Olcay Sertel

Computer-aided prognosis of neuroblastoma on whole-slide images: Classification of stromal development

We are developing a computer-aided prognosis system for neuroblastoma (NB), a cancer of the nervous system and one of the most malignant tumors affecting children. Histopathological examination is an important stage for further treatment planning in routine clinical diagnosis of NB. According to the International Neuroblastoma Pathology Classification (the Shimada system), NB patients are classified into favorable and unfavorable histology based on the tissue morphology. In this study, we propose an image analysis system that operates on digitized H&E stained whole-slide NB tissue samples and classifies each slide as either stroma-rich or stroma-poor based on the degree of Schwannian stromal development. Our statistical framework performs the classification based on texture features extracted using co-occurrence statistics and local binary patterns. Due to the high resolution of digitized whole-slide images, we propose a multi-resolution approach that mimics the evaluation of a pathologist such that the image analysis starts from the lowest resolution and switches to higher resolutions when necessary. We employ an offine feature selection step, which determines the most discriminative features at each resolution level during the training step. A modified k-nearest neighbor classifier is used to determine the confidence level of the classification to make the decision at a particular resolution level. The proposed approach was independently tested on 43 whole-slide samples and provided an overall classification accuracy of 88.4%.

Histopathological Image Analysis Using Model-Based Intermediate Representations and Color Texture: Follicular Lymphoma Grading

Follicular lymphoma (FL) is a cancer of lymph system and it is the second most common lymphoid malignancy in the western world. Currently, the risk stratification of FL relies on histological grading method, where pathologists evaluate hematoxilin and eosin (H&E) stained tissue sections under a microscope as recommended by the World Health Organization. This manual method requires intensive labor in nature. Due to the sampling bias, it also suffers from inter- and intra-reader variability and poor reproducibility. We are developing a computer-assisted system to provide quantitative assessment of FL images for more consistent evaluation of FL. In this study, we proposed a statistical framework to classify FL images based on their histological grades. We introduced model-based intermediate representation (MBIR) of cytological components that enables higher level semantic description of tissue characteristics. Moreover, we introduced a novel color-texture analysis approach that combines the MBIR with low level texture features, which capture tissue characteristics at pixel level. Experimental results on real follicular lymphoma images demonstrate that the combined feature space improved the accuracy of the system significantly. The implemented system can identify the most aggressive FL (grade III) with 98.9% sensitivity and 98.7% specificity and the overall classification accuracy of the system is 85.5%.

Computer-aided evaluation of neuroblastoma on whole-slide histology images: Classifying grade of neuroblastic differentiation

Neuroblastoma (NB) is one of the most frequently occurring cancerous tumors in children. The current grading evaluations for patients with this disease require pathologists to identify certain morphological characteristics with microscopic examinations of tumor tissues. Thanks to the advent of modern digital scanners, it is now feasible to scan cross-section tissue specimens and acquire whole-slide digital images. As a result, computerized analysis of these images can generate key quantifiable parameters and assist pathologists with grading evaluations. In this study, image analysis techniques are applied to histological images of haematoxylin and eosin (H&E) stained slides for identifying image regions associated with different pathological components. Texture features derived from segmented components of tissues are extracted and processed by an automated classifier group trained with sample images with different grades of neuroblastic differentiation in a multi-resolution framework. The trained classification system is tested on 33 whole-slide tumor images. The resulting whole-slide classification accuracy produced by the computerized system is 87.88%. Therefore, the developed system is a promising tool to facilitate grading whole-slide images of NB biopsies with high throughput.

Computerized classification of intraductal breast lesions using histopathological images

In the diagnosis of preinvasive breast cancer, some of the intraductal proliferations pose a special challenge. The continuum of intraductal breast lesions includes the usual ductal hyperplasia (UDH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS). The current standard of care is to perform percutaneous needle biopsies for diagnosis of palpable and image-detected breast abnormalities. UDH is considered benign and patients diagnosed UDH undergo routine follow-up, whereas ADH and DCIS are considered actionable and patients diagnosed with these two subtypes get additional surgical procedures. About 250 000 new cases of intraductal breast lesions are diagnosed every year. A conservative estimate would suggest that at least 50% of these patients are needlessly undergoing unnecessary surgeries. Thus, improvement in the diagnostic reproducibility and accuracy is critically important for effective clinical management of these patients. In this study, a prototype system for automatically classifying breast microscopic tissues to distinguish between UDH and actionable subtypes (ADH and DCIS) is introduced. This system automatically evaluates digitized slides of tissues for certain cytological criteria and classifies the tissues based on the quantitative features derived from the images. The system is trained using a total of 327 regions of interest (ROIs) collected across 62 patient cases and tested with a sequestered set of 149 ROIs collected across 33 patient cases. An overall accuracy of 87.9% is achieved on the entire test data. The test accuracy of 84.6% is obtained with borderline cases (26 of the 33 test cases) only, when compared against the diagnostic accuracies of nine pathologists on the same set (81.2% average), indicates that the system is highly competitive with the expert pathologists as a stand-alone diagnostic tool and has a great potential in improving diagnostic accuracy and reproducibility when used as a “second reader” in conjunction with the pathologists.

Coordinating the use of GPU and CPU for improving performance of compute intensive applications

GPUs have recently evolved into very fast parallel co-processors capable of executing general purpose computations extremely efficiently. At the same time, multi-core CPUs evolution continued and todays CPUs have 4-8 cores. These two trends, however, have followed independent paths in the sense that we are aware of very few works that consider both devices cooperating to solve general computations. In this paper we investigate the coordinated use of CPU and GPU to improve efficiency of applications even further than using either device independently. We use Anthill runtime environment, a data-flow oriented framework in which applications are decomposed into a set of event-driven filters, where for each event, the runtime system can use either GPU or CPU for its processing. For evaluation, we use a histopathology application that uses image analysis techniques to classify tumor images for neuroblas-toma prognosis. Our experimental environment includes dual and octa-core machines, augmented with GPUs and we evaluate our approachs performance for standalone and distributed executions. Our experiments show that a pure GPU optimization of the application achieved a factor of 15 to 49 times improvement over the single core CPU version, depending on the versions of the CPUs and GPUs. We also show that the execution can be further reduced by a factor of about 2 by using our runtime system that effectively choreographs the execution to run cooperatively both on GPU and on a single core of CPU. We improve on that by adding more cores, all of which were previously neglected or used ineffectively. In addition, the evaluation on a distributed environment has shown near linear scalability to multiple hosts.

Computer-Aided Detection of Centroblasts for Follicular Lymphoma Grading Using Adaptive Likelihood-Based Cell Segmentation

Follicular lymphoma (FL) is one of the most common lymphoid malignancies in the western world. FL has a variable clinical course, and important clinical treatment decisions for FL patients are based on histological grading, which is done by manually counting the large malignant cells called centroblasts (CB) in ten standard microscopic high-power fields from H&E-stained tissue sections. This method is tedious and subjective; as a result, suffers from considerable inter and intrareader variability even when used by expert pathologists. In this paper, we present a computer-aided detection system for automated identification of CB cells from H&E-stained FL tissue samples. The proposed system uses a unitone conversion to obtain a single-channel image that has the highest contrast. From the resulting image, which has a bimodal distribution due to the H&E stain, a cell-likelihood image is generated. Finally, a two-step CB detection procedure is applied. In the first step, we identify evident nonCB cells based on size and shape. In the second step, the CB detection is further refined by learning and utilizing the texture distribution of nonCB cells. We evaluated the proposed approach on 100 region-of-interest images extracted from ten distinct tissue samples and obtained a promising 80.7% detection accuracy.

Feature-based registration of histopathology images with different stains: An application for computerized follicular lymphoma prognosis

Follicular lymphoma (FL) is the second most common type of non-Hodgkins lymphoma. Manual histological grading of FL is subject to remarkable inter- and intra-reader variations. A promising approach to grading is the development of a computer-assisted system that improves consistency and precision. Correlating information from adjacent slides with different stain types requires establishing spatial correspondences between the digitized section pair through a precise non-rigid image registration. However, the dissimilar appearances of the different stain types challenges existing registration methods. This study proposes a method for the automatic non-rigid registration of histological section images with different stain types. This method is based on matching high level features that are representative of small anatomical structures. This choice of feature provides a rich matching environment, but also results in a high mismatch probability. Matching confidence is increased by establishing local groups of coherent features through geometric reasoning. The proposed method is validated on a set of FL images representing different disease stages. Statistical analysis demonstrates that given a proper feature set the accuracy of automatic registration is comparable to manual registration.

Adaptive Discriminant Wavelet Packet Transform and Local Binary Patterns for Meningioma Subtype Classification

The inherent complexity and non-homogeneity of texture makes classification in medical image analysis a challenging task. In this paper, we propose a combined approach for meningioma subtype classification using subband texture (macro) features and micro-texture features. These are captured using the Adaptive Wavelet Packet Transform (ADWPT) and Local Binary Patterns (LBPs), respectively. These two different textural features are combined together and used for classification. The effect of various dimensionality reduction techniques on classification performance is also investigated. We show that high classification accuracies can be achieved using ADWPT. Although LBP features do not provide higher overall classification accuracies than ADWPT, it manages to provide higher accuracy for a meningioma subtype that is difficult to classify otherwise.

Texture classification using nonlinear color quantization: Application to histopathological image analysis

In this paper, a novel color texture classification approach is introduced and applied to computer-assisted grading of follicular lymphoma from whole-slide tissue samples. The digitized tissue samples of follicular lymphoma were classified into histological grades under a statistical framework. The proposed method classifies the image either into low or high grades based on the amount of cytological components. To further discriminate the lower grades into low and mid grades, we proposed a novel color texture analysis approach. This approach modifies the gray level cooccurrence matrix method by using a nonlinear color quantization with self-organizing feature maps (SOFMs). This is particularly useful for the analysis of H&E stained pathological images whose dynamic color range is considerably limited. Experimental results on real follicular lymphoma images demonstrate that the proposed approach outperforms the gray level based texture analysis.

Computerized microscopic image analysis of follicular lymphoma

Follicular Lymphoma (FL) is a cancer arising from the lymphatic system. Originating from follicle center B cells, FL is mainly comprised of centrocytes (usually middle-to-small sized cells) and centroblasts (relatively large malignant cells). According to the World Health Organizations recommendations, there are three histological grades of FL characterized by the number of centroblasts per high-power field (hpf) of area 0.159 mm2. In current practice, these cells are manually counted from ten representative fields of follicles after visual examination of hematoxylin and eosin (H&E) stained slides by pathologists. Several studies clearly demonstrate the poor reproducibility of this grading system with very low inter-reader agreement. In this study, we are developing a computerized system to assist pathologists with this process. A hybrid approach that combines information from several slides with different stains has been developed. Thus, follicles are first detected from digitized microscopy images with immunohistochemistry (IHC) stains, (i.e., CD10 and CD20). The average sensitivity and specificity of the follicle detection tested on 30 images at 2×, 4× and 8× magnifications are 85.5±9.8% and 92.5±4.0%, respectively. Since the centroblasts detection is carried out in the H&E-stained slides, the follicles in the IHC-stained images are mapped to H&E-stained counterparts. To evaluate the centroblast differentiation capabilities of the system, 11 hpf images have been marked by an experienced pathologist who identified 41 centroblast cells and 53 non-centroblast cells. A non-supervised clustering process differentiates the centroblast cells from noncentroblast cells, resulting in 92.68% sensitivity and 90.57% specificity.