[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
Hemispherectomy is a neurosurgical procedure to treat children with intractable seizures. Postsurgical improvement of cognitive and behavioral functions is observed in children after hemispherectomy suggesting plastic reorganization of the brain. Our aim was to characterize changes in DTI scalars in WM tracts of the remaining hemisphere in children after hemispherectomy, assess the associations between WM DTI scalars and age at the operation and time since the operation, and evaluate the changes in GM fractional anisotropy values in patients compared with controls.
Materials and methods:
Patients with congenital or acquired neurologic diseases who required hemispherectomy and had high-quality postsurgical DTI data available were included in this study. Atlas- and voxel-based analyses of DTI raw data of the remaining hemisphere were performed. Fractional anisotropy and mean, axial, and radial diffusivity values were calculated for WM and GM regions. A linear regression model was used for correlation between DTI scalars and age at and time since the operation.
Nineteen patients after hemispherectomy and 21 controls were included. In patients, a decrease in fractional anisotropy and axial diffusivity values and an increase in mean diffusivity and radial diffusivity values of WM regions were observed compared with controls (P < .05, corrected for multiple comparisons). In patients with acquired pathologies, time since the operation had a significant positive correlation with white matter fractional anisotropy values. In all patients, an increase in cortical GM fractional anisotropy values was found compared with controls (P < .05).
Changes in DTI metrics likely reflect Wallerian and/or transneuronal degeneration of the WM tracts within the remaining hemisphere. In patients with acquired pathologies, postsurgical fractional anisotropy values correlated positively with elapsed time since the operation, suggesting a higher ability to recover compared with patients with congenital pathologies leading to hemispherectomy.
Full-text · Article · Jan 2016 · American Journal of Neuroradiology
[Show abstract][Hide abstract] ABSTRACT: The computational anatomy project has largely been a study of large deformations via diffeomorphic mapping. This article looks at various estimation problems within this setting, including disease scoring, segmentation, and template estimation. All are posed in the augmented orbit of unions of multiple atlases or templates. These make our generative Bayesian probability models multimodal, in which the posterior probability of interpreting a single image is shared across multiple atlases. We derive the maximum a posteriori estimation in this multimodal context for (i) disease scoring/classification of a single target image given multiple disease cohorts, (ii) segmentation of images, and (iii) atlas generation from populations.
[Show abstract][Hide abstract] ABSTRACT: In this paper, we propose and validate a fully automated pipeline for simultaneous skull-stripping and lateral ventricle segmentation using T1-weighted images. The pipeline is built upon a segmentation algorithm entitled fast multi-atlas likelihood-fusion (MALF) which utilizes multiple T1 atlases that have been pre-segmented into six whole-brain labels-the gray matter, the white matter, the cerebrospinal fluid, the lateral ventricles, the skull, and the background of the entire image. This algorithm, MALF, was designed for estimating brain anatomical structures in the framework of coordinate changes via large diffeomorphisms. In the proposed pipeline, we use a variant of MALF to estimate those six whole-brain labels in the test T1-weighted image. The three tissue labels (gray matter, white matter, and cerebrospinal fluid) and the lateral ventricles are then grouped together to form a binary brain mask to which we apply morphological smoothing so as to create the final mask for brain extraction. For computational purposes, all input images to MALF are down-sampled by a factor of two. In addition, small deformations are used for the changes of coordinates. This substantially reduces the computational complexity, hence we use the term "fast MALF". The skull-stripping performance is qualitatively evaluated on a total of 486 brain scans from a longitudinal study on Alzheimer dementia. Quantitative error analysis is carried out on 36 scans for evaluating the accuracy of the pipeline in segmenting the lateral ventricle. The volumes of the automated lateral ventricle segmentations, obtained from the proposed pipeline, are compared across three different clinical groups. The ventricle volumes from our pipeline are found to be sensitive to the diagnosis.
[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
Site-specific degeneration patterns of the infratentorial brain in relation to phylogenetic origins may relate to symptoms in patients with spinocerebellar degeneration, but the patterns are still unclear. We investigated macro- and microstructural changes of the infratentorial brain based on phylogenetic origins and their correlation with symptoms in patients with spinocerebellar ataxia type 6.
Materials and methods:
MR images of 9 patients with spinocerebellar ataxia type 6 and 9 age- and sex-matched controls were obtained. We divided the infratentorial brain on the basis of phylogenetic origins and performed an atlas-based analysis. Comparisons of the 2 groups and a correlation analysis assessed with the International Cooperative Ataxia Rating Scale excluding age effects were performed.
A significant decrease of fractional volume and an increase of mean diffusivity were seen in all subdivisions of the cerebellum and in all the cerebellar peduncles except mean diffusivity in the inferior cerebellar peduncle in patients compared with controls (P < .0001 to <.05). The bilateral anterior lobes showed the strongest atrophy. Fractional volume decreased mainly in old regions, whereas mean diffusivity increased mainly in new regions of the cerebellum. Reflecting this tendency, the International Cooperative Ataxia Rating Scale total score showed strong correlations in fractional volume in the right flocculonodular lobe and the bilateral deep structures and in mean diffusivity in the bilateral posterior lobes (r = 0.73 to ±0.87).
We found characteristic macro- and microstructural changes, depending on phylogenetic regions of the infratentorial brain, that strongly correlated with clinical symptoms in patients with spinocerebellar ataxia type 6.
Preview · Article · Aug 2014 · American Journal of Neuroradiology
[Show abstract][Hide abstract] ABSTRACT: Deep white matter (WM) fascicles play a major, yet poorly understood, role in the overall connectivity of human brain. Better knowledge of their anatomy is requisite to understand the clinical correlates of their lesions and develop targeted treatments. We investigated whether MR-based diffusion tensor imaging (DTI) and fibre tracking could reveal in vivo, in explicit details, the 3D WM architecture within the subthalamic region and the internal capsule.
High-resolution DTI images were acquired on six healthy volunteers on a three Tesla MR scanner. We studied using single-subject analysis WM fascicles within the subthalamic region and the internal capsule, as follows: DTI deterministic fibre tracking (FT) of fascicles; embedding fascicles in the volume-rendered brain coupled with a triplanar view; rigorous anatomic labelling of each fascicle according to classical knowledge as described by pioneer neuroanatomists. Deterministic FT effects were taken into account.
We charted most of WM fascicles of the deep brain, in particular large and complex fascicles such as the basal forebrain bundle and the ansa lenticularis. A topographic classification of subthalamic fascicles was proposed into three groups: the cerebellorubral, the reticulo-dorsal and the tegmento-peripheral one.
Beyond to demonstrate the feasibility of imaging the deepest WM fascicles in vivo, our results pave the way for a better understanding of the brain connectivity and for developing targeted neuromodulation.
[Show abstract][Hide abstract] ABSTRACT: Strong genetic evidence implicates mutations and polymorphisms in the gene Disrupted-In-Schizophrenia-1 (DISC1) as risk factors for both schizophrenia and mood disorders. Recent studies have shown that DISC1 has important functions in both brain development and adult brain function. We have described earlier a transgenic mouse model of inducible expression of mutant human DISC1 (hDISC1) that acts in a dominant-negative manner to induce the marked neurobehavioral abnormalities. To gain insight into the roles of DISC1 at various stages of neurodevelopment, we examined the effects of mutant hDISC1 expressed during (1) only prenatal period, (2) only postnatal period, or (3) both periods. All periods of expression similarly led to decreased levels of cortical dopamine (DA) and fewer parvalbumin-positive neurons in the cortex. Combined prenatal and postnatal expression produced increased aggression and enhanced response to psychostimulants in male mice along with increased linear density of dendritic spines on neurons of the dentate gyrus of the hippocampus, and lower levels of endogenous DISC1 and LIS1. Prenatal expression only resulted in smaller brain volume, whereas selective postnatal expression gave rise to decreased social behavior in male mice and depression-like responses in female mice as well as enlarged lateral ventricles and decreased DA content in the hippocampus of female mice, and decreased level of endogenous DISC1. Our data show that mutant hDISC1 exerts differential effects on neurobehavioral phenotypes, depending on the stage of development at which the protein is expressed. The multiple and diverse abnormalities detected in mutant DISC1 mice are reminiscent of findings in major mental diseases.
Full-text · Article · Mar 2011 · Molecular Psychiatry
[Show abstract][Hide abstract] ABSTRACT: RTT, caused by mutations in the methyl CPG binding protein 2 (MeCP2) gene, is a disorder of neuronal maturation and connections. Our aim was to prospectively examine FA by DTI and correlate this with certain clinical features in patients with RTT.
Thirty-two patients with RTT underwent neurologic assessments and DTI. Thirty-seven age-matched healthy female control subjects were studied for comparison. With use of a 1.5T MR imaging unit, DTI data were acquired, and FA was evaluated to investigate multiple regional tract-specific abnormalities in patients with RTT.
In RTT, significant reductions in FA were noted in the genu and splenium of the corpus callosum and external capsule, with regions of significant reductions in the cingulate, internal capsule, posterior thalamic radiation, and frontal white matter. In contrast, FA of visual pathways was similar to control subjects. FA in the superior longitudinal fasciculus, which is associated with speech, was equal to control subjects in patients with preserved speech (phrases and sentences) (P = .542), whereas FA was reduced in those patients who were nonverbal or speaking only single words (P < .001). No correlations between FA values for tracts and clinical features such as seizures, gross or fine motor skills, and head circumference were identified.
DTI, a noninvasive technique to assess white matter tract pathologic features, may add specificity to the assessment of RTT clinical severity that is presently based on the classification of MeCP2 gene mutation and X-inactivation.
Full-text · Article · Oct 2009 · American Journal of Neuroradiology
[Show abstract][Hide abstract] ABSTRACT: Stereotaxic atlases of the mouse brain are important in neuroscience research for targeting of specific internal brain structures during surgical operations. The effectiveness of stereotaxic surgery depends on accurate mapping of the brain structures relative to landmarks on the skull. During postnatal development in the mouse, rapid growth-related changes in the brain occur concurrently with growth of bony plates at the cranial sutures, therefore adult mouse brain atlases cannot be used to precisely guide stereotaxis in developing brains. In this study, three-dimensional stereotaxic atlases of C57BL/6J mouse brains at six postnatal developmental stages: postnatal day (P) 7, P14, P21, P28, P63 and in adults (P140-P160) were developed, using diffusion tensor imaging (DTI) and micro-computed tomography (CT). At present, most widely-used stereotaxic atlases of the mouse brain are based on histology, but the anatomical fidelity of ex vivo atlases to in vivo mouse brains has not been evaluated previously. To account for ex vivo tissue distortion due to fixation as well as individual variability in the brain, we developed a population-averaged in vivo magnetic resonance imaging adult mouse brain stereotaxic atlas, and a distortion-corrected DTI atlas was generated by nonlinearly warping ex vivo data to the population-averaged in vivo atlas. These atlas resources were developed and made available through a new software user-interface with the objective of improving the accuracy of targeting brain structures during stereotaxic surgery in developing and adult C57BL/6J mouse brains.
[Show abstract][Hide abstract] ABSTRACT: Diffusion tensor imaging (DTI) studies have shown significant cross-sectional differences among normal controls (NC) mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients in several fiber tracts in the brain, but longitudinal assessment is needed.
We studied 75 participants (25 NC, 25 amnestic MCI, and 25 mild AD) at baseline and 3 months later, with both imaging and clinical evaluations. Fractional anisotropy (FA) was analyzed in regions of interest (ROIs) in: (1) fornix, (2) cingulum bundle, (3) splenium, and (4) cerebral peduncles. Clinical data included assessments of clinical severity and cognitive function. Cross-sectional and longitudinal differences in FA, within each ROI, were analyzed with generalized estimating equations (GEE).
Cross-sectionally, AD patients had lower FA than NC (p<0.05) at baseline and 3 months in the fornix and anterior portion of the cingulum bundle. Compared to MCI, AD cases had lower FA (p<0.05) in these regions and the splenium at 0 and 3 months. Both the fornix and anterior cingulum correlated across all clinical cognitive scores; lower FA in these ROIs corresponded to worse performance. Over the course of 3 months, when the subjects were clinically stable, the ROIs were also largely stable.
Using DTI, findings indicate FA is decreased in specific fiber tracts among groups of subjects that vary along the spectrum from normal to AD, and that this measure is stable over short periods of time. The fornix is a predominant outflow tract of the hippocampus and may be an important indicator of AD progression.
[Show abstract][Hide abstract] ABSTRACT: A strong candidate gene for schizophrenia and major mental disorders, disrupted-in-schizophrenia 1 (DISC1) was first described in a large Scottish family in which a balanced chromosomal translocation segregates with schizophrenia and other psychiatric illnesses. The translocation mutation may result in loss of DISC1 function via haploinsufficiency or dominant-negative effects of a predicted mutant DISC1 truncated protein product. DISC1 has been implicated in neurodevelopment, including maturation of the cerebral cortex. To evaluate the neuronal and behavioral effects of mutant DISC1, the Tet-off system under the regulation of the CAMKII promoter was used to generate transgenic mice with inducible expression of mutant human DISC1 (hDISC1) limited to forebrain regions, including cerebral cortex, hippocampus and striatum. Expression of mutant hDISC1 was not associated with gross neurodevelopmental abnormalities, but led to a mild enlargement of the lateral ventricles and attenuation of neurite outgrowth in primary cortical neurons. These morphological changes were associated with decreased protein levels of endogenous mouse DISC1, LIS1 and SNAP-25. Compared to their sex-matched littermate controls, mutant hDISC1 transgenic male mice exhibited spontaneous hyperactivity in the open field and alterations in social interaction, and transgenic female mice showed deficient spatial memory. The results show that the neuronal and behavioral effects of mutant hDISC1 are consistent with a dominant-negative mechanism, and are similar to some features of schizophrenia. The present mouse model may facilitate the study of aspects of the pathogenesis of schizophrenia.
Full-text · Article · Mar 2008 · Molecular Psychiatry