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.
Non-invasive techniques to track neuroprotection and repair in degenerative states are urgently needed, and we propose to establish reproducible probes to evaluate neuroendocrine circuits and the neurovasculature. The multimodal probes will be applicable to in vivo and fluorescence imaging applications and will provide a way to visualize changes in the blood brain barrier and neuroendocrine networks that are currently undetectable using MRI. The probes with greater sensitivity and increased specificity will yield safer, earlier and more accurate diagnostics of neurophysiological states to support research and early therapeutic interventions.
