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Ultrasound Therapy Delivery Through Intact Skull

Award Number: R01EB003268
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/1998
PERIOD OF PERFORMANCE END DATE: 05/31/2023

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Ultrasound Therapy Delivery Through Intact Skull - Invasive brain interventions often result in complications and long recovery times. In addition, the delivery of therapeutic agents via the blood supply is often impossible because the Blood-Brain Barrier (BBB) protects the brain tissue from foreign molecules. Laboratory experiments and first clinical trials have shown that focused ultrasound (FUS) beams can be used for noninvasive interventions. However, the utilization of FUS in the brain has been seriously limited by the difficulty of delivering ultrasound through the skull bone. The hypothesis of this grant has been that trans-cranial therapeutic FUS exposures can be delivered noninvasively through an intact skull. This hypothesis has now been validated in multiple clinical studies that demonstrate that brain tissue can be noninvasively coagulated in the central part of the brain. During the current grant period, we furthered our initial research and developed methods to enhance FUS interaction with tissue using microbubbles, thus making whole brain sonications feasible. We have further studied the impact of ultrasound exposures on brain tissue and demonstrated chemotherapy delivery across the BBB. We have shown significant increases in animal survival with multiple treatments. We have shown similar gains by using targeted natural killer cells. We have also developed the methods for clinical BBB modulation for chemotherapy treatments using a current clinical device. Our study plan is to exploit our novel findings during this grant period and provide the methods for novel treatments. Our goals are: First, to utilize our method of super-resolution localization of individual microbubbles to explore the feasibility of micro-surgery and precision drug delivery. Second, to construct and test new array concepts that eliminate the need for a large waterbath and provide patient specific array geometry for repeated treatments. The impact of this research could be huge if even one of these new ideas could be translated to the clinic. For example, the methods proposed here could make tumor and epilepsy surgery available for a larger number of patients and the BBB modulation could increase the effectiveness of chemotherapy and potentially even provide treatments for patients with Alzheimer`s 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 = $0 )
2024	2020	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON			CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	23	2/21/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON			CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	23	8/23/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $386,836 )
2020	2020	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON	M4N 3M5		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	23	6/9/2020	NON-COMPETING CONTINUATION	$386,836
2020	2019	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON	M4N 3M5		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	22	5/8/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $386,836

Issue Date FY: 2019 ( Subtotal = $383,362 )
2019	2019	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON	M4N 3M5		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	22	9/5/2019	NON-COMPETING CONTINUATION	$383,362
2019	2018	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON	M4N 3M5		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	21	9/4/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $383,362

Issue Date FY: 2018 ( Subtotal = $515,096 )
2018	2018	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON	M4N 3M5		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	20	1/31/2018	SUPPLEMENT FOR EXPANSION	$108,000
2018	2018	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON	M4N 3M5		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	21	8/27/2018	NON-COMPETING CONTINUATION	$407,096
2018	2018	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON	M4N 3M5		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	004	20	9/20/2018	SUPPLEMENT FOR EXPANSION	$0
2018	2018	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON	M4N 3M5		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	20	6/26/2018	SUPPLEMENT FOR EXPANSION	$0
2018	2015	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON	M4N 3M5		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	003	19	9/5/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $515,096

Issue Date FY: 2017 ( Subtotal = $384,098 )
2017	2017	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON	M4N 3M5		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	20	8/14/2017	COMPETING CONTINUATION	$384,098
2017	2015	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON	M4N 3M5		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	19	8/13/2017	NON-COMPETING CONTINUATION	$0
2017	2015	SUNNYBROOK RESEARCH INSTITUTE	2075 BAYVIEW AVE	TORONTO	ON	M4N 3M5		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	19	6/26/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $384,098

Issue Date FY: 2015 ( Subtotal = $520,148 )
2015	2015	SUNNYBROOK HEALTH SCIENCES CENTRE	2075 Bayview Avenue	TORONTO				CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	19	6/18/2015	NON-COMPETING CONTINUATION	$520,148
														Subtotal = $520,148

Issue Date FY: 2014 ( Subtotal = $515,802 )
2014	2014	SUNNYBROOK HEALTH SCIENCES CENTRE	2075 Bayview Avenue	TORONTO				CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	18	8/8/2014	NON-COMPETING CONTINUATION	$515,802
														Subtotal = $515,802

Issue Date FY: 2013 ( Subtotal = $513,241 )
2013	2013	SUNNYBROOK HEALTH SCIENCES CENTRE	2075 Bayview Avenue	TORONTO				CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	17	6/14/2013	EXTENSION WITH OR WITHOUT FUNDS	$513,241
														Subtotal = $513,241

Issue Date FY: 2012 ( Subtotal = $529,471 )
2012	2012	SUNNYBROOK HEALTH SCIENCES CENTRE	2075 Bayview Avenue	TORONTO				CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	16	7/10/2012	COMPETING CONTINUATION	$529,471
2012	2011	SUNNYBROOK HEALTH SCIENCES CENTRE	2075 BAYVIEW AVENUE	TORONTO		00000		CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	15	7/10/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $529,471

Issue Date FY: 2011 ( Subtotal = $441,468 )
2011	2011	SUNNYBROOK HEALTH SCIENCES CENTRE	2075 Bayview Avenue	TORONTO				CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	15	6/6/2011	NON-COMPETING CONTINUATION	$441,468
														Subtotal = $441,468

Issue Date FY: 2010 ( Subtotal = $445,926 )
2010	2010	SUNNYBROOK & WOMENS COLL HLTH SCIS CTR	2075 Bayview Avenue	TORONTO				CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	14	6/3/2010	NON-COMPETING CONTINUATION	$445,926
														Subtotal = $445,926

Issue Date FY: 2009 ( Subtotal = $437,293 )
2009	2009	SUNNYBROOK & WOMENS COLL HLTH SCIS CTR	2075 Bayview Avenue	TORONTO				CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	003	13	7/8/2009	NON-COMPETING CONTINUATION	$437,293
2009	2008	SUNNYBROOK HEALTH SCIENCES CENTRE	2075 BAYVIEW AVENUE	TORONTO				CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	12	4/20/2009	COMPETING CONTINUATION	$0
2009	2007	SUNNYBROOK HEALTH SCIENCES CENTRE	2075 BAYVIEW AVENUE	TORONTO				CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	11	4/20/2009	NON-COMPETING CONTINUATION	$0
2009	2006	SUNNYBROOK HEALTH SCIENCES CENTRE	2075 BAYVIEW AVENUE	TORONTO				CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	10	4/20/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $437,293

Issue Date FY: 2007 ( Subtotal = $424,245 )
2007	2007	SUNNYBROOK HEALTH SCIENCES CENTRE	2075 BAYVIEW AVENUE	TORONTO				CAN	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	11	1/25/2007	NON-COMPETING CONTINUATION	$424,245
														Subtotal = $424,245

Issue Date FY: 2006 ( Subtotal = $606,583 )
2006	2006	BRIGHAM & WOMEN'S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	9	1/30/2006	NON-COMPETING CONTINUATION	$606,583
														Subtotal = $606,583

Issue Date FY: 2005 ( Subtotal = $606,177 )
2005	2005	BRIGHAM & WOMEN'S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	8	2/14/2005	NON-COMPETING CONTINUATION	$606,177
														Subtotal = $606,177

Issue Date FY: 2004 ( Subtotal = $591,480 )
2004	2004	BRIGHAM & WOMEN'S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	7	1/26/2004	NON-COMPETING CONTINUATION	$591,480
														Subtotal = $591,480

Issue Date FY: 2003 ( Subtotal = $574,495 )
2003	2003	BRIGHAM & WOMEN'S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	6		OTHER REVISION	$574,495
														Subtotal = $574,495

Grand Total All Awards = $7,875,721

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Ultrasound Therapy Delivery Through Intact Skull

Award Number: R01EB003268

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/1998

PERIOD OF PERFORMANCE END DATE: 05/31/2023

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