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Novel Ultrasound Indices of Intracranial Pressure and Brain Ischemia in Neonatal Hydrocephalus

Award Number: R01NS119473
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Novel Ultrasound Indices of Intracranial Pressure and Brain Ischemia in Neonatal Hydrocephalus - Novel Ultrasound Indices of Intracranial Pressure and Brain Ischemia in Neonatal Hydrocephalus Project Summary Neonatal hydrocephalus affects 1-2 of every 1000 live births and results in neurologic deficits in up to 78% of treated patients. A wide spectrum of etiologies including intraventricular hemorrhage, congenital aqueduct stenosis, myelomeningocele, and brain tumors cause an abnormal accumulation of cerebral spinal fluid (CSF) in this disease, resulting in cerebral ventricular dilatation and elevated intracranial pressure (ICP). While ventricular shunting is used as a surgical treatment for CSF diversion, the decision to shunt is based on ventricular size and clinical judgement which are not sensitive markers of ICP and brain health. Thus, delayed diagnosis of elevated ICP and surgical shunting can result in permanent brain damage and long-term neurologic deficits. Invasive ICP monitors are not routinely inserted due to the associated risk of bleeding and regional brain ischemia in the vulnerable neonatal brain. To provide a solution to a significant gap in clinical care of neonatal hydrocephalus, we utilize the contrast-enhanced ultrasound (CEUS) technique for noninvasive detection of ICP and brain ischemia in a well-established porcine model of hydrocephalus. CEUS uses intravascular injection of microbubbles of 2-3 µm in average size for assessment of tissue perfusion. With the use of the novel particle tracking method (so-called particle image and/or tracking velocimetry), the underlying spatial and temporal changes in cerebral microcirculation can be quantified for assessment of elevated ICP and brain ischemia. To this end, the previous R01 cycle validated a promising cerebral microvascular flow marker of ICP and brain ischemia in the acute porcine hydrocephalus model. This renewal R01 will focus on expanding the imaging biomarker repertoire and applicability to hydrocephalus of varying duration and etiology. The central hypothesis of the proposal is that CEUS will be a robust biomarker of ICP, brain ischemia and oxygenation in neonatal hydrocephalus. The overall goal of the proposal is therefore to 1) expand the novel CEUS biomarker repertoire and applicability beyond the acute phase of elevated ICP and to 2) explore the complementary use of macro- vascular diagnostic tools. As an exploratory aim, we will conduct a pilot Investigational New Drug (IND) approved clinical study as a continuous laboratory-to-clinical and reverse feedback learning and improvement mechanism in biomarker development. Our work will set the stage for clinical translation of a new noninvasive tool for assessment of ICP and brain ischemia in neonatal hydrocephalus, which can ultimately improve the guidance of shunting and long-term neurologic outcomes.


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 = $700,001 )
2025	2025	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	5/8/2025	COMPETING CONTINUATION	$701,154
2025	2023	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/26/2024	NON-COMPETING CONTINUATION	-$1,153
														Subtotal = $700,001

Issue Date FY: 2023 ( Subtotal = $641,164 )
2023	2023	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	8/23/2023	NON-COMPETING CONTINUATION	$641,164
														Subtotal = $641,164

Issue Date FY: 2022 ( Subtotal = $637,418 )
2022	2022	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/9/2022	NON-COMPETING CONTINUATION	$637,418
														Subtotal = $637,418

Issue Date FY: 2021 ( Subtotal = $633,886 )
2021	2021	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/21/2021	NON-COMPETING CONTINUATION	$633,886
														Subtotal = $633,886

Issue Date FY: 2020 ( Subtotal = $661,169 )
2020	2020	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/26/2020	NEW	$661,169
														Subtotal = $661,169

Grand Total All Awards = $3,273,638

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Novel Ultrasound Indices of Intracranial Pressure and Brain Ischemia in Neonatal Hydrocephalus

Award Number: R01NS119473

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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