A multiple center milestone study of clinical vertebra segmentation is presented in this paper. Vertebra segmentation is a fundamental step for spinal image analysis and intervention. The first half of the study was conducted in the spine segmentation challenge in 2014 International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI) Workshop on Computational Spine Imaging (CSI 2014). The objective was to evaluate the performance of several state-of-the-art vertebra segmentation algorithms on computed tomography (CT) scans using ten training and five testing dataset, all healthy cases; the second half of the study was conducted after the challenge, where additional 5 abnormal cases are used for testing to evaluate the performance under abnormal cases. Dice coefficients and absolute surface distances were used as evaluation metrics. Segmentation of each vertebra as a single geometric unit, as well as separate segmentation of vertebra substructures, was evaluated. Five teams participated in the comparative study. The top performers in the study achieved Dice coefficient of 0.93 in the upper thoracic, 0.95 in the lower thoracic and 0.96 in the lumbar spine for healthy cases, and 0.88 in the upper thoracic, 0.89 in the lower thoracic and 0.92 in the lumbar spine for osteoporotic and fractured cases. The strengths and weaknesses of each method as well as future suggestion for improvement are discussed. This is the first multi-center comparative study for vertebra segmentation methods, which will provide an up-to-date performance milestone for the fast growing spinal image analysis and intervention.

Abstract-Rupture of intracranial saccular aneurysms is the most common cause of spontaneous subarachnoid hemorrhage, which has significant morbidity and mortality. Although there is still controversy regarding the decision on which unruptured aneurysms should be treated, this is based primarily on their size. Nonetheless, many large lesions do not rupture whereas some small ones do. It is commonly accepted that hemodynamical factors are important to better understand the natural history of cerebral aneurysms. However, it might not always be practical to carry out a detailed computational analysis of such factors if a prompt assessment is required. Since shape is likely to be dependent on the balance between hemodynamic forces and the aneurysmal surrounding environment, an appropriate morphological 3-D characterization is likely to provide a practical surrogate to quickly evaluate the risk of rupture. In this paper, an efficient and novel methodology for 3-D shape characterization of cerebral aneurysms is described. The aneurysms are isolated by taking into account a portion of their adjacent vessels. Two methods to characterize the morphology of the aneurysms models using moment invariants have been considered: geometrical moment invariants (GMI) and Zernike moment invariants (ZMI). The results have been validated in a database containing 53 patients with a total of 31 ruptured aneurysms and 24 unruptured aneurysms. It has been found that ZMI indices are more robust than GMI, and seem to provide a reliable way to discriminate between ruptured and unruptured aneurysms. Correct rupture prediction rates of 80% were achieved in contrast to 66% that is found when the aspect ratio index is considered.

Anatomical labeling of the cerebral arteries forming the Circle of Willis (CoW) enables inter-subject comparison, which is required for geometric characterization and discovering risk factors associated with cerebrovascular pathologies. We present a method for automated anatomical labeling of the CoW by detecting its main bifurcations. The CoW is modeled as rooted attributed relational graph, with bifurcations as its vertices, whose attributes are characterized as points on a Riemannian manifold. The method is first trained on a set of pre-labeled examples, where it learns the variability of local bifurcation features as well as the variability in the topology. Then, the labeling of the target vasculature is obtained as maximum a posteriori probability (MAP) estimate where the likelihood of labeling individual bifurcations is regularized by the prior structural knowledge of the graph they span. The method was evaluated by cross-validation on 50 subjects, imaged with magnetic resonance angiography, and showed a mean detection accuracy of 95%. In addition, besides providing the MAP, the method can rank the labelings. The proposed method naturally handles anatomical structural variability and is demonstrated to be suitable for labeling arterial segments of the CoW.

Deep subcortical lesions (DSCL) of the brain, are present in ~60% of the ageing population, and are linked to cognitive decline and depression. DSCL are associated with demyelination, blood brain barrier (BBB) dysfunction, and microgliosis. Microglia are the main immune cell of the brain. Under physiological conditions microglia have a ramified morphology, and react to pathology with a change to a more rounded morphology as well as showing protein expression alterations. This study builds on previous characterisations of DSCL and radiologically ‘normal-appearing’ white matter (NAWM) by performing a detailed characterisation of a range of microglial markers in addition to markers of vascular integrity. The Cognitive Function and Ageing Study (CFAS) provided control white matter (WM), NAWM and DSCL human post mortem tissue for immunohistochemistry using microglial markers (Iba-1, CD68 and MHCII), a vascular basement membrane marker (collagen IV) and markers of BBB integrity (fibrinogen and aquaporin 4). The immunoreactive profile of CD68 increased in a stepwise manner from control WM to NAWM to DSCL. This correlated with a shift from small, ramified cells, to larger, more rounded microglia. While there was greater Iba-1 immunoreactivity in NAWM compared to controls, in DSCL, Iba-1 levels were reduced to control levels. A prominent feature of these DSCL was a population of Iba-1-/CD68+ microglia. There were increases in collagen IV, but no change in BBB integrity. Overall the study shows significant differences in the immunoreactive profile of microglial markers. Whether this is a cause or effect of lesion development remains to be elucidated. Identifying microglia subpopulations based on their morphology and molecular markers may ultimately help decipher their function and role in neurodegeneration. Furthermore, this study demonstrates that Iba-1 is not a pan-microglial marker, and that a combination of several microglial markers is required to fully characterise the microglial phenotype.

Abstract. This paper introduces some general properties of the gravitational metric and the natural basis of vectors and covectors in 4-dimensional emission coordinates. Emission coordinates are a class of space-time coordinates defined and generated by 4 emitters (satellites) broadcasting their proper time by means of electromagnetic signals. They are a constitutive ingredient of the simplest conceivable relativistic positioning systems. Their study is aimed to develop a theory of these positioning systems, based on the framework and concepts of general relativity, as opposed to introducing 'relativistic effects' in a classical framework. In particular, we characterize the causal character of the coordinate vectors, covectors and 2-planes, which are of an unusual type. We obtain the inequality conditions for the contravariant metric to be Lorentzian, and the non-trivial and unexpected identities satisfied by the angles formed by each pair of natural vectors. We also prove that the metric can be naturally split in such a way that there appear 2 parameters (scalar functions) dependent exclusively on the trajectory of the emitters, hence independent of the time broadcast, and 4 parameters, one for each emitter, scaling linearly with the time broadcast by the corresponding satellite, hence independent of the others.PACS numbers: 04.20.-q, 95.10.Jk

Purpose Biophysical tissue models are increasingly used in the interpretation of diffusion MRI (dMRI) data, with the potential to provide specific biomarkers of brain microstructural changes. However, it has been shown recently that, in the general Standard Model, parameter estimation from dMRI data is ill‐conditioned even when very high b‐values are applied. We analyze this issue for the Neurite Orientation Dispersion and Density Imaging with Diffusivity Assessment (NODDIDA) model and demonstrate that its extension from single diffusion encoding (SDE) to double diffusion encoding (DDE) resolves the ill‐posedness for intermediate diffusion weightings, producing an increase in accuracy and precision of the parameter estimation. Methods We analyze theoretically the cumulant expansion up to fourth order in b of SDE and DDE signals. Additionally, we perform in silico experiments to compare SDE and DDE capabilities under similar noise conditions. Results We prove analytically that DDE provides invariant information non‐accessible from SDE, which makes the NODDIDA parameter estimation injective. The in silico experiments show that DDE reduces the bias and mean square error of the estimation along the whole feasible region of 5D model parameter space. Conclusions DDE adds additional information for estimating the model parameters, unexplored by SDE. We show, as an example, that this is sufficient to solve the previously reported degeneracies in the NODDIDA model parameter estimation.

Cerebral aneurysms are a multi-factorial disease with severe consequences. A core part of the European project @neurIST was the physical characterization of aneurysms to find candidate risk factors associated with aneurysm rupture. The project investigated measures based on morphological, haemodynamic and aneurysm wall structure analyses for more than 300 cases of ruptured and unruptured aneurysms, extracting descriptors suitable for statistical studies. This paper deals with the unique challenges associated with this task, and the implemented solutions. The consistency of results required by the subsequent statistical analyses, given the heterogeneous image data sources and multiple human operators, was met by a highly automated toolchain combined with training. A testimonial of the successful automation is the positive evaluation of the toolchain by over 260 clinicians during various hands-on workshops. The specification of the analyses required thorough investigations of modelling and processing choices, discussed in a detailed analysis protocol. Finally, an abstract data model governing the management of the simulation-related data provides a framework for data provenance and supports future use of data and toolchain. This is achieved by enabling the easy modification of the modelling approaches and solution details through abstract problem descriptions, removing the need of repetition of manual processing work.Keywords: cerebral aneurysms; computational imaging and modelling; computational physiology; virtual physiological human

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