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      Automated discrimination of lower and higher grade gliomas based on histopathological image analysis

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          Abstract

          Introduction:

          Histopathological images have rich structural information, are multi-channel in nature and contain meaningful pathological information at various scales. Sophisticated image analysis tools that can automatically extract discriminative information from the histopathology image slides for diagnosis remain an area of significant research activity. In this work, we focus on automated brain cancer grading, specifically glioma grading. Grading of a glioma is a highly important problem in pathology and is largely done manually by medical experts based on an examination of pathology slides (images). To complement the efforts of clinicians engaged in brain cancer diagnosis, we develop novel image processing algorithms and systems to automatically grade glioma tumor into two categories: Low-grade glioma (LGG) and high-grade glioma (HGG) which represent a more advanced stage of the disease.

          Results:

          We propose novel image processing algorithms based on spatial domain analysis for glioma tumor grading that will complement the clinical interpretation of the tissue. The image processing techniques are developed in close collaboration with medical experts to mimic the visual cues that a clinician looks for in judging of the grade of the disease. Specifically, two algorithmic techniques are developed: (1) A cell segmentation and cell-count profile creation for identification of Pseudopalisading Necrosis, and (2) a customized operation of spatial and morphological filters to accurately identify microvascular proliferation (MVP). In both techniques, a hierarchical decision is made via a decision tree mechanism. If either Pseudopalisading Necrosis or MVP is found present in any part of the histopathology slide, the whole slide is identified as HGG, which is consistent with World Health Organization guidelines. Experimental results on the Cancer Genome Atlas database are presented in the form of: (1) Successful detection rates of pseudopalisading necrosis and MVP regions, (2) overall classification accuracy into LGG and HGG categories, and (3) receiver operating characteristic curves which can facilitate a desirable trade-off between HGG detection and false-alarm rates.

          Conclusion:

          The proposed method demonstrates fairly high accuracy and compares favorably against best-known alternatives such as the state-of-the-art WND-CHARM feature set provided by NIH combined with powerful support vector machine classifier. Our results reveal that the proposed method can be beneficial to a clinician in effectively separating histopathology slides into LGG and HGG categories, particularly where the analysis of a large number of slides is needed. Our work also reveals that MVP regions are much harder to detect than Pseudopalisading Necrosis and increasing accuracy of automated image processing for MVP detection emerges as a significant future research direction.

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          Most cited references35

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          Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas.

          Published data on prognostic and predictive factors in patients with gliomas are largely based on clinical trials and hospital-based studies. This review summarizes data on incidence rates, survival, and genetic alterations from population-based studies of astrocytic and oligodendrogliomas that were carried out in the Canton of Zurich, Switzerland (approximately 1.16 million inhabitants). A total of 987 cases were diagnosed between 1980 and 1994 and patients were followed up at least until 1999. While survival rates for pilocytic astrocytomas were excellent (96% at 10 years), the prognosis of diffusely infiltrating gliomas was poorer, with median survival times (MST) of 5.6 years for low-grade astrocytoma WHO grade II, 1.6 years for anaplastic astrocytoma grade III, and 0.4 years for glioblastoma. For oligodendrogliomas the MSTwas 11.6 years for grade II and 3.5 years for grade III. TP53 mutations were most frequent in gemistocytic astrocytomas (88%), followed by fibrillary astrocytomas (53%) and oligoastrocytomas (44%), but infrequent (13%) in oligodendrogliomas. LOH 1p/19q typically occurred in tumors without TP53 mutations and were most frequent in oligodendrogliomas (69%), followed by oligoastrocytomas (45%), but were rare in fibrillary astrocytomas (7%) and absent in gemistocytic astrocytomas. Glioblastomas were most frequent (3.55 cases per 100,000 persons per year) adjusted to the European Standard Population, amounting to 69% of total incident cases. Observed survival rates were 42.4% at 6 months, 17.7% at one year, and 3.3% at 2 years. For all age groups, survival was inversely correlated with age, ranging from an MST of 8.8 months ( 80 years). In glioblastomas, LOH 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16INK4a deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations, and was the only alteration associated with shorter survival of glioblastoma patients. Primary (de novo) glioblastomas prevailed (95%), while secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hot-spot codons 248 and 273, while in primary glioblastomas, mutations were more evenly distributed. G:C-->A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas, suggesting that the acquisition of TP53 mutations in these glioblastoma subtypes may occur through different mechanisms.
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            Morphological grayscale reconstruction in image analysis: applications and efficient algorithms.

            L Vincent (1993)
            Two different formal definitions of gray-scale reconstruction are presented. The use of gray-scale reconstruction in various image processing applications discussed to illustrate the usefulness of this transformation for image filtering and segmentation tasks. The standard parallel and sequential approaches to reconstruction are reviewed. It is shown that their common drawback is their inefficiency on conventional computers. To improve this situation, an algorithm that is based on the notion of regional maxima and makes use of breadth-first image scannings implemented using a queue of pixels is introduced. Its combination with the sequential technique results in a hybrid gray-scale reconstruction algorithm which is an order of magnitude faster than any previously known algorithm.
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              Cell Segmentation: 50 Years Down the Road [Life Sciences]

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                Author and article information

                Contributors
                Journal
                J Pathol Inform
                J Pathol Inform
                JPI
                Journal of Pathology Informatics
                Medknow Publications & Media Pvt Ltd (India )
                2229-5089
                2153-3539
                2015
                24 March 2015
                : 6
                : 15
                Affiliations
                [1]Department of Electrical Engineering, The Pennsylvania State University, University Park, PA, USA
                [1 ]Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
                [2 ]Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
                Author notes
                [* ]Corresponding author
                Article
                JPI-6-15
                10.4103/2153-3539.153914
                4382761
                25838967
                312ab8f5-427e-43f0-8283-753d2db65840
                Copyright: © 2015 Mousavi HS.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 02 August 2014
                : 05 January 2015
                Categories
                Research Article

                Pathology
                brain cancer,cell segmentation,computer-aided diagnosis,decision tree,glioblastoma multiforme,low-grade glioma,micro-vascular proliferation,morphological transformation,pathological grading,pseudopalisading necrosis,spatial analysis,spatial filters

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