245 research outputs found
Automatic tumor-stroma separation in fluorescence TMAs enables the quantitative high-throughput analysis of multiple cancer biomarkers.
No full textThe upcoming quantification and automation in biomarker based histological tumor evaluation will require computational methods capable of automatically identifying tumor areas and differentiating them from the stroma. As no single generally applicable tumor biomarker is available, pathology routinely uses morphological criteria as a spatial reference system. We here present and evaluate a method capable of performing the classification in immunofluorescence histological slides solely using a DAPI background stain. Due to the restriction to a single color channel this is inherently challenging. We formed cell graphs based on the topological distribution of the tissue cell nuclei and extracted the corresponding graph features. By using topological, morphological and intensity based features we could systematically quantify and compare the discrimination capability individual features contribute to the overall algorithm. We here show that when classifying fluorescence tissue slides in the DAPI channel, morphological and intensity based features clearly outpace topological ones which have been used exclusively in related previous approaches. We assembled the 15 best features to train a support vector machine based on Keratin stained tumor areas. On a test set of TMAs with 210 cores of triple negative breast cancers our classifier was able to distinguish between tumor and stroma tissue with a total overall accuracy of 88%. Our method yields first results on the discrimination capability of features groups which is essential for an automated tumor diagnostics. Also, it provides an objective spatial reference system for the multiplex analysis of biomarkers in fluorescence immunohistochemistry
Abstract 1917: Immunological Tumor Maps: a Landscape of Infiltrating Immune Cells in Colorectal Cancer Based on Complete Tissue Section Analyses
No full textAbstract
In colorectal cancer (CRC) large scale tissue microarray (TMA) based quantitative immune cell counts using immune cell surface molecules (CD3, CD8, Granzyme B, and CD45RO) have identified the number of infiltrating immune cells to be potentially better predictors for patient survival than the classical TNM system. The spatial heterogeneity of immune cells may not be well reflected in the highly selected, and typically small (0,6-1 mm2) tissue cores of the TMA. This represents an obstacle in the individual prognosis prediction or classification of a single patient. To investigate this aspect, the localization and distribution of immune cell subpopulations based on the analysis of complete tissue sections by a dedicated novel staining and imaging system were performed. Using a specialized staining platform and whole slide imaging & analysis by virtual microscopy (VM), immunological “tumor maps” were generated. These tumor maps are based on cell densities in fields of 1mm2 size, visualizing intratumoral heterogeneity for the surface markers CD3, CD8, Granzyme B, and CD45RO. In total, an area of 867 mm2 was automatically evaluated with an average of 48 mm2 of evaluated tumor tissue per patient slide. Cell counts varied within a patient significantly, ranging from 0 to up to 2550 cells / mm2. Further analyses revealed, that sampling of single field counts within the tumor can only yield clear diagnostic decisions for a fraction of the analyzed patients, with ambiguous decisions for 11 out of 20 patients. Interestingly, the overall degree of heterogeneity also varied between patients, with lower heterogeneity found only in samples with lower cell counts. No samples with a homogeneous high cell density distribution were observed. The observed variability has implications for the individual prognosis prediction and represents the first spatial quantitative study of immune cells in a set of CRC primary tumors. The presented tumor maps therefore are a suitable tool to visualize heterogeneity. Furthermore, whole slide imaging & analysis by VM is essential in the identification of prognostic markers as well as in their subsequent application. In the future, spatial marker signatures could contribute to individual patient classification.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1917.</jats:p
Abstract 396: Sequential metastases of colorectal cancer: Treatment, immunophenotypes and spatial distributions of infiltrating immune cells
No full textQuantification of prognostic immune cell markers in colorectal cancer using whole slide imaging tumor maps
No full textTo analyze intratumoral heterogeneity of immune cells and the resulting impact of heterogeneity on the level of individual patient prediction
Quantification of prognostic immune cell markers in colorectal cancer using whole slide imaging tumor maps
No full textTo analyze intratumoral heterogeneity of immune cells and the resulting impact of heterogeneity on the level of individual patient prediction
Abstract 795: Patterns of T-cell distribution at the invasive margin of colorectal cancer liver metastases: Downstream recruitment of T cells and spatial heterogeneity
No full textEstimation of immune cell densities in immune cell conglomerates: an approach for high-throughput quantification.
No full textBackgroundDetermining the correct number of positive immune cells in immunohistological sections of colorectal cancer and other tumor entities is emerging as an important clinical predictor and therapy selector for an individual patient. This task is usually obstructed by cell conglomerates of various sizes. We here show that at least in colorectal cancer the inclusion of immune cell conglomerates is indispensable for estimating reliable patient cell counts. Integrating virtual microscopy and image processing principally allows the high-throughput evaluation of complete tissue slides.Methodology/principal findingsFor such large-scale systems we demonstrate a robust quantitative image processing algorithm for the reproducible quantification of cell conglomerates on CD3 positive T cells in colorectal cancer. While isolated cells (28 to 80 microm(2)) are counted directly, the number of cells contained in a conglomerate is estimated by dividing the area of the conglomerate in thin tissues sections (ConclusionIn summary, we recommend our approach as an objective and robust strategy for quantifying immune cell densities in immunohistological sections which can be directly implemented into automated full slide image processing systems
Multi-stage subduction-related metasomatism recorded in whiteschists from the Dora-Maira Massif, Western Alps
No full textWhiteschists from the Dora-Maira massif (Western Alps, Italy) are Mg and K-rich metasomatised granites which experienced ultra-high pressure metamorphism and fluid-rock interaction during Alpine continental subduction. The sources and timing of fluid infiltration are a source of significant debate. In this study we present boron (B) isotopes and other fluid-mobile trace element (FME) concentrations in various generations of phengite from whiteschists and their country rock protoliths to investigate the sources and timing of metasomatic fluid influx. Reconstructed bulk rock concentrations based on modal data and mineral compositions indicate that significant amounts B and other FME were added to the rock during prograde metamorphism, but that this fluid influx postdates the main Mg metasomatic event. High B concentrations (150–350 µg/g) and light δ11B values (-16 to -4 ‰) recorded in phengite point to a B-rich sediment-derived fluid as the main source of B in the whiteschists. Further redistribution of FME during metamorphism was associated with breakdown of hydrous minerals such as talc, phlogopite and ellenbergerite. The source of the Mg-rich fluids cannot be constrained based on the B data in phengite, since its signature was overprinted by the later main B metasomatic event. Rare tourmaline-bearing whiteschists record additional information about B processes. Tourmaline δ11B values (-6 to +1 ‰) are in isotopic equilibrium with similar fluids to those recorded in most phengite, but phengites in tourmaline-bearing samples records anomalous B isotope compositions that reflect later redistribution of B. This study demonstrates the utility of in situ analyses in unravelling complex fluid-rock interaction histories, where whole rock analyses make it difficult to distinguish between different stages of fluid-rock interaction. Polymetasomatism may result in decoupling of different isotopic systems, thus complicating their interpretation. The Dora-Maira whiteschists interacted with multiple generations of fluids during subduction and therefore may represent a long-lived fluid pathway
Resensi Buku: Tak Ada Tempat untuk Mengelak
No full textJudul: Digital Disruption: The Future of Work, Skills, Leadership, Education, and Careers in a Digital WorldPenulis: Dr. Tracey WilenPenerbit: Peter Lang, New York : Pertama, 2018Cetakan: 204 halama
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