Automated microfluidic hyperpolarization reactor for neurometabolic imaging

摘要 大脑功能受分子信号和新陈代谢的调节，然而，我们追踪神经代谢的能力 与神经代谢的中心作用相比，大脑深处的转换非常不发达 神经退行性疾病或一般的脑功能。在此第一阶段SBIR中，我们的目标是建立和完善 新兴的超极化技术是一种廉价、坚固和可靠的神经代谢成像工具 可以广泛传播和应用。 目前的分子成像方法，例如PET/SPECT，需要巨大的基础设施和 都不是广泛适用的。在这项提案中，我们将生产、测试和改进两个超极化装置，以允许 用于在任何研究机构以低成本进行分子成像。具体地说，超极化器提供了安全的、可注射的 携带超极化核自旋的内源性代谢物的溶液，使用任何MRI都能检测到 系统。超极化将MRI信号增强4到7个数量级，并直接报告 研究对象中的分子转化。因此，直接成像活体中的分子路径 已启用。 这项提议的目的是使现有的超极化器原型坚固耐用。 同时，我们的目标是在临床前地点进行试点安装，以测试原型的集成能力 临床前工作流程。成功完成这一阶段的SBIR后，我们将拥有一个坚固且易于使用的 超极化器，使神经科学研究社区能够访问超极化核磁共振，并使 疾病早期代谢紊乱的非侵入性成像。反过来，老牌的 设备和工作流程导致对分子病理学的新见解和对新技术的临床前测试 干预措施和药物。

Abstract Brain function is regulated by molecular signaling and metabolism, however, our ability to track neurometabolic transformations deep in the brain is very underdeveloped compared to the central role of neurometabolism in neurodegenerative disease or brain function in general. In this Phase I SBIR, it is our goal to establish and refine emergent hyperpolarization technology as an inexpensive, sturdy and reliable neurometabolic imaging tool that can be disseminated and applied broadly. Current molecular imaging approaches, for example PET/SPECT, require an immense infrastructure and are not broadly applicable. In this proposal we will produce, test and refine two hyperpolarization units that allow for molecular imaging at low cost at any research facility. Specifically, the hyperpolarizers deliver safe, injectable solutions of endogenous metabolites that carry hyperpolarized nuclear spins, which are detected using any MRI system. The hyperpolarization enhances the MRI signals by 4 to 7 orders of magnitude and reports directly on the molecular transformations in study subjects. Hence direct imaging of molecular pathways in the living subject is enabled. The objective of this proposal is to make existing hyperpolarizer prototypes sturdy and easy to use. Simultaneously, we aim for pilot installations at pre-clinical sites in order to test the prototype’s ability to integrate with pre-clinical workflows. With successful completion this Phase I SBIR we will have a sturdy and easy-to-use hyperpolarizer that makes hyperpolarized MRI accessible to the neuroscience research community and enables non-invasive imaging of metabolic dysregulation during the earliest stages of disease. In turn the established devices and workflow lead to new insights into molecular pathology and to preclinical testing of novel interventions and drugs.