Integrating quantitative positron emission tomography (PET) and magnetic resonance imaging (MRI) to measure neuroinflammation

我们正在建立非侵入性成像方法，可以监测与身体对毒素、感染和损伤(也称为神经炎症)的免疫反应相关的大脑活动和结构的变化。神经炎症的主要特征包括：1)常驻神经炎性细胞(称为小胶质细胞)的激活，2)保护大脑免受血液中毒素影响的屏障(称为血脑屏障或BBB)的破坏，3)外周血白细胞的渗透，以及4)神经炎症的后果，包括大脑化学和结构的变化。激活的小胶质细胞可能是有益的，可以维持健康的脑细胞，清除不想要的入侵者，但长期的神经炎症会降低大脑健康，通常先于脑组织损伤和各种疾病的认知症状，包括自身免疫性疾病、精神障碍、中风和痴呆症。正因为如此，及早发现和治疗神经炎症将有利于加拿大人的长期大脑健康。为了对神经炎症及其后果进行更全面的评估，需要结合多种非侵入性成像方法的信息。这可以通过两种互补的成像技术来实现：磁共振成像(MRI)和正电子发射断层扫描(PET)。通过核磁共振成像，我们将检测对不同组织特征敏感的神经炎性细胞，在神经炎症期间过度表达的神经递质化学物质，以及血脑屏障的分解。有了PET，我们可以注射微量的放射性标记药物，直接针对激活的小胶质细胞和突触密度(大脑健康的标志)。NSERC发现基金的主要目标将是开发和验证结合PET和MRI测量神经炎症及其后果的方法。这些方法将使用男性和女性的神经炎症临床前模型和黄金标准组织分析进行验证，目标是开发一个使用同步PET/MRI评估神经炎症的综合成像平台。这项研究计划将为1)改善对大脑在健康和疾病中的理解，以及2)测试可能减缓或阻止疾病进展的治疗干预措施奠定基础。重要的是，拟议的成像研究计划和未来使用劳森健康研究所的临床PET/MRI进行的人脑疾病研究之间有一条明确的路径。一个全面的神经炎症成像平台将使脑部疾病患者的诊断检查和治疗更加成功，减少重复就诊的需要，提高诊断效率。反过来，这将为所有加拿大人带来可观的经济和社会利益。

We are building non-invasive imaging methods that can monitor changes in the activity and structure of the brain related to the body's immune response to toxins, infections, and injury (also known as neuroinflammation). Key features of neuroinflammation include: 1) activation of resident neuroinflammatory cells (known as microglia), 2) breakdown of the barrier that protects the brain from toxins in the blood (known as the blood-brain barrier or BBB) 3) infiltration of peripheral white blood cells, and 4) consequences of neuroinflammation, including changes in brain chemistry and structure. Activated microglia can be beneficial, maintaining healthy brain cells and removing unwanted invaders, but prolonged neuroinflammation can diminish brain health, often preceding brain tissue damage and cognitive symptoms in a wide variety of disorders, including autoimmune diseases, psychiatric disorders, stroke, and dementia. Because of this, early detection and treatment of neuroinflammation would be beneficial for the long-term brain health of Canadians. In order to get a more complete assessment of neuroinflammation and its consequences, approaches that combine information from multiple non-invasive imaging methods are needed. This can be accomplished with two complementary imaging technologies: magnetic resonance imaging (MRI) and positron emission tomography (PET). With MRI, we will detect neuroinflammatory cells with measurements sensitive to different tissue features, neurotransmitter chemicals that get overexpressed during neuroinflammation, and breakdown of the BBB. With PET, we can inject minute amounts of radiolabeled drugs that directly target activated microglia and synaptic density (a marker of brain health). The primary objective of this NSERC Discovery Grant will be to develop and validate methods that combine PET and MRI measures of neuroinflammation and its consequences. These methods will be validated using male and female preclinical models of neuroinflammation and gold standard tissue analysis, with the goal of developing a comprehensive imaging platform for assessing neuroinflammation using simultaneous PET/MRI. This research program will lay the groundwork for 1) improved understanding of the brain in health and disease and 2) testing therapeutic interventions that may slow or halt disease progression. Importantly, there is a clear path between the proposed imaging research program and future studies in human brain disease using the clinical PET/MRI at the Lawson Health Research Institute. A holistic neuroinflammation imaging platform will lead to more successful diagnostic exams and treatments in patients with brain disease, reducing the need for repeat visits and improving diagnostic efficacy. This, in turn, will have a substantial economic and societal benefit for all Canadians.