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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的大脑功能受分子信号传导和代谢调节，但是，我们跟踪神经代谢的能力与神经代谢中的核心作用相比，大脑深处的转化非常不发达神经退行性疾病或脑功能一般。在这个阶段I 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，坚固且可靠的神经代谢成像工具可以广泛传播和应用。当前的分子成像方法，例如PET/SPECT，需要巨大的基础设施和不广泛适用。在此提案中，我们将生产，测试和完善两个允许的超极化单元对于任何研究设施，以低成本的成本进行分子成像。具体而言，超极化器提供安全，可注射的携带超极化核自旋的内源代谢物的溶液，使用任何MRI检测系统。超极化使MRI信号提高了4至7个数量级，并直接报告研究对象中的分子转化。因此，直接对生命主题中分子途径的成像已启用。该建议的目的是使现有的超极化器原型坚固且易于使用。同时，我们的目标是在临床前站点进行试验装置，以测试原型的集成能力成功完成此阶段I SBIR，我们将拥有一个坚固且易于使用的使神经科学研究社区可以访问超极化的超极化器并启用在疾病最早的阶段，代谢失调的非侵入性成像。反过来既定设备和工作流程导致对分子病理学的新见解和新颖的临床前测试干预和毒品。