Individuals with obesity may develop intrapancreatic fat deposition (IPFD) and fatty pancreas disease (FPD). Whether this causes inflammation and fibrosis and leads to pancreatic dysfunction is less established than for liver damage in metabolic dysfunction-associated steatotic liver disease (MASLD). Moreover, the interrelations of FPD and MASLD are poorly understood. Therefore, we aimed to assess IPFD and fibro-inflammation in relation to pancreatic function and liver disease severity in individuals with MASLD. Seventy-six participants from the Amsterdam MASLD-MASH cohort (ANCHOR) study underwent liver biopsy and multiparametric MRI of the liver and pancreas, consisting of proton-density fat fraction sequences, T1 mapping and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). The prevalence of FPD was 37.3%. There was a clear correlation between pancreatic T1 relaxation time, which indicates fibro-inflammation, and parameters of glycemic dysregulation, namely HbA1c (R = 0.59; p <0.001), fasting glucose (R = 0.51; p <0.001) and the presence of type 2 diabetes (mean 802.0 ms vs. 733.6 ms; p <0.05). In contrast, there was no relation between IPFD and hepatic fat content (R = 0.03; p = 0.80). Pancreatic IVIM diffusion (IVIM-D) was lower in advanced liver fibrosis (p <0.05) and pancreatic perfusion (IVIM-f), reflecting vessel density, inversely correlated to histological MASLD activity (p <0.05). Consistent relations exist between pancreatic fibro-inflammation on MRI and endocrine function in individuals with MASLD. However, despite shared dysmetabolic drivers, our study suggests IPFD is a separate pathophysiological process from MASLD. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and 68% of people with type 2 diabetes have MASLD. However, fat infiltration and inflammation in the pancreas are understudied in individuals with MASLD. In this cross-sectional MRI study, we found no relationship between fat accumulation in the pancreas and liver in a cohort of patients with MASLD. However, our results show that inflammatory and fibrotic processes in the pancreas may be interrelated to features of type 2 diabetes and to the severity of liver disease in patients with MASLD. Overall, the results suggest that pancreatic endocrine dysfunction in individuals with MASLD may be more related to glucotoxicity than to lipotoxicity. NTR7191 (Dutch Trial Register).

Background: Desmoplasia is a central feature of the tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC). LDE225 is a pharmacological Hedgehog signaling pathway inhibitor and is thought to specifically target tumor stroma. We investigated the combined use of LDE225 and chemotherapy to treat PDAC patients. Methods: This was a multi-center, phase I/II study for patients with metastatic PDAC establishing the maximum tolerated dose of LDE225 co-administered with gemcitabine and nab-paclitaxel (phase I) and evaluating the efficacy and safety of the treatment combination after prior FOLFIRINOX treatment (phase II). Tumor microenvironment assessment was performed with quantitative MRI using intra-voxel incoherent motion diffusion weighted MRI (IVIM-DWI) and dynamic contrast-enhanced (DCE) MRI. Results: The MTD of LDE225 was 200 mg once daily co-administered with gemcitabine 1000 mg/m² and nab-paclitaxel 125 mg/m². In phase II, six therapy-related grade 4 adverse events (AE) and three grade 5 were observed. In 24 patients, the target lesion response was evaluable. Three patients had partial response (13%), 14 patients showed stable disease (58%), and 7 patients had progressive disease (29%). Median overall survival (OS) was 6 months (IQR 3.9–8.1). Blood plasma fraction (DCE) and diffusion coefficient (IVIM-DWI) significantly increased during treatment. Baseline perfusion fraction could predict OS (>222 days) with 80% sensitivity and 85% specificity. Conclusion: LDE225 in combination with gemcitabine and nab-paclitaxel was well-tolerated in patients with metastatic PDAC and has promising efficacy after prior treatment with FOLFIRINOX. Quantitative MRI suggested that LDE225 causes increased tumor diffusion and works particularly well in patients with poor baseline tumor perfusion.

Background: Pancreatic ductal adenocarcinoma (PDAC) stromal viscoelasticity can be measured using MR elastography (MRE). Bowel preparation regimens could affect MRE quality and knowledge on repeatability is crucial for clinical implementation.Purpose: To assess effects of four bowel preparation regimens on MRE quality and to evaluate repeatability and differentiate patients from healthy controls.Study Type: Prospective.Population: 15 controls (41 ± 16 years; 47% female), 16 PDAC patients (one excluded, 66 ± 12 years; 40% female) with 15 age‐/sex‐matched controls (65 ± 11 years; 40% female). Final sample size was 25 controls and 15 PDAC.Field Strength/Sequence: 3‐T, spin‐echo echo‐planar‐imaging, turbo spin‐echo, and fast field echo gradient‐echo.Assessment: Four different regimens were used: fasting; scopolaminebutyl; drinking 0.5 L water; combination of 0.5 L water and scopolaminebutyl. MRE signal‐to‐noise ratio (SNR) was compared between all regimens. MRE repeatability (test–retest) and differences in shear wave speed (SWS) and phase angle (ϕ) were assessed in PDAC and controls. Regions‐of‐interest were defined for tumor, nontumorous (n = 8) tissue in PDAC, and whole pancreas in controls. Two radiologists delineated tumors twice for evaluation of intraobserver and interobserver variability.Statistical Tests: Repeated measures analysis of variance, coefficients of variation (CoVs), Bland–Altman analysis, (un)pairedt‐test, Mann–Whitney U‐test, and Wilcoxon signed‐rank test.P‐value<0.05 was considered statistically significant.Results: Preparation regimens did not significantly influence MRE‐SNR. Therefore, the least burdensome preparation (fasting only) was continued. CoVs for tumor SWS were: intrasession (12.8%) and intersession (21.7%), and intraobserver (7.9%) and interobserver (10.3%) comparisons. For controls, CoVs were intrasession (4.6%) and intersession (6.4%). Average SWS for tumor, nontumor, and healthy tissue were: 1.74 ± 0.58, 1.38 ± 0.27, and 1.18 ± 0.16 m/sec (ϕ: 1.02 ± 0.17, 0.91 ± 0.07, and 0.85 ± 0.08 rad), respectively. Significant differences were found between all groups, except for ϕ between healthy–nontumor (P = 0.094).Data Conclusion: The proposed bowel preparation regimens may not influence MRE quality. MRE may be able to differentiate between healthy tissue–tumor and tumor–nontumor.Level of Evidence: 2Technical Efficacy Stage: 2

Background: Pancreatic ductal adenocarcinoma (PDAC) stromal disposition is thought to influence chemotherapy efficacy and increase tissue stiffness, which could be quantified noninvasively via MR elastography (MRE). Current methods cause position‐based errors in pancreas location over time, hampering accuracy. It would be beneficial to have a single breath‐hold acquisition.Purpose: To develop and test a single breath‐hold three‐dimensional MRE technique utilizing prospective undersampling and a compressed sensing reconstruction (CS‐MRE).Study Type: Prospective.Population: A total of 30 healthy volunteers (HV) (31 ± 9 years; 33% male) and five patients with PDAC (69 ± 5 years; 80% male).Field Strength/Sequence: 3‐T, GRE Ristretto MRE.Assessment: First, optimization of multi breath‐hold MRE was done in 10 HV using four combinations of vibration frequency, number of measured wave‐phase offsets, and TE and looking at MRE quality measures in the pancreas head. Second, viscoelastic parameters delineated in the pancreas head or tumor of CS‐MRE were compared against (I) 2D and (II) 3D four breath‐hold acquisitions in HV (N = 20) and PDAC patients. Intrasession repeatability was assessed for CS‐MRE in a subgroup of healthy volunteers (N = 15).Statistical Tests: Tests include repeated measures analysis of variance (ANOVA), Bland–Altman analysis, and coefficients of variation (CoVs). A P‐value <.05 was considered statistically significant.Results: Optimization of the four breath‐hold acquisitions resulted in 40 Hz vibration frequency, five wave‐phases, and echo time (TE) = 6.9 msec as the preferred method (4BH‐MRE). CS‐MRE quantitative results did not differ from 4BH‐MRE. Shear wave speed (SWS) and phase angle differed significantly between HV and PDAC patients using 4BH‐MRE or CS‐MRE. The limits of agreement for SWS were [−0.09, 0.10] m/second and the within‐subject CoV was 4.8% for CS‐MRE.Data Conclusion: CS‐MRE might allow a single breath‐hold MRE acquisition with comparable SWS and phase angle as 4BH‐MRE, and it may still enable to differentiate between HV and PDAC.Level of Evidence: 2Technical Efficacy Stage: 2

Purpose: For reliable DCE MRI parameter estimation, k‐space undersampling is essential to meet resolution, coverage, and signal‐to‐noise requirements. Pseudo‐spiral (PS) sampling achieves this by sampling k‐space on a Cartesian grid following a spiral trajectory. The goal was to optimize PS k‐space sampling patterns for abdomin al DCE MRI.Methods: The optimal PS k‐space sampling pattern was determined using an anthropomorphic digital phantom. Contrast agent inflow was simulated in the liver, spleen, pancreas, and pancreatic ductal adenocarcinoma (PDAC). A total of 704 variable sampling and reconstruction approaches were created using three algorithms using different parametrizations to control sampling density, halfscan and compressed sensing regularization. The sampling patterns were evaluated based on image quality scores and the accuracy and precision of the DCE pharmacokinetic parameters. The best and worst strategies were assessed in vivo in five healthy volunteers without contrast agent administration. The best strategy was tested in a DCE scan of a PDAC patient.Results: The best PS reconstruction was found to be PS‐diffuse based, with quadratic distribution of readouts on a spiral, without random shuffling, halfscan factor of 0.8, and total variation regularization of 0.05 in the spatial and temporal domains. The best scoring strategy showed sharper images with less prominent artifacts in healthy volunteers compared to the worst strategy. Our suggested DCE sampling strategy also showed high quality DCE images in the PDAC patient.Conclusion: Using an anthropomorphic digital phantom, we identified an optimal PS sampling strategy for abdominal DCE MRI, and demonstrated feasibility in a PDAC patient.