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Background: Moderate correlation exists between the imaging quantification of brain white matter lesions and cognitive performance in people with multiple sclerosis (MS). This may reflect the greater importance of other features, including subvisible pathology, or methodological limitations of the primary literature. Objectives: To summarise the cognitive clinico-radiological paradox and explore the potential methodological factors that could influence the assessment of this relationship. Methods: Systematic review and meta-analysis of primary research relating cognitive function to white matter lesion burden. Results: Fifty papers met eligibility criteria for review, and meta-analysis of overall results was possible in thirty-two (2050 participants). Aggregate correlation between cognition and T2 lesion burden was r = -0.30 (95% confidence interval: -0.34, -0.26). Wide methodological variability was seen, particularly related to key factors in the cognitive data capture and image analysis techniques. Conclusions: Resolving the persistent clinico-radiological paradox will likely require simultaneous evaluation of multiple components of the complex pathology using optimum measurement techniques for both cognitive and MRI feature quantification. We recommend a consensus initiative to support common standards for image analysis in MS, enabling benchmarking while also supporting ongoing innovation. [ABSTRACT FROM AUTHOR]

Nonlinear registration is an important technique to align two different images and widely applied in medical image analysis. In this paper, we develop a novel nonlinear registration framework based on the diffeomorphic demons, where a reciprocal regularizer is introduced to assume that the deformation between two images is an exact diffeomorphism. In detail, first, we adopt a bidirectional metric to improve the symmetry of the energy functional, whose variables are two reciprocal deformations. Secondly, we slack these two deformations into two independent variables and introduce a reciprocal regularizer to assure the deformations being the exact diffeomorphism. Then, we utilize an alternating iterative strategy to decouple the model into two minimizing subproblems, where a new closed form for the approximate velocity of deformation is calculated. Finally, we compare our proposed algorithm on two data sets of real brain MR images with two relative and conventional methods. The results validate that our proposed method improves accuracy and robustness of registration, as well as the gained bidirectional deformations are actually reciprocal. [ABSTRACT FROM AUTHOR]

Objectives: The extent of peritumoral tumor cell infiltrations in glioblastoma contributes to poor prognosis. We aimed to assess additive prognostic value of Minkowski functionals in analyzing heterogeneity of peritumoral hyperintensity on T2WI in glioblastoma patients. Methods: Clinical data (age, sex, extent of surgical resection), O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and pre-operative T2WI of 113 pathologically confirmed glioblastoma patients (from our institution, n = 61; from the Cancer Imaging Archive, n = 52) were retrospectively reviewed. The patients were randomly grouped into a training set (n = 80) and a test set (n = 33). Peritumoral T2 hyperintensity was manually segmented and Minkowski functionals—a texture analysis method capturing heterogeneity of MR images—were computed as a function of 11 grayscale thresholds. The Cox proportional hazards models were fitted with clinical variables, Minkowski functionals features as well as both combined. The risk prediction performances of the Minkowski functionals and combined models were validated on a separate test dataset. The sex-specific survival difference of the entire cohort was analyzed according to MGMT methylation status via Kaplan-Meier survival curves. Results: Thirty-three Minkowski features (11 area, 11 perimeter and 11 genus) for each patient were acquired giving a total of 3729 features. Cox regression models fitted with clinical data, Minkowski features, and both combined had incremental concordance indices of 0.577 (P = 0.02), 0.706 (P = 0.02) and 0.714 (P = 0.01) respectively. The prediction error rate of the combined model—having clinical and Minkowski features—was lower than that of Minkowski functionals model (0.135 and 0.161, respectively) when validated on a test dataset. No sex-specific survival difference was found according to MGMT methylation status (male, P = 0.2; female, P = 0.22). Conclusions: Minkowski functionals features computed from peritumoral hyperintensity can capture heterogeneity of glioblastoma on T2WI and have additive prognostic value in predicting survival, demonstrating their potential in complementing currently available prognostic parameters. [ABSTRACT FROM AUTHOR]

Texture analysis is an important topic in Ultrasound (US) image analysis for structure segmentation and tissue classification. In this work a novel approach for US image texture feature extraction is presented. It is mainly based on parametrical modelling of a signal version of the US image in order to process it as data resulting from a dynamical process. Because of the predictive characteristics of such a model representation, good estimations of texture features can be obtained with less data than generally used methods require, allowing higher robustness to low Signal-to-Noise ratio and a more localized US image analysis. The usability of the proposed approach was demonstrated by extracting texture features for segmenting the thyroid in US images. The obtained results showed that features corresponding to energy ratios between different modelled texture frequency bands allowed to clearly distinguish between thyroid and non-thyroid texture. A simple k-means clustering algorithm has been used for separating US image patches as belonging to thyroid or not. Segmentation of thyroid was performed in two different datasets obtaining Dice coefficients over 85%. [ABSTRACT FROM AUTHOR]

Background: Analysis of intracoronary thrombus type by optical coherence tomography (OCT) imaging is highly subjective. We aimed to compare a newly developed image analysis method to subjective visual classification of thrombus type identified by OCT. Methods: Thirty patients with acute ST elevation myocardial infarction were included. Thrombus type visually classified by two independent readers was compared with analysis using QCU-CMS software. Results: Repeatability of the computer-based measurements was good. By using a ROC, area under curve values for discrimination of white and red thrombi were 0.92 (95% confidence intervals (CI) 0.83–1.00) for median attenuation, 0.96 (95% CI 0.89–1.00) for mean backscatter and 0.96 (95% CI 0.89–1.00) for mean grayscale intensity. Median attenuation of 0.57 mm-1 (sensitivity 100%, specificity 71%), mean backscatter of 5.35 (sensitivity 92%, specificity 94%) and mean grayscale intensity of 120.1 (sensitivity 85%, specificity 100%) were identified as the best cut-off values to differentiate between red and white thrombi. Conclusions: Attenuation, backscatter and grayscale intensity of thrombi in OCT images differentiated red and white thrombi with high sensitivity and specificity. Measurement of these continuous parameters can be used as a less user-dependent method to characterize in vivo thrombi. The clinical significance of these findings needs to be tested in further studies. [ABSTRACT FROM AUTHOR]

Pathology images are color in nature due to the use of chemical staining in biopsy examination. Aware of the high color diagnosticity in pathology images, this work introduces a compact rotation-invariant texture descriptor, named quantized diagnostic counter-color pattern (QDCP), for digital pathology image understanding. On the basis of color similarity quantified by the inner product of unit-length color vectors, local counter-color textons are indexed first. Then the underlined distribution of QDCP indexes is estimated by an image-wise histogram. Since QDCP is computed based on color difference directly, it is robust to small color variation usually observed in pathology images. This study also discusses QDCP’s extraction, parameter settings, and feature fusion techniques in a generic pathology image analysis pipeline, and introduces two more descriptors QDCP-LBP and QDCP/LBP. Experimentation on public pathology image sets suggests that the introduced color texture descriptors, especially QDCP-LBP, outperform prior color texture features in terms of strong descriptive power, low computational complexity, and high adaptability to different image sets. [ABSTRACT FROM AUTHOR]

The intramuscular fat (IMF), recognized by the consumer as marbling, is an important meat quality trait. The objective of this study was to validate a new method of beef marbling evaluation by image analysis. The new assessment was compared with two known marbling measurements: chemical IMF and USDA scores. Moreover, the relationship between marbling measurements and other meat quality parameters was investigated. Samples of Longissimus thoracis et lumborum (LTL) muscle were obtained from carcasses of 39 Italian crossbred heifers and 62 Angus bred heifers, that underwent two different dietary treatments. The use of various breeds and diets was chosen to obtain different intramuscular fat levels, in order to validate the use of Image J software for the analysis of different type of beef meat. The images of fresh cuts were appraised by experienced beef graders, and the samples were used to determine fat content by chemical Soxhlet extraction. Carcasses measurements according to the EUROP system, and other physical meat proprieties were also assessed. The results demonstrated that the marbling measurements obtained by computer image analysis, such as the number of marbling particles, the average particle size (mm), and the percentage of marbling particles (%), significantly (P < 0.05) correlated with USDA scores and IMF content. Moreover, the principal component analysis (PCA) showed three principal meat components, identified as 1) color, 2) fat, and 3) water release. The second principal component (PC) explained 24.94% of variance, and was positively correlated with image analysis measures, USDA score, and IMF, while negatively correlated with the Warner–Bratzler shear force (WBSF). [ABSTRACT FROM AUTHOR]

Deeper exploration of the brain’s vast synaptic networks will require new tools for high-throughput structural and molecular profiling of the diverse populations of synapses that compose those networks. Fluorescence microscopy (FM) and electron microscopy (EM) offer complementary advantages and disadvantages for single-synapse analysis. FM combines exquisite molecular discrimination capacities with high speed and low cost, but rigorous discrimination between synaptic and non-synaptic fluorescence signals is challenging. In contrast, EM remains the gold standard for reliable identification of a synapse, but offers only limited molecular discrimination and is slow and costly. To develop and test single-synapse image analysis methods, we have used datasets from conjugate array tomography (cAT), which provides voxel-conjugate FM and EM (annotated) images of the same individual synapses. We report a novel unsupervised probabilistic method for detection of synapses from multiplex FM (muxFM) image data, and evaluate this method both by comparison to EM gold standard annotated data and by examining its capacity to reproduce known important features of cortical synapse distributions. The proposed probabilistic model-based synapse detector accepts molecular-morphological synapse models as user queries, and delivers a volumetric map of the probability that each voxel represents part of a synapse. Taking human annotation of cAT EM data as ground truth, we show that our algorithm detects synapses from muxFM data alone as successfully as human annotators seeing only the muxFM data, and accurately reproduces known architectural features of cortical synapse distributions. This approach opens the door to data-driven discovery of new synapse types and their density. We suggest that our probabilistic synapse detector will also be useful for analysis of standard confocal and super-resolution FM images, where EM cross-validation is not practical. [ABSTRACT FROM AUTHOR]

Purpose: To present and evaluate a whole-body image analysis concept, Imiomics (imaging–omics) and an image registration method that enables Imiomics analyses by deforming all image data to a common coordinate system, so that the information in each voxel can be compared between persons or within a person over time and integrated with non-imaging data. Methods: The presented image registration method utilizes relative elasticity constraints of different tissue obtained from whole-body water-fat MRI. The registration method is evaluated by inverse consistency and Dice coefficients and the Imiomics concept is evaluated by example analyses of importance for metabolic research using non-imaging parameters where we know what to expect. The example analyses include whole body imaging atlas creation, anomaly detection, and cross-sectional and longitudinal analysis. Results: The image registration method evaluation on 128 subjects shows low inverse consistency errors and high Dice coefficients. Also, the statistical atlas with fat content intensity values shows low standard deviation values, indicating successful deformations to the common coordinate system. The example analyses show expected associations and correlations which agree with explicit measurements, and thereby illustrate the usefulness of the proposed Imiomics concept. Conclusions: The registration method is well-suited for Imiomics analyses, which enable analyses of relationships to non-imaging data, e.g. clinical data, in new types of holistic targeted and untargeted big-data analysis. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate feasibility of automated 3D volumetry of central pulmonary arteries based on magnetic resonance angiography (MRA), to assess pulmonary artery volumes in patients with pulmonary hypertension compared to healthy controls, and to investigate the potential of the technique for predicting pulmonary hypertension. Methods: MRA of pulmonary arteries was acquired at 1.5T in 20 patients with pulmonary arterial hypertension and 21 healthy normotensive controls. 3D model-based image analysis software was used for automated segmentation of main, right and left pulmonary arteries (MPA, RPA and LPA). Volumes indexed to vessel length and mean, minimum and maximum diameters along the entire vessel course were assessed and corrected for body surface area (BSA). For comparison, diameters were also manually measured on axial reconstructions and double oblique multiplanar reformations. Analyses were performed by two cardiovascular radiologists, and by one radiologist again after 6 months. Results: Mean volumes of MPA, RPA and LPA for patients/controls were 5508 ± 1236/3438 ± 749, 3522 ± 934/1664 ± 468 and 3093 ± 692/1812 ± 474 μl/(cm length x m2 BSA) (all p<0.001). Mean, minimum and maximum diameters along the entire vessel course were also significantly increased in patients compared to controls (all p<0.001). Intra- and interobserver agreement were excellent for both volume and diameter measurements using 3D segmentation (intraclass correlation coefficients 0.971–0.999, p<0.001). Area under the curve for predicting pulmonary hypertension using volume was 0.998 (95% confidence interval 0.990–1.0, p<0.001), compared to 0.967 using manually measured MPA diameter (95% confidence interval 0.910–1.0, p<0.001). Conclusions: Automated MRA-based 3D volumetry of central pulmonary arteries is feasible and demonstrated significantly increased volumes and diameters in patients with pulmonary arterial hypertension compared to healthy controls. Pulmonary artery volume may serve as a superior predictor for pulmonary hypertension compared to manual measurements on axial images but verification in a larger study population is warranted. [ABSTRACT FROM AUTHOR]

Objective: Evaluation of a new iterative reconstruction algorithm (IMR) for detection/rule-out of pulmonary embolism (PE) in ultra-low dose computed tomography pulmonary angiography (CTPA). Methods: Lower dose CT data sets were simulated based on CTPA examinations of 16 patients with pulmonary embolism (PE) with dose levels (DL) of 50%, 25%, 12.5%, 6.3% or 3.1% of the original tube current setting. Original CT data sets and simulated low-dose data sets were reconstructed with three reconstruction algorithms: the standard reconstruction algorithm “filtered back projection” (FBP), the first generation iterative reconstruction algorithm iDose and the next generation iterative reconstruction algorithm “Iterative Model Reconstruction” (IMR). In total, 288 CTPA data sets (16 patients, 6 tube current levels, 3 different algorithms) were evaluated by two blinded radiologists regarding image quality, diagnostic confidence, detectability of PE and contrast-to-noise ratio (CNR). Results: iDose and IMR showed better detectability of PE than FBP. With IMR, sensitivity for detection of PE was 100% down to a dose level of 12.5%. iDose and IMR showed superiority to FBP regarding all characteristics of subjective (diagnostic confidence in detection of PE, image quality, image noise, artefacts) and objective image quality. The minimum DL providing acceptable diagnostic performance was 12.5% (= 0.45 mSv) for IMR, 25% (= 0.89 mSv) for iDose and 100% (= 3.57 mSv) for FBP. CNR was significantly (p < 0.001) improved by IMR compared to FBP and iDose at all dose levels. Conclusion: By using IMR for detection of PE, dose reduction for CTPA of up to 75% is possible while maintaining full diagnostic confidence. This would result in a mean effective dose of approximately 0.9 mSv for CTPA. [ABSTRACT FROM AUTHOR]

Stiffness and shear moduli of human trabecular bone may be analyzed in vivo by finite element (FE) analysis from image data obtained by clinical imaging equipment such as high resolution peripheral quantitative computed tomography (HR-pQCT). In clinical practice today, this is done in the peripheral skeleton like the wrist and heel. In this cadaveric bone study, fourteen bone specimens from the wrist were imaged by two dental cone beam computed tomography (CBCT) devices and one HR-pQCT device as well as by dual energy X-ray absorptiometry (DXA). Histomorphometric measurements from micro-CT data were used as gold standard. The image processing was done with an in-house developed code based on the automated region growing (ARG) algorithm. Evaluation of how well stiffness (Young’s modulus E3) and minimum shear modulus from the 12, 13, or 23 could be predicted from the CBCT and HR-pQCT imaging data was studied and compared to FE analysis from the micro-CT imaging data. Strong correlations were found between the clinical machines and micro-CT regarding trabecular bone structure parameters, such as bone volume over total volume, trabecular thickness, trabecular number and trabecular nodes (varying from 0.79 to 0.96). The two CBCT devices as well as the HR-pQCT showed the ability to predict stiffness and shear, with adjusted R2-values between 0.78 and 0.92, based on data derived through our in-house developed code based on the ARG algorithm. These findings indicate that clinically used CBCT may be a feasible method for clinical studies of bone structure and mechanical properties in future osteoporosis research. [ABSTRACT FROM AUTHOR]

The purposes of this study were to optimize a proton computed tomography system (pCT) for proton range verification and to confirm the pCT image reconstruction algorithm based on projection images generated with optimized parameters. For this purpose, we developed a new pCT scanner using the Geometry and Tracking (GEANT) 4.9.6 simulation toolkit. GEANT4 simulations were performed to optimize the geometric parameters representing the detector thickness and the distance between the detectors for pCT. The system consisted of four silicon strip detectors for particle tracking and a calorimeter to measure the residual energies of the individual protons. The optimized pCT system design was then adjusted to ensure that the solution to a CS-based convex optimization problem would converge to yield the desired pCT images after a reasonable number of iterative corrections. In particular, we used a total variation-based formulation that has been useful in exploiting prior knowledge about the minimal variations of proton attenuation characteristics in the human body. Examinations performed using our CS algorithm showed that high-quality pCT images could be reconstructed using sets of 72 projections within 20 iterations and without any streaks or noise, which can be caused by under-sampling and proton starvation. Moreover, the images yielded by this CS algorithm were found to be of higher quality than those obtained using other reconstruction algorithms. The optimized pCT scanner system demonstrated the potential to perform high-quality pCT during on-line image-guided proton therapy, without increasing the imaging dose, by applying our CS based proton CT reconstruction algorithm. Further, we make our optimized detector system and CS-based proton CT reconstruction algorithm potentially useful in on-line proton therapy. [ABSTRACT FROM AUTHOR]

Background: The mucosal changes associated with female genital schistosomiasis (FGS) encompass abnormal blood vessels. These have been described as circular, reticular, branched, convoluted and having uneven calibre. However, these characteristics are subjective descriptions and it has not been explored which of them are specific to FGS. Methods: In colposcopic images of young women from a schistosomiasis endemic area, we performed computerised morphologic analyses of the cervical vasculature appearing on the mucosal surface. Study participants where the cervix was classified as normal served as negative controls, women with clinically diagnosed FGS and presence of typical abnormal blood vessels visible on the cervical surface served as positive cases. We also included women with cervical inflammatory conditions for reasons other than schistosomiasis. By automating morphological analyses, we explored circular configurations, vascular density, fractal dimensions and fractal lacunarity as parameters of interest. Results: We found that the blood vessels typical of FGS are characterised by the presence of circular configurations (p < 0.001), increased vascular density (p = 0.015) and increased local connected fractal dimensions (p = 0.071). Using these features, we were able to correctly classify 78% of the FGS-positive cases with an accuracy of 80%. Conclusions: The blood vessels typical of FGS have circular configurations, increased vascular density and increased local connected fractal dimensions. These specific morphological features could be used diagnostically. Combined with colourimetric analyses, this represents a step towards making a diagnostic tool for FGS based on computerised image analysis. [ABSTRACT FROM AUTHOR]

Graph search is attractive for the quantitative analysis of volumetric medical images, and especially for layered tissues, because it allows globally optimal solutions in low-order polynomial time. However, because nodes of graphs typically encode evenly distributed voxels of the volume with arcs connecting orthogonally sampled voxels in Euclidean space, segmentation cannot achieve greater precision than a single unit, i.e. the distance between two adjoining nodes, and partial volume effects are ignored. We generalize the graph to non-Euclidean space by allowing non-equidistant spacing between nodes, so that subvoxel accurate segmentation is achievable. Because the number of nodes and edges in the graph remains the same, running time and memory use are similar, while all the advantages of graph search, including global optimality and computational efficiency, are retained. A deformation field calculated from the volume data adaptively changes regional node density so that node density varies with the inverse of the expected cost. We validated our approach using optical coherence tomography (OCT) images of the retina and 3-D MR of the arterial wall, and achieved statistically significant increased accuracy. Our approach allows improved accuracy in volume data acquired with the same hardware, and also, preserved accuracy with lower resolution, more cost-effective, image acquisition equipment. The method is not limited to any specific imaging modality and readily extensible to higher dimensions. [ABSTRACT FROM AUTHOR]

Functional Magnetic Resonance Imaging (fMRI) based brain connectivity analysis maps the functional networks of the brain by estimating the degree of synchronous neuronal activity between brain regions. Recent studies have demonstrated that “resting-state” fMRI-based brain connectivity conclusions may be erroneous when motion artifacts have a differential effect on fMRI BOLD signals for between group comparisons. A potential explanation could be that in-scanner displacement, due to rotational components, is not spatially constant in the whole brain. However, this localized nature of motion artifacts is poorly understood and is rarely considered in brain connectivity studies. In this study, we initially demonstrate the local correspondence between head displacement and the changes in the resting-state fMRI BOLD signal. Than, we investigate how connectivity strength is affected by the population-level variation in the spatial pattern of regional displacement. We introduce Regional Displacement Interaction (RDI), a new covariate parameter set for second-level connectivity analysis and demonstrate its effectiveness in reducing motion related confounds in comparisons of groups with different voxel-vise displacement pattern and preprocessed using various nuisance regression methods. The effect of using RDI as second-level covariate is than demonstrated in autism-related group comparisons. The relationship between the proposed method and some of the prevailing subject-level nuisance regression techniques is evaluated. Our results show that, depending on experimental design, treating in-scanner head motion as a global confound may not be appropriate. The degree of displacement is highly variable among various brain regions, both within and between subjects. These regional differences bias correlation-based measures of brain connectivity. The inclusion of the proposed second-level covariate into the analysis successfully reduces artifactual motion-related group differences and preserves real neuronal differences, as demonstrated by the autism-related comparisons. [ABSTRACT FROM AUTHOR]

In anatomic pathology, immunohistochemistry (IHC) serves as a diagnostic and prognostic method for identification of disease markers in tissue samples that directly influences classification and grading the disease, influencing patient management. However, till today over most of the world, pathological analysis of tissue samples remained a time-consuming and subjective procedure, wherein the intensity of antibody staining is manually judged and thus scoring decision is directly influenced by visual bias. This instigated us to design a simple method of automated digital IHC image analysis algorithm for an unbiased, quantitative assessment of antibody staining intensity in tissue sections. As a first step, we adopted the spectral deconvolution method of DAB/hematoxylin color spectra by using optimized optical density vectors of the color deconvolution plugin for proper separation of the DAB color spectra. Then the DAB stained image is displayed in a new window wherein it undergoes pixel-by-pixel analysis, and displays the full profile along with its scoring decision. Based on the mathematical formula conceptualized, the algorithm is thoroughly tested by analyzing scores assigned to thousands (n = 1703) of DAB stained IHC images including sample images taken from human protein atlas web resource. The IHC Profiler plugin developed is compatible with the open resource digital image analysis software, ImageJ, which creates a pixel-by-pixel analysis profile of a digital IHC image and further assigns a score in a four tier system. A comparison study between manual pathological analysis and IHC Profiler resolved in a match of 88.6% (P<0.0001, CI = 95%). This new tool developed for clinical histopathological sample analysis can be adopted globally for scoring most protein targets where the marker protein expression is of cytoplasmic and/or nuclear type. We foresee that this method will minimize the problem of inter-observer variations across labs and further help in worldwide patient stratification potentially benefitting various multinational clinical trial initiatives. [ABSTRACT FROM AUTHOR]