Molecular imaging of neurodegenerative pathology using deuterium MRI (MINDER)

问题：阿尔茨海默病是导致痴呆症的主要原因，痴呆症是一种影响老年人记忆力的疾病。目前阿尔茨海默病的临床诊断是由医生进行的，通常是问病人一系列关于他们日常经历的问题，并要求他们进行记忆测试。这些专家的临床评估有30%是错误的。在研究环境中，使用正电子发射断层扫描（PET）可以做出更准确的诊断。这些扫描使用特殊的染料来突出受疾病影响的大脑部分。不幸的是，PET扫描由于其高成本和有限的可用性而没有在常规临床应用。当新药问世时，至关重要的是要有广泛可用的工具来准确诊断患者是否患有阿尔茨海默病，并监测药物的效果。建议的解决方案：在这个项目中，我们将对现有的PET染料进行改造，使其可以用于磁共振成像（MRI）扫描。核磁共振成像比PET应用更广泛。我们将使用一种称为氘化的过程来改造PET染料，该过程涉及使用化学方法将染料中的氢原子替换为氘原子。由于活体组织只含有非常少量的氘，这将使MRI扫描仪更容易检测出患者是否患有阿尔茨海默病。方法：我们将通过一系列实验来测试我们新的“核磁共振兼容”染料，首先在高度控制的环境中（含有染料和其他已知成分的试管），然后在模拟阿尔茨海默病的活的转基因小鼠中。我们将花时间确保我们的MRI扫描尽可能高效，然后将我们提出的方法与PET扫描进行比较。好处：该方法如果成功，将为医生提供在任何医院准确诊断阿尔茨海默病的工具。

Problem: Alzheimer's disease is the main cause of dementia, a disease that affects the memory of older people. Current clinical diagnosis of Alzheimer's disease is performed by a doctor, usually by asking the patient a set of questions about their day-to-day experiences and asking them to undertake a memory test. These expert clinical assessments are wrong 30% of the time. In a research environment, it is possible to make a more accurate diagnosis using a positron emission tomography (PET) scan. These scans use special dyes that highlight parts of the brain affected by the disease. Unfortunately, PET scans are not in routine clinical use because of their high cost and limited availability. When new drugs become available, it will be vital to have widely accessible tools that can accurately diagnose whether a patient has Alzheimer's disease or not and to monitor how well the drug is working.Proposed solution: In the project we will adapt existing PET dyes so that they can be used within an magnetic resonance imaging (MRI) scan. MRI is far more widely available than PET. We will adapt the PET dye using a process called deuteration which involves using chemistry to replace hydrogen atoms within the dye with deuterium atoms. Since living tissue contains only very small amounts of deuterium, this will make it much easier for the MRI scanner to detect if the patient has Alzheimer's disease or not. Approach: We will test our new 'MRI compatible' dye using a series of experiments, first in a highly controlled environment (test tubes containing the dye and other known ingredients), then in alive genetically modified mice that mimic Alzheimer's disease. We will spend time ensuring our MRI scans are as efficient as possible, and then compare our proposed approach to PET scanning.Benefits: The approach, if successful, will provide doctors with the tools to accurately diagnose Alzheimer's disease in any hospital.