Non-invasive analysis of gallbladder bile composition in cynomolgus monkeys using in vivo 1H magnetic resonance spectroscopy

Abstract

The purpose of the present study was (i) to establish a modality for non-invasively probing bile composition in cynomolgus monkeys and (ii) to ascertain the variability in biliary metabolism by repeatedly assessing gallbladder bile in situ. Localised in vivo 1H magnetic resonance spectroscopy (MRS) provided high-resolution spectra of gallbladder bile that allowed for the first time different species of bile acids, their taurine and glycine conjugates, and phospholipids to be identified and quantified in situ. A combined cross-sectional and longitudinal study of bile composition was conducted over 4 weeks in monkeys kept under standardised nutritional conditions. All biles were composed of the same major constituents. Bile acids contributed 267 ± 47 μmol/ml whereof cholate, deoxycholate and chenodeoxycholate were the most abundant primary bile acids. Bile acid conjugation reached an extent of 100%. However, the actual quantitative contributions of different bile constituents varied distinctly. Correlation analysis revealed that intra-individual variability ( r = 0.77 ± 0.03) was significantly ( p < 0.01) smaller than inter-individual variability ( r = 0.68 ± 0.01), thus purporting the notion that bile composition is a hallmark of individual metabolism. Extension of quantitative bile analysis by in vivo 1H-MRS to pathological states will provide a rapid and non-invasive modality for monitoring an important, yet elusive compartment of cholesterol and lipid metabolism.