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International challenges have become the standard for validation of biomedical image analysis methods. Given their scientific impact, it is surprising that a critical analysis of common practices related to the organization of challenges has not yet been performed. In this paper, we present a comprehensive analysis of biomedical image analysis challenges conducted up to now. We demonstrate the importance of challenges and show that the lack of quality control has critical consequences. First, reproducibility and interpretation of the results is often hampered as only a fraction of relevant information is typically provided. Second, the rank of an algorithm is generally not robust to a number of variables such as the test data used for validation, the ranking scheme applied and the observers that make the reference annotations. To overcome these problems, we recommend best practice guidelines and define open research questions to be addressed in the future.

Hemodynamic factors are thought to be implicated in the progression and rupture of intracranial aneurysms. Current efforts aim to study the possible associations of hemodynamic characteristics such as complexity and stability of intra-aneurysmal flow patterns, size and location of the region of flow impingement with the clinical history of aneurysmal rupture. However, there are no reliable methods for measuring blood flow patterns in vivo. In this paper, an efficient methodology for patient-specific modeling and characterization of the hemodynamics in cerebral aneurysms from medical images is described. A sensitivity analysis of the hemodynamic characteristics with respect to variations of several variables over the expected physiologic range of conditions is also presented. This sensitivity analysis shows that although changes in the velocity fields can be observed, the characterization of the intra-aneurysmal flow patterns is not altered when the mean input flow, the flow division, the viscosity model, or mesh resolution are changed. It was also found that the variable that has the greater impact on the computed flow fields is the geometry of the vascular structures. We conclude that with the proposed modeling pipeline clinical studies involving large numbers cerebral aneurysms are feasible. Index Terms--Cerebral aneurysm, computational fluid dynamics, rotational angiography, sensitivity.

Recent works show that generative adversarial networks (GANs) can be successfully applied to image synthesis and semi-supervised learning, where, given a small labeled database and a large unlabeled database, the goal is to train a powerful classifier. In this paper, we trained a retinal image synthesizer and a semi-supervised learning method for automatic glaucoma assessment using an adversarial model on a small glaucoma-labeled database and a large unlabeled database. Various studies have shown that glaucoma can be monitored by analyzing the optic disc and its surroundings, and for that reason, the images used in this paper were automatically cropped around the optic disc. The novelty of this paper is to propose a new retinal image synthesizer and a semi-supervised learning method for glaucoma assessment based on the deep convolutional GANs. In addition, and to the best of our knowledge, this system is trained on an unprecedented number of publicly available images (86926 images). This system, hence, is not only able to generate images synthetically but to provide labels automatically. Synthetic images were qualitatively evaluated using t-SNE plots of features associated with the images and their anatomical consistency was estimated by measuring the proportion of pixels corresponding to the anatomical structures around the optic disc. The resulting image synthesizer is able to generate realistic (cropped) retinal images, and subsequently, the glaucoma classifier is able to classify them into glaucomatous and normal with high accuracy (AUC = 0.9017). The obtained retinal image synthesizer and the glaucoma classifier could then be used to generate an unlimited number of cropped retinal images with glaucoma labels. [ABSTRACT FROM AUTHOR]

Multi-modality medical imaging is increasingly used for comprehensive assessment of complex diseases in either diagnostic examinations or as part of medical research trials. Different imaging modalities provide complementary information about living tissues. However, multi-modal examinations are not always possible due to adversary factors, such as patient discomfort, increased cost, prolonged scanning time, and scanner unavailability. In additionally, in large imaging studies, incomplete records are not uncommon owing to image artifacts, data corruption or data loss, which compromise the potential of multi-modal acquisitions. In this paper, we propose a weakly coupled and geometry co-regularized joint dictionary learning method to address the problem of cross-modality synthesis while considering the fact that collecting the large amounts of training data is often impractical. Our learning stage requires only a few registered multi-modality image pairs as training data. To employ both paired images and a large set of unpaired data, a cross-modality image matching criterion is proposed. Then, we propose a unified model by integrating such a criterion into the joint dictionary learning and the observed common feature space for associating cross-modality data for the purpose of synthesis. Furthermore, two regularization terms are added to construct robust sparse representations. Our experimental results demonstrate superior performance of the proposed model over state-of-the-art methods. [ABSTRACT FROM PUBLISHER]

Purpose: The primary goal of this article is to achieve an automatic and objective method to compute the Pfirrmann's degeneration grade of intervertebral discs (IVD) from MRI. This grading system is used in the diagnosis and management of patients with low back pain (LBP). In addition, biomechanical models, which are employed to assess the treatment on patients with LBP, require this grading value to compute proper material properties.Materials and Methods: T2-weighted MR images of 48 patients were employed in this work. The 240 lumbar IVDs were divided into a training set (140) and a testing set (100). Three experts manually classified the whole set of IVDs using the Pfirrmann's grading system and the ground truth was selected as the most voted value among them. The developed method employs active contour models to delineate the boundaries of the IVD. Subsequently, the classification is achieved using a trained Neural Network (NN) with eight designed features that contain shape and intensity information of the IVDs.Results: The classification method was evaluated using the testing set, resulting in a mean specificity (95.5 %) and sensitivity (87.3 %) comparable to those of every expert with respect to the ground truth.Conclusions: Our results show that the automatic method and humans perform equally well in terms of the classification accuracy. However, human annotations have inherent inter- and intra-observer variabilities, which lead to inconsistent assessments. In contrast, the proposed automatic method is objective, being only dependent on the input MRI. [ABSTRACT FROM AUTHOR]

Statistical shape models (SSM) are used to introduce shape priors in the segmentation of medical images. However, such models require large training datasets in the case of multi-object structures, since it is required to obtain not only the individual shape variations but also the relative position and orientation among objects. A solution to overcome this limitation is to model each individual shape independently. However, this approach does not take into account the relative position, orientations and shapes among the parts of an articulated object, which may result in unrealistic geometries, such as with object overlaps. In this article, we propose a new Statistical Model, the Statistical Interspace Model (SIM), which provides information about the interaction of all the individual structures by modeling the interspace between them. The SIM is described using relative position vectors between pair of points that belong to different objects that are facing each other. These vectors are divided into their magnitude and direction, each of these groups modeled as independent manifolds. The SIM was included in a segmentation framework that contains an SSM per individual object. This framework was tested using three distinct types of datasets of CT images of the spine. Results show that the SIM completely eliminated the inter-process overlap while improving the segmentation accuracy. [ABSTRACT FROM AUTHOR]

This paper presents a predictive framework for the statistical personalization of ventricular fibers. To this end, the relationship between subject-specific geometry of the left (LV) and right ventricles (RV) and fiber orientation is learned statistically from a training sample of ex vivo diffusion tensor imaging datasets. More specifically, the axes in the shape space which correlate most with the myocardial fiber orientations are extracted and used for prediction in new subjects. With this approach and unlike existing fiber models, inter-subject variability is taken into account to generate latent shape predictors that are statistically optimal to estimate fiber orientation at each individual myocardial location. The proposed predictive model was applied to the task of personalizing fibers in 10 canine subjects. The results indicate that the ventricular shapes are good predictors of fiber orientation, with an improvement of 11.4% in accuracy over the average fiber model. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study is to investigate the feasibility of detecting and quantifying 3D cerebrovascular wall motion from a single 3D rotational x-ray angiography (3DRA) acquisition within a clinically acceptable time and computing from the estimated motion field for the further biomechanical modeling of the cerebrovascular wall. Methods: The whole motion cycle of the cerebral vasculature is modeled using a 4D B-spline transformation, which is estimated from a 4D to 2D+t image registration framework. The registration is performed by optimizing a single similarity metric between the entire 2D+t measured projection sequence and the corresponding forward projections of the deformed volume at their exact time instants. The joint use of two acceleration strategies, together with their implementation on graphics processing units, is also proposed so as to reach computation times close to clinical requirements. For further characterizing vessel wall properties, an approximation of the wall thickness changes is obtained through a strain calculation. Results: Evaluation on in silico and in vitro pulsating phantom aneurysms demonstrated an accurate estimation of wall motion curves. In general, the error was below 10% of the maximum pulsation, even in the situation when substantial inhomogeneous intensity pattern was present. Experiments on in vivo data provided realistic aneurysm and vessel wall motion estimates, whereas in regions where motion was neither visible nor anatomically possible, no motion was detected. The use of the acceleration strategies enabled completing the estimation process for one entire cycle in 5-10 min without degrading the overall performance. The strain map extracted from our motion estimation provided a realistic deformation measure of the vessel wall. Conclusions: The authors' technique has demonstrated that it can provide accurate and robust 4D estimates of cerebrovascular wall motion within a clinically acceptable time, although it has to be applied to a larger patient population prior to possible wide application to routine endovascular procedures. In particular, for the first time, this feasibility study has shown that in vivo cerebrovascular motion can be obtained intraprocedurally from a 3DRA acquisition. Results have also shown the potential of performing strain analysis using this imaging modality, thus making possible for the future modeling of biomechanical properties of the vascular wall. [ABSTRACT FROM AUTHOR]

The increasing volume of data describing human disease processes and the growing complexity of understanding, managing, and sharing such data presents a huge challenge for clinicians and medical researchers. This paper presents the @neurIST system, which provides an infrastructure for biomedical research while aiding clinical care, by bringing together heterogeneous data and complex processing and computing services. Although @neurIST targets the investigation and treatment of cerebral aneurysms, the system's architecture is generic enough that it could be adapted to the treatment of other diseases. [ABSTRACT FROM PUBLISHER]

Flow-mediated dilation (FMD) offers a mechanism to characterize endothelial function and, therefore, may play a role in the diagnosis of cardiovascular diseases. Computerized analysis techniques are very desirable to give accuracy and objectivity to the measurements. Virtually all methods proposed up to now to measure FMD rely on accurate edge detection of the arterial wall, and they are not always robust in the presence of poor image quality or image artifacts. A novel method for automatic dilation assessment based on a global image analysis strategy is presented. We model interframe arterial dilation as a superposition of a rigid motion and a scaling factor perpendicular to the artery. Rigid motion can be interpreted as a global compensation for patient and probe movements, an aspect that has not been sufficiently studied before. The scaling factor explains arterial dilation. The ultrasound sequence is analyzed in two phases using image registration to recover both transformation models. Temporal continuity in the registration parameters along the sequence is enforced with a Kalman filter since the dilation process is known to be a gradual physiological phenomenon. Comparing automated and gold standard measurements (average of manual measurements) we found a negligible bias (0.05%FMD) and a small standard deviation (SD) of the differences (1.05%FMD). These values are comparable with those obtained from manual measurements (bias = 0.23%FMD, S[SUBDintra -- obs] = 1.13%FMD, SD[SUBinter -- obs] = 1.20%FMD). The proposed method offers also better reproducibility (CV = 0.40%) than the manual measurements (CV = 1.04%). [ABSTRACT FROM AUTHOR]

Focuses on three-dimensional cardiovascular imaging. Diagnostic role; Mortality from cardiovascular diseases, according to the World Health Organization; Congresses on medical imaging.

Population imaging studies generate data for developing and implementing personalised health strategies to prevent, or more effectively treat disease. Large prospective epidemiological studies acquire imaging for pre-symptomatic populations. These studies enable the early discovery of alterations due to impending disease, and enable early identification of individuals at risk. Such studies pose new challenges requiring automatic image analysis. To date, few large-scale population-level cardiac imaging studies have been conducted. One such study stands out for its sheer size, careful implementation, and availability of top quality expert annotation; the UK Biobank (UKB). The resulting massive imaging datasets (targeting ca. 100,000 subjects) has put published approaches for cardiac image quantification to the test. In this paper, we present and evaluate a cardiac magnetic resonance (CMR) image analysis pipeline that properly scales up and can provide a fully automatic analysis of the UKB CMR study. Without manual user interactions, our pipeline performs end-to-end image analytics from multi-view cine CMR images all the way to anatomical and functional bi-ventricular quantification. All this, while maintaining relevant quality controls of the CMR input images, and resulting image segmentations. To the best of our knowledge, this is the first published attempt to fully automate the extraction of global and regional reference ranges of all key functional cardiovascular indexes, from both left and right cardiac ventricles, for a population of 20,000 subjects imaged at 50 time frames per subject, for a total of one million CMR volumes. In addition, our pipeline provides 3D anatomical bi-ventricular models of the heart. These models enable the extraction of detailed information of the morphodynamics of the two ventricles for subsequent association to genetic, omics, lifestyle habits, exposure information, and other information provided in population imaging studies. We validated our proposed CMR analytics pipeline against manual expert readings on a reference cohort of 4620 subjects with contour delineations and corresponding clinical indexes. Our results show broad significant agreement between the manually obtained reference indexes, and those automatically computed via our framework. 80.67% of subjects were processed with mean contour distance of less than 1 pixel, and 17.50% with mean contour distance between 1 and 2 pixels. Finally, we compare our pipeline with a recently published approach reporting on UKB data, and based on deep learning. Our comparison shows similar performance in terms of segmentation accuracy with respect to human experts. [ABSTRACT FROM AUTHOR]

Highlights • Group-wise analysis of diffusion brain magnetic resonance images. • Hybrid mixture model for quantitative analysis of group-wise differences in diffusion properties. • Comparisons between healthy subjects and patients diagnosed with mild cognitive impairment and Alzheimer's disease. • Automatic construction of study-specific atlases of white matter regions. Graphical abstract Abstract A probabilistic framework for registering generalised point sets comprising multiple voxel-wise data features such as positions, orientations and scalar-valued quantities, is proposed. It is employed for the analysis of magnetic resonance diffusion tensor image (DTI)-derived quantities, such as fractional anisotropy (FA) and fibre orientation, across multiple subjects. A hybrid Student's t-Watson-Gaussian mixture model-based non-rigid registration framework is formulated for the joint registration and clustering of voxel-wise DTI-derived data, acquired from multiple subjects. The proposed approach jointly estimates the non-rigid transformations necessary to register an unbiased mean template (represented as a 7-dimensional hybrid point set comprising spatial positions, fibre orientations and FA values) to white matter regions of interest (ROIs), and approximates the joint distribution of voxel spatial positions, their associated principal diffusion axes, and FA. Specific white matter ROIs, namely, the corpus callosum and cingulum, are analysed across healthy control (HC) subjects (K = 20 samples) and patients diagnosed with mild cognitive impairment (MCI) (K = 20 samples) or Alzheimer's disease (AD) (K = 20 samples) using the proposed framework, facilitating inter-group comparisons of FA and fibre orientations. Group-wise analyses of the latter is not afforded by conventional approaches such as tract-based spatial statistics (TBSS) and voxel-based morphometry (VBM). [ABSTRACT FROM AUTHOR]

Image registration is an essential technique to obtain point correspondences between anatomical structures from different images. Conventional non-rigid registration methods assume a continuous and smooth deformation field throughout the image. However, the deformation field at the interface of different organs is not necessarily continuous, since the organs may slide over or separate from each other. Therefore, imposing continuity and smoothness ubiquitously would lead to artifacts and increased errors near the discontinuity interface. In computational mechanics, the eXtended Finite Element Method (XFEM) was introduced to handle discontinuities without using computational meshes that conform to the discontinuity geometry. Instead, the interpolation bases themselves were enriched with discontinuous functional terms. Borrowing this concept, we propose a multiresolution eXtented Free-Form Deformation (XFFD) framework that seamlessly integrates within and extends the standard Free-Form Deformation (FFD) approach. Discontinuities are incorporated by enriching the B-spline basis functions coupled with extra degrees of freedom, which are only introduced near the discontinuity interface. In contrast with most previous methods, restricted to sliding motion, no ad hoc penalties or constraints are introduced to reduce gaps and overlaps. This allows XFFD to describe more general discontinuous motions. In addition, we integrate XFFD into a rigorously formulated multiresolution framework by introducing an exact parameter upsampling method. The proposed method has been evaluated in two publicly available datasets: 4D pulmonary CT images from the DIR-Lab dataset and 4D CT liver datasets. The XFFD achieved a Target Registration Error (TRE) of 1.17 ± 0.85 mm in the DIR-lab dataset and 1.94 ± 1.01 mm in the liver dataset, which significantly improves on the performance of the state-of-the-art methods handling discontinuities. [ABSTRACT FROM AUTHOR]

Kernel-based dimensionality reduction is a widely used technique in medical image analysis. To fully unravel the underlying nonlinear manifold the selection of an adequate kernel function and of its free parameters is critical. In practice, however, the kernel function is generally chosen as Gaussian or polynomial and such standard kernels might not always be optimal for a given image dataset or application. In this paper, we present a study on the effect of the kernel functions in nonlinear manifold embedding of medical image data. To this end, we first carry out a literature review on existing advanced kernels developed in the statistics, machine learning, and signal processing communities. In addition, we implement kernel-based formulations of well-known nonlinear dimensional reduction techniques such as Isomap and Locally Linear Embedding, thus obtaining a unified framework for manifold embedding using kernels. Subsequently, we present a method to automatically choose a kernel function and its associated parameters from a pool of kernel candidates, with the aim to generate the most optimal manifold embeddings. Furthermore, we show how the calculated selection measures can be extended to take into account the spatial relationships in images, or used to combine several kernels to further improve the embedding results. Experiments are then carried out on various synthetic and phantom datasets for numerical assessment of the methods. Furthermore, the workflow is applied to real data that include brain manifolds and multispectral images to demonstrate the importance of the kernel selection in the analysis of high-dimensional medical images. [ABSTRACT FROM AUTHOR]

The construction of statistical shape models (SSMs) that are rich, i.e., that represent well the natural and complex variability of anatomical structures, is an important research topic in medical imaging. To this end, existing works have addressed the limited availability of training data by decomposing the shape variability hierarchically or by combining statistical and synthetic models built using artificially created modes of variation. In this paper, we present instead a method that merges multiple statistical models of 3D shapes into a single integrated model, thus effectively encoding extra variability that is anatomically meaningful, without the need for the original or new real datasets. The proposed framework has great flexibility due to its ability to merge multiple statistical models with unknown point correspondences. The approach is beneficial in order to re-use and complement pre-existing SSMs when the original raw data cannot be exchanged due to ethical, legal, or practical reasons. To this end, this paper describes two main stages, i.e., (1) statistical model normalization and (2) statistical model integration. The normalization algorithm uses surface-based registration to bring the input models into a common shape parameterization with point correspondence established across eigenspaces. This allows the model fusion algorithm to be applied in a coherent manner across models, with the aim to obtain a single unified statistical model of shape with improved generalization ability. The framework is validated with statistical models of the left and right cardiac ventricles, the L1 vertebra, and the caudate nucleus, constructed at distinct research centers based on different imaging modalities (CT and MRI) and point correspondences. The results demonstrate that the model integration is statistically and anatomically meaningful, with potential value for merging pre-existing multi-modality statistical models of 3D shapes. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we present a new method for the automatic comparison of myocardial motion patterns and the characterization of their degree of abnormality, based on a statistical atlas of motion built from a reference healthy population. Our main contribution is the computation of atlas-based indexes that quantify the abnormality in the motion of a given subject against a reference population, at every location in time and space. The critical computational cost inherent to the construction of an atlas is highly reduced by the definition of myocardial velocities under a small displacements hypothesis. The indexes we propose are of notable interest for the assessment of anomalies in cardiac mobility and synchronicity when applied, for instance, to candidate selection for cardiac resynchronization therapy (CRT). We built an atlas of normality using 2D ultrasound cardiac sequences from 21 healthy volunteers, to which we compared 14 CRT candidates with left ventricular dyssynchrony (LVDYS). We illustrate the potential of our approach in characterizing septal flash, a specific motion pattern related to LVDYS and recently introduced as a very good predictor of response to CRT. [Copyright &y& Elsevier]