Methods for ultrasensitive and quantitative multimodal molecular imaging of vascular inflammation

神经退行性疾病和痴呆症影响着近40%的65岁及以上的加拿大人，到2030年，超过90万加拿大人(65%是女性)可能患有某种形式的痴呆症。炎症是神经退行性疾病的主要因素，但在体内获得有关炎症的信息是困难的。拟议研究计划的总体目标是设计、表征和验证用于超灵敏检测和量化脑血管炎症的新的显像剂和方法。这些制剂将包括微米级的氧化铁颗粒以及免疫脂质体，这些脂质体可以特异性地靶向发炎的脑血管系统，并可通过磁共振成像进行检测。该计划分为两个短期目标。第一个目标是在相关细胞系和小动物模型中准备、优化和测试新的药物。第二个目标是开发能够通过成像在体内定量这些药物的方法。对于更大的社区来说，改进炎症靶向制剂将降低这些制剂的成本和可变性。它们在体内的定量将有助于更好地了解炎症在几种疾病中的作用。最后，我们项目的成功可以将本文开发的技术转移到临床使用，包括使用成像监测治疗干预/交付。该计划将在一个竞争激烈的成像中心培训研究生，该中心拥有成像试剂临床翻译的历史。除了他们将获得的严谨的工作和科学道德之外，受训者还将在一个真正跨学科的环境中发展他们的创造力，积极促进平等、多样性和包容性。

Neurodegenerative diseases and dementia affect almost 40% of Canadians aged 65 and above, and over 900,000 Canadians (65% women) could be living with a form of dementia by 2030. Inflammation is as a major contributor to neurodegenerative diseases but gaining information on inflammation in vivo is difficult. The overall goal of the proposed research program is to design, characterize and validate novel imaging agents and methods for the ultrasensitive detection and quantification of cerebrovascular inflammation. These agents will include micron-sized particles of iron oxide as well as immunoliposomes that can specifically target inflamed brain vasculature and be detected by magnetic resonance imaging. The program is divided into two short-term goals. The first goal is to prepare, optimize and test the new agents in relevant cell lines and in small animal models. The second goal is to develop methodologies to enable quantitation of these agents in vivo by imaging. For the larger community, improving inflammation-targeted agents will reduce the cost and variability of these agents. Their in vivo quantification would help understand much better the role of inflammation in several diseases. Finally, success of our program could enable the transfer of the technologies developed herein towards clinical use, including for monitoring therapeutic interventions/delivery using imaging. The program will train graduate students in a highly competitive imaging centre with an history of clinical translation of imaging agents. Beyond the rigorous work and science ethics that they will acquire, trainees will develop their creativity in a truly interdisciplinary environment actively promoting equality, diversity and inclusion.