Initial evaluation of hepatic T1 relaxation time as an imaging marker of liver disease associated with autosomal recessive polycystic kidney disease (ARPKD)

Autosomal recessive polycystic kidney disease (ARPKD) is a potentially lethal multi-organ disease affecting both the kidneys and the liver. Unfortunately, there are currently no non-invasive methods to monitor liver disease progression in ARPKD patients, limiting the study of potential therapeutic interventions. Herein, we perform an initial investigation of T-1 relaxation time as a potential imaging biomarker to quantitatively assess the two primary pathologic hallmarks of ARPKD liver disease: biliary dilatation and periportal fibrosis in the PCK rat model of ARPKD. T-1 relaxation time results were obtained for five PCK rats at 3months of age using a Look-Locker acquisition on a Bruker BioSpec 7.0T MRI scanner. Six three-month-old Sprague-Dawley (SD) rats were also scanned as controls. All animals were euthanized after the three-month scans for histological and biochemical assessments of bile duct dilatation and hepatic fibrosis for comparison. PCK rats exhibited significantly increased liver T-1 values (mean +/- standard deviation=935 +/- 39ms) compared with age-matched SD control rats (847 +/- 26ms, p=0.01). One PCK rat exhibited severe cholangitis (mean T-1=1413ms), which occurs periodically in ARPKD patients. The observed increase in the in vivo liver T-1 relaxation time correlated significantly with three histological and biochemical indicators of biliary dilatation and fibrosis: bile duct area percent (R=0.85, p=0.002), periportal fibrosis area percent (R=0.82, p=0.004), and hydroxyproline content (R=0.76, p=0.01). These results suggest that hepatic T-1 relaxation time may provide a sensitive and non-invasive imaging biomarker to monitor ARPKD liver disease. Copyright (c) 2015 John Wiley & Sons, Ltd.