Your Donations in Action: Ali Mian, MD

Researchers have used PET imaging agents to target the synaptic vesicle glycoprotein 2A (SV2A), which is an effective surrogate for synaptic density and has potential as a biomarker in multiple neurologic conditions. However, SV2A is decreased in human epilepsy patients. Since SV2A is so ubiquitously expressed within synapses, its role in seizure development, progression and treatment remains unclear, but is being explored in vivo using animal models.

The glutamine synthetase inhibition (GSI) model of epilepsy in rats is ideal for distinguishing synaptic density loss, in general, from loss of SV2A specifically. After 72 hours of GSI, for unclear reasons, only about half of rats develop spontaneous seizures, thereby modeling early epileptogenesis, the gradual process by which a normal brain develops epilepsy.

In his 2017 RSNA Fellow Research Grant, Ali Mian, MD, looked at the density of SV2A in the methionine sulfoximine (MSO) model of epilepsy in rats. He undertook the study at Yale University School of Medicine where he and his colleagues compared SV2A binding in epileptic and wildtype rats. The research relied on a state-of-the-art animal PET scanner at the Yale PET Center, and the animals were scanned following entorhinal infusion of MSO. The model parameters were optimized to simulate early epileptogenesis. The team used the novel PET radiotracer 11C-UCB-J, developed for its favorable kinetics, high synaptic uptake and ready displacement by Levetiracetam. Dr. Mian hopes 11C-UCB-J PET will serve as a biomarker for epileptogenesis.

“The RSNA Research Fellow Grant has been a great career-building tool,” Dr. Mian said. “Perfectly situated between radiology education and academic scholarship, enabled by the R&E Foundation’s generous support, this grant helps radiology trainees learn to be effective researchers.”

“Our project gave rise to valuable collaboration among departments and forged durable connections still persisting to this day. In particular, this work bridged the departments of Laboratory Medicine under Tore Eid, MD, PhD, Radiology and Biomedical Imaging under MingKai Chen, MD, PhD, and William Zucconi, DO, and the Yale PET Center under internationally recognized PET researcher Richard Carson, PhD. This cross-pollination has led to new and unexpected avenues of research.”

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