Spatiotemporal Identification of Cell Divisions Using Symmetry Properties in Time-Lapse Phase Contrast Microscopy

A variety of biological and pharmaceutical studies, such as for anti-cancer drugs, require the quantification of cell responses over long periods of time. This is performed with time-lapse video microscopy that gives a long sequence of frames. For this purpose, phase contrast imaging is commonly used since it is minimally invasive. The cell responses of interest in this study are the mitotic cell divisions. Their manual measurements are tedious, subjective, and restrictive. This study introduces an automated method for these measurements. The method starts with preprocessing for restoration and reconstruction of the phase contrast time-lapse sequences. The data are first restored from intensity non-uniformities. Subsequently, the circular symmetry of the contour of the mitotic cells in phase contrast images is used by applying a Circle Hough Transform (CHT) to reconstruct the entire cells. The CHT is also enhanced with the ability to “vote” exclusively towards the center of curvature. The CHT image sequence is then registered for misplacements between successive frames. The sequence is subsequently processed to detect cell centroids in individual frames and use them as starting points to form spatiotemporal trajectories of cells along the positive as well as along the negative time directions, that is, anti-causally. The connectivities of different trajectories enhanced by the symmetry of the trajectories of the daughter cells provide as topological by-products the events of cell divisions together with the corresponding entries into mitoses as well as exits from cytokineses. The experiments use several experimental video sequences from three different cell lines with many cells undergoing mitoses and divisions. The quantitative validations of the results of the processing demonstrate the high performance and efficiency of the method

Brain Immunoinformatics: A Symmetrical Link between Informatics, Wet Lab and the Clinic

Breakthrough advances in informatics over the last decade have thoroughly influenced the field of immunology. The intermingling of machine learning with wet lab applications and clinical results has hatched the newly defined immunoinformatics society. Immunoinformatics of the central neural system, referred to as neuroimmunoinformatics (NII), investigates symmetrical and asymmetrical interactions of the brain-immune interface. This interdisciplinary overview on NII is addressed to bioscientists and computer scientists. We delineate the dominating trajectories and field-shaping achievements and elaborate on future directions using bridging language and terminology. Computation, varying from linear modeling to complex deep learning approaches, fuels neuroimmunology through three core directions. Firstly, by providing big-data analysis software for high-throughput methods such as next-generation sequencing and genome-wide association studies. Secondly, by designing models for the prediction of protein morphology, functions, and symmetrical and asymmetrical protein–protein interactions. Finally, NII boosts the output of quantitative pathology by enabling the automatization of tedious processes such as cell counting, tracing, and arbor analysis. The new classification of microglia, the brain’s innate immune cells, was an NII achievement. Deep sequencing classifies microglia in “sensotypes” to accurately describe the versatility of immune responses to physiological and pathological challenges, as well as to experimental conditions such as xenografting and organoids. NII approaches complex tasks in the brain-immune interface, recognizes patterns and allows for hypothesis-free predictions with ultimate targeted individualized treatment strategies, and personalizes disease prognosis and treatment response

Quantitative Assessment of Breast-Tumor Stiffness Using Shear-Wave Elastography Histograms

Purpose: Shear-wave elastography (SWE) measures tissue elasticity using ultrasound waves. This study proposes a histogram-based SWE analysis to improve breast malignancy detection. Methods: N = 22/32 (patients/tumors) benign and n = 51/64 malignant breast tumors with histological ground truth. Colored SWE heatmaps were adjusted to a 0–180 kPa scale. Normalized, 250-binned RGB histograms were used as image descriptors based on skewness and area under curve (AUC). The histogram method was compared to conventional SWE metrics, such as (1) the qualitative 5-point scale classification and (2) average stiffness (SWEavg)/maximal tumor stiffness (SWEmax) within the tumor B-mode boundaries. Results: The SWEavg and SWEmax did not discriminate malignant lesions in this database, p > 0.05, rank sum test. RGB histograms, however, differed between malignant and benign tumors, p p = 0.03, rank sum). The diagnostic accuracy of the suggested method is still low (Se = 0.30 for Se = 0.90) and a subject for improvement in future studies. Conclusions: Histogram-based SWE quantitation improved the diagnostic accuracy for malignancy compared to conventional average SWE metrics. The sensitivity is a subject for improvement in future studies

Spatiotemporal Identification of Cell Divisions Using Symmetry Properties in Time-Lapse Phase Contrast Microscopy

A variety of biological and pharmaceutical studies, such as for anti-cancer drugs, require the quantification of cell responses over long periods of time. This is performed with time-lapse video microscopy that gives a long sequence of frames. For this purpose, phase contrast imaging is commonly used since it is minimally invasive. The cell responses of interest in this study are the mitotic cell divisions. Their manual measurements are tedious, subjective, and restrictive. This study introduces an automated method for these measurements. The method starts with preprocessing for restoration and reconstruction of the phase contrast time-lapse sequences. The data are first restored from intensity non-uniformities. Subsequently, the circular symmetry of the contour of the mitotic cells in phase contrast images is used by applying a Circle Hough Transform (CHT) to reconstruct the entire cells. The CHT is also enhanced with the ability to “vote” exclusively towards the center of curvature. The CHT image sequence is then registered for misplacements between successive frames. The sequence is subsequently processed to detect cell centroids in individual frames and use them as starting points to form spatiotemporal trajectories of cells along the positive as well as along the negative time directions, that is, anti-causally. The connectivities of different trajectories enhanced by the symmetry of the trajectories of the daughter cells provide as topological by-products the events of cell divisions together with the corresponding entries into mitoses as well as exits from cytokineses. The experiments use several experimental video sequences from three different cell lines with many cells undergoing mitoses and divisions. The quantitative validations of the results of the processing demonstrate the high performance and efficiency of the method

Restoration of Bi-Contrast MRI Data for Intensity Uniformity with Bayesian Coring of Co-Occurrence Statistics

The reconstruction of MRI data assumes a uniform radio-frequency field. However, in practice, the radio-frequency field is inhomogeneous and leads to anatomically inconsequential intensity non-uniformities across an image. An anatomic region can be imaged with multiple contrasts reconstructed independently and be suffering from different non-uniformities. These artifacts can complicate the further automated analysis of the images. A method is presented for the joint intensity uniformity restoration of two such images. The effect of the intensity distortion on the auto-co-occurrence statistics of each image as well as on the joint-co-occurrence statistics of the two images is modeled and used for their non-stationary restoration followed by their back-projection to the images. Several constraints that ensure a stable restoration are also imposed. Moreover, the method considers the inevitable differences between the signal regions of the two images. The method has been evaluated extensively with BrainWeb phantom brain data as well as with brain anatomic data from the Human Connectome Project (HCP) and with data of Parkinson’s disease patients. The performance of the proposed method has been compared with that of the N4ITK tool. The proposed method increases tissues contrast at least 4 . 62 times more than the N4ITK tool for the BrainWeb images. The dynamic range with the N4ITK method for the same images is increased by up to +29.77%, whereas, for the proposed method, it has a corresponding limited decrease of - 1 . 15 % , as expected. The validation has demonstrated the accuracy and stability of the proposed method and hence its ability to reduce the requirements for additional calibration scans

Restoration of intensity uniformity of bi-contrast MRI data with bayesian co-occurrence coring

The reconstruction in MRI assumes a uniform radiofrequency field. However, this is violated, which leads to anatomically inconsequential intensity non-uniformities. An anatomic region can be imaged with multiple contrasts that result in different non-uniformities. A method is presented for the joint intensity uniformity restoration of two such images. The effect of the intensity distortion on the auto-co-occurrence statistics of each image as well as on the joint-co-occurrence statistics of the two images is modeled. Their non-stationary deconvolution gives Bayesian coring estimates of the images. Further constraints for smoothness, stability, and validity of the non-uniformity estimates are also imposed. The effectiveness and accuracy of the method has been demonstrated extensively with both BrainWeb phantom images as well as with real brain anatomic data of 29 Parkinson’s disease patients

A comparison of different automated methods for the detection of white matter lesions in MRI data

White matter hyperintensities (WMH) are the focus of intensive research and have been linked to cognitive impairment and depression in the elderly. Cumbersome manual outlining procedures make research on WMH labour intensive and prone to subjective bias. This study compares fully automated supervised detection methods that learn to identify WMH from manual examples against unsupervised approaches on the combination of FLAIR and T1 weighted images. Data were collected from ten subjects with mild cognitive impairment and another set of ten individuals who fulfilled diagnostic criteria for dementia. Data were split into balanced groups to create a training set used to optimize the different methods. Manual outlining served as gold standard to evaluate performance of the automated methods that identified each voxel either as intact or as part of a WMH. Otsu's approach for multiple thresholds which is based only on voxel intensities of the FLAIR image produced a high number of false positives at grey matter boundaries. Performance on an independent test set was similarly disappointing when simply applying a threshold to the FLAIR that was found from training data. Among the supervised methods, precision-recall curves of support vector machines (SVM) indicated advantages over the performance achieved by K-nearest-neighbor classifiers (KNN). The curves indicated a clear benefit from optimizing the threshold of the SVM decision value and the voting rule of the KNN. Best performance was reached by selecting training voxels according to their distance to the lesion boundary and repeated training after replacing the feature vectors from those voxels that did not form support vectors of the SVM. The study demonstrates advantages of SVM for the problem of detecting WMH at least for studies that include only FLAIR and T1 weighted images. Various optimization strategies are discussed and compared against each other

Computer aided detection in prostate cancer diagnostics: A promising alternative to biopsy? A retrospective study from 104 lesions with histological ground truth

<div><p>Background</p><p>Prostate cancer (PCa) diagnosis by means of multiparametric magnetic resonance imaging (mpMRI) is a current challenge for the development of computer-aided detection (CAD) tools. An innovative CAD-software (Watson Elementary^™) was proposed to achieve high sensitivity and specificity, as well as to allege a correlate to Gleason grade.</p><p>Aim/Objective</p><p>To assess the performance of Watson Elementary^™ in automated PCa diagnosis in our hospital´s database of MRI-guided prostate biopsies.</p><p>Methods</p><p>The evaluation was retrospective for 104 lesions (47 PCa, 57 benign) from 79, 64.61±6.64 year old patients using 3T T2-weighted imaging, Apparent Diffusion Coefficient (ADC) maps and dynamic contrast enhancement series. Watson Elementary^™ utilizes signal intensity, diffusion properties and kinetic profile to compute a proportional Gleason grade predictor, termed Malignancy Attention Index (MAI). The analysis focused on (i) the CAD sensitivity and specificity to classify suspect lesions and (ii) the MAI correlation with the histopathological ground truth.</p><p>Results</p><p>The software revealed a sensitivity of 46.80% for PCa classification. The specificity for PCa was found to be 75.43% with a positive predictive value of 61.11%, a negative predictive value of 63.23% and a false discovery rate of 38.89%. CAD classified PCa and benign lesions with equal probability (<i>P</i> 0.06, <i>χ</i>² test).</p><p>Accordingly, receiver operating characteristic analysis suggests a poor predictive value for MAI with an area under curve of 0.65 (<i>P</i> 0.02), which is not superior to the performance of board certified observers. Moreover, MAI revealed no significant correlation with Gleason grade (<i>P</i> 0.60, Pearson´s correlation).</p><p>Conclusion</p><p>The tested CAD software for mpMRI analysis was a weak PCa biomarker in this dataset. Targeted prostate biopsy and histology remains the gold standard for prostate cancer diagnosis.</p></div