C Geady1, H Keller2, I Siddiqui3, J Bilkey4, N C Dhani5, D A Jaffray6. 1. Department of Medical Biophysics, University of Toronto, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada. Electronic address: caryn.geady@mail.utoronto.ca. 2. Department of Radiation Oncology, University of Toronto, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada. 3. Department of Pathology, Hospital for Sick Children, Toronto, Canada. 4. STTARR, University Health Network, Toronto, Canada. 5. Department of Medicine, University of Toronto, Toronto, Canada; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Canada. 6. Department of Medical Biophysics, University of Toronto, Canada; Department of Radiation Oncology, University of Toronto, Canada; STTARR, University Health Network, Toronto, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Canada; The TECHNA Institute for the Advancement of Technology for Health, Toronto, Canada; Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.
Abstract
INTRODUCTION: Studies suggest there is utility in computed tomography (CT) radiomics for pancreatic disease; however, the precise biological interpretation of its features is unclear. In this manuscript, we present a novel approach towards this interpretation by investigating sub-micron tissue structure using digital pathology. METHODS: A classification-to attenuation (CAT) function was developed and applied to digital pathology images to create sub-micron linear attenuation maps. From these maps, grey level co-occurrence matrix (GLCM) features were extracted and compared to pathology features. To simulate the spatial frequency loss in a CT scanner, the attenuation maps were convolved with a point spread function (PSF) and subsequently down-sampled. GLCM features were extracted from these down-sampled maps to assess feature stability as a function of spatial frequency loss. RESULTS: Two GLCM features were shown to be strongly and positively correlated (r = 0.8) with underlying characteristics of the tumor microenvironment, namely percent pimonidazole staining in the tumor. All features underwent marked change as a function of spatial frequency loss; progressively larger spatial frequency losses resulted in progressively larger inter-tumor standard deviations; two GLCM features exhibited stability up to a 100 µm pixel size. CONCLUSION: This work represents a necessary step towards understanding the biological significance of radiomics. Our preliminary results suggest that cellular metrics of pimonidazole-detectable hypoxia correlate with sub-micron attenuation coefficient texture; however, the consistency of these textures in face of spatial frequency loss is detrimental for robust radiomics. Further study in larger data sets may elucidate additional, potentially more robust features of biologic and clinical relevance. Crown
INTRODUCTION: Studies suggest there is utility in computed tomography (CT) radiomics for pancreatic disease; however, the precise biological interpretation of its features is unclear. In this manuscript, we present a novel approach towards this interpretation by investigating sub-micron tissue structure using digital pathology. METHODS: A classification-to attenuation (CAT) function was developed and applied to digital pathology images to create sub-micron linear attenuation maps. From these maps, grey level co-occurrence matrix (GLCM) features were extracted and compared to pathology features. To simulate the spatial frequency loss in a CT scanner, the attenuation maps were convolved with a point spread function (PSF) and subsequently down-sampled. GLCM features were extracted from these down-sampled maps to assess feature stability as a function of spatial frequency loss. RESULTS: Two GLCM features were shown to be strongly and positively correlated (r = 0.8) with underlying characteristics of the tumor microenvironment, namely percent pimonidazole staining in the tumor. All features underwent marked change as a function of spatial frequency loss; progressively larger spatial frequency losses resulted in progressively larger inter-tumor standard deviations; two GLCM features exhibited stability up to a 100 µm pixel size. CONCLUSION: This work represents a necessary step towards understanding the biological significance of radiomics. Our preliminary results suggest that cellular metrics of pimonidazole-detectable hypoxia correlate with sub-micron attenuation coefficient texture; however, the consistency of these textures in face of spatial frequency loss is detrimental for robust radiomics. Further study in larger data sets may elucidate additional, potentially more robust features of biologic and clinical relevance. Crown