title: T2 relaxation time is related to liver fibrosis severity.
abstract: BACKGROUND
  The grading of liver fibrosis relies on liver biopsy. Imaging techniques, including elastography and relaxometric, techniques have had varying success in diagnosing moderate fibrosis. The goal of this study was to determine if there is a relationship between the T2-relaxation time of hepatic parenchyma and the histologic grade of liver fibrosis in patients with hepatitis C undergoing both routine, liver MRI and liver biopsy, and to validate our methodology with phantoms and in a rat model of liver fibrosis.
  
  
  METHODS
  This study is composed of three parts: (I) 123 patients who underwent both routine, clinical liver MRI and biopsy within a 6-month period, between July 1999 and January 2010 were enrolled in a retrospective study. MR imaging was performed at 1.5 T using dual-echo turbo-spin echo equivalent pulse sequence. T2 relaxation time of liver parenchyma in patients was calculated by mono-exponential fit of a region of interest (ROI) within the right lobe correlating to histopathologic grading (Ishak 0-6) and routine serum liver inflammation [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)]. Statistical comparison was performed using ordinary logistic and ordinal logistic regression and ANOVA comparing T2 to Ishak fibrosis without and using AST and ALT as covariates; (II) a phantom was prepared using serial dilutions of dextran coated magnetic iron oxide nanoparticles. T2 weighed imaging was performed by comparing a dual echo fast spin echo sequence to a Carr-Purcell-Meigboom-Gill (CPMG) multi-echo sequence at 1.5 T. Statistical comparison was performed using a paired t-test; (III) male Wistar rats receiving weekly intraperitoneal injections of phosphate buffer solution (PBS) control (n=4 rats); diethylnitrosamine (DEN) for either 5 (n=5 rats) or 8 weeks (n=4 rats) were MR imaged on a Bruker Pharmascan 4.7 T magnet with a home-built bird-cage coil. T2 was quantified by using a mono-exponential fitting algorithm on multi-slice multi echo T2 weighted data. Statistical comparison was performed using ANOVA.
  
  
  RESULTS
  (I) Histopathologic evaluation of both rat and human livers demonstrated no evidence of steatosis or hemochromatosis There was a monotonic increase in mean T2 value with increasing degree of fibrosis (control 65.4±2.9 ms, n=6 patients); mild (Ishak 1-2) 66.7±1.9 ms (n=30); moderate (Ishak 3-4) 71.6±1.7 ms (n=26); severe (Ishak 5-6) 72.4±1.4 ms (n=61); with relatively low standard error (~2.9 ms). There was a statistically significant difference between degrees of mild (Ishak <4) vs. moderate to severe fibrosis (Ishak >4) (P=0.03) based on logistic regression of T2 and Ishak, which became insignificant (P=0.07) when using inflammatory markers as covariates. Expanding on this model using ordinal logistic regression, there was significance amongst all 4 groups comparing T2 to Ishak (P=0.01), with significance using inflammation as a covariate (P=0.03) and approaching statistical significance amongst all groups by ANOVA (P=0.07); (II) there was a monotonic increase in T2 and statistical significance (ANOVA P<0.0001) between each rat subgroup [phosphate buffer solution (PBS) 25.2±0.8, DEN 5-week (31.1±1.5), and DEN 9-week (49.4±0.4) ms]; (III) the phantoms that had T2 values within the relevant range for the human liver (e.g., 20-100 ms), demonstrated no statistical difference between two point fits on turbo spin echo (TSE) data and multi-echo CPMG data (P=0.9).
  
  
  CONCLUSIONS
  The finding of increased T2 with liver fibrosis may relate to inflammation that may be an alternative or adjunct to other noninvasive MR imaging based approaches for assessing liver fibrosis.
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Guimaraes
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Luiz
authors.initials: L
authors.lastname: Siqueira
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Ritika
authors.initials: R
authors.lastname: Uppal
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Jamu
authors.initials: J
authors.lastname: Alford
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Fuchs
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Suguru
authors.initials: S
authors.lastname: Yamada
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Tanabe
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Chung
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Lauwers
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Chew
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Giles W
authors.initials: GW
authors.lastname: Boland
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Duhyant V
authors.initials: DV
authors.lastname: Sahani
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Vangel
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Hahn
authors.affiliation: 1 Division of Abdominal Imaging and Interventional Radiology, Department of Radiology, Massachusetts General Hospital, Boston, MA 02114, USA ; 2 Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA 02129, USA ; 3 Section for Body Imaging, Department of Radiology, Oregon Health & Sciences University, Portland, OR 97239, USA ; 4 Division of Surgical Oncology, Department of Surgery, 5 Division of Hepatology, Department of Medicine, 6 Department of Pathology, 7 Department of Biostatistics, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Caravan
keywords: MRI; T2 relaxation time; fibrosis imaging biomarkers; liver fibrosis; quantitative imaging