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Quantitative mapping of oxygenation around neural interfaces using novel PISTOL MR imaging

Award Number: UF1NS107676
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/30/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2023

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Quantitative mapping of oxygenation around neural interfaces using novel PISTOL MR imaging - Project Summary Oxygen levels (pO2) in the brain play a significant role in influencing the function of single neurons and neuronal networks during normal and pathological states. Mechanisms of such interactions between neuronal function and oxygen supply and consumption are not well understood relying largely on theoretical models and qualitative measurements. In addition, current and emerging neural implants disrupt the local blood-brain barrier as they penetrate the brain during placement potentially leading to oxidative stress in brain tissue along the path of the implant. Such oxidative stress indicative of energy imbalances can trigger multiple pathways to tissue damage. Many of the current technologies for measuring oxygen are qualitative and therefore do not provide a direct measure of oxygen partial pressure in the brain. Those that do measure oxygen quantitatively are either point measurements that do not give a spatial map, or require very specialized equipment or can only map the superficial areas. We propose here a novel PISTOL (Proton Imaging of Siloxane Tissue Oxygen Levels) based magnetic resonance (MR) imaging approach to create dynamic, quantitative spatial maps of pO2 levels with microscale resolution in the brain around implanted neural interfaces in anesthetized and conscious, head-restrained animals. We will develop a siloxane contrast agent that will be loaded in a polydimethylsiloxane (PDMS) matrix encapsulating the neural interface for long-term stability in brain tissue. The specific aims of this proposal are: 1). Develop, test and validate the sensitivity, detection limits, of 3 different embodiments of a siloxane sensor that will create quantitative spatial maps of pO2 along the length of a single microscale implant in the brain under “no stimulation” and electrical/optical stimulation conditions in rodent experiments. 2). We will develop and test a generalizable process that will encapsulate individual shanks in 16- and 256-channel custom MR compatible microelectrode arrays and Utah microelectrode arrays with a PDMS matrix loaded with siloxane contrast agent. Subsequently, we will scale the PISTOL imaging technique to create spatial maps of pO2 around multiple implant sites in the brain and 3). We will test and validate the siloxane contrast agents for their ability to map pO2 levels around multi-channel microelectrodes in chronic rodent experiments. Successful development of the proposed technology will yield unprecedented information and discoveries on (a) dynamics of oxygen supply and consumption during neuronal function and dysfunction and (b) mechanisms of tissue injury leading to failure of chronic implants. The proposed siloxane based technique is also expected to be readily translatable leading to immediate clinical impact in patients with epilepsy, stroke, hemorrhage etc.


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 = -$1,550 )
2024	2018	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	10/1/2023	NEW	-$1,550
														Subtotal = -$1,550

Issue Date FY: 2023 ( Subtotal = -$2,820 )
2023	2018	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/18/2023	NEW	$0
2023	2018	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	9/29/2023	NEW	-$2,820
														Subtotal = -$2,820

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/6/2019	NEW	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $1,819,257 )
2018	2018	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/19/2018	NEW	$1,819,257
														Subtotal = $1,819,257

Grand Total All Awards = $1,814,886

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Quantitative mapping of oxygenation around neural interfaces using novel PISTOL MR imaging

Award Number: UF1NS107676

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 09/30/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2023

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