# Imaging the Pulmonary Circulation to Aid Personalized Management of Acute Respiratory Distress Syndrome

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $827,682

## Abstract

PROJECT SUMMARY
Acute Respiratory distress syndrome (ARDS) is a life-threatening condition caused by widespread pulmonary
inflammation leading to lung injury. ARDS has a mortality that can be higher than 40% and is the main cause of
death from COVID-19. Although necessary to support life, mechanical ventilation worsens ARDS. While
computed tomography (CT) is capable of identifying characteristic abnormal airspace mechanics, the pulmonary
circulation is also altered in ARDS, with profound dysregulation of lung perfusion resulting in regional elevations
of blood flow and volume. Such misdistribution may significantly impact the trajectory of lung injury. In animal
studies, ventilated lungs suffered from stress-failure of the capillary barrier when perfused at higher blood flows
and pressures, resulting in more edema. Regions of the lung with elevated perfusion may therefore be at risk of
worse injury. The pulmonary circulation is significantly understudied in ARDS due to the paucity of accurate and
non-invasive instruments to visualize perfusion in vivo. This proposal addresses the need to elucidate the
fundamental contribution of the pulmonary circulation to ARDS trajectory. We intend to develop a comprehensive
imaging approach to characterize lung perfusion and direct treatment. We will leverage our expertise with two
imaging modalities: a) dynamic contrast enhanced (DCE) and dual energy CT (DECT), which map pulmonary
blood flow and volume with high resolution; b) electrical impedance tomography (EIT), a bedside technique that
allows rapid and frequent assessments of pulmonary perfusion without moving patients to a scanner. We will
use these techniques in animal and human studies to test our hypothesis that protecting the capillary barrier and
manipulating pulmonary perfusion to decrease capillary stress failure attenuates ARDS progression. In a
ventilated swine model of ARDS, we will demonstrate that reducing the heterogeneity of pulmonary perfusion
mitigates lung injury using two treatments that redistribute pulmonary blood flow and volume: selective
vasodilation with inhaled nitric oxide (iNO) and prone ventilation. We will match regional changes in perfusion
and inflation with the subsequent progression of lung injury. We will then show that protecting the pulmonary
capillaries in vulnerable lung regions decreases injury using Imatinib, a drug that preserves endothelial integrity,
in our swine model. Finally, after refining our translational imaging pipeline, we will perform proof-of-principle
studies in human ARDS using DECT and EIT to assess individual patient responses to iNO and prone ventilation,
aiming to integrate such information into clinical decision-making. This proposal will demonstrate that it is
possible to non-invasively assess pulmonary perfusion in order to guide ARDS treatment. Shifting the focus from
airspace mechanics to a more comprehensive management of both lung perfusion and ventilation, the proposed
approach will cons...

## Key facts

- **NIH application ID:** 10978564
- **Project number:** 1R01HL171199-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Maurizio Franco Cereda
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $827,682
- **Award type:** 1
- **Project period:** 2024-07-29 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978564

## Citation

> US National Institutes of Health, RePORTER application 10978564, Imaging the Pulmonary Circulation to Aid Personalized Management of Acute Respiratory Distress Syndrome (1R01HL171199-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10978564. Licensed CC0.

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