# Magnetic Resonance Imaging Biomarkers of Post-COVID-19 Cerebral Microvascular Dysfunction

> **NIH NIH K23** · YALE UNIVERSITY · 2024 · $231,524

## Abstract

ABSTRACT
Neurologic post-acute sequelae of SARS-CoV-2 infection (neuro-PASC) is a pressing public health issue and
little is known about the cause, duration, and potential treatments. It is defined as a new health problem occurring
three months after initial COVID infection and lasting for at least two months. Common symptoms of neuro-
PASC include headache, inattention, cognitive impairment, dizziness, insomnia, and mood changes. Emerging
evidence suggests that persistent microvascular inflammation and dysfunction play critical roles in the PASC of
the lungs and heart. Numerous post-mortem studies have demonstrated significant microvascular damage and
dysfunction in the brains of individuals who have died of acute COVID-19. In the brains of individuals living with
neuro-PASC, case-control studies have found microvascular dysfunction, cerebral hypoperfusion, and new small
vessel disease. The long-term neurologic effects of microvascular dysfunction and subsequent risk of vascular
dementia is unknown. I hypothesize that cerebral microvascular dysfunction plays a critical role in neuro-
PASC cognitive impairment and puts individuals at risk for progression of small vessel disease.
Here, I propose utilizing advanced vascular MRI techniques to investigate for biomarkers of microvascular
dysfunction in the brain to better understand the pathophysiology of neuro-PASC and risk for progression of
small vessel disease. Understanding the underlying disease process will bring us closer to identifying biomarkers
and treatment targets. In order to enrich the probability of finding MRI alterations, I will recruit participants with
cognitive impairment, which is the most common and well-documented neuro-PASC symptom. I will conduct a
longitudinal study and perform two sets of MRIs, blood tests, and neuropsychological tests on each participant.
I will recruit at least 50 adults with a documented COVID-19 infection and cognitive symptoms and compare
them to 50 adults with a documented COVID-19 infection and no residual symptoms (controls). My detailed MRI
protocol will evaluate the vessel wall, arterial, and venous vasculature and explore techniques to map the
lymphatic vasculature. In the blood, I will test markers of coagulopathy, endotheliopathy, and neurodegeneration.
I am a neurologist and physician-scientist who has developed clinical and scientific expertise in neuro-PASC
through caring for patients in the NeuroCOVID Clinic at Yale, and I am working in the neuro-infectious disease
laboratory of my primary mentor. I recently graduated from fellowship, and I am now an Instructor in the
Department of Neurology. My long-term goal is to become an independent clinician-scientist with a focus on
utilizing neuroimaging techniques to understand the pathophysiology of neuro-PASC and generate biomarkers
of disease and treatment targets. To accomplish this goal, I have assembled a world class mentorship team with
experts in neuroradiology, neuropsychology, and neuro-I...

## Key facts

- **NIH application ID:** 10885595
- **Project number:** 1K23NS133488-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Lindsay Sarah McAlpine
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $231,524
- **Award type:** 1
- **Project period:** 2024-05-15 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10885595

## Citation

> US National Institutes of Health, RePORTER application 10885595, Magnetic Resonance Imaging Biomarkers of Post-COVID-19 Cerebral Microvascular Dysfunction (1K23NS133488-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10885595. Licensed CC0.

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