Biomedical engineering Applications, Data Domain, and Opportunities in Pathology, Cancer and Genomics: Precision Medicine using Precision Pathology

Subtitle: Focus on Decision Trees and Theoretic Analytics of Flow Cytometry Phenotype Data , Microscopic Digital Image Cytometry of cancer cells or histopathologic tissue and genomics data.

APPLICATION TARGETS: CLASS I FDA MEDICAL DEVICE DATA SYSTEMS: LAB AUTOMATION: DATAPROCESSINGTOOLSFORDIGITALIMAGES

BY: Hernani Cualing MD, Medical Director IHCFLOW Inc. Assoc Prof, Univ of South Florida, Moffitt Cancer Center, Consultant to Neogenomics Molecular Lab and Member CAP/USCAP Pathology Groups

Background: DIGITAL HEALTH AND INNOVATIONS FIGURE PROMINENTLY IN CURRENT GOVERNMENT INITIATIVES. In that regard, advances in this area often require doctors and engineers putting their heads together. When I realized there are problems in pathology, cancer and genomics that may benefit from bioengineer expertise, I initiated an interdisciplinary collaboration more than 10 years ago, between computer engineers and medical doctors in pathology. One problem is precise measurement of tissue histologic parameters. Many biomarker studies require the counting of cells or evaluating tissue areas prior to decision about the type of tumor, the diagnosis, or whether it is cancer or non-cancerous type. However, one drawback of this state of the art in current diagnosis is that almost all clinical decisions on biomarker positivity or tissue morphology are based on visual estimates. While the clinical or visual estimate is the usual workflow practice, it is not the most precise, accurate or objective. This current practice of estimating percent positivity is the default du joure workflow despite its known subjectivity perhaps because of a lack of precise tools at hand. This subjectivity is widely accepted for want of a better alternative. This alternative may be approached using biomedical engineering expertise. While most of the current laboratory or clinical instruments benefit from bioengineered products that analyze cells or reactants from blood, body fluids or serum and automation as the norm, these tools are not yet widely or routinely used in the anatomic or tissue diagnostic lab where diagnosis is based on a centuries old invention: the optical microscope. Initial success show great promise when certain biomarkers are quantified using microscopic image analysis( Her2 NEU, FISH for interface nuclei with tumor mutations) preferably in combination with digital whole slide imaging pathology. Combined, these field generate more than 100 M in worldwide revenue, and estimated to quadruple by 2018.
Areas Covered: Pathology is a medical specialty that deals with diagnosis of blood, cells, tissue specimens so that precise therapy and cure is attained. The most worrisome of those is the question: is it cancer or not? Pathologists are involved in both the laboratory liquid specimen analysis ( chemistry, blood analysers, flow cytometry) or anatomic (solid tissue specimen) diagnosis such as biopsies, tumor surgical excision, evaluation of tumor margins. In today’s era of tumor specific nanomolecular targets, advanced molecular “bullets” such as antibodies, nucleic acids, peptides, nanogel antitumor-laden microparticles, kill tumor cells precisely without harming normal tissue. This “precise medicine” approach as mentioned by President Obama in the state of the union, departs from the usual tumor therapy such as radiation or chemotherapy that inadvertently harms both cancer and normal tissue( baldness or diarrhea or death from infection as given complications). Precision medicine, ALTHOUGH USUALLY EQUATED TO CANCER GENOMICS FOR PERSONALIZED THERAPY, nevertheless, requires precision pathology IN ORDER TO BE REAL AND EFFECTIVE. PATIENTS WILL NOT ONLY RESPOND TO TREATMENT IF THERE IS IMPRECISE DIAGNOSIS. For example, FOR THE DISSEMINATED melanoma( skin cancer), but there is urgent clinical need to examine its molecular profile, its nucleic acid mutation status (BRAF V600 mutation) that predict response to precise tumor-specific treatment. In SOME TYPE OF CURED leukemia, Gleevec is a precise treatment used with high effectiveness in only those tumor cells with BCR-Abl kinase enzyme mutation of which normal tissues do not express. Opportunities in anatomic and clinical pathology are numerous for biomedical engineers: these include DIGITAL microscopic imaging, INTELLIGENT classifiers of immunophenotype data, and clinical decision aids for tissue-based cytometry and other NEXT GENERATION SEQUENCING HIGH THROUGHPUT INFORMATICS. In PRECISE molecular diagnosis, panels of thousands of genes implicated in cancer, therapy and treatment resistance are routinely extracted from tissue biopsies or cytological specimen from tumor biopsy, brushing or scraping GENERATING PENTABYTE DATASETS THAT CAN ONLY BE SORTED BY EXPERT SYSTEMS. Expert Opinion: Precise pathology in anatomic and clinical pathology may benefit from bioengineers in devising clinical decision aids, MEDICAL DEVICE DATA SYSTEMS, AND DATA PROCESSING AS WELL AS work flow computerized automation using a wide variety of tools ranging from neural information systems, computerized machine classifiers, and clinical decision trees and advances in these algorithms. Inroads in these areas may help in advancing the era of Precision Medicine IN THE 21ST CENTURY.

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