# in vivo MR characterization of pathological changes in liver microstructures

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $411,707

## Abstract

in vivo MR characterization of pathological changes in liver microstructures
Summary
Liver biopsy is currently the gold standard for diagnosing and evaluating the extent of most liver diseases, but it
is an invasive procedure that carries risks such as sampling errors, rare complications, intra/inter-observer
variability, and significant patient anxiety. Noninvasive tests and imaging techniques for the diagnosis and
management of liver diseases have gained significant interest due to the limitations of liver biopsy, particularly
for identifying nonalcoholic steatohepatitis (NASH), the most severe form of Nonalcoholic fatty liver disease
(NAFLD). Due to the obesity pandemic and type 2 diabetes, an increased number of NASH patients (~ 27
million NASH patients by 2030 in the US alone) is expected in the near future. The ability to differentiate NASH
from simple steatosis is critically important for the clinical management of NAFLD patients. Currently, NASH is
exclusively diagnosed invasively through liver biopsy to assess steatosis, inflammation, ballooning and fibrosis.
While MRI-based PDFF and elastography have been shown to reliably quantify steatosis and fibrosis,
respectively, the lack of a non-invasive tool to assess inflammation in NASH remains a significant gap in the
daily clinical care of this common disease.
Our lab has developed a novel concept that cell size and cell density could serve as indicators of hepatic
inflammation and has developed a multi-compartment diffusion MRI-based method called in vivo quantitative
Temporal Diffusion Spectroscopy (qTDS), which quantifies cell size and cell density by fitting multi-b value-
multi-diffusion time fat-suppressed diffusion-weighted MRI signals to a three-compartment (blood, intra and
extracellular water) signal model. Recently, qTDS has shown promising results in in vivo NASH patients and
ex vivo human liver specimens with different pathologies, including normal liver tissues, cirrhosis, steatosis,
and cirrhotic regenerative nodules (CRN).
This grant proposal aims to establish the relationship between qTDS-derived parameters and histology values
in a mouse model of NASH, optimize a clinical qTDS protocol for reliable in vivo quantification of cell size and
cell density in human livers within a short period (less than 12 minutes), and demonstrate the efficacy of qTDS
in characterizing hepatic inflammation, a key diagnostic component for differentiating NASH from simple
steatosis. Successful completion of these aims will provide a solid foundation for a large-scale clinical trial to
develop a noninvasive diagnostic metric for NASH, offer a standard qTDS imaging protocol that can be
implemented on clinical 3T MR scanners, and provide a qTDS data processing toolbox that can be
downloaded online. These outcomes will advance the use of noninvasive microstructure imaging in the
diagnosis and management of liver diseases.

## Key facts

- **NIH application ID:** 10803245
- **Project number:** 1R01DK135950-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Xiaoyu Jiang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $411,707
- **Award type:** 1
- **Project period:** 2024-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10803245

## Citation

> US National Institutes of Health, RePORTER application 10803245, in vivo MR characterization of pathological changes in liver microstructures (1R01DK135950-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10803245. Licensed CC0.

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