Stefan Sunaert

Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis

OBJECTIVEnAim of present study was to evaluate changes in diffusion tensor imaging (DTI) parameters in the whole brain of 28 patients with amyotrophic lateral sclerosis (ALS) compared to 26 healthy controls.nnnMETHODSnIn both fibertracking and voxel-based analysis, quantitative comparisons of the diffusion parameters between ALS patients and controls were performed. Correlation analyses of diffusion parameters and disease duration and disease severity were performed. A second DTI examination was acquired, allowing the evaluation of the effect of disease progression on the diffusion parameters.nnnRESULTSnFibertracking analysis revealed that especially the precentral part of the corticospinal tract (CST) was impaired. In the voxel-based analysis, it was shown that changes of diffusion parameters occurred throughout the brain, including frontal, temporal and parietal lobes. Disease severity was inversely correlated with the fractional anisotropy (FA). In the follow-up examination, a further decline of FA over time could be demonstrated in the CST as well as in the whole brain white matter.nnnINTERPRETATIONnThis study provides support for the view of ALS as being a multisystem degenerative disease, in which abnormalities of extra-motor areas play an important role in the in vivo physiopathology.

Presurgical planning for tumor resectioning

Since the birth of functional magnetic resonance imaging (fMRI)—a noninvasive tool able to visualize brain function—now 15 years ago, several clinical applications have emerged. fMRI follows from the neurovascular coupling between neuronal electrical activity and cerebrovascular physiology that leads to three effects that can contribute to the fMRI signal: an increase in the blood flow velocity, in the blood volume and in the blood oxygenation level. The latter effect, gave the technique the name blood oxygenation level dependent (BOLD) fMRI. One of the major clinical uses is presurgical fMRI in patients with brain abnormalities. The goals of presurgical fMRI are threefold: 1) assessing the risk of neurological deficit that follows a surgical procedure, 2) selecting patients for invasive intraoperative mapping, and 3) guiding of the surgical procedure itself. These are reviewed here. Unfortunately, randomized trials or outcome studies that definitively show benefits to the final outcome of the patient when applying fMRI presurgically have not been performed. Therefore, fMRI has not yet reached the status of clinical acceptance. The final purpose of this article is to define a roadmap of future research and developments in order to tilt pre‐surgical fMRI to the status of clinical validity and acceptance. J. Magn. Reson. Imaging 2006.

Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis: Revisited

Voxel‐based analyses (VBA) are increasingly being used to detect white matter abnormalities with diffusion tensor imaging (DTI) in different types of pathologies. However, the validity, specificity, and sensitivity of statistical inferences of group differences to a large extent depend on the quality of the spatial normalization of the DTI images. Using high‐dimensional nonrigid coregistration techniques that are able to align both the spatial and orientational diffusion information and incorporate appropriate templates that contain this complete DT information may improve this quality. Alternatively, a hybrid technique such as tract‐based spatial statistics (TBSS) may improve the reliability of the statistical results by generating voxel‐wise statistics without the need for perfect image alignment and spatial smoothing. In this study, we have used (1) a coregistration algorithm that was optimized for coregistration of DTI data and (2) a population‐based DTI atlas to reanalyze our previously published VBA, which compared the fractional anisotropy and mean diffusivity maps of patients with amyotrophic lateral sclerosis (ALS) with those of healthy controls. Additionally, we performed a complementary TBSS analysis to improve our understanding and interpretation of the VBA results. We demonstrate that, as the overall variance of the diffusion properties is lowered after normalizing the DTI data with such recently developed techniques (VBA using our own optimized high‐dimensional nonrigid coregistration and TBSS), more reliable voxel‐wise statistical results can be obtained than had previously been possible, with our VBA and TBSS yielding very similar results. This study provides support for the view of ALS as a multisystem disease, in which the entire frontotemporal lobe is implicated. Hum Brain Mapp, 2009.

Construction of a stereotaxic DTI atlas with full diffusion tensor information for studying white matter maturation from childhood to adolescence using tractography-based segmentations.

Reconstruction of white matter (WM) fiber tracts based on diffusion tensor imaging (DTI) is increasingly being used in clinical and research settings to study normal and pathological WM tissue as well as the maturation of this WM tissue. Such fiber tracking (FT) methodology, however, is highly dependent on the manual delineation of anatomical landmarks and the algorithm settings, often rendering the reproducibility and reliability questionable. Predefining these regions of interest on a fractional anisotropy (FA) atlas in standard space has already been shown to improve the reliability of FT results. In this paper, we constructed a new DTI atlas, which contains the complete diffusion tensor information in ICBM152 coordinates. From this high‐dimensional DTI atlas, and using robust FT protocols, we reconstructed a large number of WM tracts. Subsequently, we created tract masks from these fiber tract bundles and evaluated the atlas framework by comparing the reproducibility of the results obtained from our standardized tract masks with regions‐of‐interest labels from the conventional FA‐based WM atlas. Finally, we assessed laterality and age‐related WM changes in 42 normal subjects aged 0 to 18 years using these tractography‐derived tract segmentations. In agreement with previous literature, we observed an FA increase with age, which was mainly due to the decrease of perpendicular diffusivity. In addition, major functional pathways in the language, motor, and limbic system, showed a significant asymmetry in terms of the observed diffusion metrics. Hum Brain Mapp, 2010.

Integrity of the inferior longitudinal fasciculus and impaired object recognition in children: a diffusion tensor imaging study

Aimu2002 In this study, we explored the integrity of the inferior longitudinal fasciculus (ILF) by means of diffusion tensor imaging tractography in children with visual perceptual impairment, and more specifically, object recognition deficits, compared with typically developing children.

Is There a Common Neuroanatomical Substrate of Language Deficit between Autism Spectrum Disorder and Specific Language Impairment

Discussion of an overlap between specific language impairment (SLI) and autism spectrum disorder (ASD) is on going. The most intriguing overlap between both phenotypes is the similarity in the observed language deficits described in SLI and a subgroup of ASD with co-occurring linguistic impairment, ASD-LI. Examining whether a similar neuroanatomical substrate underlies this phenotypical linguistic overlap, we studied the white matter microstructural properties of the superior longitudinal fascicle (SLF) of 19 ASD-LI adolescents (mean age 13.8 ± 1.6 years) and 21 age-matched controls and compared them with 13 SLI children (mean age 10.1 ± 0.4 years) and 12 age-matched controls. A linguistic profile assessment and a diffusion tensor imaging analysis of the SLF were performed. Linguistic testing revealed a mixed receptive-expressive disorder profile in both groups, confirming their overlap at phenotypical level. At neuroanatomical level, no significant differences in mean SLF fractional anisotropy (FA) and mean SLF apparent diffusion coefficient values between ASD-LI participants and controls were seen. By contrast, the mean SLF FA was significantly reduced in the SLI children as compared with their controls. The observation of structural SLF disturbances in SLI but not in ASD-LI suggests the existence of a different neuroanatomical substrate for the language deficits in both disorders.

Altered functional connectivity of the language network in ASD: Role of classical language areas and cerebellum

The development of language, social interaction and communicative skills is remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the neural correlates underlying their disrupted language development and functioning are still poorly understood. Using resting state fMRI, we investigated the functional connectivity properties of the language network in a group of ASD patients with clear comorbid language impairment (ASD-LI; N = 19) and compared them to the language related connectivity properties of 23 age-matched typically developing children. A verb generation task was used to determine language components commonly active in both groups. Eight joint language components were identified and subsequently used as seeds in a resting state analysis. Interestingly, both the interregional and the seed-based whole brain connectivity analysis showed preserved connectivity between the classical intrahemispheric language centers, Wernickes and Brocas areas. In contrast however, a marked loss of functional connectivity was found between the right cerebellar region and the supratentorial regulatory language areas. Also, the connectivity between the interhemispheric Broca regions and modulatory control dorsolateral prefrontal region was found to be decreased. This disruption of normal modulatory control and automation function by the cerebellum may underlie the abnormal language function in children with ASD-LI.

Regional gray matter volume differences and sex-hormone correlations as a function of menstrual cycle phase and hormonal contraceptives use

During the menstrual cycle, hormone-driven functional and morphological changes occur in the female brain. The influence of hormonal contraceptives on these changes has received only little attention in the medical literature. The purpose of our study is to measure regional gray matter volume changes as a function of the cycle phase and use of hormonal contraceptives, in relation to blood concentrations of sex hormones. We performed a prospective study in 30 healthy young women; 15 women had a natural menstrual cycle and 15 were using monophasic combined hormonal contraceptives. MRI examinations were acquired at 2 specific time-points in the cycle (follicular and luteal phase). MRI studies included a T1-weighted, isotropic, high-resolution 3-D gradient echo acquisition, for the purpose of performing voxel based morphometry. Peripheral venous blood samples were obtained to determine concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol, and progesterone. We found a highly significant negative correlation of regional gray matter volume in the anterior cingulate cortex with estradiol concentrations. To the best of our knowledge, this result has not been described before, and was only present in the natural cycle group, not in women using hormonal contraceptives. The anterior cingulate cortex is involved in emotion processing and there is literature describing behavioral alternations with changing hormone levels. Our findings provide a structural, morphological basis to support these data. Therefore, we advise neuroscientists to take into account the menstrual cycle phase and use of hormonal contraceptives, in order to avoid obtaining heterogeneous data sets, leading to a significant loss of accuracy and precision.

Structural and functional underconnectivity as a negative predictor for language in autism.

The development of language, social interaction, and communicative skills are remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the interplay between their brain connectivity and language performance remains largely understudied. Using diffusion tensor imaging tractography and resting‐state fMRI, the authors explored the structural and functional connectivity of the language network and its relation to the language profile in a group of healthy control subjects (N = 25) and a group of children with ASD (N = 17). The authors hypothesized that in children with ASD, a neural connectivity deficit of the language network can be related to the observed abnormal language function. They found an absence of the right‐hemispheric arcuate fascicle (AF) in 28% (7/25) of the healthy control children and in 59% (10/17) of the children with ASD. In contrast to healthy control children, the absence of the right‐hemispheric AF in children with autism was related to a lower language performance as indicated by a lower verbal IQ, lower scores on the Peabody Picture Vocabulary Test, and lower language scores on the Dutch version of the Clinical Evaluation of Language Fundamentals (CELF‐4NL). In addition, through iterative fMRI data analyses, the language impairment of children with ASD could be linked to a marked loss of intrahemispheric functional connectivity between inferior frontal and superior temporal regions, known as the cortical language network. Both structural and functional underconnectivity patterns coincide and are related to an abnormal language function in children with ASD. Hum Brain Mapp 35:3602–3615, 2014.

Does the use of hormonal contraceptives cause microstructural changes in cerebral white matter? Preliminary results of a DTI and tractography study

AbstractObjectiveTo evaluate the effect of monophasic combined oral contraceptive pill (COCP) and menstrual cycle phase in healthy young women on white matter (WM) organization using diffusion tensor imaging (DTI).MethodsThirty young women were included in the study; 15 women used COCP and 15 women had a natural cycle. All subjects underwent DTI magnetic resonance imaging during the follicular and luteal phase of their cycle, or in different COCP cycle phases. DTI parameters were obtained in different WM structures by performing diffusion tensor fibre tractography. Fractional anisotropy and mean diffusivity were calculated for different WM structures. Hormonal plasma concentrations were measured in peripheral venous blood samples and correlated with the DTI findings.ResultsWe found a significant difference in mean diffusivity in the fornix between the COCP and the natural cycle group. Mean diffusivity values in the fornix were negatively correlated with luteinizing hormone and estradiol blood concentrations.ConclusionAn important part in the limbic system, the fornix, regulates emotional processes. Differences in diffusion parameters in the fornix may contribute to behavioural alternations related to COCP use. This finding also suggests that the use of oral contraceptives needs to be taken into account when designing DTI group studies.Key Points• Diffusion tensor MRI offers new insights into brain white matter microstructure.n • The effects of oral hormonal contraception were examined in young women.n • Diffusion tensor images and hormone blood concentrations were evaluated.n • Women using hormonal contraception demonstrated higher mean diffusivity in the fornix.n • These changes may contribute to behavioural alternations related to contraception use.