This retrospective study was approved by the institutional ethics review board with a waiver of patients’ informed consent. We searched our radiologic database for abdominal MR examinations performed between August 2018 and November 2020 by using the search terms “distal common bile duct stricture,” “ampullary carcinoma,” “pancreatic ductal adenocarcinoma,” and “pancreatic mass,” and the search yielded 256 patients. We used the following inclusion criteria: (a) patients who underwent 3.0-T abdominal MRI for biliary-pancreas evaluation, including c-EPI DWI, z-EPI DWI, and MRCP before surgery or biliary interventional procedures, (b) patients with histopathological confirmation of periampullary diseases after MRI, (c) patients with surgery/diagnostic biopsy within two weeks after MRI, (d) patients with histopathological confirmation by biopsy or brush cytology with a clinical diagnosis of benign periampullary disease and follow-up CT or MRI over 12 months. On the basis of these inclusion criteria, 205 patients were excluded (Fig 1). Finally, 51 patients were included in this study. Fifteen patients (mean age, 61.4 ± 15.8 years, range 18–79; 9 men and 6 women) had benign periampullary disease and 36 patients (mean age, 60.8 ± 10.5 years, range 39–80; 18 men and 18 women) had periampullary malignancy.

Flow chart of the study population

Thirty-six lesions (tumor size 21.69 ± 10.05 mm (4.00–45.7 mm)) in 36 patients with periampullary malignancy were evaluated in our study population, and 20 small lesions with a diameter less than or equal to 20 mm (tumor size 14.78 ± 4.38 mm (4.00–20.00 mm)) were included. Of these, 25 patients underwent surgery, and 11 patients underwent only diagnostic biopsy; the findings included 13 histologically confirmed pancreatic adenocarcinomas, 15 distal common bile duct cholangiocarcinomas, four ampullary carcinoma, and four duodenal adenocarcinomas.

Of these patients with benign periampullary disease, one patient underwent surgery, and five patients underwent only diagnostic biopsy, revealing two histologically confirmed ampulla of Vater tubular adenomas, three distal common bile duct inflammatory stenosis cases, and one case with inflammation of the descending segment of the duodenum. Eight patients underwent ERCP, confirming seven common bile duct stones or sludge and one descending duodenal diverticulum. One patient was clinically diagnosed with autoimmune pancreatitis. Clinical and demographic data for the two groups are summarized in Table 1.

An upper abdomen MRI study of 51 patients was performed on a 3T whole-body MR system (MAGNETOM Prisma, Siemens Healthcare, Germany) with an 18-channel phased-array body coil as the receiver coil. Both a c-EPI DWI (b values = 50 and 800 sec/mm2) and z-EPI DWI (b values = 50 and 800 sec/mm2) of the periampullary region in the same patient were obtained. For the z-EPI DWI, a two-dimensional spatially selective RF pulse using an echo-planar transmit trajectory was applied. The z-EPI imaging parameters of DWI were as follows: 2000/61 (repetition time (ms)/echo time (ms)), 5-mm slice thickness, 230 mm × 120-mm field of view, 1.5 × 1.5 × 5 reconstructed voxel size (mm3), and 154 × 50 matrix, acquisition time was 3min20s~5min45s, depending on breathing pattern (respiration control: trigger). The c-EPI imaging parameters of DWI were as follows: 4500/56 (repetition time (ms)/echo time (ms)), 5-mm slice thickness, 350 mm × 292 mm field of view, 2.2 × 2.2 × 5 reconstructed voxel size (mm3), 158 × 121 matrix, and 1 min 52 s acquisition time (respiration control: Free-breathing). Both a breath-hold single-section 2D MRCP and navigator-triggered 3D MRCP were obtained, and the parameters were as follows: 2D MRCP: repetition time (ms)/echo time (ms), 4500/735; flip angle, 180°; slice thickness, 50mm; matrix,384×268; field of view, 300mm×300 mm; bandwidth,352-Hz/pixel; echo space(msec) 6.5ms. 3D MRCP: repetition time (ms)/echo time (ms), 2400/702; flip angle, 140°; slice thickness, 1.2mm; matrix,384×384×276; field of view, 350 mm×350 mm; bandwidth, 350-Hz/pixel; echo space(msec) 5.1 ms. The conventional sequences included a coronal breath-hold T2-weighted half-Fourier single-shot turbo spin echo sequence (HASTE) (1400/67 (repetition time (ms)/echo time (ms)), 5-mm slice thickness, 360mm × 360-mm field of view, 256 × 256 matrix), an axial fat-suppressed respiratory triggered (RT) T2-weighted turbo spin echo sequence (TSE) (3100/87 (repetition time (ms)/echo time (ms)), 5-mm slice thickness, 380mm × 380-mm field of view, 320 × 320 matrix), and a three-dimensional volumetric interpolated breath-hold examination (VIBE) sequence (3.9/1.89 (repetition time (ms)/echo time (ms)), 3-mm slice thickness, 380mm × 309-mm field of view, 288 × 187 matrix) was repeated four times for the T1-weighted dynamic contrast-enhanced (DCE) imaging (pre-enhanced phase, arterial phase, portal vein phase, and delay phase). After pre-enhanced phases, 0.1 mmol/kg of Gd-DTPA was injected at a rate of 2 mL/s. Thirty-two patients underwent DCE MRI.

All the qualitative image analyses were performed independently on a PACS workstation by two experienced radiologists (with 5 and 8 years of experience in abdominal MRI, respectively) in a randomized fashion. The reviewers were blinded to the patients’ information including the pathology and clinical diagnosis. Each reader ranked the z-EPI DWI and c-EPI DWI in terms of image quality, considering the anatomic structure visualization, artifacts, and overall image quality. The anatomic structure visualization, artifacts, and overall image quality of the DWI images acquired with both EPI techniques were evaluated according to a 4-point scale: (1) anatomic structure visualization (1, poorly visualized anatomy and non-diagnostic; 2, fairly delineated periampullary region with margin blurring; 3, good delineation of periampullary region with a sharp margin; and 4, excellent sharpness of periampullary region); (2) artifacts (1, severe and non-diagnostic; 2, moderate; 3, mild; and 4, absent); and (3) overall image quality (1, poor image quality, considered non-diagnostic; 2, fair image quality, somewhat impairing diagnostic quality; 3 good image quality, not impairing diagnostic quality; and 4, excellent image quality).

Both EPI techniques were evaluated by using a 4-point scale for lesion conspicuity (1, lesion not detectable; 2, merely recognizable lesion-to-background contrast; 3, intermediate lesion-to-background contrast or high contrast with indistinct lesion margin; and 4, excellent lesion-to background contrast and a clear lesion margin) and lesion margin (1, lesion margin not detectable; 2, obscure; 3, indistinct; and 4, distinct). Diagnostic confidence was evaluated according to a 4-point scale based on the combination of DWI and conventional T1WI (T1-weighted imaging) and T2WI (T2-weighted imaging) (1, DWI was not useful for confirming the diagnosis of malignant periampullary lesions as the lesion characterization on DWI was indeterminate or the lesion was invisible; 2, lesion characterization on DWI was consistent with the confirmed diagnostic impression on conventional imaging; 3, DWI helped to confirm the suspected diagnosis on conventional imaging; and 4, DWI helped characterize the lesion as malignant when the conventional imaging findings were indeterminate for characterization or the lesion was invisible).

Signal intensity assessment of the periampullary lesions on the two DWI image sets was also conducted. The signal intensity of the periampullary lesions visually assessed compared with the signal intensity of the liver on a 4-point scale using a b-value of 800 sec/mm2 was as follows: 0, isointense; 1, slightly hyperintense; 2, significantly hyperintense and 3 hypointense. Criteria for malignant periampullary lesions on DWI were defined as lesions showing hyperintensity. Criteria for malignant periampullary lesions on MRCP images were defined if the stricture was characterized by an eccentric and abrupt narrowing with irregular margins of the distal parts of the bile duct and/or association with the double-duct sign. Criteria for benign periampullary lesions on MRCP images were the smooth and gradual tapering of the distal parts of the bile duct. For the MRCP images, the probability of malignancy for the distal biliary stricture was rated using a 5-point scale: 1, definitely benign; 2, probably benign; 3, indeterminate; 4, probably malignant; and 5, definitely malignant. The sensitivity calculations were based on only those lesions awarded a confidence rating of 4 or 5.

Diagnostic accuracy was compared between the combined set of MRCP and c-EPI DWI and that of MRCP and z-EPI DWI. The two radiologists recorded the possibility of malignant periampullary lesions with a consensus using a 5-point confidence rating scale, as follows: 1, definitely benign (benign on MRCP without DWI hyperintensity); 2, probably benign (indeterminate on MRCP without DWI hyperintensity); 3, indeterminate (benign on MRCP with DWI hyperintensity and malignant on MRCP without DWI hyperintensity); 4, probably malignant (indeterminate on MRCP with DWI hyperintensity); and 5, definitely malignant (malignant on MRCP with DWI hyperintensity). The sensitivity calculations were also based on those lesions, awarding a confidence rating of 4 or 5. Readers first evaluated only c-EPI DWI images and, subsequently, the z-EPI DWI using the same criteria. For each EPI DWI, only high b-value images (b = 800 sec/mm2) were analyzed.

Quantitative measurements of the ADC values of malignant and benign periampullary lesions were independently performed by a single different radiologist with 6 years of experience in radiology. The radiologist was blinded to the patients’ information including the pathology and clinical diagnosis. The ADC values of the periampullary lesions were obtained by manually placing a circular region of interest (ROI) on the ADC maps acquired from both the c-EPI and z-EPI DWI sequences. ROIs were placed at near-identical locations on both sequences with care to avoid vessels, cysts, bile ducts, and pancreatic ducts. Effort was made to have 3 ROIs in the lesions. For some lesions, it was difficult to accurately measure the ADC values of most benign strictures and some malignant lesions because of their relatively small sizes. Therefore, quantitative analysis was performed in 29 patients with periampullary malignancy and 4 patients with benign periampullary lesions.

We performed all statistical analyses using SPSS Statistics 19 (IBM, Armonk/NY, USA). A P value < 0.05 was considered to be statistically significant. The Wilcoxon signed-rank test was used between c-EPI DWI and z-EPI DWI for comparing the qualitative image analysis scores. For periampullary disease, lesion conspicuity, lesion margin, and diagnostic confidence were compared with the estimates obtained. In addition, diagnostic accuracy scores were compared between the MRCP and c-EPI DWI combined set and the MRCP and z-EPI DWI combined set. The Fisher’s exact test was used between c-EPI DWI and z-EPI DWI for comparing visual assessment of DWI in the periampullary lesions. The area under the ROC curve (AUC) was calculated to determine the diagnostic accuracy between the MRCP and c-EPI DWI combined set and the MRCP and z-EPI DWI combined set. Comparisons were made using the average scores between the two readers. Inter-reader agreement for each assessed qualitative evaluation was assessed using weighted κ statistics. Inter-reader agreement was considered as slight for κ = 0.00–0.20, fair for κ = 0.21–0.40, moderate for κ = 0.41–0.60, substantial for κ = 0.61–0.80, and almost perfect for κ = 0.81–1.00. ADC values of periampullary lesions were also compared between the two DWI sequences using the Wilcoxon signed-rank test.