# Xenon MRI in Pulmonary Hypertension

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $736,853

## Abstract

ABSTRACT
The diagnosis and follow-up of patients with pulmonary arterial hypertension (PAH) continues to be challenging,
with a lack of unambiguous biomarkers that reflect the course of the disease. PAH is characterized by pulmonary
vascular remodeling with abnormal cellular proliferation and fibrosis. This leads to an obstructive vasculopathy
of the pulmonary arterioles, resulting in pulmonary hypertension (PH) and progressive right heart failure that lead
to morbidity and mortality. Hemodynamics and right heart function are commonly used to diagnose disease and
monitor progression and response to therapy. However, these readouts are altered in other common heart and
lung diseases and their changes are not specific to pulmonary vascular remodeling. This lack of specificity has
resulted in critical unmet need for noninvasive approaches for directly monitoring pulmonary vascular remodeling
in PAH that could be used to guide treatment in patients, thereby improving their health outcomes. To address
this need, we have developed 129Xe magnetic resonance imaging (129Xe MRI) as a method to produce
quantitative 3D maps of gas transfer across the pulmonary blood-gas barrier. 129Xe MRI has a distinct PAH
signature and can simultaneously measure capillary blood volume and hemodynamic changes associated with
pulmonary vascular remodeling. The objective of this project is to associate pathologic pulmonary vascular
remodeling in PAH at a cellular and pathological level with specific changes in gas exchange physiology and
hemodynamics. We hypothesize that different types of remodeling, such as inflammation, fibrosis and
proliferation, result in unique changes in gas exchange physiology and hemodynamics that can be monitored
with 129Xe MRI. Our preliminary studies have identified a 129Xe MRI signatures that differentiates PAH from other
common heart and lung diseases. This technology is also sensitive to early pulmonary vascular remodeling 1-2
weeks after exposure to monocrotaline (MCT) in a preclinical rat PH model. We will extend these studies and
determine our objective via the following specific aims. In Aim 1, we will determine the relationship between
pulmonary vascular remodeling and both gas exchange and hemodynamic abnormalities in PAH patients
undergoing lung transplant, to correlate lung pathology and cellular identity with defects in 129Xe MRI gas
exchange and spectroscopy. In Aim 2, we will determine the sensitivity of different monitoring approaches to
early remodeling and response to therapy in the MCT and Sugen-hypoxia preclinical models of PH. In Aim 3, we
will determine the ability of 129Xe MRI to longitudinally monitor disease progression in patients. The expected
outcomes of this project will be a direct link between pulmonary vascular remodeling and changes in lung
physiology, along with a novel, noninvasive biomarker for its monitoring. This proposed research is significant
because it will define the mechanistic links between pulmonary vas...

## Key facts

- **NIH application ID:** 10909083
- **Project number:** 5R01HL153872-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Bastiaan Driehuys
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $736,853
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909083

## Citation

> US National Institutes of Health, RePORTER application 10909083, Xenon MRI in Pulmonary Hypertension (5R01HL153872-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10909083. Licensed CC0.

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