New tissue priors for improved automated classification of subcortical brain structures on MRI.

Despite the constant improvement of algorithms for automated brain tissue classification, the accurate delineation of subcortical structures using magnetic resonance images (MRI) data remains challenging. The main difficulties arise from the low gray-white matter contrast of iron rich areas in T1-weighted (T1w) MRI data and from the lack of adequate priors for basal ganglia and thalamus. The most recent attempts to obtain such priors were based on cohorts with limited size that included subjects in a narrow age range, failing to account for age-related gray-white matter contrast changes. Aiming to improve the anatomical plausibility of automated brain tissue classification from T1w data, we have created new tissue probability maps for subcortical gray matter regions. Supported by atlas-derived spatial information, raters manually labeled subcortical structures in a cohort of healthy subjects using magnetization transfer saturation and R2* MRI maps, which feature optimal gray-white matter contrast in these areas. After assessment of inter-rater variability, the new tissue priors were tested on T1w data within the framework of voxel-based morphometry. The automated detection of gray matter in subcortical areas with our new probability maps was more anatomically plausible compared to the one derived with currently available priors. We provide evidence that the improved delineation compensates age-related bias in the segmentation of iron rich subcortical regions. The new tissue priors, allowing robust detection of basal ganglia and thalamus, have the potential to enhance the sensitivity of voxel-based morphometry in both healthy and diseased brains

Parkinson's disease may disrupt overlapping subthalamic nucleus and pallidal motor networks.

There is an ongoing debate about differential clinical outcome and associated adverse effects of deep brain stimulation (DBS) in Parkinson's disease (PD) targeting the subthalamic nucleus (STN) or the globus pallidus pars interna (GPi). Given that functional connectivity profiles suggest beneficial DBS effects within a common network, the empirical evidence about the underlying anatomical circuitry is still scarce. Therefore, we investigate the STN and GPi-associated structural covariance brain patterns in PD patients and healthy controls. We estimate GPi's and STN's whole-brain structural covariance from magnetic resonance imaging (MRI) in a normative mid- to old-age community-dwelling cohort (n = 1184) across maps of grey matter volume, magnetization transfer (MT) saturation, longitudinal relaxation rate (R1), effective transversal relaxation rate (R2*) and effective proton density (PD*). We compare these with the structural covariance estimates in patients with idiopathic PD (n = 32) followed by validation using a reduced size controls' cohort (n = 32). In the normative data set, we observed overlapping spatially distributed cortical and subcortical covariance patterns across maps confined to basal ganglia, thalamus, motor, and premotor cortical areas. Only the subcortical and midline motor cortical areas were confirmed in the reduced size cohort. These findings contrasted with the absence of structural covariance with cortical areas in the PD cohort. We interpret with caution the differential covariance maps of overlapping STN and GPi networks in patients with PD and healthy controls as correlates of motor network disruption. Our study provides face validity to the proposed extension of the currently existing structural covariance methods based on morphometry features to multiparameter MRI sensitive to brain tissue microstructure

The relationship between hippocampal-dependent task performance and hippocampal grey matter myelination and iron content

Individual differences in scene imagination, autobiographical memory recall, future thinking and spatial navigation have long been linked with hippocampal structure in healthy people, although evidence for such relationships is, in fact, mixed. Extant studies have predominantly concentrated on hippocampal volume. However, it is now possible to use quantitative neuroimaging techniques to model different properties of tissue microstructure in vivo such as myelination and iron. Previous work has linked such measures with cognitive task performance, particularly in older adults. Here we investigated whether performance on scene imagination, autobiographical memory, future thinking and spatial navigation tasks was associated with hippocampal grey matter myelination or iron content in young, healthy adult participants. Magnetic resonance imaging data were collected using a multi-parameter mapping protocol (0.8 mm isotropic voxels) from a large sample of 217 people with widely-varying cognitive task scores. We found little evidence that hippocampal grey matter myelination or iron content were related to task performance. This was the case using different analysis methods (voxel-based quantification, partial correlations), when whole brain, hippocampal regions of interest, and posterior:anterior hippocampal ratios were examined, and across different participant sub-groups (divided by gender and task performance). Variations in hippocampal grey matter myelin and iron levels may not, therefore, help to explain individual differences in performance on hippocampal-dependent tasks, at least in young, healthy individuals

White matter tracts characteristics in habitual decision-making circuit underlie ritual behaviors in anorexia nervosa

Anorexia nervosa (AN) is a difficult to treat, pernicious psychiatric disorder that has been linked to decision-making abnormalities. We examined the structural characteristics of habitual and goal-directed decision-making circuits and their connecting white matter tracts in 32 AN and 43 healthy controls across two independent data sets of adults and adolescents as an explanatory sub-study. Total bilateral premotor/supplementary motor area-putamen tracts in the habit circuit had a significantly higher volume in adults with AN, relative to controls. Positive correlations were found between both the number of tracts and white matter volume (WMV) in the habit circuit, and the severity of ritualistic/compulsive behaviors in adults and adolescents with AN. Moreover, we found a significant influence of the habit circuit WMV on AN ritualistic/compulsive symptom severity, depending on the preoccupations symptom severity levels. These findings suggest that AN is associated with white matter plasticity alterations in the habit circuit. The association between characteristics of habit circuit white matter tracts and AN behavioral symptoms provides support for a circuit based neurobiological model of AN, and identifies the habit circuit as a focus for further investigation to aid in development of novel and more effective treatments based on brain-behavior relationships

Photon vs. proton radiochemotherapy: Effects on brain tissue volume and perfusion

Neuro Imaging Researc

Multimodal imaging of brain reorganization in hearing late learners of sign language

The neural plasticity underlying language learning is a process rather than a single event. However, the dynamics of training - induced brain reorganization have rarely been examined, especially using a multimodal magnetic resonance imaging approach, which allows us to study the relationship between functional and structural changes. We focus on sign language acquisition in hearing adults who underwent an 8‐month long course and five neuroimaging sessions. We assessed what neural changes occurred as participants learned a new language in a different modality - as reflected by task‐based activity, connectivity changes, and co‐occurring structural alterations. Major changes in the activity pattern appeared after just 3 months of learning, as indicated by increases in activation within the modality‐independent perisylvian language network, together with increased activation in modality‐dependent parieto‐occipital, visuospatial and motion‐sensitive regions. Despite further learning, no alterations in activation were detected during the following months. However, enhanced coupling between left‐lateralized occipital and inferior frontal regions was observed as the proficiency increased. Furthermore, an increase in gray matter volume was detected in the left inferior frontal gyrus which peaked at the end of learning. Overall, these results showed complexity and temporal distinctiveness of various aspects of brain reorganization associated with learning of new language in different sensory modality

VOLUMETRIC AND VBM MEASURES IN 1.5-5 YEARS OLD CHILDREN OBTAINED USING ADULT SEGMENTATION TOOLS

MRI-based volumetric and morphometric studies in a healthy pediatric population give a unique opportunity to investigate brain development, potentially leading to development of structural markers for neurological and psychiatric diseases. However, pediatric data analysis presents significant challenges for established processing tools, which were initially developed for adult population. This study aimed to investigate sexual dimorphism and age-related changes in neural tissues in healthy 1.5-5-years-old children and to critically assess the feasibility of the use of popular software such as CAT-12, FSL SIENAX and FSL VBM to obtain volumetric and VBM measures in this age group. Results showed inter-method inconsistency in estimations of total intracranial (TIV), grey (GM) and white matter (WM) volumes. Nonetheless, TIV and GM measures proved to be highly correlated with each other regardless of the chosen processing tool. As tissue segmentation is an essential part of the VBM analysis, quality of the GM and WM segmentations were assessed using Dice coefficients against manually corrected, curated FreeSurfer segmentations. Regardless of the used method, the quality of the segmentation was higher for the group of children of age 5 compared to 1.5-2-years-old group (toddlers); and for GM compared to WM. The amount of statistically significant voxels for FSL VBM results was noticeably higher than for CAT-12. FSL VBM analysis revealed higher GM volumes in females compared to males in the left auditory cortex, while CAT-12 showed no statistically significant difference. CAT-12 and FSL VBM agreed on increased GM volumes in toddlers compared to 5-year-olds in the frontal lobe, lingual gyri and cerebellum; and in putamina in 5-year-olds compared to toddlers. The results indicate that we need to be cautious when interpreting the neuroimaging findings in younger children as they may significantly vary due to the differences in used preprocessing methods and statistical analysis

Anomalies structurelles du pallidum interne, phénotype moteur et réponse à la stimulation cérébrale profonde : étude de corrélation dans une cohorte de patients porteurs de dystonies généralisées

La dystonie représente le troisième mouvement anormal le plus fréquent tous âges confondus, après le tremblement et le parkinson. Le terme de dystonie décrit à la fois un symptôme et une maladie appartenant à un ensemble de syndromes neurologiques. La stimulation cérébrale profonde (SCP) appliquée notamment au globus pallidus interne (GPi) s’est avérée être le traitement symptomatique le plus efficace dans les formes généralisées et segmentaires de dystonie. Actuellement aucune étude d’envergure n’a adressé spécifiquement la question des corrélations entre les anomalies structurelles du GPi et la phénoménologie motrice d’une part et d’autre part, de l’impact des anomalies structurelles du GPi sur les résultats de la SCP dans les syndromes dystoniques. Ceux sont les deux objectifs de ce travail. Matériel et Méthode : Nous avons effectué une étude observationnelle rétrospective sur une cohorte de sujets traités par SCP pour un syndrome dystonique généralisé. L’évaluation du phénotype moteur a été réalisée à l’aide d’une grille d’évaluation motrice du phénotype (GEMP). L’IRM encéphalique a été analysé pour documenter des anomalies de volume et de signal du pallidum interne. Résultats : La cohorte comportait 40 sujets, 21 femmes et 19 hommes. L’âge moyen de début des symptômes était de 7,5 ans et l’âge moyen à la SCP était de 15,5 ans. La grille d’évaluation motrice du phénotype (GEMP) a permis de répertorier les conditions de survenue, la distribution, les caractéristiques de la dystonie et des mouvements anormaux associés. Nous n’avons pas identifié de différence significative (p=0,981) pour les scores BFMDRS moteurs préopératoires et du dernier suivi (p=0,434) entre les deux groupes (groupe A: sans anomalie du GPi, groupe B: avec anomalie du GPi) . Cependant à un an de suivi sous SCP, nous avons trouvé une différence significative (p=0,0157) entre les scores moteurs BFMDRS (groupe A, 14.8414.8 ; groupe B : 31,313.7). Les scores moteurs de dystonie aux différents moments du suivi sont expliqués par des variables différentes. La sévérité préopératoire est expliquée principalement par l’âge auquel la dystonie a été responsable d’un retentissement fonctionnel (37%) et l’âge de début des symptômes (35%). A 6 mois de traitement par SCP, la durée de la maladie avant la chirurgie (16%) et l’âge à la chirurgie (8%) étaient les principales variables expliquant le score moteur BFMDRS. A un an, correspondant à l’état d’équilibre sous SCP, les variables principales sont la durée de la maladie avant la chirurgie (30,8%) et l’étiologie (7%). Au dernier suivi, le type d’évolution de la dystonie (20%) et la présence de signes associés (ataxie) (15,7%) expliquent le mieux la sévérité du score. Chez les sujets porteurs de syndromes dystoniques, les anomalies structurelles pallidales sont plus susceptibles d’être associées à une bradykinésie, à une atteinte dystonique crânienne et à une réponse plus limitée à la SCP. Conclusion : Ce travail ouvre le champ d’investigation notamment à l’application de la GEMP au suivi postopératoire, permettant de documenter l’évolution non seulement de la dystonie généralisée mais aussi des mouvements associés aux syndromes dystoniques combinés ou complexes

The Combination of DAT-SPECT, Structural and Diffusion MRI Predicts Clinical Progression in Parkinson’s Disease

There is an increasing interest in identifying non-invasive biomarkers of disease severity and prognosis in idiopathic Parkinson’s disease (PD). Dopamine-transporter SPECT (DAT-SPECT), diffusion tensor imaging (DTI), and structural magnetic resonance imaging (sMRI) provide unique information about the brain’s neurotransmitter and microstructural properties. In this study, we evaluate the relative and combined capability of these imaging modalities to predict symptom severity and clinical progression in de novo PD patients. To this end, we used MRI, SPECT, and clinical data of de novo drug-naïve PD patients (n = 205, mean age 61 ± 10) and age-, sex-matched healthy controls (n = 105, mean age 58 ± 12) acquired at baseline. Moreover, we employed clinical data acquired at 1 year follow-up for PD patients with or without L-Dopa treatment in order to predict the progression symptoms severity. Voxel-based group comparisons and covariance analyses were applied to characterize baseline disease-related alterations for DAT-SPECT, DTI, and sMRI. Cortical and subcortical alterations in de novo PD patients were found in all evaluated imaging modalities, in line with previously reported midbrain-striato-cortical network alterations. The combination of these imaging alterations was reliably linked to clinical severity and disease progression at 1 year follow-up in this patient population, providing evidence for the potential use of these modalities as imaging biomarkers for disease severity and prognosis that can be integrated into clinical trials