# Molecular MR Imaging of Hepatic Fibrogenesis

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $627,398

## Abstract

Project Summary
Nonalcoholic fatty liver disease (NAFLD) is the most prominent cause of liver disease, with 20-30% of adults in
the western world now estimated to have NAFLD. In NAFLD, hepatocytes accumulate excess fat (steatosis),
which is benign and reversible. However up to 30% of patients with NAFLD will develop non-alcoholic
steatohepatitis (NASH) which is characterized by steatosis, inflammation, and scarring (fibrosis). Patients with
only steatosis have good long-term prognosis, with no increased liver related morbidity or mortality, but those
with NASH have increased risk of cirrhosis, hepatocellular carcinoma and mortality. NASH is expected to soon
be the leading indication of liver transplantation. The financial burden of NAFLD/NASH is currently estimated to
cost >$100 billion in the USA alone. There is an urgent need to identify NAFLD patients who are at risk of
developing NASH and cirrhosis so as to better manage patient healthcare through improved lifestyle, exercise
and diet. In addition, a large number of new therapies have entered clinical trials and effective diagnostics are
needed to better stratify patients into these trials and to accurately monitor response to therapy.
 Fibrosis stage, and not steatosis nor inflammation, is the only feature of disease associated with worse
outcomes in NASH. Besides biopsy we lack good tools to noninvasively detect liver fibrosis, stage fibrosis, or
monitor response to treatment. Elastography methods are not sensitive to early changes in disease. Serum
biomarkers and biomarker panels to identify NASH and/or liver fibrosis, are also limited and lack accuracy for
staging. None of these techniques has the accuracy to monitor treatment. An accurate, safe method to diagnose
and monitor NASH and associated fibrosis is of utmost importance in both clinical practice and clinical research.
We recently demonstrated in animal models that we could quantify fibrogenesis (active disease) noninvasively
using a molecular magnetic resonance (MR) probe, Gd-Hyd, that targets extracellular allysine, a chemical
modification of oxidized collagen, present only during active fibrogenesis. We showed that Gd-Hyd imaging could
detect fibrogenesis, monitor treatment response and could distinguish active fibrogenesis from stable scar in
models of lung and liver fibrosis. The overall goal of this project is to improve on this prototype to develop an
optimized fibrogenesis MR probe for robust, quantification of liver fibrogenesis in patients.

## Key facts

- **NIH application ID:** 10167705
- **Project number:** 5R01DK121789-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Peter D Caravan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $627,398
- **Award type:** 5
- **Project period:** 2019-07-03 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167705

## Citation

> US National Institutes of Health, RePORTER application 10167705, Molecular MR Imaging of Hepatic Fibrogenesis (5R01DK121789-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10167705. Licensed CC0.

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