Whole-organ 3D immunohistochemistry is revolutionizing the field of neuroscience, enablingunprecedented insight into the distribution of neural cells and neurological markers throughout the brain in healthand disease. LifeCanvas Technologies is at the forefront of the new field of spatial proteomics, providing acomplete workflow for whole-organ preservation, tissue clearing, immunohistochemical labeling, and imaging.Nevertheless, an ongoing challenge for such studies is the need to rapidly, reproducibly and rigorously quantifyterabyte-sized datasets from whole-organ imaging efforts. While progress has been made in applying ArtificialIntelligence (AI) tools to enable detection of cellular and sub-cellular markers in neural tissue, one-size-fits-allalgorithms are inadequate for analyzing complex, information-rich brain datasets due to varying biomolecularexpression patterns (e.g. nuclear, cytoplasmic, membrane-bound) and region-specific heterogeneities in celldensity and neural cell types. However, AI-driven algorithms targeting a subset of labeling patterns can beeffective provided the availability of adequate training data. LifeCanvas Technologies LCT is optimally positionedto develop highly accurate algorithms serving a wide range of detection tasks through its access to high volumesof whole-organ image data containing a variety of label expression patterns via its Contract ResearchOrganization and user base. LCT proposes to develop a data analysis program, SmartAnalytics, which willembed a suite of AI algorithms within a user-friendly software package to identify labeled cell locations andcharacterize morphological features across the whole brain at cellular and sub-cellular resolution. Specifically,LCT will use intact, 3D immunolabeled mouse brains to design AI algorithms to detect labeled cells imaged atcellular resolution and generate further algorithms for the segmentation of labeled features imaged at sub-micronresolution. Data from LCT's Contract Research Organization and academic collaborations will be continually fedback to improve and expand the library of detection algorithms available within SmartAnalytics, and thesedevelopments will drive further customer adoption and enhancement of future versions of the software.SmartAnalytics will guide users through model application, quality-control testing, and the generation of outputproducts such as figures and summary statistics. In summary, SmartAnalytics will be an evolving and user-friendly workflow execution program that enables neuroscientists to take full advantage of their 3D image data,driving new discoveries in brain function, development and disease.
Public Health Relevance Statement: Narrative. The ability to readily and accurately quantify proteomic expression patterns that define neural cell- type specific distributions and morphologies across intact brains will enable unprecedented and unbiased insights into studies of brain function. LifeCanvas Technologies' state-of-the-art tissue processing pipeline provides uniform clearing, labeling, and imaging of whole brains at cellular and sub-cellular resolution. By developing Artificial Intelligence algorithms to detect labeled cells and determine morphologies and by packaging these algorithms in a user-friendly software "SmartAnalytics', LifeCanvas will enable neuroscientists to quantify image data and derive critical results towards a more complete understanding of brain function in development, health and disease.
Project Terms: cost ; design ; designing ; submicron ; sub micron ; Three-dimensional analysis ; 3-D analysis ; 3-dimensional analysis ; 3D analysis ; user-friendly ; Biological Markers ; bio-markers ; biologic marker ; biomarker ; biomarker-driven ; Tissue imaging ; terabyte ; algorithm development ; intelligent algorithm ; smart algorithm ; segmentation algorithm ; Adoption ; Algorithms ; Antibodies ; Artificial Intelligence ; AI system ; Computer Reasoning ; Machine Intelligence ; Astrocytes ; Astrocytus ; Astroglia ; astrocytic glia ; Automobile Driving ; driving ; Back ; Dorsum ; Brain ; Brain Nervous System ; Encephalon ; Cell membrane ; Cytoplasmic Membrane ; Plasma Membrane ; plasmalemma ; Cells ; Cell Body ; Communities ; Cytoplasm ; Data Analyses ; Data Analysis ; data interpretation ; Disease ; Disorder ; Feedback ; Future ; Glial Fibrillary Acidic Protein ; Astroprotein ; GFA-Protein ; GFAP ; Glial Fibrillary Acid Protein ; Glial Intermediate Filament Protein ; Health ; Heterogeneity ; Immunohistochemistry ; Immunohistochemistry Cell/Tissue ; Immunohistochemistry Staining Method ; Institutes ; Libraries ; Maps ; Microscopy ; Mus ; Mice ; Mice Mammals ; Murine ; Neurons ; Nerve Cells ; Nerve Unit ; Neural Cell ; Neurocyte ; neuronal ; Neurosciences ; Organ Preservation ; Proteins ; Quality Control ; Rosaniline Dyes ; Fuchsins ; Magentas ; Triphenylmethane Aniline Compounds ; Computer software ; Software ; statistics ; Technology ; Testing ; Tissues ; Body Tissues ; Amyloid beta-Protein ; Alzheimer beta-Protein ; Alzheimer's Amyloid beta-Protein ; Alzheimer's amyloid ; Amyloid Alzheimer's Dementia Amyloid Protein ; Amyloid Beta-Peptide ; Amyloid Protein A4 ; Amyloid β ; Amyloid β-Peptide ; Amyloid β-Protein ; Aβ ; a beta peptide ; abeta ; amyloid beta ; amyloid-b protein ; beta amyloid fibril ; soluble amyloid precursor protein ; Generations ; Imaging Techniques ; Imaging Procedures ; Imaging Technics ; Data Set ; Dataset ; Cell Density ; base ; Organ ; Label ; improved ; Image Analysis ; Image Analyses ; image evaluation ; image interpretation ; Brain imaging ; brain visualization ; Neurologic ; Neurological ; Training ; insight ; Individual ; Binding Proteins ; Ligand Binding Protein ; Ligand Binding Protein Gene ; Protein Binding ; bound protein ; Collaborations ; Morphology ; tool ; programs ; Complex ; cell type ; Pattern ; 3-D ; 3D ; three dimensional ; 3-Dimensional ; Location ; extracellular ; Nuclear ; user friendly computer software ; user friendly software ; neural cell body ; soma ; neuronal cell body ; neural ; relating to nervous system ; novel technologies ; new technology ; Position ; Positioning Attribute ; Modeling ; Proteomics ; develop software ; developing computer software ; software development ; 3-D Imaging ; 3D imaging ; Three-Dimensional Imaging ; data processing ; computerized data processing ; 3-D Images ; 3-D image ; 3D image ; 3D images ; Three-Dimensional Image ; tissue processing ; Data ; Detection ; Research Contracts ; Resolution ; Process ; Development ; developmental ; cellular imaging ; cell imaging ; Image ; imaging ; Output ;
