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Quantifying Biomechanical and Perfusion Abnormalities in Drug-Resistant Epilepsy: Novel MR Imaging Markers of Seizure Foci and Underlying Gliosis

Award Number: R01NS150462
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: 08/15/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Quantifying Biomechanical and Perfusion Abnormalities in Drug-Resistant Epilepsy: Novel MR Imaging Markers of Seizure Foci and Underlying Gliosis - Project Summary Among the epilepsy population in the United States, drug-resistant epilepsy (DRE) accounts for most of the socioeconomic burden due to increased frequency of comorbid illnesses, psychological dysfunction, reduced quality of life and increased risk of mortality. Surgical interventions, including resective surgery, laser ablation, or neuromodulation, may offer effective relief from seizures for these individuals. However, the potential for surgical success is significantly diminished in cases where clinical MRI scans fail to identify lesional area or seizure foci. There is a critical unmet need in epilepsy to identify regions of the brain involved in seizure formation and propagation in DRE patients. Emerging evidence suggests that reactive astrogliosis, an inflammatory process involving astrocytes, plays a key role in epileptogenesis by altering tissue structure and function, including vascular remodeling and extracellular matrix changes. These alterations likely impact biomechanical and perfusion properties of the brain, measurable using non-invasive MRI methods such as magnetic resonance elastography (MRE) and arterial spin labeling (ASL). This project aims to improve epilepsy diagnosis and surgical planning by advancing MRE and ASL as novel complementary imaging markers of the epileptogenic zone (EZ). Our central hypothesis is that glial activation in epilepsy alters both tissue stiffness and perfusion, and that the coupling of these properties differs between healthy and epileptic brain regions. In this proposal, we aim: 1) to evaluate the diagnostic accuracy of brain MRE/ASL in localizing and characterizing epilepsy; and 2) to investigate brain biomechanics-perfusion coupling in DRE patients and healthy individuals. We will validate the developed MRE/ASL imaging markers by statistical comparisons of the patient groups, including lesional and non-lesional focal DRE patients with mesial temporal lobe (mTLE) or neocortical (NE) epilepsy and healthy controls, while correlating the findings with the common markers of glial activation and post-surgical histopathology to confirm glial contributions to altered tissue properties. We will also investigate biomechanics- perfusion coupling in healthy and epileptogenic brain tissue, determining normative coupling patterns in controls and comparing them to abnormalities observed in lesional and non-lesional DRE patients. This project integrates advanced imaging with molecular and histological analyses to provide the first comprehensive evaluation of brain biomechanics and perfusion in epilepsy. Imaging will be conducted using both 3T and 7T MRI scanners to ensure high accuracy and support future clinical translation. The outcomes of this study will lead to the development of complementary, non-invasive, and reliable diagnostic tools to accurately localize epileptic foci, particularly in patients without visible lesions, ultimately guiding surgical treatment and improving outcomes for individuals with DRE.


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: 2026 ( Subtotal = $646,706 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/14/2026	NEW	$646,706
														Subtotal = $646,706

Grand Total All Awards = $646,706

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Quantifying Biomechanical and Perfusion Abnormalities in Drug-Resistant Epilepsy: Novel MR Imaging Markers of Seizure Foci and Underlying Gliosis

Award Number: R01NS150462

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: 08/15/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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