# The role of quantitative CT and radiomic biomarkers for precision medicine in pulmonary fibrosis

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $762,272

## Abstract

Idiopathic pulmonary fibrosis (IPF) remains deadly despite two FDA approved therapies. Modifiable
intermediate molecular markers and other metrics for disease severity and progression remain unmet needs
for aiding drug development and clinical decision-making. Advances in image analysis enable objective
detection and quantitation of anatomy, while high-dimensional images can identify sub-visual characteristics,
often termed radiomic features – often called Quantitative CT (QCT). Data-driven texture analysis is a
previously validated method of QCT and a powerful prognostic marker. We seek to evaluate radiomic features
alone and in conjunction with other disease dimensions for prognostication and response to treatment in IPF.
The parent PRECISIONS project has completed Whole Genome Sequencing, RNA seq and proteomics on
over 1,600 ILD cases recruited thru the Pulmonary Fibrosis Foundation Registry (PFF-PR) generating novel
markers of disease progression. The PRECISIONS clinical trial tests the efficacy of N-acetylcysteine in 200
IPF patients with a TOLLIP polymorphism. However, follow-up quantitative CT is not currently included in the
trial. Our overall objectives are to identify and validate radiologic features, and intermediate response to
therapy, and understand where to position these powerful QCT markers. We hypothesize that DTA scores will
enhance prediction of disease progression, in conjunction with molecular markers. This ancillary proposal will
add CTs to the PRECISIONS trial cohort and use a registry UVA/Chicago real world cohort for replication. In
Aim 1, we will validate quantitative CT and radiomic markers for disease progression by independent
replication for prediction of progression. We will collect baseline and 1-year HRCTs in UVA/Chicago, and
PRECISIONS trial participants to evaluate: a) the prognostic value of baseline quantitative CT and radiomic
markers (i.e. DTA) in predicting time to progression, b) associations between changes in CT biomarkers on
sequential CT and changes in 1-year FVC and DLCO, and c) change in CT associated with drug treatment. In
Aim 2: We will determine if candidate genetic variants for IPF susceptibility and survival associate with DTA
score and improve predictive performance for survival. We will perform a cross-sectional analysis of PFF-PR
cases comparing quantitative CT and radiomic markers at baseline with and without “at risk” genotypes for
association with severity, and progression (decline in FVC over time). Findings will be replicated in
UVA/Chicago cohort and in the prospective PRECISIONS cohort. Lastly, in Aim 3, We will assess if DTA and
radiomic markers are additive/synergistic with plasma protein and blood transcriptome markers for disease
progression. We have chosen published markers from a 4-protein panel signature along with CCL18, as
examples given their current level of replication and promise. Will also include our 25 gene FVC predictor for
disease progression. Similar analyses as ou...

## Key facts

- **NIH application ID:** 10777799
- **Project number:** 1R01HL171918-01
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Imre Noth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $762,272
- **Award type:** 1
- **Project period:** 2024-02-05 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10777799

## Citation

> US National Institutes of Health, RePORTER application 10777799, The role of quantitative CT and radiomic biomarkers for precision medicine in pulmonary fibrosis (1R01HL171918-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10777799. Licensed CC0.

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