Altered structural connectivity of cortico-striato-pallido-thalamic networks in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome is a childhood-onset syndrome characterized by the presence and persistence of motor and vocal tics. A dysfunction of cortico-striato-pallido-thalamo-cortical networks in this syndrome has been supported by convergent data from neuro-pathological, electrophysiological as well as structural and functional neuroimaging studies. Here, we addressed the question of structural integration of cortico-striato-pallido-thalamo-cortical networks in Gilles de la Tourette syndrome. We specifically tested the hypothesis that deviant brain development in Gilles de la Tourette syndrome could affect structural connectivity within the input and output basal ganglia structures and thalamus. To this aim, we acquired data on 49 adult patients and 28 gender and age-matched control subjects on a 3 T magnetic resonance imaging scanner. We used and further implemented streamline probabilistic tractography algorithms that allowed us to quantify the structural integration of cortico-striato-pallido-thalamo-cortical networks. To further investigate the microstructure of white matter in patients with Gilles de la Tourette syndrome, we also evaluated fractional anisotropy and radial diffusivity in these pathways, which are both sensitive to axonal package and to myelin ensheathment. In patients with Gilles de la Tourette syndrome compared to control subjects, we found white matter abnormalities in neuronal pathways connecting the cerebral cortex, the basal ganglia and the thalamus. Specifically, striatum and thalamus had abnormally enhanced structural connectivity with primary motor and sensory cortices, as well as paracentral lobule, supplementary motor area and parietal cortices. This enhanced connectivity of motor cortex positively correlated with severity of tics measured by the Yale Global Tics Severity Scale and was not influenced by current medication status, age or gender of patients. Independently of the severity of tics, lateral and medial orbito-frontal cortex, inferior frontal, temporo-parietal junction, medial temporal and frontal pole also had enhanced structural connectivity with the striatum and thalamus in patients with Gilles de la Tourette syndrome. In addition, the cortico-striatal pathways were characterized by elevated fractional anisotropy and diminished radial diffusivity, suggesting microstructural axonal abnormalities of white matter in Gilles de la Tourette syndrome. These changes were more prominent in females with Gilles de la Tourette syndrome compared to males and were not related to the current medication status. Taken together, our data showed widespread structural abnormalities in cortico-striato-pallido-thalamic white matter pathways in patients with Gilles de la Tourette, which likely result from abnormal brain development in this syndrome.

Robust imaging of hippocampal inner structure at 7T: in vivo acquisition protocol and methodological choices.

OBJECTIVE: Motion-robust multi-slab imaging of hippocampal inner structure in vivo at 7T. MATERIALS AND METHODS: Motion is a crucial issue for ultra-high resolution imaging, such as can be achieved with 7T MRI. An acquisition protocol was designed for imaging hippocampal inner structure at 7T. It relies on a compromise between anatomical details visibility and robustness to motion. In order to reduce acquisition time and motion artifacts, the full slab covering the hippocampus was split into separate slabs with lower acquisition time. A robust registration approach was implemented to combine the acquired slabs within a final 3D-consistent high-resolution slab covering the whole hippocampus. Evaluation was performed on 50 subjects overall, made of three groups of subjects acquired using three acquisition settings; it focused on three issues: visibility of hippocampal inner structure, robustness to motion artifacts and registration procedure performance. RESULTS: Overall, T2-weighted acquisitions with interleaved slabs proved robust. Multi-slab registration yielded high quality datasets in 96 % of the subjects, thus compatible with further analyses of hippocampal inner structure. CONCLUSION: Multi-slab acquisition and registration setting is efficient for reducing acquisition time and consequently motion artifacts for ultra-high resolution imaging of the inner structure of the hippocampus.

Prognostic value of preoperative diffusion restriction in glioblastoma.

INTRODUCTION: Although glioblastoma (GBM) has a very poor prognosis, overall survival (OS) in treated patients shows great difference varying from few days to several months. Identifying factors explaining this difference would improve management of patient treatment. AIM: To determine the relevance of diffusion restriction in newly diagnosed treatment-naïve GBM patients. METHODS: Preoperative magnetic resonance scans of 33 patients with GBM were reviewed. Regions of interest including all the T2 hyperintense lesion were drawn on diffusion weighted B0 images and transferred to the apparent diffusion coefficient (ADC) map. For each patient, a histogram displaying the ADC values within in the regions of interest was generated. Volumetric parameters including tumor regions with restricted diffusion, parameters derived from histogram and mean ADC value of the tumor were calculated. Their relationship with OS was analyzed. RESULTS: Patients with mean ADC value < 1415x10-6 mm2/s had a significantly shorter OS (p=0.021). Among volumetric parameters, the percentage of volume within T2 lesion with a normalized ADC value <1.5 times that in white matter was significantly associated with OS (p=0.0045). Patients with a percentage>23.92% had a shorter OS. Among parameters derived from histogram, the 50th percentile showed a trend towards significance for OS (p=0.055) with patients living longer when having higher values of 50th percentile. A difference in OS was observed between patients according to ADC peak of histogram but this difference did not reach statistical significance (p=0.0959). CONCLUSION: Diffusion magnetic resonance imaging may provide useful information for predicting GBM prognosis.

Parkinson's disease patients show reduced cortical-subcortical sensorimotor connectivity.

Reduced dopamine input to cortical and subcortical brain structures, particularly those in the sensorimotor network, is a hallmark of Parkinson's disease (PD). The extent to which dopamine dysfunction affects connectivity within this and other brain networks remains to be investigated. The purpose of this study was to measure anatomical and functional connectivity in groups of PD patients and controls to determine whether connectivity deficits within the cortico-basal ganglia thalamocortical system could be attributed to PD, particularly in sensorimotor connections. A neuroimaging paradigm involving diffusion-weighted magnetic resonance imaging (MRI) and resting-state functional MRI was implemented in a large cohort of PD patients and control subjects. Probabilistic tractography and functional correlation analyses were performed to map connections between brain structures and to derive indices of connectivity that were then used to compare groups. Anatomical connectivity deficits were demonstrated in PD patients, specifically for sensorimotor connections. Functional deficits were also found in some of the same connections. In addition, functional connectivity was found to increase in associative and limbic connections in PD patients compared with controls. This study lends support to findings regarding the dysfunction of the sensorimotor circuit in PD. As deficits in anatomical and functional connectivity within this circuit were in some cases concordant in PD patients, a possible link between brain structure and function is suggested. Increases in functional connectivity in other cortico-basal ganglia thalamocortical circuits may be indicative of compensatory effects in response to system deficits elsewhere.

A Diffeomorphic Vector Field Approach to Analyze the Thickness of the Hippocampus From 7 T MRI.

OBJECTIVE: 7-Tesla MRI of the hippocampus enhances the visualization of its internal substructures. Among these substructures, the cornu Ammonis and subiculum form a contiguous folded ribbon of gray matter. Here, we propose a method to analyze local thickness measurements of this ribbon. METHODS: We introduce an original approach based upon the estimation of a diffeomorphic vector field that traverses the ribbon. The method is designed to handle specificities of the hippocampus and corresponding 7-Tesla acquisitions: highly convoluted surface, non-closed ribbon, incompletely defined inner/outer boundaries, anisotropic acquisitions. We furthermore propose to conduct group comparisons using a population template built from the central surfaces of individual subjects. RESULTS: We first assessed the robustness of our approach to anisotropy, as well as to inter-rater variability, on a post-mortem scan and on in vivo acquisitions respectively. We then conducted a group study on a dataset of in vivo MRI from temporal lobe epilepsy (TLE) patients and healthy controls. The method detected local thinning patterns in patients, predominantly ipsilaterally to the seizure focus, which is consistent with medical knowledge. CONCLUSION: This new technique allows measuring the thickness of the hippocampus from 7-Tesla MRI. It shows good robustness with respect to anisotropy and inter-rater variability and has the potential to detect local atrophy in patients. SIGNIFICANCE: As 7-Tesla MRI is increasingly available, this new method may become a useful tool to study local alterations of the hippocampus in brain disorders. It is made freely available to the community (code: https://github.com/aramis-lab/hiplay7-thickness, postmortem segmentation: https://doi.org/10.5281/zenodo.3533264).

A Bayesian framework for joint morphometry of surface and curve meshes in multi-object complexes.

We present a Bayesian framework for atlas construction of multi-object shape complexes comprised of both surface and curve meshes. It is general and can be applied to any parametric deformation framework and to all shape models with which it is possible to define probability density functions (PDF). Here, both curve and surface meshes are modelled as Gaussian random varifolds, using a finite-dimensional approximation space on which PDFs can be defined. Using this framework, we can automatically estimate the parameters balancing data-terms and deformation regularity, which previously required user tuning. Moreover, it is also possible to estimate a well-conditioned covariance matrix of the deformation parameters. We also extend the proposed framework to data-sets with multiple group labels. Groups share the same template and their deformation parameters are modelled with different distributions. We can statistically compare the groups'distributions since they are defined on the same space. We test our algorithm on 20 Gilles de la Tourette patients and 20 control subjects, using three sub-cortical regions and their incident white matter fiber bundles. We compare their morphological characteristics and variations using a single diffeomorphism in the ambient space. The proposed method will be integrated with the Deformetrica software package, publicly available at www.deformetrica.org.

Parsimonious Approximation of Streamline Trajectories in White Matter Fiber Bundles.

Fiber bundles stemming from tractography algorithms contain many streamlines. They require therefore a great amount of computer memory and computational resources to be stored, visualised and processed. We propose an approximation scheme for fiber bundles which results in a parsimonious representation of weighted prototypes. Prototypes are chosen among the streamlines and they represent groups of similar streamlines. Their weight is related to the number of approximated streamlines. Both streamlines and prototypes are modelled as weighted currents. This computational model does not need point-to-point correspondences and two streamlines are considered similar if their endpoints are close to each other and if their pathways follow similar trajectories. Moreover, the space of weighted currents is a vector space with a closed-form metric. This permits easy computation of the approximation error and the selection of the prototypes is based on the minimisation of this error. We propose an iterative algorithm which approximates independently and simultaneously all the fascicles of the bundle in a fast and accurate way. We show that the resulting representation preserves the shape of the bundle and it can be used to accurately reconstruct the original structural connectivity. We evaluate our algorithm on bundles obtained from both deterministic and probabilistic tractography algorithms. The resulting approximations use on average only 2% of the original streamlines as prototypes. This drastically reduces the computational burden of the processes where the geometry of the streamlines is considered. We demonstrate its effectiveness using as example the registration between two fiber bundles.

Biomedical image segmentation using geometric deformable models and metaheuristics.

This paper describes a hybrid level set approach for medical image segmentation. This new geometric deformable model combines region- and edge-based information with the prior shape knowledge introduced using deformable registration. Our proposal consists of two phases: training and test. The former implies the learning of the level set parameters by means of a Genetic Algorithm, while the latter is the proper segmentation, where another metaheuristic, in this case Scatter Search, derives the shape prior. In an experimental comparison, this approach has shown a better performance than a number of state-of-the-art methods when segmenting anatomical structures from different biomedical image modalities.

Joint Morphometry of Fiber Tracts and Gray Matter Structures Using Double Diffeomorphisms.

This work proposes an atlas construction method to jointly analyse the relative position and shape of fiber tracts and gray matter structures. It is based on a double diffeomorphism which is a composition of two diffeomorphisms. The first diffeomorphism acts only on the white matter keeping fixed the gray matter of the atlas. The resulting white matter, together with the gray matter, are then deformed by the second diffeomorphism. The two diffeomorphisms are related and jointly optimised. In this way, the, first diffeomorphisms explain the variability in structural connectivity within the population, namely both changes in the connected areas of the gray matter and in the geometry of the pathway of the tracts. The second diffeomorphisms put into correspondence the homologous anatomical structures across subjects. Fiber bundles are approximated with weighted prototypes using the metric of weighted currents. The atlas, the covariance matrix of deformation parameters and the noise variance of each structure are automatically estimated using a Bayesian approach. This method is applied to patients with Tourette syndrome and controls showing a variability in the structural connectivity of the left cortico-putamen circuit.

Intensity-based image registration using scatter search.

OBJECTIVE: We present a novel intensity-based algorithm for medical image registration (IR). METHODS AND MATERIALS: The IR problem is formulated as a continuous optimization task, and our work focuses on the development of the optimization component. Our method is designed over an advanced scatter search template, and it uses a combination of restart and dynamic boundary mechanisms integrated within a multi-resolution strategy. RESULTS: The experimental validation is performed over two datasets of human brain magnetic resonance imaging. The algorithm is evaluated in both a stand-alone registration application and an atlas-based segmentation process targeted to the deep brain structures, considering a total of 16 and 18 scenarios, respectively. Five established IR techniques, both feature- and intensity-based, are considered for comparison purposes, and ground-truth data is used to quantitatively assess the quality of the results. Our approach ranked first in both studies and it is able to outperform all competitors in 12 of 16 registration scenarios and in 14 of 18 registration-based segmentation tasks. A statistical analysis confirms with high confidence (p<0.014) the accuracy and applicability of our method. CONCLUSIONS: With a proper, problem-specific design, scatter search is able to provide a robust, global optimization. The accuracy and reliability of the registration process are superior to those of classic gradient-based techniques.

A prototype representation to approximate white matter bundles with weighted currents.

Quantitative and qualitative analysis of white matter fibers resulting from tractography algorithms is made difficult by their huge number. To this end, we propose an approximation scheme which gives as result a more concise but at the same time exhaustive representation of a fiber bundle. It is based on a novel computational model for fibers, called weighted currents, characterised by a metric that considers both the pathway and the anatomical locations of the endpoints of the fibers. Similarity has therefore a twofold connotation: geometrical and related to the connectivity. The core idea is to use this metric for approximating a fiber bundle with a set of weighted prototypes, chosen among the fibers, which represent ensembles of similar fibers. The weights are related to the fibers represented b y t he prototypes. The algorithm is divided into two steps. First, the main modes of the fiber bundle are detected using a modularity based clustering algorithm. Second, a prototype fiber selection process is carried on in each cluster separately. This permits to explain the main patterns of the fiber bundle in a fast and accurate way.

Detection of volume loss in hippocampal layers in Alzheimer's disease using 7 T MRI: a feasibility study.

In Alzheimer's disease (AD), the hippocampus is an early site of tau pathology and neurodegeneration. Histological studies have shown that lesions are not uniformly distributed within the hippocampus. Moreover, alterations of different hippocampal layers may reflect distinct pathological processes. 7 T MRI dramatically improves the visualization of hippocampal subregions and layers. In this study, we aimed to assess whether 7 T MRI can detect volumetric changes in hippocampal layers in vivo in patients with AD. We studied four AD patients and seven control subjects. MR images were acquired using a whole-body 7 T scanner with an eight channel transmit-receive coil. Hippocampal subregions were manually segmented from coronal T2*-weighted gradient echo images with 0.3 × 0.3 × 1.2 mm3 resolution using a protocol that distinguishes between layers richer or poorer in neuronal bodies. Five subregions were segmented in the region of the hippocampal body: alveus, strata radiatum, lacunosum and moleculare (SRLM) of the cornu Ammonis (CA), hilum, stratum pyramidale of CA and stratum pyramidale of the subiculum. We found strong bilateral reductions in the SRLM of the cornu Ammonis and in the stratum pyramidale of the subiculum (p < 0.05), with average cross-sectional area reductions ranging from -29% to -49%. These results show that it is possible to detect volume loss in distinct hippocampal layers using segmentation of 7 T MRI. 7 T MRI-based segmentation is a promising tool for AD research.

Bayesian atlas estimation for the variability analysis of shape complexes.

In this paper we propose a Bayesian framework for multiobject atlas estimation based on the metric of currents which permits to deal with both curves and surfaces without relying on point correspondence. This approach aims to study brain morphometry as a whole and not as a set of different components, focusing mainly on the shape and relative position of different anatomical structures which is fundamental in neuro-anatomical studies. We propose a generic algorithm to estimate templates of sets of curves (fiber bundles) and closed surfaces (sub-cortical structures) which have the same "form" (topology) of the shapes present in the population. This atlas construction method is based on a Bayesian framework which brings to two main improvements with respect to previous shape based methods. First, it allows to estimate from the data set a parameter specific to each object which was previously fixed by the user: the trade-off between data-term and regularity of deformations. In a multi-object analysis these parameters balance the contributions of the different objects and the need for an automatic estimation is even more crucial. Second, the covariance matrix of the deformation parameters is estimated during the atlas construction in a way which is less sensitive to the outliers of the population.

Mapping cortico-striatal connectivity onto the cortical surface: a new tractography-based approach to study Huntington disease.

Huntington disease (HD) is associated with early and severe damage to the basal ganglia and particularly the striatum. We investigated cortico-striatal connectivity modifications occurring in HD patients using a novel approach which focuses on the projection of the connectivity profile of the basal ganglia onto the cortex. This approach consists in computing, for each subcortical structure, surface connectivity measures representing its strength of connections to the cortex and comparing these measures across groups. In this study, we focused on Huntington disease as an application of this new approach. First, surface cortico-striatal connectivity measures of a group of healthy subjects were averaged in order to infer the "normal" connectivity profile of the striatum to the cortex. Second, a statistical analysis was performed from the surface connectivity measures of healthy subjects and HD patients in order to detect the cortical gyri presenting altered cortico-striatal connectivity in HD. Lastly, percentage differences of connectivity between healthy subjects and patients were inferred, for each nucleus of the striatum, from the connectivity measures of the cortical gyri presenting a significant connectivity difference between the two groups. These percentage differences characterize the axonal disruptions between the striatum and the cortex occurring in HD. We found selective region-specific degeneration of cortical connections predominating for associative and primary sensorimotor connections and with relative preservation of limbic connections. Our method can be used to infer novel connectivity-based markers of HD pathological process.

Analysis of the striato-thalamo-cortical connectivity on the cortical surface to infer biomarkers of Huntington's disease.

The deep brain nuclei play an important role in many brain functions and particularly motor control. Damage to these structures result in movement disorders such as in Parkinson's disease or Huntington's disease, or behavioural disorders such as Tourette syndrome. In this paper, we propose to study the connectivity profile of the deep nuclei to the motor, associative or limbic areas and we introduce a novel tool to build a probabilistic atlas of these connections to the cortex directly on the surface of the cortical mantel, as it corresponds to the space of functional interest. The tool is then applied on two populations of healthy volunteers and patients suffering from severe Huntington's disease to produce two surface atlases of the connectivity of the basal ganglia to the cortical areas. Finally, robust statistics are used to characterize the differences of that connectivity between the two populations, providing new connectivity-based biomarkers of the pathology.