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Background: Determining mitotic index by counting mitotic figures (MFs) microscopically from tumor areas with most abundant MF (hotspots [HS]) produces a prognostically useful tumor grading biomarker. However, interobserver concordance identifying MF and HS can be poorly reproducible. Immunolabeling MF, coupled with computer-automated counting by image analysis, can improve reproducibility. A computational system for obtaining MF values across digitized whole-slide images (WSIs) was sought that would minimize impact of artifacts, generate values clinically relatable to counting ten high-power microscopic fields of view typical in conventional microscopy, and that would reproducibly map HS topography. Materials and Methods: Relatively low-resolution WSI scans (0.50 µm/pixel) were imported in grid-tile format for feature-based MF segmentation, from naturally occurring canine melanomas providing a wide range of proliferative activity. MF feature extraction conformed to anti-phospho-histone H3-immunolabeled mitotic (M) phase cells. Computer vision image processing was established to subtract key artifacts, obtain MF counts, and employ rotationally invariant feature extraction to map MF topography. Results: The automated topometric HS (TMHS) algorithm identified mitotic HS and mapped select tissue tiles with greatest MF counts back onto WSI thumbnail images to plot HS topographically. Influence of dye, pigment, and extraneous structure artifacts was minimized. TMHS diagnostic decision support included image overlay graphics of HS topography, as well as a spreadsheet and plot of tile-based MF count values. TMHS performance was validated examining both mitotic HS counting and mapping functions. Significantly correlated TMHS MF mapping and metrics were demonstrated using repeat analysis with WSI in different orientation (R2 = 0.9916) and by agreement with a pathologist (R2 = 0.8605) as well as through assessment of counting function using an independently tuned object counting algorithm (OCA) (R2 = 0.9482). Limits of agreement analysis support method interchangeability. MF counts obtained led to accurate patient survival prediction in all (n = 30) except one case. By contrast, more variable performance was documented when several pathologists examined similar cases using microscopy (pair-wise correlations, rho range = 0.7597-0.9286). Conclusions: Automated TMHS MF segmentation and feature engineering performance were interchangeable with both observer and OCA in digital mode. Moreover, enhanced HS location accuracy and superior method reproducibility were achieved using the automated TMHS algorithm compared to the current practice employing clinical microscopy.

Digital pathology is rapidly developing, but early systems have been slow to gain traction outside of niche applications such as: Second-opinion telepathology, immunostain interpretation, and intraoperative telepathology. Pathologists have not yet developed a well-articulated plan for effectively utilizing digital imaging technology in their work. This paper outlines a proposal that is intended to begin meaningful progress toward achieving helpful computer-assisted pathology sign-out systems, such as pathologists′ computer-assisted diagnosis (pCAD). pCAD is presented as a hypothetical intelligent computer system that would integrate advanced image analysis and better utilization of existing digital pathology data from lab information systems. A detailed example of automated digital pathology is presented, as an automated breast cancer lymph node sign-out. This proposal provides stakeholders with a conceptual framework that can be used to facilitate development work, communication, and identification of new automation strategies.

Techniques for digital pathology are envisioned to provide great benefits in clinical practice, but experiences also show that solutions must be carefully crafted. The Nordic countries are far along the path toward the use of whole-slide imaging in clinical routine. The Nordic Symposium on Digital Pathology (NDP) was created to promote knowledge exchange in this area, between stakeholders in health care, industry, and academia. This article is a summary of the NDP 2014 symposium, including conclusions from a workshop on clinical adoption of digital pathology among the 144 attendees.

Data processing and learning has become a spearhead for the advancement of medicine, with pathology and laboratory medicine has no exception. The incorporation of scientific research through clinical informatics, including genomics, proteomics, bioinformatics, and biostatistics, into clinical practice unlocks innovative approaches for patient care. Computational pathology is burgeoning subspecialty in pathology that promises a better-integrated solution to whole-slide images, multi-omics data, and clinical informatics. However, computational pathology faces several challenges, including the ability to integrate raw data from different sources, limitation of hardware processing capacity, and a lack of specific training programs, as well as issues on ethics and larger societal acceptable practices that are still solidifying. The establishment of the entire industry of computational pathology requires far-reaching changes of the three essential elements connecting patients and doctors: the local laboratory, the scan center, and the central cloud hub/portal for data processing and retrieval. Computational pathology, unlocked through information integration and advanced digital communication networks, has the potential to improve clinical workflow efficiency, diagnostic quality, and ultimately create personalized diagnosis and treatment plans for patients. This review describes clinical perspectives and discusses the statistical methods, clinical applications, potential obstacles, and future directions of computational pathology.

The aim of this work is to develop a Computer-Aided-Brain-Diagnosis (CABD) system that can determine if a brain scan shows signs of Alzheimer’s disease. The method utilizes Magnetic Resonance Imaging (MRI) for classification with several feature extraction techniques. MRI is a non-invasive procedure, widely adopted in hospitals to examine cognitive abnormalities. Images are acquired using the T2 imaging sequence. The paradigm consists of a series of quantitative techniques: filtering, feature extraction, Student’s t-test based feature selection, and k-Nearest Neighbor (KNN) based classification. Additionally, a comparative analysis is done by implementing other feature extraction procedures that are described in the literature. Our findings suggest that the Shearlet Transform (ST) feature extraction technique offers improved results for Alzheimer’s diagnosis as compared to alternative methods. The proposed CABD tool with the ST + KNN technique provided accuracy of 94.54%, precision of 88.33%, sensitivity of 96.30% and specificity of 93.64%. Furthermore, this tool also offered an accuracy, precision, sensitivity and specificity of 98.48%, 100%, 96.97% and 100%, respectively, with the benchmark MRI database.

Objectives(1) To assess the methodological quality of radiomics studies investigating histological subtypes, therapy response, and survival in patients with renal cell carcinoma (RCC) and (2) to determine the risk of bias in these radiomics studies.MethodsIn this systematic review, literature published since 2000 on radiomics in RCC was included and assessed for methodological quality using the Radiomics Quality Score. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool and a meta-analysis of radiomics studies focusing on differentiating between angiomyolipoma without visible fat and RCC was performed.ResultsFifty-seven studies investigating the use of radiomics in renal cancer were identified, including 4590 patients in total. The average Radiomics Quality Score was 3.41 (9.4% of total) with good inter-rater agreement (ICC 0.96, 95% CI 0.93–0.98). Three studies validated results with an independent dataset, one used a publically available validation dataset. None of the studies shared the code, images, or regions of interest. The meta-analysis showed moderate heterogeneity among the included studies and an odds ratio of 6.24 (95% CI 4.27–9.12; p < 0.001) for the differentiation of angiomyolipoma without visible fat from RCC.ConclusionsRadiomics algorithms show promise for answering clinical questions where subjective interpretation is challenging or not established. However, the generalizability of findings to prospective cohorts needs to be demonstrated in future trials for progression towards clinical translation. Improved sharing of methods including code and images could facilitate independent validation of radiomics signatures.Key Points• Studies achieved an average Radiomics Quality Score of 10.8%. Common reasons for low Radiomics Quality Scores were unvalidated results, retrospective study design, absence of open science, and insufficient control for multiple comparisons.• A previous training phase allowed reaching almost perfect inter-rater agreement in the application of the Radiomics Quality Score.• Meta-analysis of radiomics studies distinguishing angiomyolipoma without visible fat from renal cell carcinoma show moderate diagnostic odds ratios of 6.24 and moderate methodological diversity.

The Function Biomedical Informatics Research Network (FBIRN) developed methods and tools for conducting multi-scanner functional magnetic resonance imaging (fMRI) studies. Method and tool development were based on two major goals: 1) to assess the major sources of variation in fMRI studies conducted across scanners, including instrumentation, acquisition protocols, challenge tasks, and analysis methods, and 2) to provide a distributed network infrastructure and an associated federated database to host and query large, multi-site, fMRI and clinical data sets. In the process of achieving these goals the FBIRN test bed generated several multi-scanner brain imaging data sets to be shared with the wider scientific community via the BIRN Data Repository (BDR). The FBIRN Phase 1 data set consists of a traveling subject study of 5 healthy subjects, each scanned on 10 different 1.5 to 4T scanners. The FBIRN Phase 2 and Phase 3 data sets consist of subjects with schizophrenia or schizoaffective disorder along with healthy comparison subjects scanned at multiple sites. In this paper, we provide concise descriptions of FBIRN's multi-scanner brain imaging data sets and details about the BIRN Data Repository instance of the Human Imaging Database (HID) used to publicly share the data. •This manuscript presents Function Biomedical Informatics Research Network data.•FBIRN data are shared via the BIRN Data Repository and SchizConnect.•FBIRN shares data from individuals with schizophrenia and healthy controls.•FBIRN shares structural and functional brain imaging, clinical, and cognitive data.

This protocol describes how to perform CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis), a simple and efficient method for organ clearing, imaging by light-sheet microscopy, and quantitative imaging analysis. Here we describe a protocol for advanced CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational analysis). The CUBIC protocol enables simple and efficient organ clearing, rapid imaging by light-sheet microscopy and quantitative imaging analysis of multiple samples. The organ or body is cleared by immersion for 1–14 d, with the exact time required dependent on the sample type and the experimental purposes. A single imaging set can be completed in 30–60 min. Image processing and analysis can take <1 d, but it is dependent on the number of samples in the data set. The CUBIC clearing protocol can process multiple samples simultaneously. We previously used CUBIC to image whole-brain neural activities at single-cell resolution using Arc-dVenus transgenic (Tg) mice. CUBIC informatics calculated the Venus signal subtraction, comparing different brains at a whole-organ scale. These protocols provide a platform for organism-level systems biology by comprehensively detecting cells in a whole organ or body.

Brain tumor is one of the most death defying diseases nowadays. The tumor contains a cluster of abnormal cells grouped around the inner portion of human brain. It affects the brain by squeezing/ damaging healthy tissues. It also amplifies intra cranial pressure and as a result tumor cells growth increases rapidly which may lead to death. It is, therefore desirable to diagnose/ detect brain tumor at an early stage that may increase the patient survival rate. The major objective of this research work is to present a new technique for the detection of tumor. The proposed architecture accurately segments and classifies the benign and malignant tumor cases. Different spatial domain methods are applied to enhance and accurately segment the input images. Moreover Alex and Google networks are utilized for classification in which two score vectors are obtained after the softmax layer. Further, both score vectors are fused and supplied to multiple classifiers along with softmax layer. Evaluation of proposed model is done on top medical image computing and computer-assisted intervention (MICCAI) challenge datasets i.e., multimodal brain tumor segmentation (BRATS) 2013, 2014, 2015, 2016 and ischemic stroke lesion segmentation (ISLES) 2018 respectively.

Alcohol use disorder (AUD) is an important brain disease. It alters the brain structure. Recently, scholars tend to use computer vision based techniques to detect AUD. We collected 235 subjects, 114 alcoholic and 121 non-alcoholic. Among the 235 image, 100 images were used as training set, and data augmentation method was used. The rest 135 images were used as test set. Further, we chose the latest powerful technique—convolutional neural network (CNN) based on convolutional layer, rectified linear unit layer, pooling layer, fully connected layer, and softmax layer. We also compared three different pooling techniques: max pooling, average pooling, and stochastic pooling. The results showed that our method achieved a sensitivity of 96.88%, a specificity of 97.18%, and an accuracy of 97.04%. Our method was better than three state-of-the-art approaches. Besides, stochastic pooling performed better than other max pooling and average pooling. We validated CNN with five convolution layers and two fully connected layers performed the best. The GPU yielded a 149× acceleration in training and a 166× acceleration in test, compared to CPU.