Chaoyang Yan1, Kazuaki Nakane2, Xiangxue Wang3, Yao Fu4, Haoda Lu1, Xiangshan Fan4, Michael D Feldman5, Anant Madabhushi6, Jun Xu7. 1. School of Automation, Nanjing University of Information Science & Technology, Nanjing 210044, China; Jiangsu Key Laboratory of Big Data Analysis Technique and CICAEET, Nanjing University of Information Science and Technology, Nanjing 210044, China. 2. Department of Molecular Pathology, Osaka University Graduate School of Medicine, Division of Health Science, Osaka 565-0871, Japan. 3. Dept. of Biomedical Engineering, Case Western Reserve University, OH 44106-7207, USA. 4. Dept. of Pathology, the affiliated Drum Tower Hospital, Nanjing University Medical School, 210008, China. 5. Division of Surgical Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. 6. Dept. of Biomedical Engineering, Case Western Reserve University, OH 44106-7207, USA; Louis Stokes Cleveland Veterans Medical Center, Cleveland, OH 44106. 7. School of Automation, Nanjing University of Information Science & Technology, Nanjing 210044, China; Jiangsu Key Laboratory of Big Data Analysis Technique and CICAEET, Nanjing University of Information Science and Technology, Nanjing 210044, China. Electronic address: jxx108@case.edu.
Abstract
BACKGROUND AND OBJECTIVE: Gleason grading system is currently the clinical gold standard for determining prostate cancer aggressiveness. Prostate cancer is typically classified into one of 5 different categories with 1 representing the most indolent disease and 5 reflecting the most aggressive disease. Grades 3 and 4 are the most common and difficult patterns to be discriminated in clinical practice. Even though the degree of gland differentiation is the strongest determinant of Gleason grade, manual grading is subjective and is hampered by substantial inter-reader disagreement, especially with regard to intermediate grade groups. METHODS: To capture the topological characteristics and the degree of connectivity between nuclei around the gland, the concept of Homology Profile (HP) for prostate cancer grading is presented in this paper. HP is an algebraic tool, whereby, certain algebraic invariants are computed based on the structure of a topological space. We utilized the Statistical Representation of Homology Profile (SRHP) features to quantify the extent of glandular differentiation. The quantitative characteristics which represent the image patch are fed into a supervised classifier model for discrimination of grade patterns 3 and 4. RESULTS: On the basis of the novel homology profile, we evaluated 43 digitized images of prostate biopsy slides annotated for regions corresponding to Grades 3 and 4. The quantitative patch-level evaluation results showed that our approach achieved an Area Under Curve (AUC) of 0.96 and an accuracy of 0.89 in terms of discriminating Grade 3 and 4 patches. Our approach was found to be superior to comparative methods including handcrafted cellular features, Stacked Sparse Autoencoder (SSAE) algorithm and end-to-end supervised learning method (DLGg). Also, slide-level quantitative and qualitative evaluation results reflect the ability of our approach in discriminating Gleason Grade 3 from 4 patterns on H&E tissue images. CONCLUSIONS: We presented a novel Statistical Representation of Homology Profile (SRHP) approach for automated Gleason grading on prostate biopsy slides. The most discriminating topological descriptions of cancerous regions for grade 3 and 4 in prostate cancer were identified. Moreover, these characteristics of homology profile are interpretable, visually meaningful and highly consistent with the rubric employed by pathologists for the task of Gleason grading.
BACKGROUND AND OBJECTIVE: Gleason grading system is currently the clinical gold standard for determining prostate cancer aggressiveness. Prostate cancer is typically classified into one of 5 different categories with 1 representing the most indolent disease and 5 reflecting the most aggressive disease. Grades 3 and 4 are the most common and difficult patterns to be discriminated in clinical practice. Even though the degree of gland differentiation is the strongest determinant of Gleason grade, manual grading is subjective and is hampered by substantial inter-reader disagreement, especially with regard to intermediate grade groups. METHODS: To capture the topological characteristics and the degree of connectivity between nuclei around the gland, the concept of Homology Profile (HP) for prostate cancer grading is presented in this paper. HP is an algebraic tool, whereby, certain algebraic invariants are computed based on the structure of a topological space. We utilized the Statistical Representation of Homology Profile (SRHP) features to quantify the extent of glandular differentiation. The quantitative characteristics which represent the image patch are fed into a supervised classifier model for discrimination of grade patterns 3 and 4. RESULTS: On the basis of the novel homology profile, we evaluated 43 digitized images of prostate biopsy slides annotated for regions corresponding to Grades 3 and 4. The quantitative patch-level evaluation results showed that our approach achieved an Area Under Curve (AUC) of 0.96 and an accuracy of 0.89 in terms of discriminating Grade 3 and 4 patches. Our approach was found to be superior to comparative methods including handcrafted cellular features, Stacked Sparse Autoencoder (SSAE) algorithm and end-to-end supervised learning method (DLGg). Also, slide-level quantitative and qualitative evaluation results reflect the ability of our approach in discriminating Gleason Grade 3 from 4 patterns on H&E tissue images. CONCLUSIONS: We presented a novel Statistical Representation of Homology Profile (SRHP) approach for automated Gleason grading on prostate biopsy slides. The most discriminating topological descriptions of cancerous regions for grade 3 and 4 in prostate cancer were identified. Moreover, these characteristics of homology profile are interpretable, visually meaningful and highly consistent with the rubric employed by pathologists for the task of Gleason grading.
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