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Tumefactive gallbladder sludge: the MRI findings
Clinical Radiology xxx (2016) e1ee7
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Tumefactive gallbladder sludge: the MRI findings M. Seong, T.W. Kang*, M. Kim, S.S. Kim, K.M. Jang, Y.K. Kim, S.H. Kim Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
art icl e i nformat ion Article history: Received 15 October 2015 Received in revised form 22 December 2015 Accepted 4 January 2016
AIM: To evaluate the conventional and diffusion-weighted magnetic resonance imaging (MRI) images of tumefactive gallbladder sludge. MATERIALS AND METHODS: The institutional review board approved this retrospective study. Between January 2006 and January 2015, 3478 patients were diagnosed with gallbladder sludge by ultrasonography (US). Of them, 12 patients (eight male, four female; mean age, 63.6 years) with 12 tumefactive gallbladder sludge lesions, who underwent subsequent MRI for further evaluation within 1 month, were included in this study. Data regarding the clinical features, presence of enhancement, and signal intensities of the T2-, T1-, and diffusionweighted images were collected. RESULTS: All cases of tumefactive sludge were detected incidentally. None of the patients had any predisposing factors for biliary sludge. The tumefactive gallbladder sludge was predominantly seen as a well-defined mass-like lesion. It showed hyperintensity on T1-weighted images (91.7%, 11/12), and variable signal intensities on T2-weighted images. Most of the tumefactive sludge lesions showed no enhancement on the dynamic phases (90%, 9/10). There were no cases with diffusion restriction. Among the patients with follow-up US data (n¼7), all the lesions were found to have either disappeared or decreased in size. CONCLUSION: Although tumefactive gallbladder sludge on US can mimic gallbladder cancer, its hyperintensity on a T1-weighted image, and the absence of enhancement and diffusion restriction on MRI images can be helpful for differentiating it from a tumorous condition. Ó 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Ultrasonography (US) is currently the preferred diagnostic technique in gallbladder pathology including polyps, sludge, and cholelithiasis.1 Biliary sludge is composed of a suspension of cholesterol monohydrate crystals or calcium bilirubinate granules, and/or other calcium salts embedded
* Guarantor and correspondent: T.W. Kang, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul 135-710, Republic of Korea. Tel.: þ82 2 3410 0518; fax: þ82 2 3410 0049. E-mail addresses: [email protected], [email protected] (T.W. Kang).
in mucus, a mixture of mucin and proteins.2 It is rarely seen in asymptomatic healthy adult populations. Its prevalence was reported as ranging from 0% to 0.20% in men, and 0.18% to 0.27% in women.3,4 The incidence of biliary sludge may be increased in specific clinical conditions such as pregnancy,5 total parenteral nutrition,6 rapid weight loss,7 prolonged fasting in intensive care unit,8 and octreotide treatment.9 At US, it typically appears as a low-level echo with a fluidefluid level, without posterior acoustic shadowing, that characteristically moves slowly with changes in patient position.10 In contrast, the tumefactive appearance of biliary sludge does not form a fluidefluid level, but appears as a polypoid mass in gallbladder, without movement during position change.11 Thus, tumefactive sludge, as the name
http://dx.doi.org/10.1016/j.crad.2016.01.004 0009-9260/Ó 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: Seong M, et al., Tumefactive gallbladder sludge: the MRI findings, Clinical Radiology (2016), http://dx.doi.org/ 10.1016/j.crad.2016.01.004
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suggests, can mimic a tumour in clinical practice, requiring short-term follow-up or further evaluation with additional imaging techniques including contrast-enhanced US (CEUS), computed tomography (CT), and magnetic resonance imaging (MRI).1,12 A previous study investigating the clinical follow-up for sludge using US reported that it can persist in approximately 20% of cases over a 3-year period.13 Given this, follow up studies with conventional US, CEUS, CT, or MRI studies could be applied as adjunct techniques for a definite diagnosis of tumefactive sludge. Recently, technological advances in MRI including diffusion-weighted imaging (DWI), and the use of hepatobiliary contrast agents, enable MRI to be used as a conclusive diagnostic tool for gallbladder diseases14,15; however, there has been no study analysing the MRI findings of tumefactive sludge. Thus, the aim of the present study was to evaluate the MRI findings of tumefactive sludge using a large retrospective cohort.
Materials and methods Patients This retrospective study was approved by the Institutional Review Board of Samsung Medical Center, which waived the requirement for informed consent. Patients were identified through a search of the Radiology Department’s database, for abdominal US imaging reports containing the term “sludge”, recorded between 1 January 2006 and 1 January 2014. In the initial search, 3478 patient reports were found that fitted this criterion. From those reports, reports that had the following keywords, “tumefactive sludge”, “tumour-like sludge”, “mass-like sludge”, “tumour”, and “sludge” in same sentence; and “mass” and “sludge” in same sentence were extracted. The reports thus extracted from the database by the second search, were manually reviewed by one of two board-certified fellowship-trained abdominal radiologists (M.K. or S.S.K., with 3
and 2 years of experience, respectively) to minimise classification error. This process yielded 69 patients, of whom 12 patients met the following inclusion and exclusion criteria and were finally included in the study: (a) underwent MRI for further evaluation within 1 month after the initial US, and (b) confirmation of gallbladder sludge by histopathological analysis or serial imaging follow-up. In the imaging followup, lesions with interval regression in size or disappearance on the follow-up US after the initial MRI studies were considered as tumefactive sludge. The detailed selection process is described in Fig 1.
MRI examination The images of 10 out of 12 patients were acquired using a 3 T whole-body MRI system (Intera Achieva 3.0-T, Philips Healthcare, Best, The Netherlands) with a 16-channel phased-array receiver coil. The baseline MRI images included a breath-hold multi-shot T2-weighted sequence, a T1-weighted turbo field-echo in- and out-of-phase sequence, and a respiratory-triggered single-shot T2 and heavily T2-weighted sequence.16 Gadoxetic acid was used as the contrast agent (Primovist, Bayer Schering Pharma, Berlin, Germany). For the dynamic enhancement imaging studies, the unenhanced phase, arterial phase (20e35 seconds), portal phase (60 seconds), late phase (3 minutes), and 20 minute hepatobiliary phase were acquired. The subtraction images between the arterial or portal phase and the unenhanced phase were also acquired. These were obtained using a T1-weighted threedimensional turbo field-echo sequence with a spectral attenuated inversion-recovery fat-suppression technique. The MR fluoroscopic bolus-detection technique was used to determine the timing of the arterial phase imaging.17 DWI studies with b-values of 0, 100, and 800 s/mm2 were acquired before the administration of the contrast agent, using respiratory-triggered single-shot echo planar
Figure 1 Flow diagram of the study. Please cite this article in press as: Seong M, et al., Tumefactive gallbladder sludge: the MRI findings, Clinical Radiology (2016), http://dx.doi.org/ 10.1016/j.crad.2016.01.004
M. Seong et al. / Clinical Radiology xxx (2016) e1ee7
imaging. Spectral presaturation with inversion recovery was used for the fat-suppression technique. As a high bvalue on the DWI provides a better contrast, minimising the perfusion effect and the T2 shine-through effect,18 the apparent diffusion coefficient (ADC) was calculated by a mono-exponential function using b-values of 0 and 800 s/ mm2. The detailed parameters of each pulse sequence are summarised in Table 1. The two patients who did not undergo the above protocol underwent MR cholangiopancreatography with a 1.5 T MRI system (Signa HDi, GE Medical System’, Milwaukee, WI, USA), using a four-channel phased-array torso coil. The examinations were performed using a thick-slab T2weighted turbo spin-echo sequence obtained in the coronal plane, and with a thin-slab multi-section half-Fourier acquired single-shot turbo spin-echo sequence obtained in both the coronal and transverse planes. Unenhanced T1weighted imaging was performed with the in-phase and opposed-phase spoiled gradient-echo techniques, and a three-dimensional gradient recalled echo technique (volumetric interpolated breath-hold examination) with fat saturation.19 Other detailed parameters of each pulse sequence are similar to a previous study.20
MRI image analysis The conventional MRI findings and the DWIs were assessed by two investigators with a consensus review (Y.K.K. and K.M.J., with 11 and 7 years of experience in abdominal imaging, respectively). All the images were evaluated using a picture archiving and communication system (PACS; Centricity; GE Healthcare, Chicago, IL, USA). The MRI features evaluated were (1) size of the tumefactive sludge; (2) location (fundus, body and neck); (3) margins (well-defined or ill-defined); (4) presence of enhancement after the administration of the contrast media; (5) presence of gallbladder stone; (6) presence of regional lymph node enlargement; (7) accompanying imaging findings of acute cholecystitis; (8) adjacent gallbladder wall thickening; (9) predominant signal intensity of the lesion on the T1-, T2weighted images; and (10) presence of diffusion restriction. Based on signal intensity, the lesion was classified as hyperintense, isointense, or hypointense, compared with the adjacent normal liver parenchyma. The diffusion restriction of a lesion was defined when the lesion
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predominantly showed hyperintensity on the DWI with a bvalue of 800 s/mm2, and iso- to hypointensity of the corresponding area on the ADC map, compared to the adjacent normal liver parenchyma.14
Review of clinical information and US images The following factors were reviewed using the electronic medical records: the presence of associated symptoms (i.e., right upper quadrant pain); the predisposing factor for biliary sludge2; the time interval between the US and MRI images; history of cholecystectomy for confirmation of tumefactive sludge; and the duration for its decrement in size or its disappearance during the follow-up. In addition, the presence or absence of vascularity of tumefactive sludge on colour Doppler US imaging at the time of US diagnosis was retrospectively evaluated using PACS. All of these review processes were performed by one of the authors (M.S.).
Statistical analysis Descriptive statics were used in the present study. Median with range was used to express the values for continuous variables related to the patient baseline and imaging characteristics. Categorical variables were expressed as frequency with proportion. All the statistical analyses were performed using commercially available statistical software (MedCalc Software, MedCalc, Mariakerke, Belgium).
Results Baseline characteristics This study included a total of 12 patients, with 12 tumefactive sludge lesions. All the patients were asymptomatic at the time of the US and MRI examinations. No patient was found to have an associated predisposing factor for biliary sludge, including pregnancy, total parenteral nutrition, and intensive care unit setting. The median time interval between the US and MRI examinations was 10 days (range, 1e27 days). On the formal reports of the US examination at the time of diagnosis, the possibility of gallbladder cancer could not be excluded in the majority of patients. Detailed baseline characteristics of the study participants are described in Table 2.
Table 1 MRI parameters for 3-T system. Sequence
TR/TE (ms)
Flip angle (degrees)
Section thickness (mm)
Matrix size
Bandwidth (Hx/pixel)
Field of view (cm)
Acquisition time (s)
T1-weighted 2D dual GRE T1-weighted 3D GRE Breath-hold multi-shot T2-weighted imaging Respiratory-triggered single-shot T2-weighted imaging Respiratory-triggered single-shot heavily T2-weighted imaging DWI
10/1.15e2.3 31e1.5 2161/70
15 10 90
6 2 5
288230 256256 324235
434.4 955.7 235.2
32e38 32e38 32e38
1342/80
90
5
320256
506.4
32e38
120
1573/160
90
5
320256
317.9
32e38
120
1600/70
90
5
112112
14.5
32e38
126
14 16.6 55
2D, two-dimensional; 3D, three-dimensional; GRE, gradient recalled echo; TR, repetition time; TE, echo time; DWI, diffusion-weighted imaging.
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Table 2 Baseline characteristics of study patients. Variables
Study patients (n¼12)
Age at time of diagnosis (year) Male Presence of symptoms of acute cholecystitis Methods of final diagnosis Surgical specimen Imaging follow-up Risk factors for biliary sludge Movability on US Presence of vascularity on colour Doppler imaginga Time interval between US and MRI images (day) Results of formal US reports Probable or definite sludge Indeterminate Probable or definite gallbladder cancer Results of formal MRI reports Probable or definite sludge Indeterminate Probable or definite gallbladder cancer
63 (45e77) 8 (66.7) 0 5 (41.7) 7 (58.3) 0 0 0 10 (1e27) 0 9 (75.0) 3 (25.0) 12 (100) 0 0
Data are presented as the median with range or as numbers of patients with percentages in parentheses. US, ultrasound; MRI, magnetic resonance imaging. a Five patients underwent colour Doppler imaging study.
MRI analysis The median size of the tumefactive sludge was 1.7 cm (range, 1.3e3.4 cm), and it was usually located in the body of the gallbladder (41.7%, 5/12) as a well-defined mass-like lesion. Gallbladder stones were not frequently associated with tumefactive sludge (25%, 3/12). The predominant signal intensity of the lesion on the T1-weighted images was hyperintense, whereas the corresponding T2 signal intensity of the lesion was variable. After the injection of the MRI contrast medium, most of the lesions showed an absence of enhancement on the dynamic enhancement MRI images (91.7%, 11/12). On DWI, diffusion restriction of tumefactive sludge was not noted in any of the patients (Figs 2 and 3; Table 3).
Clinical follow-up Using the MRI images, all the lesions were correctly diagnosed as tumefactive sludge, based on the formal reading of the reports. Five patients underwent preventive laparoscopic cholecystectomy. The other patients had follow-up US with or without CT studies. The median follow-up period in these patients was 11 months (range, 6e26 months). The tumefactive sludge had disappeared on follow-up US in one patient, and the lesions of the other patients had decreased in size. The interval change in size ranged from 0.3 to 1.4 cm (median, 1 cm) on follow-up US. There were no cases of concomitant gallbladder cancer during the follow-up period.
Discussion Tumefactive sludge refers to a non-mobile polypoid mass in the gallbladder that does not move despite positional
change of the patient.1 In clinical practice, it is difficult to differentiate from mass-forming gallbladder cancer on a cross-sectional conventional US examination. Therefore, serial follow-up US or further evaluation with CEUS, CT or MRI is needed for confirmative diagnosis. Of these diagnostic approaches, MRI offers the advantages of improved lesion conspicuity and absence of ionising radiation, compared to CT.21,22 Unlike MRI studies, US is prone to operator dependency, especially CEUS, due to the short temporal window of the vascular phase.23 Thus, MRI has assumed an increasing role as an adjunct technique for gallbladder imaging15; however, the MRI findings of tumefactive sludge have not been described so far. The results of the present study demonstrate that tumefactive sludge in the gallbladder shows hyperintensity on T1weighted imaging, with the absence of enhancement on the dynamic phase, and diffusion restriction on MRI images. Biliary sludge can develop into gallstones or bile duct stones, and is thought to be a necessary precursor of biliary stones.24,25 Based on this, one might assume that the MRI findings of tumefactive sludge would be similar with those of biliary stones; however, in the present study, most of the tumefactive sludge lesions showed hyperintensity on T1weighted images, and variable signal intensities on the T2-weighted images. These results differ somewhat from the previous MRI findings of gallstones. In general, gallstones, which are composed of cholesterol and pigment, appear hypointense on T2-weighted images, and have variable signal intensities on T1-weighted imaging. Accordingly, cholesterol stones tend to be hypointense, whereas pigment stones show hyperintensity on T1-weighted images.15 The discrepancies between the imaging findings of the gallbladder sludge and gallstones may be associated with the differences in their chemical composition,26 because the MR signal intensity depends on the degree of the cholesterol, mucin, and protein composition of the biliary sludge or stones. In the present enhancement study, most of the lesions showed an absence of enhancement, and this corresponds to a previous study, which reported that gallbladder sludge did not show enhancement on CEUS.27 In addition, regarding the enhancement pattern of gallbladder lesions on MRI images, Yoshimitsu et al.28 demonstrated that early prolonged enhancement was more common in malignant lesions than in benign lesions. Although there was enhancement in one patient (10%, 1/10) in the present study, enhancement studies will provide valuable clues to enable a correct diagnosis of tumefactive sludge. Recently, DWI has been used for the detection and prediction of cancer, as malignant tumours tend to show higher signal intensity on DWI images, and a lower ADC value than normal tissues.29 This characteristic is increasingly being used to discriminate between benign and malignant lesions in the gallbladder, where the increased tissue cellularity of the malignant tumours restricts water movement in the reduced extracellular space.14,30 Similarly, in the present analysis, diffusion restriction was not seen in any of the patients with tumefactive sludge. Based on these results, DWI can contribute to the differentiation between
Please cite this article in press as: Seong M, et al., Tumefactive gallbladder sludge: the MRI findings, Clinical Radiology (2016), http://dx.doi.org/ 10.1016/j.crad.2016.01.004
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Figure 2 A 74-year-old man with typical MRI findings of tumefactive gallbladder sludge. (a) At transabdominal US, a 1.9-cm mass-like lesion (arrow) is noted in the body of the gallbladder, with no movement on position change. (b) On T2-weighted MRI images, a well-defined mass-like lesion (arrow) with hyperintensity is shown. (c) On T1-weighted images, the lesion (arrow) predominantly shows hyperintensity. (d) On subtraction images using pre-enhanced and portal phases, there is no enhancement of the lesion (arrow). (e) On DWI with a b-value of 800 s/mm2, the lesion (arrow) shows high signal intensity compared to the adjacent hepatic parenchyma. (f) On the ADC map, the visual signal intensity of the mass (arrow) is slightly higher than the adjacent hepatic parenchyma, indicating the absence of diffusion restriction. At follow-up US, 7 months later, the size of the lesion had decreased to 0.8 cm.
tumefactive sludge and mass-forming gallbladder cancer; however, the high viscosity of biliary sludge may restrict the motion of water protons in the tumefactive sludge, while the compact tumour cellularity and the fibrotic component
of adenocarcinoma in gallbladder cancer may cause diffusion restriction. Thus, diagnosis should be based on a combination of other MRI findings including conventional T1- and T2-weighted images, with enhancement studies.
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Figure 3 A 47-year-old man with atypical MRI findings of tumefactive gallbladder sludge. (a) At US, a 1.9 cm well-defined echogenic mass (arrow) is noted in the neck of gallbladder. (b) On T2-weighted MRI images, the lesion (arrow) shows a 1.2 cm well-defined mass-like lesion with hyperintensity and an interval decrease in size since the sonographic evaluation. (c) On T1-weighted images, the lesion (arrow) shows hypointensity predominantly. (d) On subtraction images using pre-enhanced and portal phases, there is enhancement in the peripheral portion of the mass (arrow). (e, f) In addition, the lesion (arrow) shows the absence of diffusion restriction on DWI with a b-value of 800 s/mm2 and ADC map. At follow-up US 16 months later, it had disappeared.
There are several limitations to the present study. First, there is the possibility of a selection bias related to the retrospective design. Second, only those patients who had undergone MRI for further evaluation were included, and
therefore, the present cohort did not reflect the entire spectrum of patients with tumefactive sludge. Third, although a large retrospective cohort was reviewed, the sample size was relatively small. Additional studies with
Please cite this article in press as: Seong M, et al., Tumefactive gallbladder sludge: the MRI findings, Clinical Radiology (2016), http://dx.doi.org/ 10.1016/j.crad.2016.01.004
M. Seong et al. / Clinical Radiology xxx (2016) e1ee7 Table 3 MRI findings of patients with tumefactive gallbladder sludge. Variables
Study patients (n¼12)
Size (cm) Location of lesion Fundus Body Neck Well-defined margins Presence of enhancement Presence of gallbladder stone Presence of regional lymph node enlargement Accompanying imaging findings of acute cholecystitis Adjacent gallbladder wall thickening T2-weighted image Hyperintensity Isointensity Hypointensity T1-weighted image Hyperintensity Isointensity Hypointensity Presence of diffusion restriction
1.7 (1.3e3.4) 4 (33.3) 5 (41.7) 3 (25.0) 12 (100) 1 (8.4) 3 (25.0) 1 (8.4) 0 0 1 (8.4) 9 (75.0) 2 (16.6) 12 (100) 0 0 1 (8.4)
Data are presented as the median with range or as numbers of patients with percentages in parentheses.
larger sample sizes will be needed for further validation of the present results. Despite the above limitations, the results represent the first-ever data regarding the analysis of the MRI findings of tumefactive gallbladder sludge. In clinical practice, although benign and malignant gallbladder polyps, such as cholesterol polyps, inflammatory polyps, adenocarcinoma, metastasis, and lymphoma, could be considered as differential diagnoses based on MRI findings,1 the present results will be helpful in the interpretation of MRI images in patients with suspected tumefactive gallbladder sludge. In conclusion, the MRI features of a well-defined masslike lesion, hyperintensity on a T1-weighted image, and the absence of both enhancement and diffusion restriction are highly suggestive of tumefactive sludge. Based on these findings, MRI studies can be useful in the confirmative diagnosis of tumefactive sludge.
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7. Shiffman ML, Sugerman HJ, Kellum JM, et al. Gallstone formation after rapid weight loss: a prospective study in patients undergoing gastric bypass surgery for treatment of morbid obesity. Am J Gastroenterol 1991;86:1000e5. 8. Murray FE, Stinchcombe SJ, Hawkey CJ. Development of biliary sludge in patients on intensive care unit: results of a prospective ultrasonographic study. Gut 1992;33:1123e5. 9. Catnach SM, Anderson JV, Fairclough PD, et al. Effect of octreotide on gall stone prevalence and gall bladder motility in acromegaly. Gut 1993;34:270e3. 10. Rosenthal SJ, Cox GG, Wetzel LH, et al. Pitfalls and differential diagnosis in biliary sonography. RadioGraphics 1990;10:285e311. 11. Fakhry J. Sonography of tumefactive biliary sludge. AJR Am J Roentgenol 1982;139:717e9. 12. Sparchez Z, Radu P. Role of CEUS in the diagnosis of gallbladder disease. Med Ultrason 2012;14:326e30. 13. Lee SP, Maher K, Nicholls JF. Origin and fate of biliary sludge. Gastroenterology 1988;94:170e6. 14. Kang TW, Kim SH, Park HJ, et al. Differentiating xanthogranulomatous cholecystitis from wall-thickening type of gallbladder cancer: added value of diffusion-weighted MRI. Clin Radiol 2013;68:992e1001. 15. Catalano OA, Sahani DV, Kalva SP, et al. MRI of the gallbladder: a pictorial essay. RadioGraphics 2008;28:135e55. quiz 324. 16. Kang TW, Kim SH, Jang KM, et al. Gastrointestinal stromal tumours: correlation of modified NIH risk stratification with diffusion-weighted MRI as an imaging biomarker. Eur J Radiol 2015;84:33e40. 17. Haradome H, Grazioli L, Tsunoo M, et al. Can MR fluoroscopic triggering technique and slow rate injection provide appropriate arterial phase images with reducing artifacts on gadoxetic acid-DTPA (Gd-EOB-DTPA)enhanced hepatic MRI? J Magn Reson Imaging 2010;32:334e40. 18. Asbach P, Hein PA, Stemmer A, et al. Free-breathing echo-planar imaging based diffusion-weighted magnetic resonance imaging of the liver with prospective acquisition correction. J Comput Assist Tomogr 2008;32:372e8. 19. Park HS, Lee JM, Choi JY, et al. Preoperative evaluation of bile duct cancer: MRI combined with MR cholangiopancreatography versus MDCT with direct cholangiography. AJR Am J Roentgenol 2008;190:396e405. 20. Park HS, Lee JM, Choi HK, et al. Preoperative evaluation of pancreatic cancer: comparison of gadolinium-enhanced dynamic MRI with MR cholangiopancreatography versus MDCT. J Magn Reson Imaging 2009;30:586e95. 21. Yeh BM, Liu PS, Soto JA, et al. MRI and CT of the biliary tract. RadioGraphics 2009;29:1669e88. 22. Yoshimitsu K, Honda H, Aibe H, et al. Radiologic diagnosis of adenomyomatosis of the gallbladder: comparative study among MRI, helical CT, and transabdominal US. J Comput Assist Tomogr 2001;25:843e50. 23. Lee MW. Fusion imaging of real-time ultrasonography with CT or MRI for hepatic intervention. Ultrasonography 2014;33:227e39. 24. Keizman D, Ish-Shalom M, Konikoff FM. The clinical significance of bile duct sludge: is it different from bile duct stones? Surg Endosc 2007;21:769e73. 25. Jungst C, Kullak-Ublick GA, Jungst D. Gallstone disease: microlithiasis and sludge. Best Pract Res Clin Gastroenterol 2006;20:1053e62. 26. Weerakoon H, Navaratne A, Ranasinghe S, et al. Chemical characterization of gallstones: an approach to explore the aetiopathogenesis of gallstone disease in Sri Lanka. PLoS One 2015;10:e0121537. 27. Xie XH, Xu HX, Xie XY, et al. Differential diagnosis between benign and malignant gallbladder diseases with real-time contrast-enhanced ultrasound. Eur Radiol 2010;20:239e48. 28. Yoshimitsu K, Honda H, Kaneko K, et al. Dynamic MRI of the gallbladder lesions: differentiation of benign from malignant. J Magn Reson Imaging 1997;7:696e701. 29. Charles-Edwards EM, deSouza NM. Diffusion-weighted magnetic resonance imaging and its application to cancer. Cancer Imaging 2006;6:135e43. 30. Irie H, Kamochi N, Nojiri J, et al. High b-value diffusion-weighted MRI in differentiation between benign and malignant polypoid gallbladder lesions. Acta Radiol 2011;52:236e40.
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Tumefactive gallbladder sludge: the MRI findings M. Seong, T.W. Kang*, M. Kim, S.S. Kim, K.M. Jang, Y.K. Kim, S.H. Kim Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
art icl e i nformat ion Article history: Received 15 October 2015 Received in revised form 22 December 2015 Accepted 4 January 2016
AIM: To evaluate the conventional and diffusion-weighted magnetic resonance imaging (MRI) images of tumefactive gallbladder sludge. MATERIALS AND METHODS: The institutional review board approved this retrospective study. Between January 2006 and January 2015, 3478 patients were diagnosed with gallbladder sludge by ultrasonography (US). Of them, 12 patients (eight male, four female; mean age, 63.6 years) with 12 tumefactive gallbladder sludge lesions, who underwent subsequent MRI for further evaluation within 1 month, were included in this study. Data regarding the clinical features, presence of enhancement, and signal intensities of the T2-, T1-, and diffusionweighted images were collected. RESULTS: All cases of tumefactive sludge were detected incidentally. None of the patients had any predisposing factors for biliary sludge. The tumefactive gallbladder sludge was predominantly seen as a well-defined mass-like lesion. It showed hyperintensity on T1-weighted images (91.7%, 11/12), and variable signal intensities on T2-weighted images. Most of the tumefactive sludge lesions showed no enhancement on the dynamic phases (90%, 9/10). There were no cases with diffusion restriction. Among the patients with follow-up US data (n¼7), all the lesions were found to have either disappeared or decreased in size. CONCLUSION: Although tumefactive gallbladder sludge on US can mimic gallbladder cancer, its hyperintensity on a T1-weighted image, and the absence of enhancement and diffusion restriction on MRI images can be helpful for differentiating it from a tumorous condition. Ó 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Ultrasonography (US) is currently the preferred diagnostic technique in gallbladder pathology including polyps, sludge, and cholelithiasis.1 Biliary sludge is composed of a suspension of cholesterol monohydrate crystals or calcium bilirubinate granules, and/or other calcium salts embedded
* Guarantor and correspondent: T.W. Kang, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-gu, Seoul 135-710, Republic of Korea. Tel.: þ82 2 3410 0518; fax: þ82 2 3410 0049. E-mail addresses: [email protected], [email protected] (T.W. Kang).
in mucus, a mixture of mucin and proteins.2 It is rarely seen in asymptomatic healthy adult populations. Its prevalence was reported as ranging from 0% to 0.20% in men, and 0.18% to 0.27% in women.3,4 The incidence of biliary sludge may be increased in specific clinical conditions such as pregnancy,5 total parenteral nutrition,6 rapid weight loss,7 prolonged fasting in intensive care unit,8 and octreotide treatment.9 At US, it typically appears as a low-level echo with a fluidefluid level, without posterior acoustic shadowing, that characteristically moves slowly with changes in patient position.10 In contrast, the tumefactive appearance of biliary sludge does not form a fluidefluid level, but appears as a polypoid mass in gallbladder, without movement during position change.11 Thus, tumefactive sludge, as the name
http://dx.doi.org/10.1016/j.crad.2016.01.004 0009-9260/Ó 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
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suggests, can mimic a tumour in clinical practice, requiring short-term follow-up or further evaluation with additional imaging techniques including contrast-enhanced US (CEUS), computed tomography (CT), and magnetic resonance imaging (MRI).1,12 A previous study investigating the clinical follow-up for sludge using US reported that it can persist in approximately 20% of cases over a 3-year period.13 Given this, follow up studies with conventional US, CEUS, CT, or MRI studies could be applied as adjunct techniques for a definite diagnosis of tumefactive sludge. Recently, technological advances in MRI including diffusion-weighted imaging (DWI), and the use of hepatobiliary contrast agents, enable MRI to be used as a conclusive diagnostic tool for gallbladder diseases14,15; however, there has been no study analysing the MRI findings of tumefactive sludge. Thus, the aim of the present study was to evaluate the MRI findings of tumefactive sludge using a large retrospective cohort.
Materials and methods Patients This retrospective study was approved by the Institutional Review Board of Samsung Medical Center, which waived the requirement for informed consent. Patients were identified through a search of the Radiology Department’s database, for abdominal US imaging reports containing the term “sludge”, recorded between 1 January 2006 and 1 January 2014. In the initial search, 3478 patient reports were found that fitted this criterion. From those reports, reports that had the following keywords, “tumefactive sludge”, “tumour-like sludge”, “mass-like sludge”, “tumour”, and “sludge” in same sentence; and “mass” and “sludge” in same sentence were extracted. The reports thus extracted from the database by the second search, were manually reviewed by one of two board-certified fellowship-trained abdominal radiologists (M.K. or S.S.K., with 3
and 2 years of experience, respectively) to minimise classification error. This process yielded 69 patients, of whom 12 patients met the following inclusion and exclusion criteria and were finally included in the study: (a) underwent MRI for further evaluation within 1 month after the initial US, and (b) confirmation of gallbladder sludge by histopathological analysis or serial imaging follow-up. In the imaging followup, lesions with interval regression in size or disappearance on the follow-up US after the initial MRI studies were considered as tumefactive sludge. The detailed selection process is described in Fig 1.
MRI examination The images of 10 out of 12 patients were acquired using a 3 T whole-body MRI system (Intera Achieva 3.0-T, Philips Healthcare, Best, The Netherlands) with a 16-channel phased-array receiver coil. The baseline MRI images included a breath-hold multi-shot T2-weighted sequence, a T1-weighted turbo field-echo in- and out-of-phase sequence, and a respiratory-triggered single-shot T2 and heavily T2-weighted sequence.16 Gadoxetic acid was used as the contrast agent (Primovist, Bayer Schering Pharma, Berlin, Germany). For the dynamic enhancement imaging studies, the unenhanced phase, arterial phase (20e35 seconds), portal phase (60 seconds), late phase (3 minutes), and 20 minute hepatobiliary phase were acquired. The subtraction images between the arterial or portal phase and the unenhanced phase were also acquired. These were obtained using a T1-weighted threedimensional turbo field-echo sequence with a spectral attenuated inversion-recovery fat-suppression technique. The MR fluoroscopic bolus-detection technique was used to determine the timing of the arterial phase imaging.17 DWI studies with b-values of 0, 100, and 800 s/mm2 were acquired before the administration of the contrast agent, using respiratory-triggered single-shot echo planar
Figure 1 Flow diagram of the study. Please cite this article in press as: Seong M, et al., Tumefactive gallbladder sludge: the MRI findings, Clinical Radiology (2016), http://dx.doi.org/ 10.1016/j.crad.2016.01.004
M. Seong et al. / Clinical Radiology xxx (2016) e1ee7
imaging. Spectral presaturation with inversion recovery was used for the fat-suppression technique. As a high bvalue on the DWI provides a better contrast, minimising the perfusion effect and the T2 shine-through effect,18 the apparent diffusion coefficient (ADC) was calculated by a mono-exponential function using b-values of 0 and 800 s/ mm2. The detailed parameters of each pulse sequence are summarised in Table 1. The two patients who did not undergo the above protocol underwent MR cholangiopancreatography with a 1.5 T MRI system (Signa HDi, GE Medical System’, Milwaukee, WI, USA), using a four-channel phased-array torso coil. The examinations were performed using a thick-slab T2weighted turbo spin-echo sequence obtained in the coronal plane, and with a thin-slab multi-section half-Fourier acquired single-shot turbo spin-echo sequence obtained in both the coronal and transverse planes. Unenhanced T1weighted imaging was performed with the in-phase and opposed-phase spoiled gradient-echo techniques, and a three-dimensional gradient recalled echo technique (volumetric interpolated breath-hold examination) with fat saturation.19 Other detailed parameters of each pulse sequence are similar to a previous study.20
MRI image analysis The conventional MRI findings and the DWIs were assessed by two investigators with a consensus review (Y.K.K. and K.M.J., with 11 and 7 years of experience in abdominal imaging, respectively). All the images were evaluated using a picture archiving and communication system (PACS; Centricity; GE Healthcare, Chicago, IL, USA). The MRI features evaluated were (1) size of the tumefactive sludge; (2) location (fundus, body and neck); (3) margins (well-defined or ill-defined); (4) presence of enhancement after the administration of the contrast media; (5) presence of gallbladder stone; (6) presence of regional lymph node enlargement; (7) accompanying imaging findings of acute cholecystitis; (8) adjacent gallbladder wall thickening; (9) predominant signal intensity of the lesion on the T1-, T2weighted images; and (10) presence of diffusion restriction. Based on signal intensity, the lesion was classified as hyperintense, isointense, or hypointense, compared with the adjacent normal liver parenchyma. The diffusion restriction of a lesion was defined when the lesion
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predominantly showed hyperintensity on the DWI with a bvalue of 800 s/mm2, and iso- to hypointensity of the corresponding area on the ADC map, compared to the adjacent normal liver parenchyma.14
Review of clinical information and US images The following factors were reviewed using the electronic medical records: the presence of associated symptoms (i.e., right upper quadrant pain); the predisposing factor for biliary sludge2; the time interval between the US and MRI images; history of cholecystectomy for confirmation of tumefactive sludge; and the duration for its decrement in size or its disappearance during the follow-up. In addition, the presence or absence of vascularity of tumefactive sludge on colour Doppler US imaging at the time of US diagnosis was retrospectively evaluated using PACS. All of these review processes were performed by one of the authors (M.S.).
Statistical analysis Descriptive statics were used in the present study. Median with range was used to express the values for continuous variables related to the patient baseline and imaging characteristics. Categorical variables were expressed as frequency with proportion. All the statistical analyses were performed using commercially available statistical software (MedCalc Software, MedCalc, Mariakerke, Belgium).
Results Baseline characteristics This study included a total of 12 patients, with 12 tumefactive sludge lesions. All the patients were asymptomatic at the time of the US and MRI examinations. No patient was found to have an associated predisposing factor for biliary sludge, including pregnancy, total parenteral nutrition, and intensive care unit setting. The median time interval between the US and MRI examinations was 10 days (range, 1e27 days). On the formal reports of the US examination at the time of diagnosis, the possibility of gallbladder cancer could not be excluded in the majority of patients. Detailed baseline characteristics of the study participants are described in Table 2.
Table 1 MRI parameters for 3-T system. Sequence
TR/TE (ms)
Flip angle (degrees)
Section thickness (mm)
Matrix size
Bandwidth (Hx/pixel)
Field of view (cm)
Acquisition time (s)
T1-weighted 2D dual GRE T1-weighted 3D GRE Breath-hold multi-shot T2-weighted imaging Respiratory-triggered single-shot T2-weighted imaging Respiratory-triggered single-shot heavily T2-weighted imaging DWI
10/1.15e2.3 31e1.5 2161/70
15 10 90
6 2 5
288230 256256 324235
434.4 955.7 235.2
32e38 32e38 32e38
1342/80
90
5
320256
506.4
32e38
120
1573/160
90
5
320256
317.9
32e38
120
1600/70
90
5
112112
14.5
32e38
126
14 16.6 55
2D, two-dimensional; 3D, three-dimensional; GRE, gradient recalled echo; TR, repetition time; TE, echo time; DWI, diffusion-weighted imaging.
Please cite this article in press as: Seong M, et al., Tumefactive gallbladder sludge: the MRI findings, Clinical Radiology (2016), http://dx.doi.org/ 10.1016/j.crad.2016.01.004
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Table 2 Baseline characteristics of study patients. Variables
Study patients (n¼12)
Age at time of diagnosis (year) Male Presence of symptoms of acute cholecystitis Methods of final diagnosis Surgical specimen Imaging follow-up Risk factors for biliary sludge Movability on US Presence of vascularity on colour Doppler imaginga Time interval between US and MRI images (day) Results of formal US reports Probable or definite sludge Indeterminate Probable or definite gallbladder cancer Results of formal MRI reports Probable or definite sludge Indeterminate Probable or definite gallbladder cancer
63 (45e77) 8 (66.7) 0 5 (41.7) 7 (58.3) 0 0 0 10 (1e27) 0 9 (75.0) 3 (25.0) 12 (100) 0 0
Data are presented as the median with range or as numbers of patients with percentages in parentheses. US, ultrasound; MRI, magnetic resonance imaging. a Five patients underwent colour Doppler imaging study.
MRI analysis The median size of the tumefactive sludge was 1.7 cm (range, 1.3e3.4 cm), and it was usually located in the body of the gallbladder (41.7%, 5/12) as a well-defined mass-like lesion. Gallbladder stones were not frequently associated with tumefactive sludge (25%, 3/12). The predominant signal intensity of the lesion on the T1-weighted images was hyperintense, whereas the corresponding T2 signal intensity of the lesion was variable. After the injection of the MRI contrast medium, most of the lesions showed an absence of enhancement on the dynamic enhancement MRI images (91.7%, 11/12). On DWI, diffusion restriction of tumefactive sludge was not noted in any of the patients (Figs 2 and 3; Table 3).
Clinical follow-up Using the MRI images, all the lesions were correctly diagnosed as tumefactive sludge, based on the formal reading of the reports. Five patients underwent preventive laparoscopic cholecystectomy. The other patients had follow-up US with or without CT studies. The median follow-up period in these patients was 11 months (range, 6e26 months). The tumefactive sludge had disappeared on follow-up US in one patient, and the lesions of the other patients had decreased in size. The interval change in size ranged from 0.3 to 1.4 cm (median, 1 cm) on follow-up US. There were no cases of concomitant gallbladder cancer during the follow-up period.
Discussion Tumefactive sludge refers to a non-mobile polypoid mass in the gallbladder that does not move despite positional
change of the patient.1 In clinical practice, it is difficult to differentiate from mass-forming gallbladder cancer on a cross-sectional conventional US examination. Therefore, serial follow-up US or further evaluation with CEUS, CT or MRI is needed for confirmative diagnosis. Of these diagnostic approaches, MRI offers the advantages of improved lesion conspicuity and absence of ionising radiation, compared to CT.21,22 Unlike MRI studies, US is prone to operator dependency, especially CEUS, due to the short temporal window of the vascular phase.23 Thus, MRI has assumed an increasing role as an adjunct technique for gallbladder imaging15; however, the MRI findings of tumefactive sludge have not been described so far. The results of the present study demonstrate that tumefactive sludge in the gallbladder shows hyperintensity on T1weighted imaging, with the absence of enhancement on the dynamic phase, and diffusion restriction on MRI images. Biliary sludge can develop into gallstones or bile duct stones, and is thought to be a necessary precursor of biliary stones.24,25 Based on this, one might assume that the MRI findings of tumefactive sludge would be similar with those of biliary stones; however, in the present study, most of the tumefactive sludge lesions showed hyperintensity on T1weighted images, and variable signal intensities on the T2-weighted images. These results differ somewhat from the previous MRI findings of gallstones. In general, gallstones, which are composed of cholesterol and pigment, appear hypointense on T2-weighted images, and have variable signal intensities on T1-weighted imaging. Accordingly, cholesterol stones tend to be hypointense, whereas pigment stones show hyperintensity on T1-weighted images.15 The discrepancies between the imaging findings of the gallbladder sludge and gallstones may be associated with the differences in their chemical composition,26 because the MR signal intensity depends on the degree of the cholesterol, mucin, and protein composition of the biliary sludge or stones. In the present enhancement study, most of the lesions showed an absence of enhancement, and this corresponds to a previous study, which reported that gallbladder sludge did not show enhancement on CEUS.27 In addition, regarding the enhancement pattern of gallbladder lesions on MRI images, Yoshimitsu et al.28 demonstrated that early prolonged enhancement was more common in malignant lesions than in benign lesions. Although there was enhancement in one patient (10%, 1/10) in the present study, enhancement studies will provide valuable clues to enable a correct diagnosis of tumefactive sludge. Recently, DWI has been used for the detection and prediction of cancer, as malignant tumours tend to show higher signal intensity on DWI images, and a lower ADC value than normal tissues.29 This characteristic is increasingly being used to discriminate between benign and malignant lesions in the gallbladder, where the increased tissue cellularity of the malignant tumours restricts water movement in the reduced extracellular space.14,30 Similarly, in the present analysis, diffusion restriction was not seen in any of the patients with tumefactive sludge. Based on these results, DWI can contribute to the differentiation between
Please cite this article in press as: Seong M, et al., Tumefactive gallbladder sludge: the MRI findings, Clinical Radiology (2016), http://dx.doi.org/ 10.1016/j.crad.2016.01.004
M. Seong et al. / Clinical Radiology xxx (2016) e1ee7
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Figure 2 A 74-year-old man with typical MRI findings of tumefactive gallbladder sludge. (a) At transabdominal US, a 1.9-cm mass-like lesion (arrow) is noted in the body of the gallbladder, with no movement on position change. (b) On T2-weighted MRI images, a well-defined mass-like lesion (arrow) with hyperintensity is shown. (c) On T1-weighted images, the lesion (arrow) predominantly shows hyperintensity. (d) On subtraction images using pre-enhanced and portal phases, there is no enhancement of the lesion (arrow). (e) On DWI with a b-value of 800 s/mm2, the lesion (arrow) shows high signal intensity compared to the adjacent hepatic parenchyma. (f) On the ADC map, the visual signal intensity of the mass (arrow) is slightly higher than the adjacent hepatic parenchyma, indicating the absence of diffusion restriction. At follow-up US, 7 months later, the size of the lesion had decreased to 0.8 cm.
tumefactive sludge and mass-forming gallbladder cancer; however, the high viscosity of biliary sludge may restrict the motion of water protons in the tumefactive sludge, while the compact tumour cellularity and the fibrotic component
of adenocarcinoma in gallbladder cancer may cause diffusion restriction. Thus, diagnosis should be based on a combination of other MRI findings including conventional T1- and T2-weighted images, with enhancement studies.
Please cite this article in press as: Seong M, et al., Tumefactive gallbladder sludge: the MRI findings, Clinical Radiology (2016), http://dx.doi.org/ 10.1016/j.crad.2016.01.004
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Figure 3 A 47-year-old man with atypical MRI findings of tumefactive gallbladder sludge. (a) At US, a 1.9 cm well-defined echogenic mass (arrow) is noted in the neck of gallbladder. (b) On T2-weighted MRI images, the lesion (arrow) shows a 1.2 cm well-defined mass-like lesion with hyperintensity and an interval decrease in size since the sonographic evaluation. (c) On T1-weighted images, the lesion (arrow) shows hypointensity predominantly. (d) On subtraction images using pre-enhanced and portal phases, there is enhancement in the peripheral portion of the mass (arrow). (e, f) In addition, the lesion (arrow) shows the absence of diffusion restriction on DWI with a b-value of 800 s/mm2 and ADC map. At follow-up US 16 months later, it had disappeared.
There are several limitations to the present study. First, there is the possibility of a selection bias related to the retrospective design. Second, only those patients who had undergone MRI for further evaluation were included, and
therefore, the present cohort did not reflect the entire spectrum of patients with tumefactive sludge. Third, although a large retrospective cohort was reviewed, the sample size was relatively small. Additional studies with
Please cite this article in press as: Seong M, et al., Tumefactive gallbladder sludge: the MRI findings, Clinical Radiology (2016), http://dx.doi.org/ 10.1016/j.crad.2016.01.004
M. Seong et al. / Clinical Radiology xxx (2016) e1ee7 Table 3 MRI findings of patients with tumefactive gallbladder sludge. Variables
Study patients (n¼12)
Size (cm) Location of lesion Fundus Body Neck Well-defined margins Presence of enhancement Presence of gallbladder stone Presence of regional lymph node enlargement Accompanying imaging findings of acute cholecystitis Adjacent gallbladder wall thickening T2-weighted image Hyperintensity Isointensity Hypointensity T1-weighted image Hyperintensity Isointensity Hypointensity Presence of diffusion restriction
1.7 (1.3e3.4) 4 (33.3) 5 (41.7) 3 (25.0) 12 (100) 1 (8.4) 3 (25.0) 1 (8.4) 0 0 1 (8.4) 9 (75.0) 2 (16.6) 12 (100) 0 0 1 (8.4)
Data are presented as the median with range or as numbers of patients with percentages in parentheses.
larger sample sizes will be needed for further validation of the present results. Despite the above limitations, the results represent the first-ever data regarding the analysis of the MRI findings of tumefactive gallbladder sludge. In clinical practice, although benign and malignant gallbladder polyps, such as cholesterol polyps, inflammatory polyps, adenocarcinoma, metastasis, and lymphoma, could be considered as differential diagnoses based on MRI findings,1 the present results will be helpful in the interpretation of MRI images in patients with suspected tumefactive gallbladder sludge. In conclusion, the MRI features of a well-defined masslike lesion, hyperintensity on a T1-weighted image, and the absence of both enhancement and diffusion restriction are highly suggestive of tumefactive sludge. Based on these findings, MRI studies can be useful in the confirmative diagnosis of tumefactive sludge.
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Please cite this article in press as: Seong M, et al., Tumefactive gallbladder sludge: the MRI findings, Clinical Radiology (2016), http://dx.doi.org/ 10.1016/j.crad.2016.01.004