Illuminating Brain Diseases Using Smart Multiread-out MRI

使用智能多重读出 MRI 阐明脑部疾病

• 批准号: MR/X034046/1
• 负责人: Peter Harvey
• 金额: $ 226.67万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX034046%2F1
• 关键词: Illuminating; Brain; Diseases; Using; Smart

The brain is a black-box when it comes to understanding disease. It is full of crucial details that could give untold information on how to treat and manage neurological diseases and disorders, but we lack the tools to effectively read those details. While imaging technologies give us a window to observe certain processes, they are often extremely limited. A good example is magnetic resonance imaging (MRI), which has led to countless breakthroughs in the clinic and is used to diagnose and manage patients every day. It is, however, typically limited to a single channel - essentially, we are looking at the brain in black and white instead of colour. This limitation is particularly true when looking at chemical and biological properties of the brain. There are some techniques that begin to allow imaging of multiple signals (i.e. colours), but they are limited to substances present at very high abundances within the brain. A classic example where this would be relevant is in Alzheimer's disease. There is a well-established relationship between the devastating neurodegeneration observed and brain's natural defence system. This co-occurring condition, neuroinflammation, is linked to the long-term deterioration seen in patients, but we struggle to fully understand how they are connected and how they interplay. Much like the classic chicken and egg conundrum, we are often unsure on which comes first or how that comes to be. If we could simultaneously watch how these different processes work at the same time in a living brain, we would significantly improve our understanding and be able to monitor the effects of treatments and interventions more closely. This scenario is not just limited to Alzheimer's disease, but in almost every neurological disease we can think of. Every neurodegenerative disease, brain tumours, stroke, and even mental health issues would all benefit from an improved understanding of the real-time interplay of various biological systems all working - or, more importantly, failing to work - together. I have developed a technique that greatly expands the range and sensitivity of multi-signal MRI by using carefully designed contrast agents in a process called PARASHIFT MRI. This approach allows much lower levels of compounds to be detected in the living brain with multiple readouts available. We have previously demonstrated its approach in the body, and I now aim to focus on applying the technique to study markers of brain disease in much more detail than we are currently able. This pioneering MRI technique will be supplemented by complementary cutting-edge techniques, such as mass spectrometry imaging, to further understand the brain in unprecedented depth. I will focus on stroke and brain cancer as exemplar model systems in the initial stage of my fellowship as they represent clinically vital examples of both acute and chronic inflammation, respectively. Beyond, the findings from my work will have key applications in neurodegenerative disease and across a broad spectrum of neurological disorders. By combining these new tools for comprehensively detecting, characterising, and monitoring brain disease markers, my approach will reimagine how we look at the diseased brain and retrieve untold levels of information to help us tackle this pressing societal burden.

在理解疾病方面，大脑是一个黑匣子。它充满了关键的细节，可以提供关于如何治疗和管理神经系统疾病和障碍的未知信息，但我们缺乏有效阅读这些细节的工具。虽然成像技术为我们提供了观察某些过程的窗口，但它们通常非常有限。一个很好的例子是磁共振成像（MRI），它在临床上带来了无数的突破，每天都被用来诊断和管理病人。然而，它通常仅限于一个单一的通道-本质上，我们是在黑色和白色，而不是彩色看大脑。这种局限性在研究大脑的化学和生物学特性时尤为明显。有一些技术开始允许对多种信号（即颜色）进行成像，但它们仅限于大脑内以非常高的丰度存在的物质。一个典型的例子是阿尔茨海默病。在观察到的破坏性神经变性和大脑的自然防御系统之间有一个明确的关系。这种共同发生的疾病，神经炎症，与患者的长期恶化有关，但我们很难完全理解它们是如何联系在一起的，以及它们是如何相互作用的。就像经典的鸡和蛋的难题一样，我们经常不确定哪个先来，或者是如何来的。如果我们能够同时观察这些不同的过程是如何在活体大脑中同时工作的，我们将大大提高我们的理解，并能够更密切地监测治疗和干预的效果。这种情况不仅限于阿尔茨海默病，而且几乎在我们能想到的所有神经系统疾病中。每一种神经退行性疾病，脑肿瘤，中风，甚至心理健康问题都将受益于对各种生物系统实时相互作用的更好理解，这些生物系统都在一起工作，或者更重要的是，不能一起工作。我开发了一种技术，通过在称为PARASHIFT MRI的过程中使用精心设计的造影剂，极大地扩展了多信号MRI的范围和灵敏度。这种方法允许在活体大脑中检测到更低水平的化合物，并提供多个读数。我们之前已经在体内证明了它的方法，我现在的目标是专注于应用这项技术来研究大脑疾病的标记物，比我们目前所能做的更详细。这种开创性的MRI技术将得到互补的尖端技术的补充，例如质谱成像，以进一步以前所未有的深度了解大脑。我将专注于中风和脑癌作为我研究的初始阶段的示范模型系统，因为它们分别代表了急性和慢性炎症的临床重要例子。除此之外，我的研究结果将在神经退行性疾病和广泛的神经系统疾病中具有关键应用。通过结合这些新工具来全面检测，表征和监测大脑疾病标志物，我的方法将重新想象我们如何看待患病的大脑，并检索未知的信息水平，以帮助我们解决这一紧迫的社会负担。