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Trimodal Vitality Imaging of Neural Progenitor Cells in the Spinal Cord

Award Number: R01NS117613
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2020
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Trimodal Vitality Imaging of Neural Progenitor Cells in the Spinal Cord - ABSTRACT Spinal cord diseases and disorders such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS) are debilitating, often resulting in loss of mobility and decreased quality of life for those affected. One promising treatment involves the transplantation of neural progenitor cells (NPC) into the spinal cord, which has been shown to have neuroprotective properties. However, most NPC-based therapies fail after reaching clinical trials, and without a method to monitor the injected cells and viability, locating injected NPCs is limited to postmortem histology. The ability to track and assess the viability of transplanted cells could be crucial in understanding whether the failure is technical or biological in nature, such as whether the injected cells were delivered to and remain at the correct location or survived transplantation. We propose the development of multi-modal contrast agents and a clinical ultrasound and photoacoustic (US/PA) imaging system for image guided delivery of trans- planted cells and longitudinal monitoring. Together with clinical magnetic resonance imaging (MRI), the use of US/PA imaging can allow for pre-, intra- and post-operative visualization of the cells. The MRI and US imaging modalities are well established in the clinic, and PA can be easily integrated with existing clinical US imaging systems. We hypothesize that visualizing the location and viability of injected neural progenitor cells obtained through the labeling of NPCs with contrast agents will allow for better understanding of transplanted cell behavior and improved translation of cell based therapies. Two contrast agents will be developed: photo-magnetic nano- particles, which will allow for photoacoustic and MRI tracking, and a dye-based apoptosis reporter, which will provide photoacoustic contrast upon apoptotic activity. These will be delivered to the cytosol of the neural pro- genitor cells and assessed for labeling efficiency and toxicity. Once optimized, labeled NPCs in different ratios of live to dead will be injected into the spinal cords of rats to assess the feasibility of distinguishing live and dead cells in vivo. After injection, the NPCs will be monitored longitudinally using trimodal US/PA/MR imaging. After validating the performance of the contrast agents in vivo, a clinical US/PA imaging system will be developed to demonstrate real-time image guided-delivery, US/PA/MRI longitudinal tracking, and PA viability assessment of the labeled cells. The ability to monitor the transplanted cells at every point during and after the procedure will allow for more accurate delivery of the cells and could elucidate common issues and behaviors of injected NPCs that could lead to therapeutic improvements. Furthermore, if successful, it will validate both the contrast agents and US/PA as a valuable tool for tracking and monitoring cell-based therapies to improve clinical translation.


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 = $618,303 )
2025	2025	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/26/2025	NON-COMPETING CONTINUATION	$618,303
														Subtotal = $618,303

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	8/7/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $624,903 )
2023	2023	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/16/2023	NON-COMPETING CONTINUATION	$624,903
														Subtotal = $624,903

Issue Date FY: 2022 ( Subtotal = $627,178 )
2022	2022	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/20/2022	NON-COMPETING CONTINUATION	$627,178
														Subtotal = $627,178

Issue Date FY: 2021 ( Subtotal = $606,281 )
2021	2021	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/23/2021	NON-COMPETING CONTINUATION	$606,281
														Subtotal = $606,281

Issue Date FY: 2020 ( Subtotal = $476,500 )
2020	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/21/2020	NEW	$476,500
														Subtotal = $476,500

Grand Total All Awards = $2,953,165

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Trimodal Vitality Imaging of Neural Progenitor Cells in the Spinal Cord

Award Number: R01NS117613

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2020

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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