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An optical approach to 3-dimensional micro-mechanical imaging of the extra-cellular matrix (ECM)

Award Number: R21EB028951
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract The goal of this proposal is to develop and validate a laser SpeckLe fIeld Microrheology (SLIM) technology for micromechanical mapping of the tissue ECM, with lateral resolution of 10 μm, axial resolution of 60 μm, and a penetration depth of 5 mm penetration depth. ECM stiffness, as perceived by cells, is emerging as a prominent micro-mechanical cue that precedes pathogenesis and directs its progression by orchestrating nearly all aspects of cellular behavior. Excessive and irregular micro-mechanical remodeling of the ECM is implicated in a broad spectrum of pathologies, including cardiovascular disease, fibrotic disorders, and cancer, which together account for over 50% of death worldwide. Nevertheless, our understanding of the underlying mechanisms is severely limited as currently there are no imaging tools available for micromechanical mapping of the ECM at length scales pertinent to cells. SLIM measures the time-varying speckle intensity fluctuations. Speckle is a grainy intensity pattern, formed when a coherent laser beam is back scattered from tissue. Brownian displacements of scattering particles within the ECM dynamically modulate the speckle fluctuations. These fluctuations in turn are intimately related to the viscoelastic properties of imaged tissue. In compliant regions, unrestricted Brownian displacements provoke rapidly fluctuating speckle spots, whereas in rigid areas, restrained motions elicit limited intensity variations of speckle grains. Pixel-wise correlation analysis of intensity fluctuations provides a 2D depth-integrated map of mechanical properties within the tissue. However, the resolution of this map is limited to the speckle grain size, set by the Numerical Aperture (NA) of optics. In addition, due to multiple scattering of light, speckle fluctuations are modulated by the Brownian displacements of the scattering particles within the entire illuminated volume. As a result, the evaluated map lacks depth information. Therefore, the first goal of this proposal is to address these issues by introducing an innovative SLIM platform, capable of high resolution, depth-resolved, large FoV, micromechanical mapping of the ECM, without physical scanning and refocusing on the sample. Our second goal is then to identify the link between the micromechanical properties of ECM and known hallmarks of disease progression, by focusing on breast cancer as a model. The unique capability of SLIM for micro-mechanical tomography of ECM enables identifying the key biomechanical mediators of pathogenies. It also opens multiple avenues based on targeting the cell-ECM micromechanical interactions for therapeutic management of disease.


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: 2024 ( Subtotal = -$22,556 )
2024	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	003	3	2/9/2024	NON-COMPETING CONTINUATION	-$48,316
2024	2023	UNIVERSITY OF MASSACHUSETTS LOWELL	600 SUFFOLK ST STE 450	LOWELL	MA	01854	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	004	4	2/9/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$204,538
2024	2023	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 212	LOWELL	MA	01854	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	006	4	2/29/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$139,128
2024	2023	UNIVERSITY OF MASSACHUSETTS LOWELL	600 SUFFOLK ST STE 450	LOWELL	MA	01854	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	007	4	3/1/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2024	2023	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 212	LOWELL	MA	01854	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	12/5/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$139,128
2024	2023	UNIVERSITY OF MASSACHUSETTS	600 SUFFOLK ST STE 212	LOWELL	MA	01854	MIDDLESEX	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	005	4	2/26/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$139,128
2024	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	12/4/2023	NON-COMPETING CONTINUATION	-$161,684
2024	2022	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	2	2/9/2024	NON-COMPETING CONTINUATION	-$156,222
														Subtotal = -$22,556

Issue Date FY: 2023 ( Subtotal = $210,000 )
2023	2023	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	3/17/2023	NON-COMPETING CONTINUATION	$210,000
														Subtotal = $210,000

Issue Date FY: 2022 ( Subtotal = $210,000 )
2022	2022	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	6/13/2022	NON-COMPETING CONTINUATION	$210,000
														Subtotal = $210,000

Issue Date FY: 2021 ( Subtotal = $252,000 )
2021	2021	MASSACHUSETTS GENERAL HOSPITAL, THE	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	6/11/2021	NEW	$252,000
														Subtotal = $252,000

Grand Total All Awards = $649,444

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An optical approach to 3-dimensional micro-mechanical imaging of the extra-cellular matrix (ECM)

Award Number: R21EB028951

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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