Magnetic Resonance Elastography of the Brain

 描述(由申请人提供)：这项探索性提案的目标是验证磁共振弹性成像(MRE)作为一种方法的有效性，该方法提供关于神经病理进展的独特信息，更重要的是，提供它们对治疗的反应。我们的团队是世界上少数几个使用定制设置建立非侵入性小鼠脑MRE的团队之一，该设置具有该领域最高的空间分辨率和信噪比。我们假设，这种独特的结构信息(类似于非侵入性的颅内“触诊”)将使人们能够跟踪影响脑组织弹性的病理过程的变化，甚至在疾病进展期间检测具有不同物理特性的“隔室”的出现，这可能有助于对药物分布进行建模和定制治疗。我们建议研究两种神经病理学，它们在神经组织形态和物理性质上产生广泛的变化，但起源和时间进程截然不同。阿尔茨海默病(AD)将在AIM 1中进行研究。AD是一种毁灭性的疾病，估计影响着520万美国人，是一个巨大的公共卫生问题。这是一个神经病理学的例子，其中大脑僵硬可能会随着时间的推移而缓慢变化，原因是斑块沉积、蛋白质缠结的形成、缓慢的神经元死亡和血管变化。恶性脑瘤(胶质瘤)将在目标2中进行研究。这些快速生长的肿瘤是最常见的原发脑肿瘤，也是预后最差的癌症类型之一。胶质瘤是一个例子，由于肿瘤的生长和血管的增殖，局部僵硬的变化可以迅速预料到，并且僵硬的变化可以提供关于治疗和血管正常化的反应的信息。我们将使用MRE研究这两种疾病的时间进展，并将我们的放射学结果与明确定义的组织学特征和疾病组织中的分子标志物相关联，目的是建立MRE作为一种具有诊断价值的新的、高对比度的成像方法的价值。此外，在我们的胶质瘤模型中，我们将研究与常规化疗方法(细胞毒性和抗血管生成)导致的组织灌注(DCE-MRI)相比的弹性变化(MRE)，这也将与成像后的组织学和分子变化相关。这将使我们能够确定MRE与肿瘤治疗后预后随访的相关性。这些特定目标的成功实现将使我们能够展示MRE作为一种新型的脑成像手段，它可以补充MRI，提供关于这些和其他神经疾病的进展和治疗反应的更全面的信息。

 DESCRIPTION (provided by applicant): The goal of this exploratory proposal is to validate magnetic resonance elastography (MRE) as a method that provides unique information about the progression of neuropathologies and, importantly, their response to therapy. Our team is one of the few worldwide that has established non-invasive mouse brain MRE using a customized setup with the highest spatial resolution and signal to noise ratio in the field. We hypothesize that this unique structural information (akin to a non-invasive intracranial "palpation") will allow one to follow changes in pathological processes that affect brain tissue elasticity, and even detect the appearance of "compartments" with different physical properties during disease progression, which could help to model drug distribution and tailor therapies. We propose to study two neuropathologies that produce extensive changes in neural tissue morphology and physical properties, but with vastly different origins and time course. Alzheimer's disease (AD) will be studied in Aim 1. AD is a devastating disease affecting an estimated 5.2 million Americans and is an enormous public health issue. It is an example of a neuropathology in which brain stiffness may change slowly over time due to plaque deposition, formation of protein tangles, slow neuronal death and vascular changes. Malignant brain tumors (gliomas) will be studied in Aim 2. These fast growing tumors are the most common primary brain tumors and one of the types of cancer with the worst prognosis. Gliomas are an example where local changes in stiffness are rapidly expected due to tumor growth and vascular proliferation, and where changes in stiffness can provide information about response to therapy and vascular normalization. We will study the temporal progression of both diseases using MRE and will correlate our radiographic results with well-defined histological features and molecular markers in the diseased tissues, with the goal of establishing the value of MRE as a novel, high-contrast, imaging approach with diagnostic value. Moreover, in our glioma models we will study changes in elasticity (MRE) compared to tissue perfusion (DCE-MRI) resulting from conventional chemotherapeutic approaches (cytotoxic and anti-angiogenic), which will also be correlated with histological and molecular changes after imaging. This will allow us to establish the relevance of MRE for prognostic follow-up after tumor therapy. Successful achievement of these Specific Aims will allow us to demonstrate MRE as a novel brain imaging modality that can complement MRI to provide more comprehensive information about progression and response to therapy in these and other neural diseases.