Background: Pancreatic fat accumulation may cause or aggravate the process of acute pancreatitis, β-cell dysfunction, T2DM disease, and even be associated with pancreatic tumors. The pathophysiology of fatty pancreas remains overlooked and lacks effective imaging diagnostics. Purpose: To automatically measure the distribution of pancreatic fat deposition on Dixon MRI in multicenter/population datasets using nnU-Net models. Study Type: Retrospective. Population: A total of 176 obese/nonobese subjects (90 males, 86 females; mean age, 27.2 AE 19.7) were enrolled, including a training set (N = 132) and a testing set (N = 44).

The LMNA gene encodes for the nuclear envelope proteins lamin A and C (lamin A/C). A novel R133L heterozygous mutation in the LMNA gene causes atypical progeria syndrome (APS). However, the underlying mechanism remains unclear. Here, we used transgenic mice (LmnaR133L/+ mice) that expressed a heterozygous LMNA R133L mutation and 3T3‐L1 cell lines with stable overexpression of LMNA R133L (by lentiviral transduction) as in vivo and in vitro models to investigate the mechanisms of LMNA R133L mutations that mediate the APS phenotype. We found that a heterozygous R133L mutation in LMNA induced most of the metabolic disturbances seen in patients with this mutation, including ectopic lipid accumulation, limited subcutaneous adipose tissue (SAT) expansion, and insulin resistance. Mitochondrial dysfunction and senescence promote ectopic lipid accumulation and insulin resistance. In addition, the FLAG‐mediated pull‐down capture followed by mass spectrometry assay showed that p160 Myb‐binding protein (P160 MBP; Mybbp1a$$ a $$), the critical transcriptional repressor of PGC‐1α, was bound to lamin A/C. Increased Mybbp1a$$ a $$ levels in tissues and greater Mybbp1a$$ a $$‐lamin A/C binding in nuclear inhibit PGC‐1α activity and promotes mitochondrial dysfunction. Our findings confirm that the novel R133L heterozygous mutation in the LMNA gene caused APS are associated with marked mitochondrial respiratory chain impairment, which were induced by decreased PGC‐1α levels correlating with increased Mybbp1a levels in nuclear, and a senescence phenotype of the subcutaneous fat.

PurposeMeasuring lipid composition provides more information than just total lipid content. Hence, the non‐invasive measurement of unsaturated lipid protons with both high efficiency and precision is of pressing need. This study was to optimize echo time (TE) for the best resolving of J‐difference editing of unsaturated lipid resonances.MethodsThe TE dependence of J‐difference‐edited (JDE) MRS was verified in the density‐matrix simulation, soybean oil phantom, in‐vivo experiments of white adipose tissue (WAT), and skeletal muscles using single‐voxel MEGA‐PRESS sequence at 3T. The peak SNRs and Cramér‐Rao lower bounds (CRLBs) acquired at the proposed TE of 45 ms and previously published TE of 70 ms were compared (eight pairs) in WAT, extramyocelluar lipids (EMCLs), and intramyocellular lipids (IMCLs). The lipid composition in skeletal muscles was compared between healthy males (n = 7) and females (n = 7).ResultsThe optimal TE was suggested as 45 ms. Compared to 70 ms, the mean signal gains at TE of 45 ms were 151% in WAT, 168% in EMCL, 204% in IMCL for allylic resonance, and 52% in EMCL for diallylic resonance. CRLBs were significantly reduced at TE of 45 ms in WAT, EMCL, IMCL for allylic resonance and in EMCL for diallylic resonance. With TE of 45 ms, significant gender differences were found in the lipid composition in EMCL pools, while no difference in IMCL pools.ConclusionThe JDE‐MRS protocol with TE of 45 ms allows improved quantification of unsaturated lipid resonances in vivo and future lipid metabolism investigations.

In this study, J-difference editing was applied to unsaturated lipid protons. Density-matrix simulations were devised to demonstrate the TE-dependent signal evolution of J-coupled protons. Phantom and in-vivo experiments on human muscles were performed to verify the simulation results. The optimal TE was determined as 45 ms with the signals gain of 148.03% for allylic and 2.37% for diallylic groups on phantom and 160.16% for allylic and 13.22% for diallylic groups on human muscles, when compared to TE of 70 ms. This edited-MRS protocol allows robust quantification of unsaturated lipid composition in-vivo and investigation on lipid metabolism in future.

Measurement of lipid composition in liver is of high importance. The J-difference-edited MRS allows detection of low-level overlapped metabolites, including hepatic unsaturated lipid. This study was to investigate the efficacy of J-editing on human hepatic unsaturated lipid, with different experimental setup. Multiple potential influencing factors such as breath control and voxel localization were parallelly compared. In-vivo hepatic MRS data was acquired in three healthy subjects. The statistical analysis of experimental variance and test re-test reliability demonstrates that MEGA-PRESS with respiratory-gating at lower level in liver allows consistent and robust in-vivo measurement of different human hepatic unsaturated lipid molecules.