title: Initial evaluation of hepatic T1 relaxation time as an imaging marker of liver disease associated with autosomal recessive polycystic kidney disease (ARPKD).
abstract: 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 T1 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. T1 relaxation time results were obtained for five PCK rats at 3 months of age using a Look-Locker acquisition on a Bruker BioSpec 7.0 T 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 T1 values (mean ± standard deviation = 935 ± 39 ms) compared with age-matched SD control rats (847 ± 26 ms, p = 0.01). One PCK rat exhibited severe cholangitis (mean T1  = 1413 ms), which occurs periodically in ARPKD patients. The observed increase in the in vivo liver T1 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 T1 relaxation time may provide a sensitive and non-invasive imaging biomarker to monitor ARPKD liver disease.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Ying
authors.identifier: http://orcid.org/0000-0002-1010-591X
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Radiology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Bernadette O
authors.initials: BO
authors.lastname: Erokwu
authors.affiliation: Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: DeSantis
authors.affiliation: Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Croniger
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Schur
authors.affiliation: Department of Radiology, Case Western Reserve University, Cleveland, OH, USA.|Department of Urology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Lu
authors.affiliation: CWRU Center for the Study of Kidney Disease and Biology, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Mariappuram
authors.affiliation: CWRU Center for the Study of Kidney Disease and Biology, Case Western Reserve University, Cleveland, OH, USA.|Cleveland Clinic Children's, Cleveland, OH, USA.|Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Dell
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.|Department of Radiology, Case Western Reserve University, Cleveland, OH, USA.|Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Chris A
authors.initials: CA
authors.lastname: Flask
mesh_terms: D000818:Animals; D015415:Biomarkers; D008099:Liver / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017044:Polycystic Kidney, Autosomal Recessive / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers
keywords: FISP; T1; autosomal recessive polycystic kidney disease (ARPKD); biliary dilatation; fibrosis; high-field MRI; liver disease