# Quantitative magnetic resonance imaging of pulmonaryperfusion

> **NIH NIH R03** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $122,788

## Abstract

Project Summary/Abstract
The goal of this project is to establish a pharmacokinetic model for absolute quantification of pulmonary
perfusion and microvascular parameters and validate this model in large animal models with independent tissue
analyses of perfusion, vascular permeability, and pathological features. Idiopathic pulmonary fibrosis (IPF) is a
progressive and ultimately fatal disease with highly variable clinical courses and poorly understood pathogenic
mechanisms. Accumulating evidence shows that abnormalities in the pulmonary endothelium set off a cascade
of events that promote increased vascular permeability, fibroblast activation, and excessive extracellular matrix
deposition, ultimately leading to the development of fibrotic lung tissue and impaired lung function. However,
the changes in the pulmonary endothelium of the fibrotic lung have not been well defined. Dynamic contrast-
enhanced MRI (DCE-MRI) is a powerful imaging technique whereby the kinetics of an intravenous contrast bolus
such as the FDA-approved agent Gd-DOTA can be modeled for quantitative measurement of tissue perfusion
and vascular permeability. Accurate assessment of these changes in IPF will provide an improved
understanding of the pathophysiology of pulmonary fibrosis, which is valuable for improving patient care and
facilitating drug development for this deadly disease. Previously, we demonstrated that DCE-MRI with model-
free analysis allows for indirect but sensitive detection of alterations in perfusion, permeability, or extracellular
extravascular volume in patients with IPF or prior COVID infection compared to healthy volunteers, thus providing
in vivo regional functional information not otherwise available. However, the pathophysiological interpretation of
these results remains to be elucidated because the model-free approach indirectly measures a collective effect
of changes in perfusion and microvascular parameters. The standard pharmacokinetic model in common use
for DCE-MRI, Tofts model, is oversimplified, assuming instantaneous intercompartmental water exchange and
negligible blood volume which are not valid for the lung and thus propagates into significant systematic errors in
physiological parameters extracted from DCE data. To overcome these challenges, I propose to extend the
standard Tofts model to encompass intercompartmental water exchange rate and true compartmental fractions
for DCE-MRI of the lung and validate the physiological measurements derived from this extended model with
independent tissue analyses in a large animal model of IPF. The output of this project will be a robust analytical
tool for absolute quantification of pulmonary perfusion and microvascular parameters in the lung, which will not
only provide a quantitative understanding of the pathophysiologic mechanism underlying IPF and other
pulmonary diseases but also be valuable for improving patient care and facilitating drug development for this
deadly disease.

## Key facts

- **NIH application ID:** 10947547
- **Project number:** 1R03HL174682-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Iris Yuwen Zhou
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $122,788
- **Award type:** 1
- **Project period:** 2024-09-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10947547

## Citation

> US National Institutes of Health, RePORTER application 10947547, Quantitative magnetic resonance imaging of pulmonaryperfusion (1R03HL174682-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10947547. Licensed CC0.

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