# An Early Imaging Marker of Emphysema

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $474,531

## Abstract

PROJECT SUMMARY/ ABSTRACT
Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death in the US, with nearly 60
million confirmed cases world-wide. Emphysema and small airways disease (SAD) are two main components of
COPD. Emphysema, associated with severe COPD, results in alveolar destruction and is a leading cause of
mortality in this population. Considered at the tissue level an end-stage disease, there are limited treatment
options once diagnosed. As such, there is a clear unmet clinical need to identify markers that predict the early
onset of emphysema. Small airways disease, a treatable component of COPD, has been identified in recent
studies as a potential precursor of emphysema. Although promising, clinical techniques were unable to measure
SAD hindering its use as a marker. This limitation was overcome through our development of a 3D analytical
technique called Parametric Response Mapping (PRM). When applied to computed tomography (CT) scans,
PRM identifies non-emphysematous air trapping, an indirect measure of SAD, even in the presence of
emphysema. In fact, we have demonstrated that the relative lung volume of PRM-derived functional SAD
(%PRMfSAD) predicted spirometric decline in COPD patients, highlighting its potential as an indicator of COPD
progression. Nevertheless, %PRMfSAD provides only a whole-lung assessment, limiting its potential at detecting
the onset and local progression of emphysema. To fully realize PRMfSAD as a predictor of emphysema, we have
advanced our PRM technique by applying topological methods, based on the Minkowski Functionals, to our 3D
PRM classification maps. Referred to as topological PRM (tPRM), this method reported in Scientific Reports
extracts and quantifies features from 3D PRMfSAD resulting in 3D maps of relative density (V; analogous to
%PRMfSAD), surface area (S), mean breadth (B) and Euler-Poincaré statistic (χ). Our preliminary results have
shown that tPRMfSAD correlated better to clinical measures than the %PRMfSAD. Based on these findings, we
hypothesize that our approach will improve PRM sensitivity to disease progression while providing the spatial
information needed to detect the onset of emphysema. We have set out three aims to test our hypothesis. In
Aim 1, we will evaluate the sensitivity of our tPRM method to CT signal variability associated with scanner type,
CT acquisition and reconstruction kernel, as well as corroborate correlations in tPRM to various clinical measures
as previously reported. In Aim 2, we will determine distinctions in tPRM to contributions of emphysema and SAD
as measured from microCT analysis of frozen explanted lung cores obtained from lung transplant recipients with
end-stage COPD. Finally, in Aim 3, we will correlate longitudinal changes over a 5-yr interval in tPRM to clinically-
relevant measures. These aims will be accomplished through support from the NIH-sponsored clinical trial
COPDGene and continued multi-center and multi-disciplinary...

## Key facts

- **NIH application ID:** 10159304
- **Project number:** 5R01HL139690-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Craig J Galban
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $474,531
- **Award type:** 5
- **Project period:** 2019-05-28 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159304

## Citation

> US National Institutes of Health, RePORTER application 10159304, An Early Imaging Marker of Emphysema (5R01HL139690-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10159304. Licensed CC0.

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