In vivo ¹H MRS of human gallbladder bile in understanding the pathophysiology of primary sclerosing cholangitis (PSC): Immune‐mediated disease versus bile acid‐induced injury

Abstract

Primary sclerosing cholangitis (PSC) has been considered to be either an "autoimmune disease" or a "bile acid-induced injury." In vitro MRS studies on PSC patients have limitations due to the contamination of bile with contrast agent (commonly administered during endoscopic retrograde cholangiopancreatography) and/or the use of patient cohorts with other diseases as controls. The objective of this study was to quantify biliary metabolites using in vivo 1 H MRS and gain insight into the pathogenesis of PSC. Biliary metabolites in 10 PSC patients and 14 healthy controls were quantified in vivo using 1 H MRS on a 3 T MR scanner. The concentrations of total bile acids plus cholesterol, glycine-conjugated bile acids, taurine-conjugated bile acids, and cholinecontaining phospholipids (chol-PLs) were compared between the two groups. There were statistically significant decreases in the levels of the above mentioned biliary metabolites in the PSC patients compared with controls. The reduction in bile acid secretion in bile of PSC patients indicates accumulation of bile acids in hepatocytes.Moreover, reduction in the levels of chol-PLs in bile may increase the toxic effects of bile acids. Our findings suggest that the bile duct injury in PSC patients is most likely due to "bile acid-induced injury." KEYWORDS choline-containing phospholipids, glycine-conjugated bile acids, human bile, in vivo 1 H MRS, L-COSY, pathogenesis, primary sclerosing cholangitis, taurine-conjugated bile acids

In Vivo 1H MR Spectroscopy of Biliary Components of Human Gallbladder at 7T

“…Lower concentrations of bile components in patients with PSC have already been reported. 10 The authors of that study suggested that the reduction in bile acid secretion could indicate accumulation of bile acids in hepatocytes. The results reported in our study support previous findings.…”

“…More recent MRS studies of healthy subjects and patients with PSC were performed at 3T. 9,10 Ultrahigh field of 7T has promising advantages for MRS, such as high spectral resolution and higher signal-tonoise ratio (SNR), which could help better resolve bile components and acquire spectra faster.…”

Determination of bile acids from human gallbladder by 1H‐MRS—Protocol optimization and estimation of reproducibility

“…The study in humans by Prescot et al 8 was performed at 1.5 T, which limited the number of detectable metabolites. The two other 1 H‐MRS studies in human gallbladder, both by Mohajeri et al, 9,10 show excellent 1D and 2D spectra acquired on a 3 T MR scanner. A 1 H‐MRS study performed at 4.7 T in the gallbladder of cynomolgus monkeys also demonstrated good 1 H‐spectra, 11 and intra‐ and inter‐individual variability was determined.…”

“…Other techniques such as extended 2D-COSY scans provide extended information on the bile composition, eg differentiation of phosphatidylcholine from its hydrolysis products. 9,10 However, this benefit comes at prolonged measurement times of approximately 50 min, which might be challenging for some patients due to the prone position.…”

“…To the best of our knowledge, only three studies have been performed previously in humans [8][9][10] and one study in cynomolgus monkeys 11 investigating bile from gallbladder in vivo using 1 H-MRS. Total bile acids (TBAs), glycine and taurine conjugated bile acids (GCBAs and TCBAs) and lipids including choline-containing phospholipids (chol-PLs) were determined in these studies. Cholesterol was found to contribute little to the MR spectra at normal concentrations due to short T 2 relaxation times.…”