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TRANSCRANIAL FUS THERAPY WITH CLOSED-LOOP US IMAGE GUIDANCE AND CIRCULATING

Award Number: R37CA239039
ORGANIZATION: NATIONAL CANCER INSTITUTE
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: 04/30/2027

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TRANSCRANIAL FUS THERAPY WITH CLOSED-LOOP US IMAGE GUIDANCE AND CIRCULATING - Project summary A major obstacle towards attaining sufficient accumulation of blood-borne therapeutics in the brain and brain tumors is posed by the blood-brain barrier. Circulating microbubbles upon ultrasound exposure can exert mechanical stress in brain vessels to trigger a range of responses pertinent to key regulatory processes of the blood brain barrier, including local increase in the blood brain barrier permeability and activation of inflammatory signaling and phenotypes. While these transient phenotypic changes have led to novel and highly potent therapeutic and, more recently, diagnostic interventions against brain tumors, they also raised major safety concerns, which may hinder their effective translation to the clinic. Although, recent developments in microbubble emissions based closed-loop controllers have shown that it is possible to fine-tune the ultrasound excitation amplitude and mitigate major safety concerns, these methods can only control the relative strength of the observed biological responses and not the type of the responses, which inevitably leads to a very narrow treatment window. The central hypothesis of this proposal is that microbubbles resonant effects in brain capillaries can offer new ways to modulate the blood brain barrier signaling and function, thereby allowing to establish tumor-specific therapeutic windows (spatial, temporal, and molecular) to increase drug efficacy with minimal side effects. To test this hypothesis and understand the impact of microbubble resonant effects on blood- brain barrier signaling and function this research will combine high fidelity mathematical modeling of microbubbles dynamics in vessels with prospective experimental investigations. First, the microbubble resonance effects and exerted stress in brain vessels will be analyzed using mathematical modeling. Then, in prospective investigations the impact of ultrasound frequency-controlled microbubble-induced mechanical stress on the blood-brain barrier signaling and function in healthy rodents will be assessed. Subsequently, the potential of the proposed research to promote safer and more effective targeted drug delivery along with the abilities of cancer soluble biomarkers, such as cell free tumor DNA, to support the longitudinal monitoring of the treatment will be evaluated in brain tumor-bearing rodents. Moreover, to be able to excite and control the microbubble dynamics over a broad range of amplitudes and frequencies, this proposal will investigate the combined transmit and receive capabilities of capacitive micromachined ultrasound technology for implementing the proposed ultrasound frequency-controlled methods of microbubble dynamics. If successful, the proposed research will develop novel technologies and create unique opportunities for safer and more effective diagnosis, treatment, and treatment monitoring of brain cancer.


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 = $452,110 )
2025	2025	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Cancer Detection and Diagnosis Research	000	6	5/14/2025	EXTENSION WITH OR WITHOUT FUNDS	$452,110
														Subtotal = $452,110

Issue Date FY: 2024 ( Subtotal = $355,482 )
2024	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Cancer Detection and Diagnosis Research	000	5	4/15/2024	NON-COMPETING CONTINUATION	$355,482
														Subtotal = $355,482

Issue Date FY: 2023 ( Subtotal = $421,668 )
2023	2023	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Cancer Detection and Diagnosis Research	000	4	6/21/2023	NON-COMPETING CONTINUATION	$421,668
														Subtotal = $421,668

Issue Date FY: 2022 ( Subtotal = $537,084 )
2022	2022	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Cancer Detection and Diagnosis Research	000	3	5/6/2022	NON-COMPETING CONTINUATION	$537,084
														Subtotal = $537,084

Issue Date FY: 2021 ( Subtotal = $556,557 )
2021	2021	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Cancer Detection and Diagnosis Research	000	2	4/30/2021	NON-COMPETING CONTINUATION	$556,557
														Subtotal = $556,557

Issue Date FY: 2020 ( Subtotal = $566,412 )
2020	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Cancer Detection and Diagnosis Research	000	1	7/20/2020	NEW	$566,412
														Subtotal = $566,412

Grand Total All Awards = $2,889,313

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TRANSCRANIAL FUS THERAPY WITH CLOSED-LOOP US IMAGE GUIDANCE AND CIRCULATING

Award Number: R37CA239039

ORGANIZATION: NATIONAL CANCER INSTITUTE

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: 04/30/2027

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