ProbaStem, a pipeline towards the first high-resolution probabilistic atlas of the whole human brainstem.

The brainstem plays an essential role in many vital functions, such as autonomic control, consciousness and sleep, motricity, somatic afferent function, and cognition. Its involvement in several neurological diseases and the definition of brainstem targets for deep brain stimulation (DBS) explain the need for brainstem atlases describing its structural organization and connectivity from several modalities, from histology to ultrahigh field ex vivo MRI. Nonetheless, these atlases are often limited to a subpart of the brainstem or only include a single subject, the brainstem variability being considered low. This paper proposes a pipeline to create a high-resolution multisubject probabilistic atlas of the whole human brainstem based on four ultrahigh field ex vivo MRI datasets. The variability of the brainstem structures appears higher than usually considered, both for the volume and position of the central gray matter structures of the brainstem. This justifies the creation of atlases that capture the anatomical variability across subjects. The one we present here only included four specimens, but can easily be incremented due to its highly flexible design.

A novel male Japanese quail structural connectivity atlas using ultra-high field diffusion MRI at 11.7 T.

The structural connectivity of animal brains can be revealed using post-mortem diffusion-weighted magnetic resonance imaging (MRI). Despite the existence of several structural atlases of avian brains, few of them address the bird's structural connectivity. In this study, a novel atlas of the structural connectivity is proposed for the male Japanese quail (Coturnix japonica), aiming at investigating two lines divergent on their emotionality trait: the short tonic immobility (STI) and the long tonic immobility (LTI) lines. The STI line presents a low emotionality trait, while the LTI line expresses a high emotionality trait. 21 male Japanese quail brains from both lines were scanned post-mortem for this study, using a preclinical Bruker 11.7 T MRI scanner. Diffusion-weighted MRI was performed using a 3D segmented echo planar imaging (EPI) pulsed gradient spin-echo (PGSE) sequence with a 200 [Formula: see text]m isotropic resolution, 75 diffusion-encoding directions and a b-value fixed at 4500 s/mm2. Anatomical MRI was likewise performed using a 2D anatomical T2-weighted spin-echo (SE) sequence with a 150 [Formula: see text]m isotropic resolution. This very first anatomical connectivity atlas of the male Japanese quail reveals 34 labeled fiber tracts and the existence of structural differences between the connectivity patterns characterizing the two lines. Thus, the link between the male Japanese quail's connectivity and its underlying anatomical structures has reached a better understanding.

WIKIBrainStem: An online atlas to manually segment the human brainstem at the mesoscopic scale from ultrahigh field MRI.

The brainstem is one of the most densely packed areas of the central nervous system in terms of gray, but also white, matter structures and, therefore, is a highly functional hub. It has mainly been studied by the means of histological techniques, which requires several hundreds of slices with a loss of the 3D coherence of the whole specimen. Access to the inner structure of the brainstem is possible using Magnetic Resonance Imaging (MRI), but this method has a limited spatial resolution and contrast in vivo. Here, we scanned an ex vivo specimen using an ultra-high field (11.7T) preclinical MRI scanner providing data at a mesoscopic scale for anatomical T2-weighted (100 µm and 185 µm isotropic) and diffusion-weighted imaging (300 µm isotropic). We then proposed a hierarchical segmentation of the inner gray matter of the brainstem and defined a set of rules for each segmented anatomical class. These rules were gathered in a freely accessible web-based application, WIKIBrainStem (https://fibratlas.univ-tours.fr/brainstems/index.html), for 99 structures, from which 13 were subdivided into 29 substructures. This segmentation is, to date, the most detailed one developed from ex vivo MRI of the brainstem. This should be regarded as a tool that will be complemented by future results of alternative methods, such as Optical Coherence Tomography, Polarized Light Imaging or histology… This is a mandatory step prior to segmenting multiple specimens, which will be used to create a probabilistic automated segmentation method of ex vivo, but also in vivo, brainstem and may be used for targeting anatomical structures of interest in managing some degenerative or psychiatric disorders.

MEDUSA: A GPU-based tool to create realistic phantoms of the brain microstructure using tiny spheres.

A GPU-based tool to generate realistic phantoms of the brain microstructure is presented. Using a spherical meshing technique which decomposes each microstructural item into a set of overlapping spheres, the phantom construction is made very fast while reliably avoiding the collisions between items in the scene. This novel method is applied to the construction of human brain white matter microstructural components, namely axonal fibers, oligodendrocytes and astrocytes. The algorithm reaches high values of packing density and angular dispersion for the axonal fibers, even in the case of multiple white matter fiber populations and enables the construction of complex biomimicking geometries including myelinated axons, beaded axons, and glial cells. The method can be readily adapted to model gray matter microstructure.

Post-mortem inference of the human hippocampal connectivity and microstructure using ultra-high field diffusion MRI at 11.7 T.

The human hippocampus plays a key role in memory management and is one of the first structures affected by Alzheimer's disease. Ultra-high magnetic resonance imaging provides access to its inner structure in vivo. However, gradient limitations on clinical systems hinder access to its inner connectivity and microstructure. A major target of this paper is the demonstration of diffusion MRI potential, using ultra-high field (11.7 T) and strong gradients (750 mT/m), to reveal the extra- and intra-hippocampal connectivity in addition to its microstructure. To this purpose, a multiple-shell diffusion-weighted acquisition protocol was developed to reach an ultra-high spatio-angular resolution with a good signal-to-noise ratio. The MRI data set was analyzed using analytical Q-Ball Imaging, Diffusion Tensor Imaging (DTI), and Neurite Orientation Dispersion and Density Imaging models. High Angular Resolution Diffusion Imaging estimates allowed us to obtain an accurate tractography resolving more complex fiber architecture than DTI models, and subsequently provided a map of the cross-regional connectivity. The neurite density was akin to that found in the histological literature, revealing the three hippocampal layers. Moreover, a gradient of connectivity and neurite density was observed between the anterior and the posterior part of the hippocampus. These results demonstrate that ex vivo ultra-high field/ultra-high gradients diffusion-weighted MRI allows the mapping of the inner connectivity of the human hippocampus, its microstructure, and to accurately reconstruct elements of the polysynaptic intra-hippocampal pathway using fiber tractography techniques at very high spatial/angular resolutions.

Fronto-Subcortical Circuits for Cognition and Motivation: Dissociated Recovery in a Case of Loss of Psychic Self-Activation.

In humans and non-humans primates, extensive evidence supports the existence of subcortico-cortical circuits for cognition and behavior. Lesions studies are critical to understand the clinical significance of these functionally segregated circuits. Mapping these circuits from lesion studies is difficult given the heterogeneous etiology of the lesions, the lack of long-term and systematic testing of cognitive and behavioral disturbances, as well as the scarcity of neuroimaging data for identifying the precise location and extent of subcortical lesions. Here, we report the long-term follow-up study of a patient who developed a loss of psychic self-activation associated to a dysexecutive syndrome following resuscitation from cardiac arrest. Neuroimaging revealed extensive bilateral lesions in the putamen, with a relative spare of the caudate, and exhibiting a dorsoventral gradient that was predominantly rostrally to the anterior commissure and spared most of the ventral striatum. In comprehensive neuropsychological and neuropsychiatric assessments, we observed dissociation between the improvement of the self-activation deficits and the stability of the dysexecutive syndrome. The pattern of recovery after this lesion lends support to current models proposing the existence of two main subcortico-cortical circuits: a dorsal circuit, mostly mediating cognitive processes, and a ventral circuit, implicated in motivation.

High nigral iron deposition in LRRK2 and Parkin mutation carriers using R2* relaxometry.

OBJECTIVES: The goal of this work was to investigate iron deposition in the basal ganglia and thalamus in symptomatic and asymptomatic leucine-rich repeat kinase 2 (LRRK2) and Parkin-associated Parkinson's disease (PD), using R2* relaxometry rate. METHODS: Twenty subjects with genetic PD (four symptomatic and two asymptomatic Parkin subjects, nine symptomatic and five asymptomatic LRRK2 subjects) were compared with 20 patients with idiopathic PD (IPD) and 20 healthy subjects. Images were obtained at 3 teslas, using multi-echo T2 and T2* sequences. R2 and R2* values were calculated in the substantia nigra (SN), the striatum, the globus pallidus, and the thalamus. RESULTS: The R2* values in the SN were increased in IPD and mutation-carrying patients as compared with controls and in mutation-carrying patients as compared with IPD. Asymptomatic mutation carriers showed higher R2* values than controls and did not differ from IPD patients. No changes were seen in the other structures or in R2 values. CONCLUSION: These results are consistent with increased iron load in LRRK2- and Parkin-mutation carriers. The increased R2* in asymptomatic PD-mutation carriers suggests that iron deposition occurs early during the preclinical phase of the disease. R2* measurements may be used as markers for investigating nigrostriatal damage in preclinical mutation-carrying patients.

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.

Noise correction for HARDI and HYDI data obtained with multi-channel coils and sum of squares reconstruction: an anisotropic extension of the LMMSE.

Parallel magnetic resonance imaging (MRI) yields noisy magnitude data, described in most cases as following a noncentral χ distribution when the signals received by the coils are combined as the sum of their squares. One well-known case of this noncentral χ noise model is the Rician model, but it is only valid in the case of single-channel acquisition. Although the use of parallel MRI is increasingly common, most of the correction methods still perform Rician noise removal, yielding an erroneous result due to an incorrect noise model. Moreover, the existence of noise correlations in phased array systems renders noise nonstationary and further modifies the noise description in parallel MRI. However, the noncentral χ model has been demonstrated to work as a good approximation as long as effective voxelwise parameters are used. A good correction step, adapted to the right noise model, is of paramount importance, especially when working with diffusion-weighted MR data, whose signal-to-noise ratio is low. In this paper, we present a noise removal technique designed to be fast enough for integration into a real-time reconstruction system, thus offering the convenience of obtaining corrected data almost instantaneously during the MRI scan. Our method employs the noncentral χ noise model and uses a simplified method to account for noise correlations; this leads to an efficient and rapid correction. The method consists of an anisotropic extension of the Linear Minimum Mean Square Error estimator (LMMSE) that is a far better edge-preserving method than the traditional LMMSE and addresses noncentral χ distributions along with empirically computed global effective parameters. The results on simulated and real data demonstrate that this anisotropic extended LMMSE outperforms the original LMMSE on images corrupted by noncentral χ noise. Moreover, in comparison with the existing LMMSE technique incorporating the estimation of voxelwise effective parameters, our method yields improved results.

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.

Parallel MRI noise correction: an extension of the LMMSE to non central chi distributions.

Parallel MRI leads to magnitude data corrupted by noise described in most cases as following a Rician or a non central chi distribution. And yet, very few correction methods perform a non central chi noise removal. However, this correction step, adapted to the correct noise model, is of very much importance, especially when working with Diffusion Weighted MR data yielding a low SNR. We propose an extended Linear Minimum Mean Square Error estimator (LMMSE), which is adapted to deal with non central chi distributions. We demonstrate on simulated and real data that the extended LMMSE outperforms the original LMMSE on images corrupted by a non central chi noise.

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.

Mean q-ball strings obtained by constrained procrustes analysis with point sliding.

The idea underpinning the work we present herein is to design robust and objective tools for brain white matter (WM) morphometry. We focus on WM tracts, and propose to represent them by their mean lines, to which we associate the attributes derived from high-angular resolution diffusion imaging (HARDI). The definition of the tract mean line derives directly from the geometry of the tract fibres. We determine the fibre point correspondences and impact factors of individual fibres, upon which we estimate average HARDI models along the tract mean lines. This way we obtain a compact tract representation that exploits all the available information, and is at the same time free of the outlier influence and undesired tract edge effects.

New diffusion phantoms dedicated to the study and validation of high-angular-resolution diffusion imaging (HARDI) models.

We present new diffusion phantoms dedicated to the study and validation of high-angular-resolution diffusion imaging (HARDI) models. The phantom design permits the application of imaging parameters that are typically employed in studies of the human brain. The phantoms were made of small-diameter acrylic fibers, chosen for their high hydrophobicity and flexibility that ensured good control of the phantom geometry. The polyurethane medium was filled under vacuum with an aqueous solution that was previously degassed, doped with gadolinium-tetraazacyclododecanetetraacetic acid (Gd-DOTA), and treated by ultrasonic waves. Two versions of such phantoms were manufactured and tested. The phantom's applicability was demonstrated on an analytical Q-ball model. Numerical simulations were performed to assess the accuracy of the phantom. The phantom data will be made accessible to the community with the objective of analyzing various HARDI models.

Real-time MR diffusion tensor and Q-ball imaging using Kalman filtering.

Diffusion magnetic resonance imaging (dMRI) has become an established research tool for the investigation of tissue structure and orientation. In this paper, we present a method for real-time processing of diffusion tensor and Q-ball imaging. The basic idea is to use Kalman filtering framework to fit either the linear tensor or Q-ball model. Because the Kalman filter is designed to be an incremental algorithm, it naturally enables updating the model estimate after the acquisition of any new diffusion-weighted volume. Processing diffusion models and maps during ongoing scans provides a new useful tool for clinicians, especially when it is not possible to predict how long a subject may remain still in the magnet. First, we introduce the general linear models corresponding to the two diffusion tensor and analytical Q-ball models of interest. Then, we present the Kalman filtering framework and we focus on the optimization of the diffusion orientation sets in order to speed up the convergence of the online processing. Last, we give some results on a healthy volunteer for the online tensor and the Q-ball model, and we make some comparisons with the conventional offline techniques used in the literature. We could achieve full real-time for diffusion tensor imaging and deferred time for Q-ball imaging, using a single workstation.

Characterization and correction of distortions in stereotactic magnetic resonance imaging for bilateral subthalamic stimulation in Parkinson disease.

OBJECT: High-frequency stimulation of the subthalamic nucleus (STN) is effective for treating refractory idiopathic Parkinson disease (PD). In stereotactic conditions magnetic resonance (MR) imaging is used by many teams to perform preoperative targeting of the STN. The goal of this study was to analyze and correct the geometrically observed MR imaging acquisitions used for targeting of the STN. METHODS: A dedicated phantom of known geometry was used. The authors calculated existing shifts between measured points and theoretically defined points on the same T1- and T2-weighted sequences used to target the STN. A shifting volume was built to correct the phantom images and images acquired preoperatively in 13 patients with PD. A quantitative study of the correction was conducted using the phantom images and acquisitions acquired in these patients. To quantify the distortion corrections, the authors segmented the lateral ventricles and calculated the overlap of the corrected and uncorrected values between T1 and T2 segmentation. The authors found that the distortions were greater in the direction of slice selection and frequency encoding and weaker on three-dimensional T1-weighted acquisitions. On T2-weighted acquisitions, the maximum shifts were 2.19 mm in the frequency-encoding direction and 3.81 mm in slice selection. The geometrical distortion was significantly reduced and smaller than pixel size after distortion correction. Assessment of the patients' scans showed that the mean ventricular overlap was 76% before and 94% after correction. CONCLUSIONS: The authors found that significant distortions can be observed on T2-weighted images used to demonstrate the STN. These distortions can be corrected using appropriate software.

Foot, hand, face and eye representation in the human striatum.

The present study aimed at determining the three-dimensional organization of striatal activation during foot, hand, face and eye movements. Seven right-handed, healthy volunteers were studied at 1.5 T using blood oxygen level dependent (BOLD) contrast. The tasks consisted of self-paced flexion/extension of the right and left fingers and right toes, contraction of the lips and saccadic eye movements. For foot, hand and face movements, striatal activation was mainly found in the putamen with a somatotopical organization, the foot area being dorsal, the face area more ventral and medial, the hand area in between. Overlap between somatotopic territories was present, more prominent for hand-face than for foot-face or foot-hand areas. In the putamen, the activated areas of the ipsi- and contralateral hand areas were not identical, suggesting a partial segregation of the ipsi- and contralateral striatal sensorimotor projections. For saccadic eye movements, bilateral activation was observed at the junction between the body and the head of the caudate nucleus and in the right putamen. These data present evidence for a somatotopic organization of the human striatum which corresponds with the topography of corticostriatal projections described in the non-human primates.

Monitoring disease progression in CADASIL with diffusion magnetic resonance imaging: a study with whole brain histogram analysis.

BACKGROUND AND PURPOSE: In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a large increase in water diffusion has been found both inside and outside the cerebral lesions as detected on conventional MRI. The aim of the present study was to assess the sensitivity of diffusion tensor imaging for monitoring the progression of cerebral tissue damage during the course of CADASIL. METHODS: With the use of diffusion tensor imaging, whole brain trace of the diffusion tensor [Trace(D)] histograms were obtained in 22 CADASIL patients and 12 age-matched controls at baseline, in 14 patients after a mean delay of 21 months, and in 5 controls after a mean delay of 29 months. Parameters derived from these histograms (mean value, peak height, and peak location) were analyzed at baseline and during the follow-up. RESULTS: At baseline, all the histogram parameters differed between patients and controls and were found to be significantly correlated with both the Mini-Mental State Examination score and Rankin Scale score in the patient group. The follow-up study showed a decrease in the peak height associated with an increase in the mean value of whole brain Trace(D) histograms in the 14 CADASIL patients scanned twice. The diffusion changes appeared larger in the patients whose Rankin score increased during the study period. CONCLUSIONS: These results suggest that the measurement of water diffusion over time is a sensitive marker for the progression of tissue damage in the brain. Thus, quantitative diffusion MRI can be used to monitor disease progression in CADASIL and possibly in other types of small-vessel brain disorders.