High-resolution multi-modal ultrasound imaging of brain development in Batten disease models

巴顿病模型中大脑发育的高分辨率多模态超声成像

基本信息

批准号：
10429881
负责人：
Marvin M Doyley
金额：
$ 22.98万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-07 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10429881
关键词：
Address Affect Age Animal Experimentation Animal Model Animals Auditory Evoked Potentials Auditory Perception Axon Biological Biological Markers Blindness Blood flow Brain Brain Diseases Brain imaging Cells Clinical Complement Coupling Data Dementia Demyelinations Development Disease Progression Disease model Effectiveness Electroencephalography Electrophysiology (science)Event Foundations Frequencies Functional Magnetic Resonance Imaging Genetic Models Goals Gold Growth Histologic Human Image Imaging Techniques Imaging technology Inherited Intellectual and Developmental Disabilities Research Centers Language Disorders Link Maps Measurement Measures Mechanics Microscopy Modulus Mus Mutation Nerve Degeneration Neurobiology Neurologic Neuromechanics Neurons Neuropil Neurosciences Research Optics Other Genetics Pathologic Pathway interactions Penetration Phase Primates Property Research Personnel Research Project Grants Resolution Resources Seizures Sensory Signal Transduction Spielmeyer-Vogt Disease Stimulus Structure Symptoms System Techniques Technology Testing Therapeutic Intervention Thinness Time Tissues Translating Translations Ultrasonography Universities Work attenuation auditory processing auditory stimulus base brain morphology cranium early childhood effective therapy elastography experience gene therapy gray matter imaging biomarker imaging system improved laboratory experience mechanical properties millisecond mouse model multimodality multiscale data myelination nervous system disorder neuroimaging neurovascular neurovascular coupling new technology novel strategies optical imaging pre-clinical real-time images relating to nervous system response routine practice sensory stimulus spatiotemporal targeted treatment temporal measurement tool ultrasound

项目摘要

Batten disease, which has no treatment, is a devastating neurological disorder characterized by severe seizures, loss of vision, language disabilities, and dementia. The absence of objective neurologic biomarkers of disease progression is one reason why there has been limited progress in developing effective therapies for Batten and other genetic neurological disorders. This application will advance a radically new approach to track functional and structural changes in progressive neurologic disorders by using functional ultrasound (fUS) and shear wave elastography (SWE). The structural and functional ultrasound imaging data acquired across the brain will provide a critical link between single-cell properties afforded by optical imaging and large-scale functional organization afforded by functional magnetic resonance imaging (fMRI). Together, these multi-modal and multi-scale data will complement the current electroencephalography (EEG)-based neuromarkers of Batten disease and provide a more detailed and comprehensive view of brain structural and functional changes during disease progression. Using a Batten disease mouse model, we will measure fUS sensitivity to changes in the functional connectivity between cortical and subcortical brain structures in response to various sensory stimuli. We will conduct histological analysis to confirm the validity of the activation maps. To determine how mechanical properties of the brain change during disease progression and with different stimuli, we will perform studies using a preclinical SWE system to assess structural and mechanical changes in Batten disease mouse models. In this phase of the project, we will develop advanced elastography techniques to visualize changes in brain morphology. This exciting project brings together two experienced researchers, Dr. Marvin Doyley, an expert in ultrasound and elastography imaging, and Dr. Kuan Hong Wang, an expert in neurobiology and genetic models of brain disorders, to establish imaging biomarkers for studying progressive neurological disorders such as Batten disease. This project will demonstrate that it is feasible to use emerging ultrasound imaging techniques to understand the pathological changes in progressive neurologic disorders and facilitate testing and translation of different therapeutic interventions.

没有治疗的巴顿疾病是一种毁灭性的神经系统疾病，其特征是严重癫痫发作，视力丧失，语言残疾和痴呆症。缺乏客观的疾病神经生物标志物进展是为什么开发有效疗法的进展有限的原因之一其他遗传神经系统疾病。该应用程序将推进一种完全新的方法来跟踪功能通过使用功能超声（FUS）和剪切波进行进行性神经系统疾病的结构变化弹性图（SWE）。整个大脑中获得的结构和功能性超声成像数据将提供光学成像和大规模功能组织提供的单细胞特性之间的关键联系功能磁共振成像（fMRI）提供。这些多模式和多尺度数据将在一起补充当前的脑电脑术（EEG）基于BATTEN疾病的神经标志物，并提供疾病进展过程中大脑结构和功能变化的更详细，更全面的看法。使用板条疾病小鼠模型，我们将测量对功能连通性变化的FUS敏感性响应各种感觉刺激的皮质和皮质下脑结构之间。我们将进行组织学分析以确认激活图的有效性。确定如何机械性能疾病进展过程中的大脑变化和不同的刺激，我们将使用临床前进行研究 SWE系统评估Batten病小鼠模型中的结构和机械变化。在这个阶段该项目，我们将开发先进的弹性技术来可视化脑形态的变化。这激动人心的项目汇集了两名经验丰富的研究人员，超声波专家Marvin Doyley博士弹性成像和神经生物学和大脑遗传模型的专家Kuan Hong Wang博士疾病，建立成像生物标志物，用于研究诸如Batten之类的进行性神经系统疾病疾病。该项目将证明使用新兴的超声成像技术是可行的了解进行性神经系统疾病的病理变化，并促进测试和翻译不同的治疗干预措施。