Abstract
Noninvasive measurements of liver perfusion and fibrosis in cirrhotic small animals can help develop treatments for haemodynamic complications of liver disease. Here, we measure liver perfusion in cirrhotic rodents using flow‐sensitive alternating inversion recovery arterial spin labelling (FAIR ASL), evaluating agreement with previously validated caval subtraction phase‐contrast magnetic resonance imaging (PCMRI) total liver blood flow (TLBF). Baseline differences in cirrhotic rodents and the haemodynamic effects of acute inflammation were investigated using FAIR ASL and tissue T1. Sprague–Dawley rats (nine bile duct ligated [BDL] and ten sham surgery controls) underwent baseline hepatic FAIR ASL with T1 measurement and caval subtraction PCMRI (with two‐dimensional infra‐/supra‐hepatic inferior vena caval studies), induction of inflammation with intravenous lipopolysaccharide (LPS) and repeat liver FAIR ASL with T1 measurement after ~90 minutes. The mean difference between FAIR ASL hepatic perfusion and caval subtraction PCMRI TLBF was −51 ± 30 ml/min/100 g (Bland–Altman 95% limits‐of‐agreement ±258 ml/min/100 g). The FAIR ASL coefficient of variation was smaller than for caval subtraction PCMRI (29.3% vs 50.1%; P = .03). At baseline, FAIR ASL liver perfusion was lower in BDL rats (199 ± 32 ml/min/100 g vs sham 316 ± 24 ml/min/100 g; P = .01) but liver T1 was higher (BDL 1533 ± 50 vs sham 1256 ± 18 ms; P = .0004). Post‐LPS FAIR ASL liver perfusion response differences were observed between sham/BDL rats (P = .02), approaching significance in sham (+78 ± 33 ml/min/100 g; P = .06) but not BDL rats (−49 ± 40 ml/min/100 g; P = .47). Post‐LPS differences in liver tissue T1 were nonsignificant (P = .35). FAIR ASL hepatic perfusion and caval subtraction PCMRI TLBF agreement was modest, with significant baseline FAIR ASL liver perfusion and tissue T1 differences in rodents with advanced cirrhosis compared with controls. Following inflammatory stress, differences in hepatic perfusion response were detected between cirrhotic/control animals, but liver T1 was unaffected. Findings underline the potential of FAIR ASL in the assessment of vasoactive treatments for patients with chronic liver disease and inflammation.
Highlights
Liver cirrhosis causes profound changes in hepatic blood flow, modifying contributions from the portal vein (PV) and hepatic artery (HA), total liver blood flow (TLBF) and downstream tissue perfusion.[1]
We have demonstrated that Flow-sensitive alternating inversion recovery (FAIR) Arterial spin labelling (ASL) measurements of hepatic perfusion are feasible in cirrhotic rats and can be used to investigate haemodynamic phenomena in the setting of super-added inflammation and sepsis
We have shown modest agreement with previously invasively validated caval subtraction phase-contrast MRI (PCMRI) TLBF and that FAIR ASL tends to underestimate hepatic perfusion relative to that suggested by PCMRI, across both animal groups
Summary
Liver cirrhosis causes profound changes in hepatic blood flow, modifying contributions from the portal vein (PV) and hepatic artery (HA), total liver blood flow (TLBF) and downstream tissue perfusion.[1]. It has been used previously to demonstrate differences in compensated vs decompensated chronic liver disease patients[8] and changes in liver tumour perfusion in mice.[9] Static liver tissue T1 maps generated by FAIR ASL are potentially useful, as liver T1 is known to vary with fibrosis severity[10] and has been proposed as a measure of tissue inflammation.[11] Histological endotoxin-induced acute hepatic inflammation has been demonstrated previously,[12,13] noninvasive measurement of liver inflammation would be clinically useful, in the context of chronic inflammatory conditions such as nonalcoholic steatohepatitis (NASH).[14]. In this study we used a rodent model of cirrhosis to assess agreement between FAIR ASL measurements of hepatic perfusion and caval subtraction PCMRI, to characterise baseline differences between cirrhotic and control animals, and to investigate the effects of super-imposed inflammatory stress on FAIR ASL liver perfusion and tissue T1 in the setting of chronic liver disease
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