Establishing Network Connectivity and Microvascular Imaging Biomarkers for Tuberous Sclerosis Complex
Abstract
Tuberous sclerosis complex (TSC) often results in regions in the brain where the tissue did not develop normally. These regions, known as tubers, can vary widely among patients in their number, size, and location. Often, the presence of these tubers results in seizures. However, some patients may have no seizures, some may have recurring seizures that can be controlled by drugs (known as drug-sensitive epilepsy), and some have recurring seizures that do not respond to drugs (known as drug-resistant epilepsy). TSC and associated seizures can also lead to cognitive impairment. Though the severity of TSC symptoms appears to increase with the number of tubers (tuber burden), there is no clear association with the type of epilepsy experienced by the patient. When epilepsy resulting from TSC is drug-resistant, surgery to remove seizure generating tissue may be pursued for treatment. The challenge for TSC surgical treatment is that often a patient will have multiple spatially scattered tubers. Currently, techniques to target tubers likely to cause seizures are highly invasive, requiring electrodes to be inserted directly into brain tissue. Given this background, there is clear need for tuber characterization that can identify, track, and potentially predict epilepsy symptoms, drug resistance, and cognitive effects. Ultimately, treatment of seizures would benefit from a noninvasive and reliable method to identify tubers likely to be seizure sources. This project will address these needs by considering not just the number and location of tubers, but how the presence of those tubers might disrupt how the brain is connected. The brain is intrinsically comprised of networks of interconnected regions that drive behavior and cognition. The way a set of tubers might influence normal networks may relate to TSC symptoms. Going further, we consider in a complementary way how the vasculature of tuber tissue might implicate individual tubers as the driver of symptoms. We will apply advanced imaging techniques to extract functional network connectivity features of tubers as well as the density of microvasculature in individual tubers. We will use these measurements to determine the type of epilepsy in patients and to track any changes in epilepsy type over time. Finally, we will lay the groundwork for using our imaging measures to identify tubers that need to be removed in order to treat TSC patients with drug-resistant epilepsy. These approaches address two stated Focus Areas for TSC. First, the tuber connectivity and microvascular characterizations can improve epilepsy treatment by providing predictors for epilepsy type and laying the foundation for noninvasively targeting tubers for removal, allowing for earlier intervention, decreasing exposure to seizures, and improving cognitive outcomes. Second, these tuber features may also track and predict changes in cognitive status of TSC patients, enabling earlier and more targeted interventions. This project will in the short term provide tuber markers to identify, track, and possibly predict epilepsy symptoms in TSC patients even when they have many tubers. Longer term, after larger studies of patients undergoing epilepsy surgery, we may form the basis for noninvasively labeling tubers as seizure-generating or not.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210633
Entities
People
- Mark DiFrancesco
Organizations
- United States Army