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Localizing epileptic networks using novel 7T MRI glutamate imaging

使用新型 7T MRI 谷氨酸成像定位癫痫网络

基本信息

批准号：
9894851
负责人：
Kathryn Adamiak Davis
金额：
$ 19.73万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9894851
关键词：
Affect American Astrocytes Autopsy Bilateral Biological Markers Brain Brain Mapping Brain region Chemicals Clinical Cortical Dysplasia Data Development Devices Disease Down-Regulation Electroencephalography Epilepsy Epileptogenesis Equilibrium Excision Extratemporal Epilepsy Faculty Freedom Functional disorder Generations Glutamate-Ammonia Ligase Glutamates Glutamine Goals Hippocampus (Brain)Human Image Image Analysis Imaging Techniques Impairment Intractable Epilepsy Knowledge Lesion Lobectomy Location Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Maps Measurement Measures Medical Mentors Metabolic Methods Microdialysis Morbidity - disease rate Multimodal Imaging Neurology Neurotransmitters Operative Surgical Procedures Outcome Partial Epilepsies Patient-Focused Outcomes Patients Pennsylvania Pharmaceutical Preparations Refractory Research Research Personnel Research Training Resistance Resolution Role Scientist Sclerosis Seizures Techniques Temporal Lobe Temporal Lobe Epilepsy Testing Time Tissues Training Translating Translational Research Universities Work animal data base care costs career development clinical imaging cohort design experience extracellular gamma-Aminobutyric Acid human data imaging biomarker imaging modality improved improved outcome interest neocortical nervous system disorder neuroimaging neuroimaging marker new technology novel patient population professor programs public health relevance senior faculty success surgery outcome treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Epilepsy affects 65 million people worldwide, one-third of who have seizures that cannot be controlled by medications. Localizing where seizures are generated in the brain can dramatically improve outcome from epilepsy surgery and anti-seizure devices in these patients. Unfortunately current clinical imaging techniques are unable to identify the seizure-generating region in approximately one-third of patients with localization related epilepsy. This proposal applies a novel 7T MRI technique, GluCEST, which images the excitatory neurotransmitter glutamate at high resolution, to localize epileptic networks. Glutamate is widely believed to be central to seizure-generation, and preliminary data indicates that this technique can identify seizure generating regions in patients not-localized by other techniques. GluCEST will be obtained in large cohort patients with lesion and nonlesional epilepsy and in control subjects. Magnetic resonance spectroscopy will be used to validate GluCEST derived glutamate measures and to investigate excitatory/ inhibitory mismatch thought to be present in epileptogenic regions. We expect to demonstrate that GluCEST can identify the epileptic network in patients with temporal lobe and neocortical epilepsies both with and without lesions present on current clinical imaging. The proposed work will produce novel scientific results with the potential to improve treatment for medication-resistant epilepsy, advance our knowledge of its underlying mechanisms, and to be quickly translated to the bedside. GluCEST has the potential to improve accuracy and outcome from epilepsy surgery, and to become a valuable biomarker for assessing novel treatment strategies. Equally important, the proposed project is designed to provide critical career development training to the candidate, an Assistant Professor of Neurology in the Epilepsy Division at the University of Pennsylvania. The proposal builds upon the candidate's established interest in multimodality imaging in epilepsy and her prior training in translational research. The candidate will be mentored by an experienced interdisciplinary team of senior faculty, led by: (1) primary mentor Dr. John Detre, a world renowned expert in neuroimaging who has been critical to development of the novel technique utilized in this work, (2) Dr. Brian Litt, an established investigator with tremendous experience i clinical epilepsy, developing new technologies to localize epileptic networks, epilepsy surgery and implantable brain devices, and (3) Dr. Ravinder Reddy, an established investigator expert in multinuclear magnetic resonance imaging and spectroscopic techniques. These faculty, together with Dr. Davis's other mentors, will assure that the research and training experience proposed in this submission will enable her to establish an independent research program as a clinician-scientist developing and applying multimodality imaging techniques to investigate epilepsy.

描述（由申请人提供）：癫痫影响全球6500万人，其中三分之一的癫痫发作无法通过药物控制。定位癫痫发作在大脑中产生的位置可以显着改善这些患者的癫痫手术和抗癫痫装置的结果。不幸的是，目前的临床成像技术无法识别大约三分之一的癫痫患者的癫痫发生区域。该建议应用了一种新的7 T MRI技术，GluCEST，它以高分辨率成像兴奋性神经递质谷氨酸，以定位癫痫网络。谷氨酸被广泛认为是神经元生成的核心，初步数据表明，该技术可以识别其他技术无法定位的患者癫痫发作发生区域。GluCEST将在大队列病变性和非病变性癫痫患者以及对照受试者中获得。磁共振波谱将用于验证GluCEST衍生的谷氨酸测量，并研究认为存在于致癫痫区域的兴奋性/抑制性失配。我们希望证明GluCEST可以识别颞叶和新皮质癫痫患者的癫痫网络，无论是否存在当前临床成像上的病变。拟议的工作将产生新的科学成果，有可能改善耐药性癫痫的治疗，提高我们对其潜在机制的认识，并迅速转化为临床应用。GluCEST有可能提高癫痫手术的准确性和结果，并成为评估新治疗策略的有价值的生物标志物。同样重要的是，拟议的项目旨在为候选人提供关键的职业发展培训，宾夕法尼亚大学癫痫科神经病学助理教授。该提案建立在候选人对癫痫多模态成像的既定兴趣以及她之前在转化研究方面的培训基础上。候选人将由资深教师组成的经验丰富的跨学科团队指导，由以下人员领导：（1）主要导师John Detre博士，世界著名的神经影像学专家，他对这项工作中使用的新技术的开发至关重要，（2）Brian Litt博士，一位在临床癫痫方面具有丰富经验的知名研究者，开发新技术来定位癫痫网络，癫痫手术和植入式大脑设备，以及（3）Ravinder Reddy博士，多核磁共振成像和光谱技术方面的既定研究专家。Davis的其他导师，将确保本提交文件中提出的研究和培训经验将使她能够建立一个独立的研究计划，作为临床科学家开发和应用多模态成像技术来研究癫痫。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Patterns of seizure spread in temporal lobe epilepsy are associated with distinct white matter tracts.

DOI：
10.1016/j.eplepsyres.2021.106571
发表时间：
2021-03
期刊：
Epilepsy research
影响因子：
2.2
作者：
Gleichgerrcht E;Greenblatt AS;Kellermann TS;Rowland N;Vandergrift WA;Edwards J;Davis KA;Bonilha L
通讯作者：
Bonilha L

Epilepsy Lesion Localization is not Predicted by Developmental Venous Anomaly Location or its FDG-PET Metabolic Activity.

DOI：
10.1111/jon.12722
发表时间：
2020-07
期刊：
Journal of neuroimaging : official journal of the American Society of Neuroimaging
影响因子：
0
作者：
Lazor JW;Stein JM;Schmitt JE;Davis KA;Nabavizadeh SA
通讯作者：
Nabavizadeh SA

Developing and Implementing a Standardized Ictal Examination in the Epilepsy Monitoring Unit.

在癫痫监测部门制定和实施标准化发作检查。

DOI：
10.1212/cpj.0000000000000815
发表时间：
2021
期刊：
Neurology. Clinical practice
影响因子：
0
作者：
O'Kula,SusannaS;Faillace,Lisa;Kulick-Soper,CatherineV;Reyes-Esteves,Sahily;Raab,Jackie;Davis,KathrynA;Kheder,Ammar;Hill,ChloeE
通讯作者：
Hill,ChloeE

Multimodal in vivo recording using transparent graphene microelectrodes illuminates spatiotemporal seizure dynamics at the microscale.

DOI：
10.1038/s42003-021-01670-9
发表时间：
2021-01-29
期刊：
Communications biology
影响因子：
5.9
作者：
Driscoll N;Rosch RE;Murphy BB;Ashourvan A;Vishnubhotla R;Dickens OO;Johnson ATC;Davis KA;Litt B;Bassett DS;Takano H;Vitale F
通讯作者：
Vitale F

Unilateral thalamic lesion mimicking genetic generalized epilepsy.