Central Nervous System (CNS) disorders place an enormous burden on society and have provento be among the most challenging areas for which to develop a therapeutic. A major reason forthis is that the brain is a complex, 3D, multiscale organ, with a heterogenous distribution ofcomponents across hundreds of brain regions. Extensive BRAIN Initiative efforts are underwayto map this complexity by conducting surveys of connectivity pattern and cells types. Digitalbrain atlases such as the Allen Mouse Brain CCF v3.0 have become essential tools in organizingthe results of these endeavors.The availability of the Allen CCFV3.0 and whole-brain surveys are transforming CNS studies.However, brain mapping still too frequently requires access to expensive equipment, specializedtechniques, and dedicated personnel. Moreover, many newer techniques are incompatible withestablished histology protocols, which severely limits the contribution of foundationaltechniques to brain mapping efforts. In addition, the tedious manual production of slidesremains a significant obstacle to high throughput histology. These difficulties present asignificant barrier to the field and hinders progress in understanding the CNS.This proposal will remove these barriers by developing an affordable, table-top hardware andsoftware mouse brain imaging and tissue processing platform accessible to the non-specialistneuroscience lab. It is based on the proven microtomy, section capture, and slide mountingtechnology contained in TissueVision's commercially successfully state-of-the-art multiphoton-based TissueCyte platform. This proposal will extend the capabilities of our current system andextend it to sections as thin as 15 microns and replace the TissueCyte's advanced multiphotonimaging with less expensive block-face imaging. In Phase II we will be package the integratedtissue processing technology into a convenient, compact instrument. This table-top, affordabledevice will combine the ease of working from 2D sections with the power of 3D brain analysesand help propel forward the development of new therapeutics.This product will be brought to market by a team of world-class experts at TissueVision whohave successful commercialization experience in instrumentation for high throughput histologyand brain mapping. We will be aided by a superb network of partners in leading neurosciencelabs who will beta test the product and provide crucial feedback in Phase II to ensure asuccessful product launch and acceptance into the marketplace.
Public Health Relevance Statement: PROJECT NARRATIVE
This proposal describes the development of a ground-breaking automated whole-brain mapping
platform. It will image and section whole mouse brains into a series of thin sections mounted on
glass slides that are indexed to their correct location within the 3D brain. It will offer wide
compatible with existing histology methods including classical CNS and neurodegenerative
markers and immunohistochemistry protocols worked out on 2D sections in many laboratories.
The integrated brain mapping software that comes with this table-top device will allow
individual research labs to conduct whole brain mapping studies without the need for
specialized equipment or personnel.
Project Terms: Agar ; Anatomy ; Anatomic ; Anatomic Sites ; Anatomic structures ; Anatomical Sciences ; Atlases ; Brain ; Brain Nervous System ; Encephalon ; Brain Mapping ; Budgets ; Central Nervous System Diseases ; CNS Diseases ; CNS disorder ; Central Nervous System Disorders ; Client ; Equipment ; Face ; faces ; facial ; Feedback ; Fluorescence ; Foundations ; Glass ; Histology ; Immunohistochemistry ; Immunohistochemistry Cell/Tissue ; Immunohistochemistry Staining Method ; indexing ; Institutes ; instrumentation ; Laboratories ; Manuals ; Maps ; Methods ; Microtomy ; Thin Sectioning ; Mus ; Mice ; Mice Mammals ; Murine ; Names ; Nerve Degeneration ; Neuron Degeneration ; neural degeneration ; neurodegeneration ; neurodegenerative ; neurological degeneration ; neuronal degeneration ; Neurosciences ; Production ; Research ; Societies ; Computer software ; Software ; Software Tools ; Computer Software Tools ; Stains ; Staining method ; Surveys ; Survey Instrument ; Technology ; Testing ; Thinness ; Leanness ; Tissues ; Body Tissues ; tomography ; Work ; Price ; pricing ; base ; image processing ; Organ ; Humidifier ; Microscope ; Microtome - medical device ; microtome ; improved ; Brain imaging ; brain visualization ; Area ; Phase ; Series ; Ensure ; Individual ; Therapeutic ; Conifera ; yew ; Taxus ; tool ; instrument ; Complex ; Protocol ; Protocols documentation ; Slide ; cell type ; Pattern ; Techniques ; System ; 3-D ; 3D ; three dimensional ; 3-Dimensional ; Location ; interest ; experience ; neural ; relating to nervous system ; Devices ; Manpower ; personnel ; Human Resources ; design and construct ; design and construction ; develop software ; developing computer software ; software development ; tissue preparation ; CNS Nervous System ; Central Nervous System ; Neuraxis ; Brain region ; Thickness ; Thick ; tissue processing ; Address ; Slice ; To specify ; Process ; sample fixation ; Fixation ; Development ; developmental ; Image ; imaging ; cost ; two-photon ; 2-photon ; digital ; cost effective ; novel therapeutics ; new drug treatments ; new drugs ; new therapeutics ; new therapy ; next generation therapeutics ; novel drug treatments ; novel drugs ; novel therapy ; commercialization ; BRAIN initiative ; Brain Research through Advancing Innovative Neurotechnologies initiative ; Tissue imaging ; secondary analysis ; multiphoton imaging ; multi-photon imaging ;
