# Improving lung transplant outcomes through the use of imaging in a DBD rat model

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $759,350

## Abstract

Summary
Along with complications stemming from primary graft dysfunction (PGD), a significant shortage
of available donor lungs has prevented lung transplantation from achieving widespread utilization
as a treatment for end-stage lung disease. Despite a growing number of lung transplants taking
place worldwide, the number of patients awaiting them is growing faster—prompting numerous
efforts aimed at expanding the donor pool through aggressive donor management and innovative
organ preservation strategies aimed primarily at improving transplant outcomes for ‘marginal’
lungs harvested after donor brain death (DBD).
DBD Lung allografts are at increased risk of PGD due to the combination of hemodynamic injury
and inflammatory upregulation that brain death causes in the donor lung. Recent studies have
identified several strategies that successfully prevent and/or combat this injury and its deleterious
post-transplant effects—including donor pre-treatment, delayed organ recovery, and ex-vivo lung
perfusion (EVLP). However, advances in this area are limited by an incomplete understanding of
the mechanisms by which DBD compromises graft viability.
In response to this need and in accordance with the primary focus of this RFA, the proposed
project will use an integrated imaging method which our lab has created for quantitatively
measuring regional structural, functional and metabolic parameters of the lung in order to provide
an early, objective assessment of organ quality prior to procurement. Using a combination of
hyperpolarized (HP) gas-MRI and HP carbon-13 magnetic resonance spectroscopic imaging
(MRSI), we will establish the early cellular dynamics of donor lung injury subsequent to brain
death and track this injury’ progression over time and in response to various treatment and
preservation strategies.
The first task of this project will be to use our combined imaging technique to establish an imaging
profile of acute lung injury immediately following donor brain death in a rat model. Second, we will
use these imaging parameters to identify an optimal window for organ recovery by tracking the
progression of donor lung injury over time, both in the absence of and in response to several
already proven pre-treatments. Third, we will use phosphorus and 13C MR spectra to evaluate
metabolic activity in the donor lung during ex-vivo perfusion, whose parameters will have been
suggested by our pre-harvest imaging of the organ. We will use the combination of our imaging
parameters and histology to compare graft performance after transplantation among all cohorts
and to evaluate the success of given therapeutic strategies in preventing PGD. Finally, we will
repeat perform EVLP studies on several human lungs in order to assess the translational potential
of our imaging technique and parameters.

## Key facts

- **NIH application ID:** 10198021
- **Project number:** 5R01HL142258-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** RAHIM R RIZI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $759,350
- **Award type:** 5
- **Project period:** 2018-08-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198021

## Citation

> US National Institutes of Health, RePORTER application 10198021, Improving lung transplant outcomes through the use of imaging in a DBD rat model (5R01HL142258-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10198021. Licensed CC0.

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