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. 1998 May;42(5):735–743. doi: 10.1136/gut.42.5.735

In vivo and in vitro hepatic phosphorus-31 magnetic resonance spectroscopy and electron microscopy in chronic ductopenic rejection of human liver allografts

S Taylor-Robinson 1, J Sargentoni 1, J Bell 1, E Thomas 1, C Marcus 1, K Changani 1, N Saeed 1, H Hodgson 1, B Davidson 1, A Burroughs 1, K Rolles 1, C Foster 1, I Cox 1
PMCID: PMC1727114  PMID: 9659173

Abstract

Background—In vivo hepatic phosphorus-31 magnetic resonance spectroscopy (MRS) provides non-invasive information about phospholipid metabolism. 
Aims—To delineate MRS abnormalities in patients with chronic ductopenic rejection (CDR) and to characterise spectral changes by in vitro MRS and electron microscopy. 
Patients and methods—Sixteen liver transplant recipients (four with CDR; 12 with good graft function) and 29 controls (23healthy volunteers; six patients with biliary duct strictures) were studied with in vivo 31P MRS. Peak area ratios of phosphomonoesters (PME) and phosphodiesters (PDE), relative to nucleotide triphosphates (NTP) were measured. In vitro MRS and electron microscopy were performed on biopsy specimens from five patients with CDR, freeze clamped at retransplantation. Phosphoethanolamine (PE), phosphocholine (PC), glycerophosphorylethanolamine (GPE), and glycerophosphorylcholine (GPC) concentrations were measured. 
Results—The 12 patients with good graft function displayed no spectral abnormalities in vivo; the four patients with CDR showed significantly elevated PME:NTP (p<0.01) and PDE:NTP ratios (p<0.005). Patients with biliary strictures had significant differences in PME:NTP (p<0.01) from patients with CDR, but not in mean PDE:NTP. In vitro spectra from CDR patients showed elevated PE and PC, mirroring the in vivo changes in PME, but reduced GPE and GPC concentrations were observed, at variance with the in vivo PDE findings. On electron microscopy, there was no proliferation in hepatocyte endoplasmic reticulum. 
Conclusions—The increase in PME:NTP reflects altered phospholipid metabolism in patients with CDR, while the increase in PDE:NTP may represent a significant contribution from bile phospholipid. 



Keywords: in vivo 31P magnetic resonance spectroscopy; in vitro 31P magnetic resonance spectroscopy; liver transplantation; chronic ductopenic rejection; electron microscopy; phospholipids

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Figure 1 .

Figure 1

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In vivo hepatic 31P MR spectra from (A) a healthy volunteer, (B) a patient with good graft function, and (C) a patient with chronic ductopenic rejection. 


Figure 2 .

Figure 2

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Scattergram of PME:NTP values plotted against the length of postoperative period prior to in vivo MRS examination. 


Figure 3 .

Figure 3

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Scattergram of PDE:NTP values plotted against the length of postoperative period prior to in vivo MRS examination. 


Figure 4 .

Figure 4

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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. 


Figure 5 .

Figure 5

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In vitro hepatic 31P MR spectrum from a perchloric acid extract of liver tissue from a patient with chronic ductopenic rejection. (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; MDP, methylene diphosphonate. 


Figure 6 .

Figure 6

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Electron micrograph of liver (original magnification × 10 000) from a patient with chronic ductopenic rejection. 


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