words: hepatobiliary scintigraphy, chronic cholecystitis, chronic gallbladder disease, biliary transit, gallbladder ejection fraction (Clin Nucl Med 2018;43: 721–727) H epatobiliary scintigraphy (HBS) is frequently obtained for evaluation of patients with symptoms concerning for recurrent biliary disease. Although a depressed gallbladder (GB) ejection fraction (GBEF) is generally considered the most accurate and common scintigraphic means for identifying chronic GB disease (CGBD), other secondary scintigraphic findings have long been considered somewhat specific for the presence of chronic chole- cystitis including delayed small bowel (SB) transit, slow GB filling, and reversal of the normal GB followed by SB filling sequence. 1–8 Many of these studies demonstrated limitations, including small study sizes, subjects with a very high prevalence of gallstones, use of ultrasound and/or oral cholecystography as the gold standard for disease diagnosis, or application of varying cholecystokinin (CCK) administration protocols that have since been shown to have poor specificity. These factors bring into question the generalizabil- ity of such associations with CGBD. In today’s typical medical practice, patients suspected of hav- ing CGBD undergo ultrasound (US) evaluation. 9 If US is positive for features of chronic cholecystitis (eg, gallstones and/or wall thickening), patients are frequently offered laparoscopic cholecys- tectomy without further imaging. In cases where US findings are negative or equivocal, patients often undergo further evaluation with HBS for a determination of GBEF. 10–12 After appropriate administration of CCK, a GBEF of 38% or greater is considered normal, and a GBEF less than 38% equates with a diagnosis of CGBD. 7 Given this modern paradigm for the evaluation and man- agement of patients with CGBD, we hypothesize that the aforemen- tioned classical HBS findings for chronic cholecystitis are not applicable to today’s scintigraphic diagnosis of CGBD. Chronic GB disease may be designated by a variety of terms including biliary dyskinesia, chronic cholecystitis, chronic acalculous cholecystitis, acalculous biliary disease, acalculous cholecystopathy, and functional GB disorder. 7,9 These terms are often used inter- changeably, leading to confusion. The association between a low GBEF and many forms of CGBD has been well documented; however, the secondary, classical HBS findings discussed previ- ously have been studied predominantly in the setting of chronic calculous cholecystitis. 1,2,7,8,13 The primary objective of this study was to determine if the scintigraphic findings of delayed SB transit (>60 minutes), slow filling of the GB (late in the first hour of dynamic imaging), reversal of the normal GB and SB filling sequence (ie, GB visualized after SB), or the difference in time between GB fill and SB transit are associated with CGBD. The secondary objectives were to determine if the GBEF correlated with GB fill time, SB transit time, or the dif- ference between GB fill and SB transit times. If these classical find- ings were to correlate with CGBD, it would be possible to forgo the additional hour of imaging and CCK administration necessary for GBEF determination. PATIENTS AND METHODS Institutional review board approval was obtained for the study. Written informed consent was waived, given the retrospective nature of the study. We reviewed all HBS exams performed at our institution from January 2014 through April 2015, totaling 366 studies (Fig. 1). We included HBS exams that used the 1-hour CCK infu- sion protocol for GBEF determination and evaluation of symptoms concerning for chronic biliary disease. We excluded patients with factors known to alter normal biliary flow, including a history of Received for publication April 16, 2018; revision accepted July 5, 2018. From the *Department of Radiology, Brooke Army Medical Center, San Antonio, TX; and †Department of Radiology, Uniformed Services University of the Health Sciences, Bethesda, MD. C.T.C. and J.G.P. are cofirst authors. Conflicts of interest and sources of funding: none declared. Correspondence to: Justin G. Peacock, MD, PhD, Brooke Army Medical Center, 3551 Roger Brooke Dr, San Antonio, TX 78234. E-mail: justin. g.peacock@gmail.com. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0363-9762/18/4310–0721 DOI: 10.1097/RLU.0000000000002242 ORIGINAL ARTICLE Clinical Nuclear Medicine • Volume 43, Number 10, October 2018 www.nuclearmed.com 721 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.