Multimodal probes for imaging neuroendocrine circuits and the neurovasculature

用于神经内分泌回路和神经血管系统成像的多模态探针

• 批准号: 9757763
• 负责人: Robert J Clements
• 金额: $ 7.49万
• 依托单位: KENT STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-07 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9757763
• 关键词: 3-Dimensional; Animals; Architecture; Binding; Blood - brain barrier anatomy; Brain; Clinical; Confocal Microscopy; Contrast Media; Coupling; Data; Data Analyses; Data Set; Development; Diagnosis; Diagnostic; Dimensions; Disease; Dose; Early Diagnosis; Evaluation; Evans blue stain; Extravasation; Feeding behaviors; Fluorescence; Fluorescence Microscopy; Fluorescent Probes; Formulation; Future; Growth; Heart failure; Homeostasis; Hypothalamic structure; Image; Injections; Knowledge; Label; Magnetic Resonance Imaging; Maintenance; Malignant Neoplasms; Maps; Mental Depression; Methods; Microscopic; Modification; Monitor; Multimodal Imaging; Mus; Nerve Degeneration; Nerve Tissue; Neuraxis; Neurocognitive; Neuroendocrine Cell; Neuroendocrinology; Neurophysiology - biologic function; Neurosecretory Systems; Optics; Patient-Focused Outcomes; Pattern; Personal Satisfaction; Play; Population; Procedures; Property; Protocols documentation; Publishing; Quality of life; Regulation; Reproducibility; Reproduction; Research; Research Support; Resolution; Role; Sodium Chloride; Specificity; System; Techniques; Therapeutic Intervention; Toxic effect; Tracer; Work; animal imaging; brain health; chemical synthesis; clinical Diagnosis; contrast enhanced; data mining; digital; digital models; flexibility; fluorescence imaging; imaging modality; imaging probe; in vivo; innovation; intraperitoneal; multimodality; nanoparticle; neural network; neuroinformatics; neurophysiology; neuroprotection; neurovascular; non-invasive imaging; non-invasive monitor; novel; online repository; relating to nervous system; repaired; repository; submicron; targeted delivery; tomography

In this proposal, we aim to develop two highly sensitive and multimodal magnetic resonance imaging (MRI) and fluorescence probes for non-invasively monitoring neuroendocrine cells and the neurovascular system. The project seeks to change current imaging practices and methods for monitoring (long term) changes in nerve tissue that are critically important in many (developmental) states and disease. Our approach is to label two existing and validated fluorescent probes with a newly developed nanoparticle contrast agent. Subsequently, the probes will be injected into mice and the ability to provide targeted contrast evaluated using MRI and confirmed using microscopic techniques. The completed project will create multimodal probes with specificity to non-invasively label neuroendocrine cells and the micro-vascular system. Further, we will employ the probes and the three imaging modalities to create co-registered spatial maps with unparalleled three dimensional (3D) resolution of entire neuroendocrine circuits and the neurovascular system. Undoubtedly, the hypothalamic neuroendocrine system maintains homeostasis and when malfunctions can result in many abnormal states disrupting salt regulation, reproduction, growth, neurocognitive, and feeding behaviors as well as exacerbate and cause disease states including heart failure, depression, neurodegeneration and cancer. In addition, the maintenance of the BBB and proper functioning of the neurovascular system is critically important to maintaining and protecting brain health and plays a role in many degenerative states. As such, being able to (non-invasively) evaluate both systems in the research and clinical setting is of great importance to provide more accurate and early diagnostics as well as disease monitoring, and will result in the development and application of more efficient therapeutic interventions that will increase quality of life and survival. The groundbreaking approach will permit more specific, less toxic and targeted exposure of neural changes known to precede those that are currently detectable resulting in earlier and more precise diagnoses. The developed probes will also provide a new and flexible platform for multi-modal imaging applications. Cutting edge nanoparticle synthesis and labeling techniques will be used to generate the new probes and b ased on preliminary data, we anticipate that the probes will reliably label neuroendocrine cells and the microvasculature respectively to provide enhanced MR and fluorescent contrast. The work will have far reaching and sustained impact on many fields including neuroendocrinology, blood brain barrier, clinical diagnosis/monitoring, neuroinformatics, neural disease, chemical synthesis and emergent properties of neural networks.

在本提案中，我们的目标是开发两种高灵敏度和多模态磁共振成像（MRI） 用于非侵入性监测神经内分泌细胞和神经血管系统的荧光探针。 该项目旨在改变当前的成像实践和监测（长期）变化的方法 在许多（发育）状态和疾病中至关重要的神经组织。我们的方法是标记 两种现有且经过验证的荧光探针与新开发的纳米颗粒造影剂。 随后，将探针注射到小鼠体内，并使用评估提供目标对比度的能力 MRI 并使用显微技术证实。已完成的项目将创建多模式探针 特异性非侵入性标记神经内分泌细胞和微血管系统。此外，我们将聘请 探头和三种成像模式创建具有无与伦比的三者共同配准的空间图 整个神经内分泌回路和神经血管系统的三维（3D）分辨率。毫无疑问， 下丘脑神经内分泌系统维持体内平衡，当出现故障时会导致许多 异常状态也会破坏盐调节、繁殖、生长、神经认知和进食行为 加剧并导致疾病状态，包括心力衰竭、抑郁症、神经退行性变和癌症。在 此外，维持血脑屏障和神经血管系统的正常功能至关重要 维持和保护大脑健康，并在许多退化状态中发挥作用。因此，能够 （非侵入性）评估研究和临床环境中的两个系统对于提供 更准确和早期的诊断以及疾病监测，并将导致发展和 应用更有效的治疗干预措施将提高生活质量和生存率。这 突破性的方法将允许更具体、毒性更小和有针对性地暴露已知的神经变化 领先于目前可检测到的疾病，从而实现更早、更准确的诊断。所开发的 探头还将为多模态成像应用提供一个新的、灵活的平台。前沿 纳米粒子合成和标记技术将用于生成新的探针和b 上 初步数据显示，我们预计探针将可靠地标记神经内分泌细胞和微血管系统 分别提供增强的 MR 和荧光对比度。 这项工作将产生深远而持久的影响 对神经内分泌学、血脑屏障、临床诊断/监测等多个领域产生影响 神经信息学、神经疾病、化学合成和神经网络的新兴特性。