# Validating Quantitative Magnetic Resonance Imaging Biomarkers of Idiopathic Pulmonary Fibrosis

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2022 · $751,069

## Abstract

Pulmonary fibrosis contributes to morbidity and mortality in a wide spectrum of lung diseases. While it can result
from environmental exposures or acute injuries, the events that initiate lung fibrosis are typically unknown. This
Idiopathic Pulmonary Fibrosis (IPF) is the most common form of interstitial lung disease, and it is associated with
a post-diagnosis survival of only 3 years. Despite decades of research, only 2 drugs are FDA approved to treat
IPF, and both merely slow its progression. Failure to produce treatments to reverse or halt disease progression
can be attributed to poorly understood IPF etiology. In turn, poor understanding can be attributed to an inability
to detect and quantify early fibrosis and relate regional parenchymal remodeling to the functional, biomechanical,
and molecular processes that initiate fibrosis. Eliminating this gap will require significant scientific and technical
developments involving both biologically realistic disease models and sensitive and specific imaging technology.
The long-term goal of this research is to quantify early pulmonary remodeling and relate it to profibrotic mecha-
nisms and emergent pathophysiology. Our objectives in this application are to 1) determine the biophysical origin
of magnetic resonance imaging (MRI) relaxation in fibrotic lung tissue, 2) quantify alveolar ventilation, 3) apply
these metrics to two realistic, transgenic mouse models, and 4) extend quantitative ventilation MRI to IPF pa-
tients. Our central hypothesis is that relaxation and ventilation will correlate with ex vivo measures of fibrosis
(e.g., regional collagen content) and provide sensitive, noninvasive methods of quantifying fibrosis progression
in vivo. Our rationale is that imaging markers—once validated in animal models and IPF patients—can readily
be applied in mechanistic preclinical studies and in assessing IPF progression and therapy efficacy. Guided by
strong preliminary data and theoretical work describing MR signal dynamics in the lungs, our central hypothesis
will be tested by completing the following three Specific Aims: 1) validate transverse relaxation as a marker of
lung fibrosis; 2) quantify impaired ventilation with multi-breath HP 129Xe washout; and 3) demonstrate the sensi-
tivity of HP 129Xe washout MRI to impaired ventilation in IPF patients. Under Aim 1, we have developed the MRI
sequences and reconstruction pipeline needed to complete the work. Under Aim 2, we have constructed and
validated a hyperpolarized gas and MRI-compatible ventilator and developed the image processing tools to
quantify regional tissue density. Under Aim 3, we have pioneered the use of efficient 3D spiral MRI sequences
and keyhole-based image reconstruction to produce high-quality, quantitative human lung images. The proposed
research is innovative both biologically and technically, because it will develop and validate noninvasive, regional
measures of biophysical tissue properties and ventilation. These results ...

## Key facts

- **NIH application ID:** 10322979
- **Project number:** 5R01HL143011-04
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** ZACKARY I CLEVELAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $751,069
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10322979

## Citation

> US National Institutes of Health, RePORTER application 10322979, Validating Quantitative Magnetic Resonance Imaging Biomarkers of Idiopathic Pulmonary Fibrosis (5R01HL143011-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10322979. Licensed CC0.

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