Abstracts

Magnetic Resonance Imaging (MRI) is a non-invasive method often used for the assessment of patients with epilepsy. More than a quarter of patients who present with drug-resistant epilepsy due to cortical dysplasia (CD) show no MRI abnormalities. The role of differential expression of glutamate receptors as a substrate for hyperexcitability in epilepsy has been shown. We intended to develop a non-invasive and sensitive imaging technique to be used with specific biomarkers for epileptic tissue., Anti-NMDA receptor subunit 1 (NR1) antibody (Chemicon AB1516) was labeled with Gd-DOTA (NR1/Gd-DOTA) using an activated carboxyl to create an amide coupling. In a first study, [italic]ex vivo[/italic] human brain slice tissue was maintained alive immediately following surgical resection, and optimized T1-weighted MRI was acquired using a 9.4T MRI scanner. Following baseline MRI, each tissue was treated with NR1/Gd-DOTA or NR1 without Gd-DOTA for two hours and washed for one hour to remove non-specific binding. In a second study, MRI (7.0T) was acquired before and after [italic]ex vivo[/italic] live rat brain slices were treated with NR1/Gd-DOTA or control treatments (vehicle only, Gd-DOTA only or anti-NR1 only). Additional 3-hour washing followed by MRI was conducted in order to verify signal variation over time., The first study (Figure) demonstrated that optimized high-field MRI and antibody-based MRI probes can be used to non-invasively detect cell receptors within freshly resected brain tissue. The second study validated that MRI contrast was due to specific binding of the labeled antibody to cell receptors. Fading in the signal detected after additional washing revealed a temporal dependence on the amount of antibody probe bound to tissue slices., Our preliminary data show that NR1 protein can be detected in freshly harvested human and rat brain tissue samples using high field MRI techniques. The development and application of new antibody-based MRI probes that can be selectively detected and quantified will provide a new platform technology for visualizing molecular substrates of epileptogenic brain areas and other pathologies.[figure1], (Supported by Northeastern Ohio Animal Imaging Resource Center, an NIH funded program #R24CA110943, part of the Case Center for Imaging Research; and R21 NS42354 from NINDS to IN.)