# Predicting the onset of chronic rejection in lung transplant recipients using hyperpolarized 129Xe imaging

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $803,146

## Abstract

Summary
Up to 80% of lung transplant recipients who survive beyond five years will develop chronic lung allograft
dysfunction (CLAD), a heterogenous, progressive condition characterized by the gradual and irreversible
functional decline eventually leading to death. Once developed, the majority of CLAD types do not respond
well to currently available therapeutic interventions. Early diagnosis of suspected CLAD is therefore crucial to
efforts aimed at the delaying disease onset and/or progression, which usually proceed via the aggressive
treatment of associated immunological risk factors.
Despite recently revised criteria, the current clinical reliance on spirometry to diagnose suspected CLAD
suffers from several disadvantages: namely, the global nature of the measurements provided by pulmonary
function tests (PFTs), their failure to differentiate between rejection and infection as the cause of functional
decline, frequent inter-observer disagreement in interpreting their results and, finally, their inability to improve
the targeting of transbronchial biopsy. An imaging modality capable of sensitively and accurately detecting
CLAD-onset earlier and with more spatial specificity would provide significant clinical value.
In response to this need, the proposed project will use the sensitive, regional measurements of lung function
which various hyperpolarized xenon-129 MRI techniques are uniquely capable of providing to develop a set of
imaging markers capable of diagnosing suspected CLAD before spirometric measurements reveal a clinically
significant functional decline; ideally, these markers will also enable a distinction to be made between
obstructive and restrictive forms of CLAD before either becomes symptomatic.
The first task of this project will be to use multi-breath HP xenon-129 MR imaging to establish regional specific
ventilation (SV) and alveolar oxygen tension (PAO2) as imaging markers for the early diagnosis of obstructive
CLAD: increased heterogeneity in these sensitive measures of gas replacement dynamics within the
transplanted lung will offer an earlier indication of CLAD-associated functional decline than spirometry. Next,
we will use dissolved-phase HP xenon-129 imaging to quantify the efficiency of alveolar gas exchange and
transport in order to detect the fibrotic and bloodflow impediments to pulmonary function associated with
restrictive CLAD. Finally, we will attempt to radiologically define several novel sub-classifications of CLAD
related to known associated risk factors such as ischemia reperfusion injury, respiratory infection, antibody-
mediated injury and gastroesophageal reflux.

## Key facts

- **NIH application ID:** 9998566
- **Project number:** 1R01HL151153-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** RAHIM R RIZI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $803,146
- **Award type:** 1
- **Project period:** 2020-06-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998566

## Citation

> US National Institutes of Health, RePORTER application 9998566, Predicting the onset of chronic rejection in lung transplant recipients using hyperpolarized 129Xe imaging (1R01HL151153-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9998566. Licensed CC0.

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