Automated microfluidic hyperpolarization reactor for neurometabolic imaging

用于神经代谢成像的自动化微流体超极化反应器

• 批准号: 10383423
• 负责人: Carlos Dedesma
• 金额: $ 44.8万
• 依托单位: VIZMA LIFE SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-12 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10383423
• 关键词: 2,4-Dinitrophenol; Adoption; Anatomy; Animals; Automation; Biological Sciences; Bolus Infusion; Brain; Clinical; Communities; Complex; Contrast Media; Development; Devices; Diagnostic; Disease; Early Diagnosis; Ensure; Face; Functional disorder; General Hospitals; Goals; Hospitals; Human Resources; Image; Imaging Device; Imaging technology; Infrastructure; Injectable; Injections; Intervention; Lead; Licensing; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Massachusetts; Measurable; Measures; Metabolism; Methods; Microdialysis; Microfluidics; Molecular; Molecular Disease; NMR Spectroscopy; Neurodegenerative Disorders; Neurosciences Research; Non-Invasive Cancer Detection; Nuclear; Oncology; Organ; Pathway interactions; Penetration; Pharmaceutical Preparations; Phase; Physiological; Positron-Emission Tomography; Preclinical Testing; Public Health; Pyruvate; Quality Control; Radiation; Reporting; Reproducibility; Research; Research Personnel; Risk; Role; Signal Transduction; Site; Small Business Innovation Research Grant; Study Subject; Symptoms; System; Technology; Testing; Time; Tissue imaging; Tissues; Training; Universities; brain tissue; clinical application; clinical research site; clinical translation; cost; cranium; diagnostic value; experimental study; imaging approach; imaging modality; innovation; insight; instrument; metabolic imaging; molecular imaging; molecular pathology; non-invasive imaging; novel; novel diagnostics; operation; pre-clinical; prototype; research facility; single photon emission computed tomography; success

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.

摘要 大脑功能受分子信号和代谢的调节，然而，我们跟踪神经代谢的能力 与神经代谢的中心作用相比，大脑深处的转化是非常不发达的。 神经退行性疾病或大脑功能。在第一阶段SBIR中，我们的目标是建立和完善 紧急超极化技术作为一种廉价，坚固和可靠的神经代谢成像工具， 可以广泛推广应用。 目前的分子成像方法，例如PET/SPECT，需要巨大的基础设施， 并不广泛适用。在这个建议中，我们将生产，测试和改进两个超极化单元， 用于任何研究机构的低成本分子成像。具体来说，超极化剂提供安全，可注射 携带超极化核自旋的内源性代谢物溶液，使用任何MRI都可以检测到 系统超极化使MRI信号增强4至7个数量级，并直接报告 研究对象的分子转变。因此，直接成像的分子途径，在生活的主题 已启用。 该提案的目的是使现有的超偏振器原型坚固且易于使用。 与此同时，我们的目标是在临床前现场进行试点安装，以测试原型的整合能力 临床前工作流程。随着第一阶段SBIR的成功完成，我们将拥有一个坚固且易于使用的 超极化器，使超极化MRI可用于神经科学研究社区， 在疾病的最早阶段进行代谢失调的非侵入性成像。反过来， 设备和工作流程导致对分子病理学的新见解，并导致新的临床前测试。 干预和药物。