# Assessment of Lung Injury with integrated Imaging Techniques

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $531,795

## Abstract

SUMMARY
Acute respiratory distress syndrome (ARDS) is characterized by diffuse pulmonary edema that impairs gas
exchange and leads to hypoxemia. ARDS can be caused by direct or indirect lung injury from a variety of
common conditions including sepsis, pneumonia, trauma, acid aspiration, ischemia-reperfusion, chemical
inhalation, and overdistension by mechanical ventilation. Due to its diverse etiology, extremely high hospital
case-fatality rates, and poor long-term prognosis, the syndrome has increasingly been recognized by the NIH
and biomedical investigators as an important public health concern.
Unfortunately, options for treating ARDS remain extremely limited. The only proven methods for enhancing
survival are protective, low-tidal-volume mechanical ventilation and prone positioning, both of which are
implemented once a patient is in poor enough condition to require intubation. As such, the last decade has
witnessed a strong effort among researchers to develop therapies that can prevent lung injury from
progressing to ARDS, a trend that has been buttressed by the establishment by the NIH of the Prevention and
Early Treatment of Acute Lung Injury (PETAL) multi-site network of clinical trials. A number of promising drugs
for ARDS prevention are in the early translational stages of research, including transient receptor potential
vanilloid 4 (TRPV4) inhibitors, which block calcium channels whose activation is an important facilitator of
pulmonary endothelial hyperpermeability and edema.
Administration of these preventive ARDS therapeutics to patients with optimal sensitivity and specificity
requires the corollary development of diagnostic tools that can identify individuals who are particularly at risk of
progressing to severe lung injury before this progression occurs. In response to this need and in line with the
guiding focus of this RFA, the proposed project will develop a molecular probe capable of detecting the early
metabolic signs of lung injury before edema develops. Through injecting hyperpolarized (HP) 13C-labeled
pyruvate and imaging the subject with magnetic resonance (MR), we are able to track its real-time conversion
to lactate and bicarbonate in the lung. Decreased conversion to bicarbonate and increased conversion to
lactate indicate mitochondrial dysfunction and upregulated glycolysis, respectively, which have been
associated with the endothelial hyperpermeability that allows formation of edema.
The first fundamental task of this project will be to demonstrate that HP 13C pyruvate can non-invasively detect
lung injury in rodent models before conventional clinical metrics (chest x-ray/computed tomography [CT] to
identify edema and alveolar blood gas testing to identify hypoxemia). Second, we will investigate the
bioenergetics effects of TRPV4 inhibitors using 13C pyruvate, thereby gaining an idea of how blockage of the
TRPV4 channel affects the metabolic characteristics that our probe is measuring. Third, we will assess
whether ...

## Key facts

- **NIH application ID:** 9963343
- **Project number:** 5R01HL139066-04
- **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:** $531,795
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963343

## Citation

> US National Institutes of Health, RePORTER application 9963343, Assessment of Lung Injury with integrated Imaging Techniques (5R01HL139066-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9963343. Licensed CC0.

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