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Integrating Multi-Modal Data and Biomechanics in COPD: Toward Robust and Interpretable Biomarkers for Disease Subtyping and Progression

Award Number: R01HL141813
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2018
PERIOD OF PERFORMANCE END DATE: 02/28/2030

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Integrating Multi-Modal Data and Biomechanics in COPD: Toward Robust and Interpretable Biomarkers for Disease Subtyping and Progression - Abstract Chronic Obstructive pulmonary disease (COPD) is a devastating, progressive disease affecting 13 million Americans and 300 million globally. The disease is highly heterogeneous, with both behavioral risk (e.g., smoking) and genetic predisposition. Patient-specific biomechanics also play a crucial role in determining the progression of the disease. While the global lung function test is used for clinical diagnosis, it is insufficient to understand the underlying mechanism of the disease. High-resolution CT imaging is also used to quantify the two major phenotypes of the disease (e.g., emphysema and airway inflammation). However, current classical radiomics measures lack the sensitivity to quantify the progression. While Deep Learning radiomics have shown promising results, they are unimodal, lack interpretability, and are sensitive to data acquisition protocols such as scanner type. We aim to extend our prior project, which demonstrated that deep learning radiomics features trained via a self- supervised approach extract features more generalizable than traditional supervised methods. Our novel radiomics features predict disease progression effectively and when combined with blood transcriptomics, facilitate the identification of distinct disease subtypes. We hypothesize that our multi-modal deep learning approach, which integrates imaging, genomic data, and lung biomechanics, will enhance understanding of COPD progression with the capability to provide robust, interpretable, and accurate clinical predictions. In this proposal, we seek to develop new radiomic features that derive insights from CT images and are informed by genetic and genomic data, enhancing their robustness by integrating biological insights into imaging patterns (Aim 1). We train the model on a vast dataset of over 65,000 CT images to enhance its robustness across various imaging protocols, including low-dose and high-dose CT scans. We will develop a novel high- dimensional mediation analysis technique to discover the causal pathways of the disease subtypes. In Aim 2, we will develop a method to estimate the biomechanical properties of the parenchyma, more specifically tissue stiffness, from CT images using a novel Biomechanically-Informed Neural Network, which is highly interpretable. We will validate our method ex-vivo with lung Cristal ribcage, a transparent ribcage model allowing for multiscale optical imaging from the whole organ down to single cells. The technology developed in this proposal can potentially impact beyond COPD to other pulmonary diseases that impact the biomechanical properties of the extracellular matrix.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $685,572 )
2025	2025	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Lung Diseases Research	000	7	5/15/2025	COMPETING CONTINUATION	$685,572
														Subtotal = $685,572

Issue Date FY: 2024 ( Subtotal = -$1 )
2024	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	000	5	9/9/2024	NON-COMPETING CONTINUATION	-$1
														Subtotal = -$1

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	000	5	6/19/2023	NON-COMPETING CONTINUATION	-$478,218
2023	2022	TRUSTEES OF BOSTON UNIVERSITY	1 SILBER WAY	BOSTON	MA	02215	SUFFOLK	USA	Lung Diseases Research	001	6	6/20/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$478,218
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $564,472 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	000	5	4/15/2022	NON-COMPETING CONTINUATION	$508,023
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	001	5	6/14/2022	NON-COMPETING CONTINUATION	$56,449
														Subtotal = $564,472

Issue Date FY: 2021 ( Subtotal = $564,472 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Lung Diseases Research	000	4	5/3/2021	NON-COMPETING CONTINUATION	$564,472
														Subtotal = $564,472

Issue Date FY: 2020 ( Subtotal = $564,472 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Lung Diseases Research	000	3	4/16/2020	NON-COMPETING CONTINUATION	$564,472
														Subtotal = $564,472

Issue Date FY: 2019 ( Subtotal = $564,472 )
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Cardiovascular Diseases Research	000	2	5/23/2019	NON-COMPETING CONTINUATION	$564,472
														Subtotal = $564,472

Issue Date FY: 2018 ( Subtotal = $570,906 )
2018	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Cardiovascular Diseases Research	001	1	5/31/2018	NEW	-$13,520
2018	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Cardiovascular Diseases Research	000	1	4/30/2018	NEW	$584,426
														Subtotal = $570,906

Grand Total All Awards = $3,514,365

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Integrating Multi-Modal Data and Biomechanics in COPD: Toward Robust and Interpretable Biomarkers for Disease Subtyping and Progression

Award Number: R01HL141813

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2018

PERIOD OF PERFORMANCE END DATE: 02/28/2030

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