Current and future applications of in vitro magnetic resonance spectroscopy in hepatobiliary disease

Abstract

Nuclear magnetic resonance spectroscopy allows the study of cellular biochemistry and metabolism, both in the whole body in vivo and at higher magnetic field strengths in vitro. Since the technique is non-invasive and non-selective, magnetic resonance spectroscopy methodologies have been widely applied in biochemistry and medicine. In vitro magnetic resonance spectroscopy studies of cells, body fluids and tissues have been used in medical biochemistry to investigate pathophysiological processes and more recently, the technique has been used by physicians to determine disease abnormalities in vivo. This highlighted topic illustrates the potential of in vitro magnetic resonance spectroscopy in studying the hepatobiliary system. The role of in vitro proton and phosphorus magnetic resonance spectroscopy in the study of malignant and non-malignant liver disease and bile composition studies are discussed, particularly with reference to correlative in vivo whole-body magnetic resonance spectroscopy applications. In summary, magnetic resonance spectroscopy techniques can provide non-invasive biochemical information on disease severity and pointers to underlying pathophysiological processes. Magnetic resonance spectroscopy holds potential promise as a screening tool for disease biomarkers, as well as assessing therapeutic response.

Figure 1

400-MHz ¹H HR-MAS NMR spectra of a human liver biopsy sample (rotation rate 4 kHz). A: Standard 1D spectrum; B: Spin-echo (CPMG) spectrum; C: JRES f2 projection. L1: lipid CH₃; L2: lipid (CH₂)n; L3: lipid CH₂CH₂CO; L4: lipid CH₂-CH=CH; L5: lipid CH₂CO; L6: lipid CH=CH-CH₂-CH=CH; L7: lipid CH=CH; Cho: choline; PC: phosphocholine; GPC: glycerophosphocholine; TMAO: trimethylamine-N-oxide; Bet: betaine; Glc: glucose; Val: valine; Leu, leucine; Ala: alanine; Gln: glutamine; Gly: glycine; Tyr: tyrosine; Urd: uridine; Ado: adenosine. Reprinted with permission from Duarte et al Anal Chem 2005; 77: 5570-5578. Copyright (2005) American Chemical Society.

Figure 2

A: A transverse image through the abdomen showing the two voxel positions used to study regional variation in hepatic fat content; B: Typical proton magnetic resonance liver spectra from three volunteers showing progressive degrees of fatty infiltration. Spectrum (a) shows a liver with minimal fatty infiltration (1.0%), spectrum (b) shows a liver with moderate fatty infiltration (10.2%), and spectrum (c) shows a liver with severe fatty infiltration (74.9%). Resonances from water and IHCL-(CH₂)n- can be clearly identified. Values refer to the peak area of the IHCL peak with reference to the water peak after correcting for T₁ and T₂. IHCL: intrahepatocellular lipids. Reproduced from Thomas et al Gut 2005; 54: 122-127, with permission from the BMJ Publishing Group.

Figure 3

Typical proton decoupled in vitro ³¹P MR spectrum of perchloric acid extracted normal liver tissue. A: Full spectrum; B: PME and PDE regions. PME: phosphomonoesters; PDE: phosphodiesters; NTP: nucleotide triphosphates; NDP: nucleotide diphosphate; PE: phosphoethanolamine; PC: phosphocholine; GPE: glycerophosphorylethanolamine; GPC: glycerophosphorylcholine; PCr:phosphocreatine; MDP: methylene diphosphonate. Reproduced from Taylor-Robinson et al Gut 1998; 42: 735-743, with permission from the BMJ Publishing Group.

Figure 4

Typical ³¹P magnetic resonance spectrum from the liver of a healthy volunteer (TR 10 000 ms). PME: phosphomonoester; Pi: inorganic phosphate; PDE: phosphodiester; NTP: nucleoside triphosphate; ppm: parts per million. Reproduced from Mullenbach et al Gut 2004; 54: 829-834, with permission from the BMJ Publishing Group.

Figure 5

A: ¹H nuclear magnetic resonance spectrum of bile collected at laparoscopic cholecystectomy, after a history of recurrent cholecystitis. The spectrum has no contamination from contrast agents. The major peaks are assigned to phosphatidylcholine (PTC), bile acids, cholesterol (Chol), taurine (Tau) and the reference, sodium trimethylsilyl-[²H₄] propionate (TSP); B: Corresponding ³¹P nuclear magnetic resonance spectrum. The major peak is assigned to PTC. ppm, Parts per million. Reproduced from Khan SA, Cox IJ, Thillainayagam AV, Bansi DS, Thomas HC, Taylor-Robinson SD. Proton and phosphorus-31 nuclear magnetic resonance spectroscopy of human bile in hepatopancreaticobiliary cancer. Eur J Gastroenterol Hepatol 2005; 17: 733-738, with permission from Lippincott Williams & Wilkins, Inc.