title: A study of T₁ relaxation time as a measure of liver fibrosis and the influence of confounding histological factors.
abstract: Liver biopsy is the standard test for the assessment of fibrosis in liver tissue of patients with chronic liver disease. Recent studies have used a non-invasive measure of T1 relaxation time to estimate the degree of fibrosis in a single slice of the liver. Here, we extend this work to measure T1 of the whole liver and investigate the effects of additional histological factors such as steatosis, inflammation and iron accumulation on the relationship between liver T1 and fibrosis. We prospectively enrolled patients who had previously undergone liver biopsy to have MR scans. A non-breath-holding, fast scanning protocol was used to acquire MR relaxation time data (T1 and T2*), and blood serum was used to determine the enhanced liver fibrosis (ELF) score. Areas under the receiver operator curves (AUROCs) for T1 to detect advanced fibrosis and cirrhosis were derived in a training cohort and then validated in a second cohort. Combining the cohorts, the influence of various histology factors on liver T1 relaxation time was investigated. The AUROCs (95% confidence interval (CI)) for detecting advanced fibrosis (F ≥ 3) and cirrhosis (F = 4) for the training cohort were 0.81 (0.65-0.96) and 0.92 (0.81-1.0) respectively (p < 0.01). Inflammation and iron accumulation were shown to significantly alter T1 in opposing directions in the absence of advanced fibrosis; inflammation increasing T1 and iron decreasing T1. A decision tree model was developed to allow the assessment of early liver disease based on relaxation times and ELF, and to screen for the need for biopsy. T1 relaxation time increases with advanced fibrosis in liver patients, but is also influenced by iron accumulation and inflammation. Together with ELF, relaxation time measures provide a marker to stratify patients with suspected liver disease for biopsy.
authors.affiliation: SPMIC, School of Physics and Astronomy, University of Nottingham, UK.|NIHR Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals NHS Trust and University of Nottingham, UK.
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Hoad
authors.affiliation: NIHR Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals NHS Trust and University of Nottingham, UK.
authors.forename: Naaventhan
authors.initials: N
authors.lastname: Palaniyappan
authors.affiliation: NIHR Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals NHS Trust and University of Nottingham, UK.|Department of Cellular Pathology, Nottingham University Hospitals NHS Trust, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Kaye
authors.affiliation: NIHR Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals NHS Trust and University of Nottingham, UK.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Chernova
authors.affiliation: NIHR Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals NHS Trust and University of Nottingham, UK.
authors.forename: Martin W
authors.initials: MW
authors.lastname: James
authors.affiliation: SPMIC, School of Physics and Astronomy, University of Nottingham, UK.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Costigan
authors.affiliation: Derby Royal Hospital, Derby, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Austin
authors.affiliation: NIHR Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals NHS Trust and University of Nottingham, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Marciani
authors.affiliation: SPMIC, School of Physics and Astronomy, University of Nottingham, UK.
authors.forename: Penny A
authors.initials: PA
authors.lastname: Gowland
authors.affiliation: NIHR Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals NHS Trust and University of Nottingham, UK.
authors.forename: Indra N
authors.initials: IN
authors.lastname: Guha
authors.affiliation: SPMIC, School of Physics and Astronomy, University of Nottingham, UK.
authors.forename: Susan T
authors.initials: ST
authors.lastname: Francis
authors.affiliation: NIHR Nottingham Digestive Diseases Biomedical Research Unit at the Nottingham University Hospitals NHS Trust and University of Nottingham, UK.
authors.forename: Guruprasad P
authors.initials: GP
authors.lastname: Aithal
mesh_terms: D000328:Adult; D016477:Artifacts; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000150:complications / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D007501:Iron
keywords: fibrosis; hepatobiliary; inflammation; iron; other applications; relaxometry