# CT-Derived Functional Imaging for Predicting Disease Progression in COPD

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2024 · $363,700

## Abstract

PROJECT SUMMARY
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States, imposing
a significant economic burden due to its high morbidity and mortality. The Global Initiative for Chronic Obstructive
Lung Disease (GOLD) criteria is a universally accepted disease severity staging score. However, GOLD score
is not a strong predictor for mortality or progression risk at early or pre-disease stages. Early intervention is
crucial for slowing COPD progression and improving quality of life. Therefore, there is a need to develop robust,
quantitative metrics for characterizing disease state and progression risk. Existing quantitative computer
tomography (CT) methods are based on analyzing variations in CT Hounsfield Units (HU) and have shown
moderate to strong correlation with disease state. However, HU values are known to be breathing-effort
dependent. As a result, quantitative CT methods require heuristic normalization schemes to adjust for varying
lung inflation levels and are known to lack reproducibility. We previously developed a robust class of CT-derived
ventilation (CTV) methods that calculate breathing-induced volume changes apparent on inhale/exhale CT (IE-
CT) image pairs, as a surrogate for ventilation. In addition to numerical stability, our CTV demonstrated a higher
correlation with nuclear medicine-based ventilation imaging than any other method in the literature. We recently
extended the CTV framework to calculate changes in blood mass apparent on IE-CT, as a surrogate for
pulmonary perfusion. Our novel CT-Perfusion (CTP), taken together with CTV, comprise our CT-derived
functional imaging (CTFI) methodology. CTFIis the first to mathematically describe changes in inhale/exhale HU
values in terms of ventilation and perfusion. This allows us to compute VQ (ventilation/perfusion) ratio imaging
that is inherently normalized to patient breathing effort. Thus, any early microvascular changes or VQ mismatch
associated with COPD disease severity can potentially be detected and quantified on IE-CT images. We
hypothesize that a CTFI-informed machine learning model has higher discriminative power in assessing survival
and disease progression than traditional methods such as FEV1, BODE index and other quantitative imaging
markers. To test this hypothesis, we will utilize data from the Genetic Epidemiology of COPD (COPDgene) study,
a multicenter observational study designed to identify genetic factors associated with COPD. We will adapt state-
of-the art unsupervised deep learning methods and fully leverage the rich COPDgene data set to train a lung
lobe segmentation model and automate the CTFI calculation pipeline. Next, we will develop and validate both
physics-based and deep learning-based CTFI VQ scoring methods. Finally, we will develop a machine learning
model which takes clinical information and patient CTFI lobar scores (ventilation, perfusion, & VQ) as input, and
quantifies disease severity, predic...

## Key facts

- **NIH application ID:** 10882833
- **Project number:** 1R01HL169869-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Edward Castillo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $363,700
- **Award type:** 1
- **Project period:** 2024-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10882833

## Citation

> US National Institutes of Health, RePORTER application 10882833, CT-Derived Functional Imaging for Predicting Disease Progression in COPD (1R01HL169869-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10882833. Licensed CC0.

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