Mapping hepatocyte size in vivo using temporal diffusion spectroscopy MRI.

Abstract

The goal of this study is to implement a noninvasive method for in vivo mapping of hepatocyte size. This method will have a broad range of clinical and preclinical applications, as pathological changes in hepatocyte sizes are relevant for the accurate diagnosis and assessments of treatment response of liver diseases. Building on the concepts of temporal diffusion spectroscopy in MRI, a clinically feasible imaging protocol named IMPULSED (Imaging Microstructural Parameters Using Limited Spectrally Edited Diffusion) has been developed, which is able to report measurements of cell sizes noninvasively. This protocol acquires a selected set of diffusion imaging data and fits them to a model of water compartments in tissues to derive robust estimates of the cellular structures that restrict free diffusion. Here, we adapt and further develop this approach to measure hepatocyte sizes in vivo. We validated IMPULSED in livers of mice and rats and implemented it to image healthy human subjects using a clinical 3T MRI scanner. The IMPULSED-derived mean hepatocyte sizes for rats and mice are about 15-20 µm and agree well with histological findings. Maps of mean hepatocyte size for humans can be achieved in less than 15 minutes, a clinically feasible scan time. Our results suggest that this method has potential to overcome major limitations of liver biopsy and provide noninvasive mapping of hepatocyte sizes in clinical applications.