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

巴滕病是一种毁灭性的神经疾病，其特征是严重的癫痫发作，目前尚无治疗方法。 视力丧失、语言障碍和痴呆症。缺乏客观的神经系统疾病生物标志物 进展是为什么在开发巴顿和巴顿的有效治疗方法方面进展有限的原因之一 其他遗传性神经疾病。这个应用程序将推进一种全新的方法来跟踪函数 功能超声(FUS)和剪切波在进行性神经功能障碍中的结构变化 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 由功能磁共振成像(FMRI)提供。总而言之，这些多模式和多尺度的数据将 补充目前基于脑电(EEG)的巴顿病神经标记物，并提供 更详细、更全面地了解疾病进展过程中大脑结构和功能的变化。 使用巴顿病小鼠模型，我们将测量FUS对功能连接性变化的敏感性 皮层和皮质下大脑结构对各种感官刺激的反应。我们将进行 组织学分析以确认激活图谱的有效性。要确定机械特性如何 在疾病进展和不同刺激下的大脑变化，我们将使用临床前研究 SWE系统评估巴顿病小鼠模型的结构和力学变化。在这一阶段 在这个项目中，我们将开发先进的弹性成像技术来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，马文·多伊利博士，超声波专家和 弹性成像，以及神经生物学和脑遗传模型专家王宽宏博士 疾病，建立成像生物标记物来研究进行性神经疾病，如巴顿 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 不同的治疗干预措施。

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.