The Assessment Of Nuclear Atypia, Mitotic Count And...

The assessment of nuclear atypia, mitotic count and lymphocyte infiltration in invasive lesions are challenging areas of diagnostic pathology with significant discordance among pathologists. This significant inter- and intra-observer discordance can have a negative impact on clinical care, as these factors can be used to guide clinical decisions today (e.g., use of chemotherapy in high-grade breast cancer) and may have an even larger impact on clinical decisions in the future (e.g., assessment of tumor infiltrating lymphocytes to guide the use of immunotherapies). Thus, the accurate pathological diagnosis represents a critical decision-point in clinical medicine, and there would be tremendous clinical utility to a more objective, reproducible and informative technology for the assessment of breast pathology. During my PhD training, I developed methods for mitosis detection in color and multispectral breast cancer histopathological images8,9, and I was a recipient of a copyright from CNRS France (CNRS Software No. DL 05963-01). In the ICPR 2012 contest on mitosis detection in breast cancer histological images, the color method I developed ranked second of 17 participants and the multispectral method I developed significantly outperformed other contestants’ results. Building on this prior work, in Specific Aim 3, I will extend these methods for advanced microscopy to analyze nuclei atypia, mitotic activity and lymphocytic infiltration from 3D lightsheet microscopy images, and