# Spatiotemporal evolution of lung injury during ventilator-induced lung injury

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2020 · $40,724

## Abstract

Project Summary
Severe injury and illness may lead to Acute Respiratory Distress Syndrome (ARDS), a high mortality acute
respiratory failure that has an incidence of up to 80 cases per 100,000 person/years and a mortality rate of
approximately 40%. The syndrome is associated with surfactant dysfunction and airspace edema that lead to
alveolar collapse (derecruitment). Because of the degeneration of lung structure and function, mechanical
ventilation is required to manage ARDS and maintain adequate gas exchange. However, mechanical ventilation
induces ventilator-induced lung injury (VILI) which exacerbates the effects of ARDS through tissue
overdistension and the cyclic collapse and reopening of alveoli and distal airways. Great strides have been made
in understanding the basic mechanisms of VILI so that ventilation may be prescribed to reduce VILI while
maintaining gas exchange. However, these two demands are frequently in conflict and identifying optimal
mechanical ventilation parameters remains a challenging task for even the most skilled clinician. Determining
the mechanisms of injury, and thus protective ventilation patterns, is complicated by the spatiotemporal
heterogeneity of ARDS and VILI. It is thought that this heterogeneity may contribute to the progression of these
diseases through the physical interconnectivity of the delicate alveoli. In this scenario, reduced distensibility of a
flooded or collapsed alveoli will increase the strain in adjacent patent regions. This proposal will therefore test
the overall hypothesis that edema and cellular injury will start in high stress locations; these initially injured
areas will create stress foci, which make the proximal areas highly susceptible to further injury. To test this
hypothesis, we will use a combination of experimental and computational techniques to illustrate the existence
of injury heterogeneity and its progression, quantify the influence of injured regions on new damage,
and predict the mechanisms that cause injury to spread. Novel image analysis techniques and custom-built
computer software will quantify the micro- and macro- scale distribution of cellular injury in mouse VILI. These
measurements will, for the first time, quantify the spatial distribution of cellular-scale injury. To interpret these
data, we will implement a new type of statistical model to determine the range and strength of interdependence
between existing and new cellular injury. These simulations will allow interpretation of my experimental
measurements and, in future studies, facilitate the identification of ventilation regimes that prevent the spread of
injury to reduce ARDS mortality. Finally, novel formulations of a finite element alveolar network will be used to
determine if the clustering of cell injury may be attributed increased mechanical strain caused by the physical
interconnectivity of the alveoli. In addition to these scientific goals, this proposal will support the development of
a promising y...

## Key facts

- **NIH application ID:** 10058766
- **Project number:** 5F31HL149268-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Courtney Mattson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $40,724
- **Award type:** 5
- **Project period:** 2019-08-16 → 2022-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058766

## Citation

> US National Institutes of Health, RePORTER application 10058766, Spatiotemporal evolution of lung injury during ventilator-induced lung injury (5F31HL149268-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10058766. Licensed CC0.

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