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

巴顿病是一种无法治疗的毁灭性神经系统疾病，其特征是严重的癫痫发作， 视力丧失、语言障碍和痴呆症。缺乏疾病的客观神经生物标志物 进展是为什么在开发针对Batten的有效疗法方面进展有限的一个原因， 其他遗传性神经系统疾病该应用程序将推进一种全新的方法来跟踪功能 进行性神经系统疾病的功能超声（fUS）和剪切波的结构变化 弹性成像（SWE）。通过大脑获取的结构和功能超声成像数据将提供 光学成像提供的单细胞特性与大规模功能组织之间的关键联系 功能性磁共振成像（fMRI）。这些多模态和多尺度数据将共同 补充了目前基于脑电图（EEG）的Batten病神经标志物，并提供了一个 更详细和全面地了解疾病进展期间大脑结构和功能的变化。 使用Batten病小鼠模型，我们将测量fUS对功能连接变化的敏感性， 大脑皮层和皮层下结构对各种感官刺激的反应。我们会进行 组织学分析以确认激活图的有效性。为了确定 大脑在疾病进展过程中的变化，并与不同的刺激，我们将进行研究，使用临床前 SWE系统评估Batten病小鼠模型中的结构和机械变化。这一阶段 在这个项目中，我们将开发先进的弹性成像技术，以可视化大脑形态的变化。这 令人兴奋的项目汇集了两位经验丰富的研究人员，Marvin Doyley博士，超声专家， 弹性成像，以及神经生物学和大脑遗传模型专家Kuan Hong Wang博士 建立用于研究进行性神经系统疾病的成像生物标志物， 疾病该项目将证明，使用新兴的超声成像技术来 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。

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.