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Development of a fast scanning, extended field-of-view multiphoton microscope for clinical skin imaging

Award Number: R01EB026705
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Development of a fast scanning, extended field-of-view multiphoton microscope for clinical skin imaging - Summary The study of mammalian immune cells and their interactions with tissue in situ is critical for understanding how they regulate processes ranging from wound healing to autoimmune disease initiation to cancer and for designing better therapeutic strategies to treat these prevalent conditions. Intravital multiphoton microscopy (MPM) combined with a rich repertoire of fluorescent reporter mouse models and in vivo cell and tissue labeling techniques have made it possible to visualize immune cell-tissue interactions at a subcellular level in skin and other organs. However, there are significant differences in the structure and immune milieu of human skin that limits the translatability of these findings to the human cutaneous immune response. Our group has recently developed a fast large area multiphoton exoscope (FLAME), a unique imaging platform optimized for efficient clinical skin imaging to rapidly generate macroscopic images (mm to cm-scale) with microscopic resolution (0.5- 1µm) based on label-free molecular contrast (fluorescence intensity and lifetime). In this application, we leverage our extensive experience in MPM technology development and clinical imaging of more than 400 patients over the past several years to develop the first MPM-based clinical device (iFLAME) as a research imaging tool optimized for, and dedicated to, in vivo label-free imaging of immune cell populations and their dynamics in human skin. In Aim 1, we develop iFLAME as a clinical research tool for efficient in vivo label-free imaging of dermal cell populations and their dynamics in human skin. This work involves development of detection and analytic approaches as well as optical and computational methods to enable rapid fluorescence lifetime detection and analysis necessary to automate measurements of the cellular morphological and metabolic signatures. In Aim 2, we validate iFLAME performance by demonstrating in vivo characterization of immune cells in normal and inflamed human skin. In Aim 3, we develop quantitative morphological and metabolic MPM imaging endpoints to assess immune infiltrates and their dynamics in human skin in the context of monitoring wound healing. This work represents the first attempt to use intrinsic sources of MPM contrast to image, identify, and quantify key immune cells in human skin in vivo based on their optical signatures and migratory behavior. Our long-term goal is to develop iFLAME as a clinical research tool for rapid, label-free imaging of immune cells in skin based on cellular morphologic and metabolic imaging endpoints. These can be used to better understand, evaluate and optimize wound healing, autoimmune skin diseases and therapeutic responses.


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 = $525,093 )
2025	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	7	3/20/2025	NON-COMPETING CONTINUATION	$525,093
														Subtotal = $525,093

Issue Date FY: 2024 ( Subtotal = $583,873 )
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	6	5/17/2024	NON-COMPETING CONTINUATION	$583,873
2024	2021	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	5/10/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $583,873

Issue Date FY: 2023 ( Subtotal = $580,419 )
2023	2023	UNIVERSITY OF CALIFORNIA, IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	5	3/17/2023	COMPETING CONTINUATION	$580,419
														Subtotal = $580,419

Issue Date FY: 2021 ( Subtotal = $466,802 )
2021	2021	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	5/26/2021	NON-COMPETING CONTINUATION	$0
2021	2021	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	4/13/2021	NON-COMPETING CONTINUATION	$466,802
														Subtotal = $466,802

Issue Date FY: 2020 ( Subtotal = $483,207 )
2020	2020	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	3	4/6/2020	NON-COMPETING CONTINUATION	$483,207
														Subtotal = $483,207

Issue Date FY: 2019 ( Subtotal = $487,499 )
2019	2019	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	3/29/2019	NON-COMPETING CONTINUATION	$487,499
2019	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	10/29/2018	NEW	$0
														Subtotal = $487,499

Issue Date FY: 2018 ( Subtotal = $504,130 )
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	5/31/2018	NEW	$504,130
														Subtotal = $504,130

Grand Total All Awards = $3,631,023

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Development of a fast scanning, extended field-of-view multiphoton microscope for clinical skin imaging

Award Number: R01EB026705

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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