# Noninvasive Evaluation of Renal Allograft Fibrosis by MRI

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2021 · $191,695

## Abstract

Renal fibrosis is a final pathway and important biomarker of injury common to aging and to most forms of
chronic kidney diseases (CKD). It is assessed primarily by renal biopsy, which is prohibitively invasive and is
limited by inadequate sampling. However, reliable strategies to detect renal fibrosis are yet to be identified.
These notions underscore the need for reliable noninvasive tools for early detection of kidney injury,
to enhance development and monitoring of therapeutic strategies.
 CKD involves high morbidity and mortality and substantial healthcare cost, and might eventuate in end-
stage renal failure requiring renal replacement therapy. However, graft survival after kidney transplantation (KT)
is suboptimal, and deterioration in function and loss of allografts are often associated with interstitial fibrosis.
Monitoring the extent of fibrosis noninvasively could decrease the cost and potential complications associated
with repeated biopsies, and help direct and optimize management. KT recipients also undergo protocol
biopsies, which can serve as a reference and allow evaluation of techniques that aim to assess renal fibrosis.
 Magnetization transfer imaging (MTI) magnetic resonance imaging (MRI) is a novel noninvasive method to
evaluate the tissue macromolecular composition. We have demonstrated that MTI can assess ischemic kidney
fibrosis in murine and swine models. However, the clinical utility of MT-MRI to assess renal fibrosis is currently
limited, because it is inherently semi-quantitative. In contrast, quantitative MT (qMT), based on biophysical
compartment models, provides more objective measurement of tissue MT properties. A model fitting of MR
signal acquired with various MT pulse amplitudes and offset frequencies, combined with scan-specific B0/B1/T1
maps, give rise to a more complete definition of tissue parameters, including a “bound pool fraction”, a direct
measure of the macromolecular content in tissue (an index of fibrosis).
 The hypothesis underlying this proposal is that qMT reliably detects development of allograft fibrosis in
human subjects after KT. To test this hypothesis, we will correlate the qMT-derived bound pool fraction with
renal fibrosis as per biopsy in 20 patients 4 or 7 years after living donor KT. We will also compare the bound
pool fraction to renal blood flow, oxygenation, and function, and will test the ability of qMT to provide consistent
assessments of fibrosis at different magnetic field strengths. Two specific aims will test the hypotheses that:
Specific Aim 1: qMT provides reliable and consequential assessment of fibrosis in human kidney allografts.
Specific Aim 2: Renal fibrosis assessed by qMT in human kidney allografts is reproducible at 1.5 T and 3.0 T.
 The proposed studies may therefore establish a reliable, noninvasive, and clinically feasible strategy to
quantify kidney fibrosis, a key biomarker for renal aging, disease progression, and outcomes.

## Key facts

- **NIH application ID:** 10176331
- **Project number:** 5R21AG062104-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Lilach O Lerman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $191,695
- **Award type:** 5
- **Project period:** 2020-06-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176331

## Citation

> US National Institutes of Health, RePORTER application 10176331, Noninvasive Evaluation of Renal Allograft Fibrosis by MRI (5R21AG062104-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10176331. Licensed CC0.

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