TriResNet: A Deep Triple-stream Residual Network for Histopathology Grading

While microscopic analysis of histopathological slides is generally considered as the gold standard method for performing cancer diagnosis and grading, the current method for analysis is extremely time consuming and labour intensive as it requires pathologists to visually inspect tissue samples in a detailed fashion for the presence of cancer. As such, there has been significant recent interest in computer aided diagnosis systems for analysing histopathological slides for cancer grading to aid pathologists to perform cancer diagnosis and grading in a more efficient, accurate, and consistent manner. In this work, we investigate and explore a deep triple-stream residual network (TriResNet) architecture for the purpose of tile-level histopathology grading, which is the critical first step to computer-aided whole-slide histopathology grading. In particular, the design mentality behind the proposed TriResNet network architecture is to facilitate for the learning of a more diverse set of quantitative features to better characterize the complex tissue characteristics found in histopathology samples. Experimental results on two widely-used computer-aided histopathology benchmark datasets (CAMELYON16 dataset and Invasive Ductal Carcinoma (IDC) dataset) demonstrated that the proposed TriResNet network architecture was able to achieve noticeably improved accuracies when compared with two other state-of-the-art deep convolutional neural network architectures. Based on these promising results, the hope is that the proposed TriResNet network architecture could become a useful tool to aiding pathologists increase the consistency, speed, and accuracy of the histopathology grading process.Comment: 9 page

Pattern Recognition Software and Techniques for Biological Image Analysis

The increasing prevalence of automated image acquisition systems is enabling new types of microscopy experiments that generate large image datasets. However, there is a perceived lack of robust image analysis systems required to process these diverse datasets. Most automated image analysis systems are tailored for specific types of microscopy, contrast methods, probes, and even cell types. This imposes significant constraints on experimental design, limiting their application to the narrow set of imaging methods for which they were designed. One of the approaches to address these limitations is pattern recognition, which was originally developed for remote sensing, and is increasingly being applied to the biology domain. This approach relies on training a computer to recognize patterns in images rather than developing algorithms or tuning parameters for specific image processing tasks. The generality of this approach promises to enable data mining in extensive image repositories, and provide objective and quantitative imaging assays for routine use. Here, we provide a brief overview of the technologies behind pattern recognition and its use in computer vision for biological and biomedical imaging. We list available software tools that can be used by biologists and suggest practical experimental considerations to make the best use of pattern recognition techniques for imaging assays

Lymphocyte Segmentation using the Transferable Belief Model

Abstract. In the context of several pathologies, the presence of lymphocytes has been correlated with disease outcome. The ability to automatically detect lymphocyte nuclei on histopathology imagery could potentially result in the development of an image based prognostic tool. In this paper we present a method based on the estimation of a mixture of Gaussians for determining the probability distribution of the principal image component. Then, a post-processing stage eliminates regions, whose shape is not similar to the nuclei searched. Finally, a Transferable Belief Model is used to detect the lymphocyte nuclei, and a shape based algorithm possibly splits them under an equal area and an eccentricity constraint principle.

Two-dimensional fiber optical data link using self-electrooptic effect device modulators and OEIC detectors

A 4 × 4 (16-channel) parallel optical data link was demonstrated that used extensible arrays of selfelectrooptic effect device (SEED) modulators1 and an array of commercially available OEIC detectors. The link consisted of a GaAs quantum well modulator array, a custom multimode fiber bundle conduit, and a multichip module receiver array. A laser diode was used for the optical power supply and was mounted on an aluminum V-plate along with the modulator array and commercially available optics for imaging the SEED output into the fiber bundle. Each modulator consisted of a single MQW diode of a symmetric SEED pair, thus the links were single rail. Sixteen SEED modulators with 10-μm round windows were used within a 16 × 8 array spaced on a 160 × 160 μm pitch. The receiver multichip module consisted of sixteen Antel AOE1003 integrated detector/amplifiers mounted in a 4 × 4 format on a 2.62-mm pitch. The system operated synchronously at 35 Mbps/channel. We show link performance (speed, crosstalk, skew, power dissipation) and describe possible uses of this system for board to board interconnection.</jats:p

Computerized Histologic Image-Based Risk Score (IbRiS) Classifier for ER+ Breast Cancer.

Abstract Background: Measurement of estrogen receptor (ER) expression is a routine part of clinical evaluation of individual breast cancers and is used to guide treatment. However not all ER+ breast cancers show equal benefit from hormonal or other treatment. The RT-PCR based Oncotype Dx assay, has been recently shown to robustly stratify early stage ER+ breast cancer and identify those tumors that will have low recurrence rates when treated with adjuvant hormonal therapy alone. Interestingly, standard pathologic grading, based on visual analysis of tumor morphology by trained pathologists, has a strong correlation with Oncotype Dx recurrence scores; low recurrence tumors are mostly low grade, and high recurrence tumors are mostly high grade. However, a major problem with use of pathologist-assigned histologic grade as a prognostic tool is the lack of reproducibility of histological grading between different pathologists. Computer aided image analysis and machine learning techniques offer a way to obtain highly reproducible image-based classification of ER+ breast cancer. These analyses can be performed on digital images of routinely obtained breast cancer histology and be incorporated into a prognostic assay.Materials and Methods: High resolution digital images were obtained for a series of ER+ breast cancers for which associated Oncotype Dx Assay results were available. Regions of invasive breast cancer were identified and then processed by computer-assisted image analysis methods. An automated nuclear detection scheme based on Expectation Maximization algorithm was used to identify cancer cell nuclei, followed by graph-based feature extraction using the Voronoi graph, Delaunay Triangulation and Minimum Spanning Trees, and dimensionality reduction using Graph Embedding with Support Vector Machine based classification. The final manifold generated by GE was unwrapped into a linear space and a Euclidean distance metric was used to generate a single score (Image Based Risk Score- (IbRiS)) for each sample. Correlations between IbRS, clinical features such as grade, and Oncotype Dx Recurrance Score were determined.Results: Unsupervised analysis of image-based features of high resolution digital images of ER+ breast cancer histology leads to natural separation of tumors, with low grade tumors separating from high grade tumors. There is also a robust separation of tumors with high Oncotype Dx Recurrance Scores from tumors with low Recurrance Scores.Discussion: Unsupervised analysis of high resolution image-based features can stratify ER+ breast cancers in a fashion that correlates well with a gene-expression based prognostic assay, Oncotype Dx. These data suggest that tumors with distinct gene-expression profiles also have distinct image-based features that can be measured by computer-aided image analysis and used to build prognostic and predictive assays. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3046.</jats:p

Abstract P2-03-01: Computer extracted image texture features on T2-weighted MRI appear to correlate with nuclear morphologic descriptors from H&amp;E-stained histopathology in estrogen receptor positive breast cancers

Abstract Oncotype DX (ODX) is a 21 panel gene-expression based assay for predicting whether patients with estrogen receptor-positive (ER+) breast cancer (BCa) are candidates for adjuvant chemotherapy. However, the time and expense associated with genomic assays suggests the need for a non-invasive, imaging-based, pre-therapeutic tool for assessment of disease risk and selection of an appropriate treatment regimen. The objective of this research was to determine whether (a) computer extracted image features on T2-weighted (T2w) MRI and H&amp;E stained histopathology are independently able to distinguish ER+ BCa with low and high ODX recurrence scores (RS) and (b) to determine whether there is a correlation between MRI and histologic features identified as being predictive of low and high ODX risk categories. A total of 11 ER+ BCa patients were considered in this study, based on availability of in vivo 1.5 Tesla T2w MRI. For each study, the corresponding formalin-fixed paraffin-embedded H&amp;E stained tissue specimens were digitized at 20x (0.5 μm/pixel) using a whole-slide scanner. Of the 11 patients, 8 were identified in the low ODX (RS &amp;lt; 18) and 3 in the high ODX (RS &amp;gt; 30) risk categories. Each dataset was accompanied by expert annotations of (a) the lesion ROI on MRI and (b) boundaries of epithelial nuclei from a representative field-of-view on the digitized histology slide. For each MRI study, a multi-scale, multi-orientation Gabor filter bank was convolved with the annotated lesion area providing a set of 192 texture features (FMRI). For each corresponding histology image, 471 features (FHIST) were extracted describing both nuclear morphology (NM) and Laws texture (LT) within the nuclear regions. Independent 2-sample t-tests were used to identify salient features in FMRI and FHIST that are able to distinguish low and high ODX risk categories. We found that, for the MRI dataset, Gabor texture features at several scales and orientations yielded salient features (p &amp;lt; 0.05) while on histopathology, nuclear texture and convexity (shape) features were identified as the top discriminative features (p &amp;lt; 0.01). Relationships between significant features were evaluated via Spearman's rank correlation test (see table), where high correlations were observed between lesion texture on T2w MRI and nuclear texture and shape on histology. Correlation of histologic and MRI features able to distinguish low and high ODX RSHistologic feature correlated with ODXMRI feature correlated with ODXCorrelation coefficient (ρ)p-valueLT: 70 Mean HSVGF: Scale 2: Orientation 3: min/max-0.85450.0008NM: ConvexityGF: Scale 5: Orientation 6: mean-0.85450.0008LT: 70 Mean HSVGF: Scale 2: Orientation 3: min/max-0.83640.0013LT: 70 Mean HSVGF: Scale 3: Orientation 8: mean-0.83640.0013LT: 70 Mean HSVGF: Scale 3: Orientation 2: mean-0.81820.0021 Our results suggest that quantitative features extracted on both T2w MRI and histopathology can independently distinguish between low and high risk ODX classes. Moreover, some of these MRI and histologic features appear to be significantly correlated, suggesting that information regarding tumor biology is reflected in both MRI and histologic image features. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-03-01.</jats:p