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High Fidelity Diffusion MRI for Children with Cerebral Palsy in Stem Cell Therapy

Award Number: R01NS075017
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: 02/15/2012
PERIOD OF PERFORMANCE END DATE: 06/30/2023

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High Fidelity Diffusion MRI for Children with Cerebral Palsy in Stem Cell Therapy - Abstract: Cerebral palsy (CP) is the most prevalent motor disorder of childhood with complications in other cognitive impairments, affecting 3 out of every 1,000 children. Largely due to in utero or perinatal injuries to the developing brain, CP results in white matter pathology including impairments to the motor pathway. Diffusion MRI (e.g. diffusion tensor imaging, or DTI) can help characterize these white matter impairments, as well as any potential connectivity improvement during treatment. Over the past five years, we have applied high-fidelity diffusion MRI in pediatric CP patients during autologous umbilical cord blood (UCB) stem cell therapies, and developed an understanding of the impact and benefit autologous UCB stem cells have on improving functional outcome and brain connectivity in pediatric CP patients. Specifically, we have found strong evidences in relevant brain networks that: 1) brain connectivity impairments account for the motor and cognitive abnormalities in children with CP at the pre-treatment baseline, 2) brain connectivity increases have a direct impact on functional and behavioral improvements during UCB stem cell therapy, 3) brain connectivity increases beyond that of typical development trajectory have a direct correlation with stem cell dosage above a potential threshold of 1.98 x 107 cells/kg, and 4) the severity of baseline connectivity abnormalities predicts the risk of further decline and the benefit of cell therapy. It was also found that the brain connectivity increase may be associated with improved myelination during cell therapy, through additional preliminary investigations using quantitative susceptibility mapping (QSM). Advancing from this solid foundation, we propose this renewal application to further develop ultrahigh resolution diffusion MRI and connectivity imaging methodologies to study the positive effect of allogenic stem cells derived from UCB (stored at the North Carolina Cord Blood Bank), which can both reach the necessary high dosage (as opposed to the limited autologous UCB stem cells) and be applied to more CP patients (rather than just the ones with UCB saved at birth). Specifically, we propose to: 1) achieve unprecedented magnetic field homogeneity based on our recent innovation on simultaneous RF reception and Bo shimming technology to enable the highest possible spatial resolution and fidelity, 2) achieve multi-band multi-shot 3D diffusion MRI acquisition with ultrahigh submillimeter spatial resolution, optimized SNR and high throughput, and 3) acquire and analyze ultrahigh resolution diffusion MRI and brain connectome maps, as well as DTI-guided myelin-sensitive QSM along white matter pathways and throughout the brain connectome, in pediatric CP patients during the course of innovative therapies using UCB-derived allogenic stem cells. It is expected that our continued and concerted efforts will greatly advance our understanding of the neural mechanisms on both connectivity impairments in children with CP at the baseline and on the impact of stem cell therapy on connectivity restorations, ultimately providing compelling evidence to help plan the best treatment options.


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 = -$4,043 )
2024	2021	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	10	4/18/2024	NON-COMPETING CONTINUATION	-$4,043
2024	2019	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	4/17/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = -$4,043

Issue Date FY: 2021 ( Subtotal = $352,188 )
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	6/15/2021	NON-COMPETING CONTINUATION	$352,188
														Subtotal = $352,188

Issue Date FY: 2020 ( Subtotal = $352,188 )
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	6/9/2020	NON-COMPETING CONTINUATION	$352,188
2020	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	1/21/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $352,188

Issue Date FY: 2019 ( Subtotal = $352,188 )
2019	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	8	8/8/2019	NON-COMPETING CONTINUATION	$0
2019	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	8	7/3/2019	NON-COMPETING CONTINUATION	$352,188
2019	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	2/8/2019	NON-COMPETING CONTINUATION	$0
2019	2017	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	1/16/2019	COMPETING CONTINUATION	$0
														Subtotal = $352,188

Issue Date FY: 2018 ( Subtotal = $350,728 )
2018	2018	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	7	6/8/2018	NON-COMPETING CONTINUATION	$350,364
2018	2017	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	6	2/27/2018	COMPETING CONTINUATION	$151,818
2018	2017	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	10/30/2017	COMPETING CONTINUATION	$364
2018	2016	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	2/27/2018	EXTENSION WITH OR WITHOUT FUNDS	-$151,818
														Subtotal = $350,728

Issue Date FY: 2017 ( Subtotal = $347,813 )
2017	2017	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	9/15/2017	COMPETING CONTINUATION	$347,813
2017	2016	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	9/15/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $347,813

Issue Date FY: 2016 ( Subtotal = $341,118 )
2016	2016	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	1/22/2016	EXTENSION WITH OR WITHOUT FUNDS	$34,112
2016	2016	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	1/15/2016	EXTENSION WITH OR WITHOUT FUNDS	$307,006
														Subtotal = $341,118

Issue Date FY: 2015 ( Subtotal = $341,163 )
2015	2015	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	1/22/2015	NON-COMPETING CONTINUATION	$341,163
														Subtotal = $341,163

Issue Date FY: 2014 ( Subtotal = $337,796 )
2014	2014	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/8/2014	NON-COMPETING CONTINUATION	$307,086
2014	2014	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	3/7/2014	NON-COMPETING CONTINUATION	$30,710
														Subtotal = $337,796

Issue Date FY: 2013 ( Subtotal = $329,307 )
2013	2013	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	5/23/2013	NON-COMPETING CONTINUATION	$22,181
2013	2013	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/17/2013	NON-COMPETING CONTINUATION	$307,126
														Subtotal = $329,307

Issue Date FY: 2012 ( Subtotal = $341,294 )
2012	2012	DUKE UNIVERSITY	BOX 104004	DURHAM	NC	27708	DURHAM	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/6/2012	NEW	$341,294
														Subtotal = $341,294

Grand Total All Awards = $3,441,740

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High Fidelity Diffusion MRI for Children with Cerebral Palsy in Stem Cell Therapy

Award Number: R01NS075017

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: 02/15/2012

PERIOD OF PERFORMANCE END DATE: 06/30/2023

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