An Experimental Platform for Tomographic Reconstruction of Tissue Images in Brightfield Microscopy.

(1) Background: Reviewing biological material under the microscope is a demanding and time-consuming process, prone to diagnostic pitfalls. In this study, a methodology for tomographic imaging of tissue sections is presented, relying on the idea that each tissue sample has a finite thickness and, therefore, it is possible to create images at different levels within the sample, revealing details that would probably not be seen otherwise. (2) Methods: Optical slicing was possible by developing a custom-made microscopy stage controlled by an ARDUINO. The custom-made stage, besides the normal sample movements that it should provide along the x-, y-, and z- axes, may additionally rotate the sample around the horizontal axis of the microscope slide. This rotation allows the conversion of the optical microscope into a CT geometry, enabling optical slicing of the sample using projection-based tomographic reconstruction algorithms. (3) Results: The resulting images were of satisfactory quality, but they exhibited some artifacts, which are particularly evident in the axial plane images. (4) Conclusions: Using classical tomographic reconstruction algorithms at limited angles, it is possible to investigate the sample at any desired optical plane, revealing information that would be difficult to identify when focusing only on the conventional 2D images.

Correction: Kogionou et al. Radiotherapy-Related Gene Signature in Prostate Cancer. Cancers 2022, 14, 5032.

The authors wish to make the following corrections to this paper [...].

A Robust Machine Learning Framework Built Upon Molecular Representations Predicts CYP450 Inhibition: Toward Precision in Drug Repurposing.

Human cytochrome P450 (CYP450) enzymes play a crucial role in drug metabolism and pharmacokinetics. CYP450 inhibition can lead to toxicity, in particular when drugs are co-administered with other drugs and xenobiotics or in the case of polypharmacy. Predicting CYP450 inhibition is also important for rational drug discovery and development, and precision in drug repurposing. In this overarching context, digital transformation of drug discovery and development, for example, using machine and deep learning approaches, offers prospects for prediction of CYP450 inhibition through computational models. We report here the development of a majority-voting machine learning framework to classify inhibitors and noninhibitors for seven major human liver CYP450 isoforms (CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4). For the machine learning models reported herein, we employed interaction fingerprints that were derived from molecular docking simulations, thus adding an additional layer of information for protein-ligand interactions. The proposed machine learning framework is based on the structure of the binding site of isoforms to produce predictions beyond previously reported approaches. Also, we carried out a comparative analysis so as to identify which representation of test compounds (molecular descriptors, molecular fingerprints, or protein-ligand interaction fingerprints) affects the predictive performance of the models. This work underlines the ways in which the structure of the enzyme catalytic site influences machine learning predictions and the need for robust frameworks toward better-informed predictions.

Potential Health Benefits of Banana Phenolic Content during Ripening by Implementing Analytical and In Silico Techniques.

Banana ranks as the fifth most cultivated agricultural crop globally, highlighting its crucial socio-economic role. The banana's health-promoting benefits are correlated with its composition in bioactive compounds, such as phenolic compounds. Thus, the present study attempts to evaluate the potential health benefits of banana phenolic content by combing analytical and in silico techniques. Particularly, the total phenolic content and antioxidant/antiradical activity of banana samples during ripening were determined spectrophotometrically. In parallel, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was implemented to unravel the variations in the phenolic profile of banana samples during ripening. Chlorogenic acid emerged as a ripening marker of banana, while apigenin and naringenin were abundant in the unripe fruit. In a further step, the binding potential of the elucidated phytochemicals was examined by utilizing molecular target prediction tools. Human carbonic anhydrase II (hCA-II) and XII (hCA-XII) enzymes were identified as the most promising targets and the inhibitory affinity of phenolic compounds was predicted through molecular docking studies. This class of enzymes is linked to a variety of pathological conditions, such as edema, obesity, hypertension, cancer, etc. The results assessment indicated that all assigned phenolic compounds constitute great candidates with potential inhibitory activity against CA enzymes.

Radiotherapy-Related Gene Signature in Prostate Cancer.

Radiotherapy for localized prostate cancer has increased the cure and survival rates of patients. Besides its local tumoricidal effects, ionizing radiation has been linked to mechanisms leading to systemic immune activation, a phenomenon called the abscopal effect. In this study, we performed gene expression analysis on peripheral blood from prostate cancer patients obtained post- radiotherapy and showed that 6 genes, including CCR7, FCGR2B, BTLA, CD6, CD3D, and CD3E, were down-regulated by a range of 1.5-2.5-fold as compared to pre-radiotherapy samples. The expression of the signature consisting of these six genes was also significantly lower post- vs. pre-radiotherapy. These genes are involved in various tumor-promoting immune pathways and their down-regulation post-radiotherapy could be considered beneficial for patients. This is supported by the fact that low mRNA expression levels for the 6-gene signature in the prostate tumor tissue was linked to better survival. Importantly, we report that this 6-gene signature strongly correlated with a favorable prognosis regardless of poor standard clinicopathological parameters (i.e., Gleason score ≥ 8 and T3 (including T3a and T3b). Our pioneering data open the possibility that the 6-gene signature identified herein may have a predictive value, but this requires further long-term studies.

A 3-miRNA Signature Enables Risk Stratification in Glioblastoma Multiforme Patients with Different Clinical Outcomes.

Malignant gliomas constitute a complex disease phenotype that demands optimum decision-making as they are highly heterogeneous. Such inter-individual variability also renders optimum patient stratification extremely difficult. microRNA (hsa-miR-20a, hsa-miR-21, hsa-miR-21) expression levels were determined by RT-qPCR, upon FFPE tissue sample collection of glioblastoma multiforme patients (n = 37). In silico validation was then performed through discriminant analysis. Immunohistochemistry images from biopsy material were utilized by a hybrid deep learning system to further cross validate the distinctive capability of patient risk groups. Our standard-of-care treated patient cohort demonstrates no age- or sex- dependence. The expression values of the 3-miRNA signature between the low- (OS > 12 months) and high-risk (OS < 12 months) groups yield a p-value of <0.0001, enabling risk stratification. Risk stratification is validated by a. our random forest model that efficiently classifies (AUC = 97%) patients into two risk groups (low- vs. high-risk) by learning their 3-miRNA expression values, and b. our deep learning scheme, which recognizes those patterns that differentiate the images in question. Molecular-clinical correlations were drawn to classify low- (OS > 12 months) vs. high-risk (OS < 12 months) glioblastoma multiforme patients. Our 3-microRNA signature (hsa-miR-20a, hsa-miR-21, hsa-miR-10a) may further empower glioblastoma multiforme prognostic evaluation in clinical practice and enrich drug repurposing pipelines.

Three-dimensional tissue volume generation in conventional brightfield microscopy.

The purpose of the study is to develop and automate a series of steps for enabling digital 3D tissue volume generation in conventional Brightfield microscopy for histopathology applications. Tissue samples were retrieved from the General Hospital of Athens "Hippocration", Greece. Samples were placed on a microtome that produced consecutive 2 µm sections. Each section was stained using Hematoxylin and Eosin and placed on microscope slides. A histopathologist specified the region of interest (ROI) on each slide. A 2D image was created from each ROI using a LEICA DM2500 microscope with a LEICA DFC 420C camera. Τhe 3D volume was created by stacking consecutive 2D images using a deep learning image interpolation method. The reconstructed 3D tissue volumes were evaluated by an expert histopathologist. Results showed that the 3D volumes might reveal information that is not clearly visible or even undetectable in the conventional 2D Brightfield images. In contrast to other 3D tissue imaging technologies, the proposed method (a) does not depend on the distance of the sample from the objectives producing 3D tissue volumes at any desired magnification, (b) does not require a special instrument, it may be implemented with any conventional Brightfield microscope, and (c) can be used for any given routine application, not only for some specialized clinical studies. The proposed study provides the basis for a feasible, cost-less and time-less upgrade of any standard 2D microscope into a 3D imaging instrument that may enhance the quality of diagnostic assessments in histopathology. HIGHLIGHTS: A method for 3D tissue volume generation. 3D volumes reveal information not clearly visible or even undetectable in 2D images. A method for feasible, cost-less and time-less upgrade of any Brightfield 2D microscope into a 3D imaging instrument.

Employing machine learning and microscopy images of AIB1-stained biopsy material to assess the 5-year survival of patients with colorectal cancer.

Our purpose was to employ microscopy images of amplified in breast cancer 1 (AIB1)-stained biopsy material of patients with colorectal cancer (CRC) to: (a) find statistically significant differences (SSDs) in the texture and color of the epithelial gland tissue, between 5-year survivors and non-survivors after the first diagnosis and (b) employ machine learning (ML) methods for predicting the CRC-patient 5-year survival. We collected biopsy material from 54 patients with diagnosed CRC from the archives of the University Hospital of Patras, Greece. Twenty-six of the patients had survived 5 years after the first diagnosis. We selected regions of interest containing the epithelial gland at different microscope lens magnifications. We computed 69 textural and color features. Furthermore, we identified features with SSDs between the two groups of patients and we designed a supervised ML system for predicting the CRC-patient 5-year survival. Additionally, we employed the VGG16 pretrained convolution neural network to extract deep learning (DL) features, the support vector machines classifier, and the bootstrap cross-validation method for boosting the accuracy of predicting 5-year survival. Fourteen features sustained SSDs between the two groups of patients. The supervised ML system achieved 87% accuracy in predicting 5-year survival. In comparison, the DL system, using images from all magnifications, gave 97% classification accuracy. Glandular texture in 5-year non-survivors appeared to be of lower contrast, coarseness, roughness, local pixel correlation, and lower AIB1 variation, all indicating loss of textural definition. The supervised ML system revealed useful information regarding features that discriminate between 5-year survivors and non-survivors while the DL system displayed superior accuracy by employing DL features.

Assessment of HPV Risk Type in H&E-stained Biopsy Specimens of the Cervix by Microscopy Image Analysis.

OBJECTIVES: The objective of this study was (a) to identify, by computer processing of digitized images of hematoxylin and eosin (H&E)-stained biopsy material of the cervix, differences in the structure of nuclei between high-risk (HR) and low-risk (LR) human papillomavirus virus (HPV) types and (b) to assess the HPV risk type by designing a decision-support system (DSS). MATERIALS AND METHODS: Clinical material comprised H&E-stained biopsies from squamous intraepithelial lesions of 55 patients with polymerase chain reaction-verified HR-HPV (26 patients) or LR-HPV (29 patients) infection. From each patient's biopsy specimen, we digitized 1 region of interest, guided by the expert physician. After the segmentation of nuclei, we quantified from each nucleus 77 textural and morphologic features. We represented each patient by a 77-feature vector, the feature means of all nuclei, and we created 2 classes for HR-HPV and LR-HPV types. We carried out (a) a statistical analysis to determine features with statistically significant differences between the 2 classes and (b) a discriminant analysis, by designing a DSS, to estimate the HPV risk type. RESULTS: Statistical analysis revealed 40 features with between-classes statistically significant differences and discriminant analysis showed that the best DSS design achieved a high accuracy of about 93% in identifying the HPV risk type on data not used in the design of the DSS. CONCLUSIONS: Nuclei of HR-HPV types were of higher intensity, contained larger structures, had higher edges, were coarser, rougher, had higher contrast, were larger, and attained more irregular shapes. The proposed DSS indicates that discrimination of HPV risk type from images of H&E-stained biopsy material of the cervix is promising.

GPU-enabled design of an adaptable pattern recognition system for discriminating squamous intraepithelial lesions of the cervix.

The aim of the present study was to design an adaptable pattern recognition (PR) system to discriminate low- from high-grade squamous intraepithelial lesions (LSIL and HSIL, respectively) of the cervix using microscopy images of hematoxylin and eosin (H&E)-stained biopsy material from two different medical centers. Clinical material comprised H&E-stained biopsies of 66 patients diagnosed with LSIL (34 cases) or HSIL (32 cases). Regions of interest were selected from each patient's digitized microscopy images. Seventy-seven features were generated, regarding the texture, morphology and spatial distribution of nuclei. The probabilistic neural network (PNN) classifier, the exhaustive search feature selection method, the leave-one-out (LOO) and the bootstrap validation methods were used to design the PR system and to assess its precision. Optimal PR system design and evaluation were made feasible by the employment of graphics processing unit (GPU) and Compute Unified Device Architecture (CUDA) technologies. The accuracy of the PR-system was 93% and 88.6% when using the LOO and bootstrap validation methods, respectively. The proposed PR system for discriminating LSIL from HSIL of the cervix was designed to operate in a clinical environment, having the capability of being redesigned when new verified cases are added to its repository and when data from other medical centers are included, following similar biopsy material preparation procedures.

Correlating Changes in the Epithelial Gland Tissue With Advancing Colorectal Cancer Histologic Grade, Using IHC Stained for AIB1 Expression Biopsy Material.

OBJECTIVE: The objective of this study was to study the textural and color changes occurring in the epithelial gland tissue with advancing colorectal cancer (CRC), utilizing immunohistochemical stain for AIB1 expression biopsy material. MATERIAL AND METHODS: Clinical material comprised biopsy specimens of 67 patients with a diagnosis of CRC. Two experienced pathologists used H&E-stained material for grading CRC lesions and immunohistochemical (IHC) stain for AIB1 expression. Twenty six patients were diagnosed with grade I, 28 with grade II, and 13 with grade III CRC. Guided by pathologists, we selected the regions of interest from AIB1-digitized images of each patient, encompassing the epithelial gland, and we computed 69 features, quantifying textural and color properties of the AIB1-stained lesions. We evaluated the statistical differences between grades by means of the Wilcoxon statistical test for each feature, and we assessed changes in feature values with advancing tumor grade by means of the Point Biserial Correlation. RESULTS: Statistical analysis revealed 14 single features, quantifying textural and color properties of the epithelial gland, which sustained statistically significant differences between LG-CRC and HG-CRC cases. These features were drawn from the gray-level image histogram, the cooccurrence matrix, the run length matrix, the discrete wavelet transform, the Tamura method, and the L*a*b color transform. CONCLUSIONS: A systematic statistical analysis of AIB1-stained biopsy material showed that high-grade CRC lesions contain higher intensity levels, appear coarser, are more homogeneous with smooth variation across the image, have lower contrast that is slowly varying across the image, have lower AIB1 staining, and have lower edges. A combination of textural and color attributes, evaluating image gray-tone distribution, textural roughness, inhomogeneity, AIB1 staining, and image coarseness should be considered in evaluating AIB1-stained CRC lesions.

Multifeature Quantification of Nuclear Properties from Images of H&E-Stained Biopsy Material for Investigating Changes in Nuclear Structure with Advancing CIN Grade.

Background: Cervical dysplasia is a precancerous condition, and if left untreated, it may lead to cervical cancer, which is the second most common cancer in women. The purpose of this study was to investigate differences in nuclear properties of the H&E-stained biopsy material between low CIN and high CIN cases and associate those properties with the CIN grade. Methods: The clinical material comprised hematoxylin and eosin- (H&E-) stained biopsy specimens from lesions of 44 patients diagnosed with cervical intraepithelial neoplasia (CIN). Four or five nonoverlapping microscopy images were digitized from each patient's H&E specimens, from regions indicated by the expert physician. Sixty-three textural and morphological nuclear features were generated for each patient's images. The Wilcoxon statistical test and the point biserial correlation were used to estimate each feature's discriminatory power between low CIN and high CIN cases and its correlation with the advancing CIN grade, respectively. Results: Statistical analysis showed 19 features that quantify nuclear shape, size, and texture and sustain statistically significant differences between low CIN and high CIN cases. These findings revealed that nuclei in high CIN cases, as compared to nuclei in low CIN cases, have more irregular shape, are larger in size, are coarser in texture, contain higher edges, have higher local contrast, are more inhomogeneous, and comprise structures of different intensities. Conclusion: A systematic statistical analysis of nucleus features, quantified from the H&E-stained biopsy material, showed that there are significant differences in the shape, size, and texture of nuclei between low CIN and high CIN cases.

Image quilting and wavelet fusion for creation of synthetic microscopy nuclei images.

BACKGROUND AND OBJECTIVE: In this study a texture simulation methodology is proposed for composing synthetic tissue microscopy images that could serve as a quantitative gold standard for the evaluation of the reliability, accuracy and performance of segmentation algorithms in computer-aided diagnosis. METHODS: A library of background and nuclei regions was generated using pre-segmented Haematoxylin and Eosin images of brain tumours. Background image samples were used as input to an image quilting algorithm that produced the synthetic background image. Randomly selected pre-segmented nuclei were randomly fused on the synthetic background using a wavelet-based fusion approach. To investigate whether the produced synthetic images are meaningful and similar to real world images, two different tests were performed, one qualitative by an experienced histopathologist and one quantitative using the normalized mutual information and the Kullback-Leibler tests. To illustrate the challenges that synthetic images may pose to object recognition algorithms, two segmentation methodologies were utilized for nuclei detection, one based on the Otsu thresholding and another based on the seeded region growing approach. RESULTS: Results showed a satisfactory to good resemblance of the synthetic with the real world images according to both qualitative and quantitative tests. The segmentation accuracy was slightly higher for the seeded region growing algorithm (87.2%) than the Otsu's algorithm (86.3%). CONCLUSIONS: Since we know the exact coordinates of the regions of interest within the synthesised images, these images could then serve as a 'gold standard' for evaluation of segmentation algorithms in computer-aided diagnosis in tissue microscopy.

Adaptable pattern recognition system for discriminating Melanocytic Nevi from Malignant Melanomas using plain photography images from different image databases.

OBJECTIVE: The aim of this study was to propose features that evaluate pictorial differences between melanocytic nevus (mole) and melanoma lesions by computer-based analysis of plain photography images and to design a cross-platform, tunable, decision support system to discriminate with high accuracy moles from melanomas in different publicly available image databases. MATERIAL AND METHODS: Digital plain photography images of verified mole and melanoma lesions were downloaded from (i) Edinburgh University Hospital, UK, (Dermofit, 330moles/70 melanomas, under signed agreement), from 5 different centers (Multicenter, 63moles/25 melanomas, publicly available), and from the Groningen University, Netherlands (Groningen, 100moles/70 melanomas, publicly available). Images were processed for outlining the lesion-border and isolating the lesion from the surrounding background. Fourteen features were generated from each lesion evaluating texture (4), structure (5), shape (4) and color (1). Features were subjected to statistical analysis for determining differences in pictorial properties between moles and melanomas. The Probabilistic Neural Network (PNN) classifier, the exhaustive search features selection, the leave-one-out (LOO), and the external cross-validation (ECV) methods were used to design the PR-system for discriminating between moles and melanomas. RESULTS: Statistical analysis revealed that melanomas as compared to moles were of lower intensity, of less homogenous surface, had more dark pixels with intensities spanning larger spectra of gray-values, contained more objects of different sizes and gray-levels, had more asymmetrical shapes and irregular outlines, had abrupt intensity transitions from lesion to background tissue, and had more distinct colors. The PR-system designed by the Dermofit images scored on the Dermofit images, using the ECV, 94.1%, 82.9%, 96.5% for overall accuracy, sensitivity, specificity, on the Multicenter Images 92.0%, 88%, 93.7% and on the Groningen Images 76.2%, 73.9%, 77.8% respectively. CONCLUSION: The PR-system as designed by the Dermofit image database could be fine-tuned to classify with good accuracy plain photography moles/melanomas images of other databases employing different image capturing equipment and protocols.

Development of a Reference Image Collection Library for Histopathology Image Processing, Analysis and Decision Support Systems Research.

Histopathology image processing, analysis and computer-aided diagnosis have been shown as effective assisting tools towards reliable and intra-/inter-observer invariant decisions in traditional pathology. Especially for cancer patients, decisions need to be as accurate as possible in order to increase the probability of optimal treatment planning. In this study, we propose a new image collection library (HICL-Histology Image Collection Library) comprising 3831 histological images of three different diseases, for fostering research in histopathology image processing, analysis and computer-aided diagnosis. Raw data comprised 93, 116 and 55 cases of brain, breast and laryngeal cancer respectively collected from the archives of the University Hospital of Patras, Greece. The 3831 images were generated from the most representative regions of the pathology, specified by an experienced histopathologist. The HICL Image Collection is free for access under an academic license at http://medisp.bme.teiath.gr/hicl/ . Potential exploitations of the proposed library may span over a board spectrum, such as in image processing to improve visualization, in segmentation for nuclei detection, in decision support systems for second opinion consultations, in statistical analysis for investigation of potential correlations between clinical annotations and imaging findings and, generally, in fostering research on histopathology image processing and analysis. To the best of our knowledge, the HICL constitutes the first attempt towards creation of a reference image collection library in the field of traditional histopathology, publicly and freely available to the scientific community.

Computer-based automated estimation of breast vascularity and correlation with breast cancer in DCE-MRI images.

Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) with gadolinium constitutes one of the most promising protocols for boosting up the sensitivity in breast cancer detection. The aim of this study was twofold: first to design an image processing methodology to estimate the vascularity of the breast region in DCE-MRI images and second to investigate whether the differences in the composition/texture and vascularity of normal, benign and malignant breasts may serve as potential indicators regarding the presence of the disease. Clinical material comprised thirty nine cases examined on a 3.0-T MRI system (SIGNA HDx; GE Healthcare). Vessel segmentation was performed using a custom made modification of the Seeded Region Growing algorithm that was designed in order to identify pixels belonging to the breast vascular network. Two families of features were extracted: first, morphological and textural features from segmented images in order to quantify the extent and the properties of the vascular network; second, textural features from the whole breast region in order to investigate whether the nature of the disease causes statistically important changes in the texture of affected breasts. Results have indicated that: (a) the texture of vessels presents statistically significant differences (p<0.001) between normal, benign and malignant cases, (b) the texture of the whole breast region for malignant and non-malignant breasts, produced statistically significant differences (p<0.001), (c) the relative ratios of the texture between the two breasts may be used for the discrimination of non-malignant from malignant patients, and (d) an area under the receiver operating characteristic curve of 0.908 (AUC) was found when features were combined in a logistic regression prediction rule according to ROC analysis.

Microscopy image analysis of p63 immunohistochemically stained laryngeal cancer lesions for predicting patient 5-year survival.

The aim of the present study was to design a microscopy image analysis (MIA) system for predicting the 5-year survival of patients with laryngeal squamous cell carcinoma, employing histopathology images of lesions, which had been immunohistochemically (IHC) stained for p63 expression. Biopsy materials from 42 patients, with verified laryngeal cancer and follow-up, were selected from the archives of the University Hospital of Patras, Greece. Twenty six patients had survived more than 5 years and 16 less than 5 years after the first diagnosis. Histopathology images were IHC stained for p63 expression. Images were first processed by a segmentation method for isolating the p63-expressed nuclei. Seventy-seven features were evaluated regarding texture, shape, and physical topology of nuclei, p63 staining, and patient-specific data. Those features, the probabilistic neural network classifier, the leave-one-out (LOO), and the bootstrap cross-validation methods, were used to design the MIA-system for assessing the 5-year survival of patients with laryngeal cancer. MIA-system accuracy was about 90 % and 85 %, employing the LOO and the Bootstrap methods, respectively. The image texture of p63-expressed nuclei appeared coarser and contained more edges in the 5-year non-survivor group. These differences were at a statistically significant level (p < 0.05). In conclusion, this study has proposed an MIA-system that may be of assistance to physicians, as a second opinion tool in assessing the 5-year survival of patients with laryngeal cancer, and it has revealed useful information regarding differences in nuclei texture between 5-year survivors and non-survivors.

Computer based correlation of the texture of P63 expressed nuclei with histological tumour grade, in laryngeal carcinomas.

BACKGROUND: P63 immunostaining has been considered as potential prognostic factor in laryngeal cancer. Considering that P63 is mainly nuclear stain, a possible correlation between the texture of P63-stained nuclei and the tumor's grade could be of value to diagnosis, since this may be related to biologic information imprinted as texture on P63 expressed nuclei. OBJECTIVE: To investigate the association between P63 stained nuclei and histologic grade in laryngeal tumor lesions. METHODS: Biopsy specimens from laryngeal tumour lesions of 55 patients diagnosed with laryngeal squamous cell carcinomas were immunohistochemically (IHC) stained for P63 expression. Four images were digitized from each patient's IHC specimens. P63 positively expressed nuclei were identified, the percentage of P63 expressed nuclei was computed, and 118 textural, morphological, shape, and architectural features were calculated from each one of the 55 laryngeal lesions. Data were split into the low grade (21 grade I lesions) and high grade (34 grade II and grade III lesions) classes for statistical analysis. RESULTS: With advancing grade, P63 expression decreased, P63 stained nuclei appeared of lower image intensity, more inhomogeneous, of higher local contrast, contained smaller randomly distributed dissimilar structures and had irregular shape. CONCLUSION: P63 expressed nuclei contain important information related to histologic grade.

Computer-based image analysis system designed to differentiate between low-grade and high-grade laryngeal cancer cases.

OBJECTIVE: To design a pattern recognition (PR) system for discriminating between low- and high-grade laryngeal cancer cases, employing immunohistochemically stained, for p63 expression, histopathology images. STUDY DESIGN: The PR system was designed to assist in the physician's diagnosis for improving patient survival. The material comprised 55 verified cases of laryngeal cancer, 21 of low-grade and 34 of high-grade malignancy. Histopathology images were first processed for automatically segmenting p63 expressed nuclei. Fifty-two features were next extracted from the segmented nuclei, concerning nuclei texture, shape, and physical topology in the image. Those features and the Probabilistic Neural Network classifier were used to design the PR system on the multiprocessors of the Nvidia 580 GTX graphics processing unit (GPU) card using the Compute Unified Device Architecture parallel programming model and C++ programming language. RESULTS: PR system performance in classifying laryngeal cancer cases as low grade and high grade was 85.7% and 94.1%, respectively. The system's overall accuracy was 90.9%, using 7 features, and its estimated accuracy to "unseen" by the system cases was 80%. CONCLUSION: Optimum system design was feasible after employing parallel processing techniques and GPU technology. The proposed system was structured so as to function in a clinical environment, as a research tool, and with the capability of being redesigned on site when new verified cases are added to its repository.

Multimodality GPU-based computer-assisted diagnosis of breast cancer using ultrasound and digital mammography images.

PURPOSE: To improve the computer-aided diagnosis of breast lesions, by designing a pattern recognition system (PR-system) on commercial graphics processing unit (GPU) cards using parallel programming and textural information from multimodality imaging. MATERIAL AND METHODS: Patients with histologically verified breast lesions underwent both ultrasound (US) and digital mammography (DM), lesions were outlined on the images by an experienced radiologist, and textural features were calculated. The PR-system was designed to provide highest possible precision by programming in parallel the multiprocessors of the NVIDIA's GPU cards, GeForce 8800GT or 580GTX, and using the CUDA programming framework and C++. The PR-system was built around the probabilistic neural network classifier, and its performance was evaluated by a re-substitution method, for estimating the system's highest accuracy, and by the external cross-validation method, for assessing the PR-system's unbiased accuracy to new, "unseen" by the system, data. RESULTS: Classification accuracies for discriminating malignant from benign lesions were as follows: 85.5 % using US-features alone, 82.3 % employing DM features alone, and 93.5 % combining US and DM features. Mean accuracy to new "unseen" data for the combined US and DM features was 81 %. Those classification accuracies were about 10 % higher than accuracies achieved on a single CPU, using sequential programming methods, and 150-fold faster. CONCLUSION: The proposed PR-system improves breast-lesion discrimination accuracy, it may be redesigned on site when new verified data are incorporated in its depository, and it may serve as a second opinion tool in a clinical environment.