Nectome will create technologies to enable whole-brain nanoscale preservation and imaging, a vital step towards a deep understanding of the mind and of the brain's diseases. Current brain-processing technologies compromise between whole-brain applicability or nanoscale resolution; our technologies will achieve both si- multaneously. Similar to the way that next-generation genetic sequencing has helped to unlock the potential of genomics, these technologies will provide a foundation and set the path for the next generation of brain imag- ing. We will modify the two most promising nanoscale brain preparation techniques, expansion microscopy (1) and plastic embedding (2), to use vascular perfusion (3) instead of diffusion. This will enable them to overcome their current thickness limit of 150 microns in order to scale to whole brain samples. We will also integrate both methods with aldehyde-stabilized cryopreservation (ASC), a powerful brain-banking technique which can durably preserve the nanoscale structure of whole brains for centuries with no decay (4). Electron microscopy (EM) has been used for over 50 years to analyze brain tissue and is considered the gold standard for nanoscale brain imaging. Expansion microscopy (ExM) is a very recently developed brain imaging technique that physically expands brain tissue to 1020 times its original size, enabling nanoscale resolution of brain tissue with normal light microscopes and with ?uorescent labels to detect a diverse array of molecules normally invisible with electron microscopy. Whole-brain adaptations of EM and ExM will be of great interest to pharmaceutical companies wishing to evaluate the effects of drugs on brain ultrastructure and seeking to avoid wasting large amounts of brain tissue as is currently done in many studies. We also see immense application in the burgeoning ?eld of Connectomics (the study of the brain's detailed pattern of connectivity), and in brain banks wishing to store important brain samples with unprecedented detail. We foresee commercial opportunity in offering brain preservation and processing both as a service for processing whole brains, and as a kit for researchers who wish to accomplish this nanoscale preservation and imaging in their own labs.
Public Health Relevance Statement: Project Narrative We will create technologies to enable whole-brain nanoscale imaging and preservation. These technologies for whole-brain analysis are a vital step towards deep understanding of the mind and of many brain diseases they promise to do for neuroscience what whole-genome analysis has done for biology.
Project Terms: abstracting; Aldehydes; Animals; Architecture; Archives; base; Biological; Biological Preservation; Biology; Blood Vessels; Brain; Brain Diseases; Brain imaging; Brain region; brain tissue; Chemistry; connectome; Cryopreservation; design; Diffusion; Electron Microscopy; Failure; Formaldehyde; Foundations; Genetic; genome analysis; Genomics; Germany; Glutaral; Goals; Gold; Grant; Human; Image; Imaging Techniques; Institutes; interest; Label; Laboratories; Light Microscope; light microscopy; Marketing; Methods; Microscopy; Mind; Modeling; Molecular; Molecular Analysis; Mus; nanoscale; Nature; nervous system disorder; Neurobiology; Neurosciences; next generation; Osmium; Osmium Tetroxide; Pattern; Perfusion; Pharmaceutical Preparations; Pharmacologic Substance; Plant Resins; Plastic Embedding; Preparation; Process; Protocols documentation; Research Personnel; Resolution; Sampling; Services; Slice; Staining method; Stains; Structure; Techniques; Technology; Thick; Time; tool; Vision; wasting; whole genome; Work
