Diffusion MRI Derived per Area Vessel Density as a Surrogate Biomarker for Detecting Viral Hepatitis B-Induced Liver Fibrosis: A Proof-of-Concept Study.

Liver vessel density can be evaluated by an imaging biomarker diffusion-derived vessel density (DDVD): DDVD/area(b0b2) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the liver signal when b is 0 or 2 (s/mm2); ROIarea0 and ROIarea2 refer to the region of interest (ROI) on b = 0 or 2 images; and Sb2 may be replaced by Sb15 (b = 15). This concept was validated in this study. Liver diffusion images were acquired at 1.5 T. For a scan-rescan repeatability study of six subjects, b values of 0 and 2 were used. The validation study was composed of 26 healthy volunteers and 19 consecutive suspected chronic viral hepatitis B patients, and diffusion images with b values of 0, 2, 15, 20, 30, 45, 50, 60, 80, 100, 200, 300, 600, and 800 were acquired. Four patients did not have liver fibrosis, and the rest were four stage 1, three stage 2, four stage 3, and one stage 4 patients, respectively. The intraclass correlation coefficient for repeatability was 0.994 for DDVD/area(Sb0Sb2) and 0.978 for DDVD/area(Sb0Sb15). In the validation study, DDVD/area(Sb0Sb2) and area(Sb0Sb15) were 14.80 ± 3.06 and 26.58 ± 3.97 for healthy volunteers, 10.51 ± 1.51 and 20.15 ± 2.21 for stage 1-2 fibrosis patients, and 9.42 ± 0.87 and 19.42 ± 1.89 for stage 3-4 fibrosis patients. For 16 patients where IVIM analysis was performed, a combination of DDVD/area, PF, and Dfast achieved the best differentiation for nonfibrotic livers and fibrotic livers. DDVD/area were weakly correlated with PF or Dfast. Both DDVD/area(Sb0Sb2) and area(Sb0Sb15) are useful imaging biomarkers to separate fibrotic and nonfibrotic livers, with fibrotic livers having lower measurements.