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A Microscopic Phenotypic Assay for the Quantification of Intracellular Mycobacteria Adapted for High-throughput/High-content Screening
Published on: January 17, 2014
Detecting and characterizing cellular responses to Mycobacterium tuberculosis from histology slides
M Khalid Khan Niazi1, Gillian Beamer, Metin N Gurcan
1Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio.
Insights
A new computational framework, DeHiDe, accurately identifies and classifies high cell-density regions in lung tissue slides. This tool aids in distinguishing granulomas and lymphocytic cuffs in Mycobacterium tuberculosis (M.tb) infection research.
Area of Science:
- Pathology
- Computational Biology
- Immunology
Background:
- Mycobacterium tuberculosis (M.tb) infection causes immune cell accumulation in the lungs, forming distinct granulomas and lymphocytic cuffs.
- These structures are crucial for understanding the host's immune response to tuberculosis.
- Accurate identification of these regions in histology slides is essential for research.
Purpose of the Study:
- To develop a computational framework for automated detection and classification of high cell-density regions in H&E-stained lung tissue slides.
- To accurately differentiate between granulomas and lymphocytic cuffs based on morphological characteristics, primarily cell density.
Main Methods:
- Development of DeHiDe, a computational framework utilizing internuclei geodesic distance and Dulmange Mendelsohn permutation.
- Training and validation of DeHiDe on 21 digitized H&E-stained lung tissue slides from M.tb-infected mice.
- Evaluation based on detection accuracy and classification accuracy of high cell-density regions.
Main Results:
- DeHiDe achieved a high detection accuracy of 99.39% for high cell-density regions.
- The framework correctly classified 90.87% of detected regions into granulomas and lymphocytic cuffs.
- Demonstrated ability to identify these regions in complex cellular environments with non-convex shapes.
Conclusions:
- DeHiDe offers a robust computational solution for analyzing M.tb-induced lung pathology.
- The framework facilitates precise characterization of immune cell aggregates in tuberculosis research.
- Automated analysis can improve the efficiency and accuracy of histological assessment in infectious disease studies.
Abstract:
Infection with Mycobacterium tuberculosis (M.tb) results in immune cell recruitment to the lungs, forming macrophage-rich regions (granulomas) and lymphocyte-rich regions (lymphocytic cuffs). The objective of this study was to accurately identify and characterize these regions from hematoxylin and eosin (H&E)-stained tissue slides. The two target regions (granulomas and lymphocytic cuffs) can be identified by their morphological characteristics. Their most differentiating characteristic on H&E slides is cell density. We developed a computational framework, called DeHiDe, to detect and classify high cell-density regions in histology slides. DeHiDe employed a novel internuclei geodesic distance calculation and Dulmange Mendelsohn permutation to detect and classify high cell-density regions. Lung tissue slides of mice experimentally infected with M.tb were stained with H&E and digitized. A total of 21 digital slides were used to develop and train the computational framework. The performance of the framework was evaluated using two main outcome measures: correct detection of potential regions, and correct classification of potential regions into granulomas and lymphocytic cuffs. DeHiDe provided a detection accuracy of 99.39% while it correctly classified 90.87% of the detected regions for the images where the expert pathologist produced the same ground truth during the first and second round of annotations. We showed that DeHiDe could detect high cell-density regions in a heterogeneous cell environment with non-convex tissue shapes.
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