MR spectroscopic imaging to detect the development of latent epilepsy

描述（由申请人提供）：磁共振光谱成像（MRSI）已被许多研究小组开发并用于定位人类癫痫的损伤和发作区域。其成功的本质是即使在没有组织体积损失的情况下也会发现代谢功能障碍，例如，在mri阴性的颞叶癫痫病例中已经显示出来。虽然这种成功的检测对癫痫的后续靶向治疗和手术治疗是有用的，但人们已经认识到，如果早期检测是可行和准确的，癫痫的治疗可以得到实质性的改变和改善。从人类和动物模型的经验来看，获得性癫痫的病理生理是由脑损伤（例如，相当常见的发热或发热性癫痫发作、头部创伤或感染）引发的，随后是在明显的自发性复发性癫痫发作（“SRS”）即癫痫发作之前的一段潜伏期。如果能够早期发现，有几种强有力的潜在治疗方法可能会降低发生临床癫痫的可能性

DESCRIPTION (provided by applicant): Magnetic resonance spectroscopic imaging (MRSI) has been developed and used by many groups to localize the regions of injury and seizure onset in human epilepsy. Intrinsic to its success is the common finding of metabolic dysfunction even in the absence of tissue volume loss, e.g., as has been shown in MRI-negative cases of temporal lobe epilepsy. Although this successful detection is useful for subsequent targeted and surgical management of epilepsy, it has been recognized that the treatment of epilepsy could be substantively changed and improved if early detection were feasible and accurate. From both human and animal model experience, the pathophysiology of acquired epilepsy is initiated by a cerebral insult (e.g., the fairly common event of fever-induced or febrile seizures, head trauma or infection), followed by a latent period that precedes the onset of overt spontaneous recurrent seizures ("SRS"), i.e., epilepsy. If early detection were available, there are several strong potential therapeutics that might decrease the likelihood of developing clinical epilepsy (distinct from therapy that simply decreases the likelihood of seizures), e.g., erythropoietin, anti-inflammatory compounds, anti- oxidants. In this study we examine whether MRSI can detect incipient epilepsy during this latent period. We do this using the rat perforant path stimulation (PPS) model, which replicates many of the defining features of acquired human medial temporal lobe epilepsy. Importantly this model does not show widespread brain injury commonly seen in chemoconvulsant models. Our preliminary brain extract data from this 24hour PPS model show that by 4days after initial insult, substantial changes in myo-inositol, glutamine, GABA and N-acetyl aspartate are seen. In this project, we will test the ability of in vivo MRSI to detect 4 das after the stimulation injury the level of injury and the development of incipient epilepsy using a severe and mild version of the PPS model. This will be done in a blinded fashion. As all animals will also be video and EEG monitored, we will also be able to test the ability of the MRSI to identify those animals who go on to develop overt recurrent seizures.