Interaction of Developmental Venous Anomalies with Resting-State Functional MRI Measures.

BACKGROUND AND PURPOSE: Functional MR imaging of the brain, used for both clinical and neuroscientific applications, relies on measuring fluctuations in blood oxygenation. Such measurements are susceptible to noise of vascular origin. The purpose of this study was to assess whether developmental venous anomalies, which are frequently observed normal variants, can bias fMRI measures by appearing as true neural signal. MATERIALS AND METHODS: Large developmental venous anomalies (1 in each of 14 participants) were identified from a large neuroimaging cohort (n = 814). Resting-state fMRI data were decomposed using independent component analysis, a data-driven technique that creates distinct component maps representing aspects of either structured noise or true neural activity. We searched all independent components for maps that exhibited a spatial distribution of their signals following the topography of developmental venous anomalies. RESULTS: Of the 14 developmental venous anomalies identified, 10 were clearly present in 17 fMRI independent components in total. While 9 (52.9%) of these 17 independent components were dominated by venous contributions and 2 (11.8%) by motion artifacts, 2 independent components (11.8%) showed partial neural signal contributions and 5 independent components (29.4%) unambiguously exhibited typical neural signal patterns. CONCLUSIONS: Developmental venous anomalies can strongly resemble neural signal as measured by fMRI. They are thus a potential source of bias in fMRI analyses, especially when present in the cortex. This could impede interpretation of local activity in patients, such as in presurgical mapping. In scientific studies with large samples, developmental venous anomaly confounds could be mainly addressed using independent component analysis-based denoising.

Corpus callosum involvement is a consistent feature of amyotrophic lateral sclerosis.

OBJECTIVE: While the hallmark of amyotrophic lateral sclerosis (ALS) is corticospinal tract in combination with lower motor neuron degeneration, the clinical involvement of both compartments is characteristically variable and the site of onset debated. We sought to establish whether there is a consistent signature of cerebral white matter abnormalities in heterogeneous ALS cases. METHODS: In this observational study, diffusion tensor imaging was applied in a whole-brain analysis of 24 heterogeneous patients with ALS and well-matched healthy controls. Tract-based spatial statistics were used, with optimized voxel-based morphometry of T1 images to determine any associated gray matter involvement. RESULTS: A consistent reduction in fractional anisotropy was demonstrated in the corpus callosum of the ALS group, extending rostrally and bilaterally to the region of the primary motor cortices, independent of the degree of clinical upper motor neuron involvement. Matched regional radial diffusivity increase supported the concept of anterograde degeneration of callosal fibers observed pathologically. Gray matter reductions were observed bilaterally in primary motor and supplementary motor regions, and also in the anterior cingulate and temporal lobe regions. A post hoc group comparison model incorporating significant values for fractional anisotropy, radial diffusivity, and gray matter was 92% sensitive, 88% specific, with an accuracy of 90%. CONCLUSION: Callosal involvement is a consistent feature of ALS, independent of clinical upper motor neuron involvement, and may reflect independent bilateral cortical involvement or interhemispheric spread of pathology. The predominantly rostral corticospinal tract involvement further supports the concept of independent cortical degeneration even in those patients with ALS with predominantly lower motor neuron involvement clinically.

Longitudinal changes in grey and white matter during adolescence.

Brain development continues actively during adolescence. Previous MRI studies have shown complex patterns of apparent loss of grey matter (GM) volume and increases in white matter (WM) volume and fractional anisotropy (FA), an index of WM microstructure. In this longitudinal study (mean follow-up=2.5+/-0.5 years) of 24 adolescents, we used a voxel-based morphometry (VBM)-style analysis with conventional T1-weighted images to test for age-related changes in GM and WM volumes. We also performed tract-based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) data to test for age-related WM changes across the whole brain. Probabilistic tractography was used to carry out quantitative comparisons across subjects in measures of WM microstructure in two fiber tracts important for supporting speech and motor functions (arcuate fasciculus [AF] and corticospinal tract [CST]). The whole-brain analyses identified age-related increases in WM volume and FA bilaterally in many fiber tracts, including AF and many parts of the CST. FA changes were mainly driven by increases in parallel diffusivity, probably reflecting increases in the diameter of the axons forming the fiber tracts. FA values of both left and right AF (but not of the CST) were significantly higher at the end of the follow-up than at baseline. Over the same period, widespread reductions in the cortical GM volume were found. These findings provide imaging-based anatomical data suggesting that brain maturation in adolescence is associated with structural changes enhancing long-distance connectivities in different WM tracts, specifically in the AF and CST, at the same time that cortical GM exhibits synaptic "pruning".

Changes in white matter microstructure during adolescence.

Postmortem histological studies have demonstrated that myelination in human brain white matter (WM) continues throughout adolescence and well into adulthood. We used in vivo diffusion-weighted magnetic resonance imaging to test for age-related WM changes in 42 adolescents and 20 young adults. Tract-Based Spatial Statistics (TBSS) analysis of the adolescent data identified widespread age-related increases in fractional anisotropy (FA) that were most significant in clusters including the body of the corpus callosum and right superior corona radiata. These changes were driven by changes in perpendicular, rather than parallel, diffusivity. These WM clusters were used as seeds for probabilistic tractography, allowing us to identify the regions as belonging to callosal, corticospinal, and prefrontal tracts. We also performed voxel-based morphometry-style analysis of conventional T1-weighted images to test for age-related changes in grey matter (GM). We identified a cluster including right middle frontal and precentral gyri that showed an age-related decrease in GM density through adolescence and connected with the tracts showing age-related WM FA increases. The GM density decrease was highly significantly correlated with the WM FA increase in the connected cluster. Age-related changes in FA were much less prominent in the young adult group, but we did find a significant age-related increase in FA in the right superior longitudinal fascicle, suggesting that structural development of this pathway continues into adulthood. Our results suggest that significant microstructural changes in WM continue throughout adolescence and are associated with corresponding age-related changes in cortical GM regions.

Increased white matter connectivity in euthymic bipolar patients: diffusion tensor tractography between the subgenual cingulate and the amygdalo-hippocampal complex.

Bipolar disorder has been associated with anatomical as well as functional abnormalities in a brain network that mediates normal and impaired emotion regulation. Previous brain imaging studies have highlighted the subgenual cingulate (SC) and the amygdalo-hippocampal (AH) complex as core regions of this network. Thus we investigated white matter (WM) fiber tracts between the SC and the AH region, the uncinate fasciculus, as well as between two control regions (pons and cerebellum), using diffusion tensor imaging tractography in 16 euthymic bipolar patients (BP) and 16 sex-, age- and handedness-matched controls. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of the reconstructed fiber bundle and the number of virtual reconstructed fibers were compared between groups. The tractography results revealed a significantly increased number of reconstructed fibers between the left SC and left AH in BP as compared to healthy controls. FA and ADC of the reconstructed fiber tract did not differ significantly between the groups. Furthermore, no significant group differences were observed neither for reconstructed fiber tracts between the right SC and right AH nor between the control regions. The present results suggest an altered WM pathway between the left SC and AH region and thus extend previous findings of anatomical and functional modifications in these structures in BP.

Distribution of grey matter atrophy in Huntington's disease patients: a combined ROI-based and voxel-based morphometric study.

The striatum, a subcortical structure, is the principal target of the neurodegenerative process in Huntington's disease (HD). The measurement of striatal atrophy using the bicaudate ratio on CT scanner images has therefore been used for years to assess disease progression, but this measure only takes into account unidimensional changes in the head of the caudate nucleus. Recently, voxel-based morphometry (VBM), which permits automated statistical comparisons of whole-brain MRI images, has been proposed to quantify striatal atrophy. However, VBM was not originally designed to study subcortical structures, and severe deep brain deformations that occur in HD may hamper the automatic processing of VBM. Here, we validate the use of the optimised protocol of VBM to quantify subcortical atrophy in HD by comparing results obtained with this method to those provided by manual segmentation of subcortical structures. We studied 20 patients with early HD and 12 controls matched for age, sex and handedness using an improved T1-weighted sequence that eased grey matter segmentation. Both manual and automated methods evidenced the dorso-ventral gradient of striatal atrophy, a loss of grey matter in the globus pallidus and the thalamus, and similar correlations between clinical scores and subcortical atrophy. Furthermore, we were able to detect with VBM grey matter loss in the substantia nigra, the hypothalamus, the amygdala, the insular cortex and the premotor and sensorimotor cortices. Finally, VBM provided results consistent with previous post mortem results and proved to be a sensitive biomarker capable of correctly managing subcortical distortions throughout HD patients' brains.

PET evidence for a role of the basal ganglia in patients with ring chromosome 20 epilepsy.

BACKGROUND: Studies in animal models and epileptic patients have suggested that circuits of the basal ganglia may control epileptic seizures and that striatal dopaminergic transmission plays a key role in seizure interruption. Ring chromosome 20 (r[20]) epilepsy is a very homogenous type of epilepsy and is clinically characterized by long-lasting seizures suggesting a dysfunction in the seizure control system. The hypothesis that these long-lasting seizures are associated with a reduction of striatal dopamine was addressed in the present study in drug-resistant patients with r(20) epilepsy using PET. METHOD: The authors performed [18F]fluoro-l-DOPA PET in 14 patients with r(20) epilepsy and compared uptake constants in the putamen and the caudate with those of 10 controls. In addition, the authors examined the correlation between these constants and the percentage of cells with r(20) mosaicism. RESULTS: [18F]fluoro-l-DOPA uptake was significantly decreased bilaterally in the putamen and in the caudate nucleus of patients. This reduction was equal for both nuclei and was not correlated to the percentage of cells with r(20). CONCLUSION: Striatal dopamine is modulated in r(20) epilepsy; dysfunction of this neurotransmission may impair the mechanisms that interrupt seizures.