Quantitative diffusion analysis of white matter (WM) tracts has been utilised in many diseases for determining damage to, and changes in, WM tracts throughout the brain. However, there are limited ...studies investigating associations between quantitative measures in WM tracts and anatomically linked grey matter (GM), due to the difficulty in determining GM regions connected with a given WM tract.
This work describes a straightforward method for extending a WM tract through GM based on geometry. The tract is extended by following a straight line from each point on the tract boundary to the outer boundary of the cortex. A comparison between a multiplanar 2D approach and a 3D method was made. This study also tested an analysis pipeline from tracking WM tracts to quantifying magnetisation transfer ratios (MTR) in the associated cortical GM, and assessed the applicability of the method to healthy control subjects. Tract and associated cortical volumes and MTR values for the cortico-spinal tracts, genu and body of the corpus callosum were extracted; the between-subjects standard deviation was calculated.
It was found that a multiplanar 2D approach produced a more anatomically plausible volume of GM than a 3D approach, at the expense of possible overestimation of the GM volume. The between-subjects standard deviation of the tract specific quantitative measurements (from both the WM and GM masks) ranged between 1.2 and 7.3% for the MTR measures, and between 10 and 45% for the absolute volume measures.
The results show that the method can be used to produce anatomically plausible extensions of the WM tracts through the GM, and regions defined in this way yield reliable estimates of the MTR from the regions.
Previous work showed that pericalcarine cortical volume loss is evident early after presentation with acute clinically isolated optic neuritis (ON). The aims of this study were: (1) to determine ...whether pericalcarine atrophy in patients with ON is associated with conversion to multiple sclerosis (MS); (2) to investigate whether regional atrophy preferentially affects pericalcarine cortex; and (3) to investigate potential causes of early pericalcarine atrophy using MRI.
28 patients with acute ON and 10 controls underwent structural MRI (brain and optic nerves) and were followed-up over 12 months. Associations between the development of MS, optic nerve, optic radiation and pericalcarine cortical damage measures were investigated using multiple linear regression models. Regional cortical volumetric differences between patients and controls were calculated using t tests.
The development of MS at 12 months was associated with greater whole brain and optic radiation lesion loads, shorter acute optic nerve lesions and smaller pericalcarine cortical volume at baseline. Regional atrophy was not evident in other sampled cortical regions. Pericalcarine atrophy was not directly associated with whole brain lesion load, optic radiation measures or optic nerve lesion length. However, the association between pericalcarine atrophy and MS was not independent of these parameters.
Reduced pericalcarine cortical volumes in patients with early clinically isolated ON were associated with the development of MS but volumes of other cortical regions were not. Hence pericalcarine cortical regions appear particularly susceptible to early damage. These findings could be explained by a combination of pathological effects to visual grey and white matter in patients with ON.
The aim of this study is to propose methods for assessing the reproducibility of diffusion tractography algorithms in future clinical studies and to show their application to the tractography ...algorithm developed in our unit, fast marching tractography (FMT). FMT estimates anatomical connectivity between brain regions using the information provided by diffusion tensor imaging. Three major white-matter pathways were investigated in 11 normal subjects—anterior callosal fibers, optic radiations, and pyramidal tracts. FMT was used to generate maps of connectivity metric, and regions of voxels with highest connectivity metric to an anatomically defined starting point were identified for each tract under investigation. The reproducibilities of tract-“normalized” volume (NV) and fractional anisotropy (FA) measurements were assessed over such regions. The values of tract volumes are consistent with the postmortem data. Coefficients of variation (CVs) for FA and NV ranged from 1.7 to 7.1% and from 2.2 to 18.6%, respectively. CVs were lowest in the anterior callosal fibers (range: 1.7– 7.8%), followed by the optic radiations (range: 1.2–18.6%) and pyramidal tracts (range: 2.6–15.5%), suggesting that fiber organization plays a role in determining the level of FMT reproducibility. In conclusion, these findings underline the importance of assessing the reliability of diffusion tractography before investigating white matter pathology.
In multiple sclerosis (MS), brain atrophy quantification is affected by white matter lesions. LEAP and FSL-lesion_filling, replace lesion voxels with white matter intensities; however, they require ...precise lesion identification on 3DT1-images.
To determine whether 2DT2 lesion masks co-registered to 3DT1 images, yield grey and white matter volumes comparable to precise lesion masks.
2DT2 lesion masks were linearly co-registered to 20 3DT1-images of MS patients, with nearest-neighbor (NNI), and tri-linear interpolation. As gold-standard, lesion masks were manually outlined on 3DT1-images. LEAP and FSL-lesion_filling were applied with each lesion mask. Grey (GM) and white matter (WM) volumes were quantified with FSL-FAST, and deep gray matter (DGM) volumes using FSL-FIRST. Volumes were compared between lesion mask types using paired Wilcoxon tests.
Lesion-filling with gold-standard lesion masks compared to native images reduced GM overestimation by 1.93 mL (p < .001) for LEAP, and 1.21 mL (p = .002) for FSL-lesion_filling. Similar effects were achieved with NNI lesion masks from 2DT2. Global WM underestimation was not significantly influenced. GM and WM volumes from NNI, did not differ significantly from gold-standard. GM segmentation differed between lesion masks in the lesion area, and also elsewhere. Using the gold-standard, FSL-FAST quantified as GM on average 0.4% of the lesion area with LEAP and 24.5% with FSL-lesion_filling. Lesion-filling did not influence DGM volumes from FSL-FIRST.
These results demonstrate that for global GM volumetry, precise lesion masks on 3DT1 images can be replaced by co-registered 2DT2 lesion masks. This makes lesion-filling a feasible method for GM atrophy measurements in MS.
Tractography uses diffusion tensor imaging data to trace white matter pathways in vivo within the brain. We have constructed group maps that represent three major white matter tracts—the anterior ...callosal fibers, optic radiations, and pyramidal tracts—in a group of 21 volunteers. For each individual tract the fast marching tractography (FMT) algorithm was used to generate a VSC (voxel scale connectivity) map in native space. Using SPM99 these maps were transformed into a standard reference frame and three group mapping techniques were investigated: the first averaged the individual VSC maps, the second produced maps that demonstrate intersubject tract variability and degree of overlap, and the third used an SPM analysis to construct a statistical image that represents the group effect. The group maps reconstructed for each tract under investigation conform well to known anatomy and are consistent with data derived from postmortem human brains. Greater intersubject variability is found around the terminal projections of the tracts adjacent to cerebral cortex, whereas the “core” of each tract is characterized by lower variability. No significant differences were found between the left and right side of the pyramidal tracts and optic radiations. The group mapping techniques utilize the VSC maps in different but complementary ways. In the future, group mapping could investigate in vivo white matter differences between normal subjects and patients affected by neurological and psychiatric diseases.
Abstract Background Enhancing remyelination in MS might improve function and protect axons from future damage. Lesion magnetisation transfer ratio (MTR) is sensitive to myelin content, and may be a ...useful measure for trials evaluating potential remyelinating agents. Objective Estimating sample sizes required for a parallel group, placebo-controlled trial in MS using change in mean MTR of all T2 lesions as a primary outcome measure. Methods The primary sample size calculation was derived from data from a natural history study of relapsing remitting MS ( n =18). The MTR values observed in demyelinated and remyelinated lesions in an ex vivo study were used to estimate the effect of remyelination on lesion MTR. The ex vivo data were also used to independently calculate sample sizes in order to inform the robustness of the in vivo estimates. Results Calculations suggest that 30% remyelination of T2 lesions could be detected with 80% power in 38 (95% confidence interval 12–96) patients per arm based on the in vivo data, and in 66 per arm based on the ex vivo data. Conclusion The sample sizes derived are in a range that makes MTR a feasible outcome measure for proof-of-concept trials of putative therapies achieving remyelination in MS lesions.
Grey matter (GM) pathology in multiple sclerosis (MS) is associated with progressive long-term disability. Detection of GM abnormalities in early MS may therefore be valuable in understanding and ...predicting the long-term course. However, structural MRI measures such as volume loss have shown only modest abnormalities in early relapsing-remitting MS (RRMS). We therefore investigated for evidence of abnormality in GM perfusion, consistent with metabolic dysfunction, in early RRMS.
25 RRMS patients with ≤5 years disease duration and 25 age-matched healthy controls underwent 3 Tesla MRI with a pseudo-continuous arterial spin labelling sequence to quantify GM perfusion and a volumetric T1-weighted sequence to measure GM volume. Neurological status was assessed in patients and neuropsychological evaluation undertaken in all subjects. Voxel-based analysis was used to compare regional GM perfusion and volume measures in patients and controls.
There was reduced global GM perfusion in patients versus controls (50.6±5.8 mL/100 g/min vs 54.4±7.6 mL/100 g/min, p=0.04). Voxel-based analysis revealed extensive regions of decreased cortical and deep GM perfusion in MS subjects. Reduced perfusion was associated with impaired memory scores. There was no reduction in global or regional analysis of GM volume in patients versus controls.
The decrease in GM perfusion in the absence of volume loss is consistent with neuronal metabolic dysfunction in early RRMS. Future studies in larger cohorts and longitudinal follow-up are needed to investigate the functional and prognostic significance of the early GM perfusion deficits observed.
Patients with multiple sclerosis (MS) activate a more diffuse cortical network than do healthy subjects when they perform motor tasks. This brain functional reorganisation might contribute to the ...limiting of disability, but it is unclear whether there is a loss of regional activation in more advanced disease. The aim of this study was to assess whether functional reorganisation diminishes in more disabled patients with primary progressive (PP) MS. The differences in the fMRI response to active and passive movements of the dominant ankle of 13 patients and 16 controls were assessed. The relationships between functional activation and disability and brain lesion load and atrophy were investigated.Patients showed greater fMRI activation than controls with passive movements in the superior temporal gyrus, rolandic operculum, and putamen. The fMRI response to active and passive movements in the ipsilateral inferior frontal gyrus was lower in patients with greater disability and greater brain T2 lesion load, respectively. Furthermore, the fMRI activation with active movements in the contralateral cerebellum was lower in patients with worse mobility. The increased activity with passive movements in regions that participate in sensori-motor integration, such as the putamen, reflects true functional reorganisation, since passive movements induce brain activation through sensory afferents only. The inverse correlation between the fMRI response in regions that are associated with motor control, and clinical or MRI measures of disease progression, suggests that there is a loss of distributed activation in more disabled patients. This may inform future treatment strategies.
A method is presented for determining paths of anatomical connection between regions of the brain using magnetic resonance diffusion tensor information. Level set theory, applied using fast marching ...methods, is used to generate three-dimensional time of arrival maps, from which connection paths between brain regions may be identified. The method is demonstrated in the normal brain and it is shown that major white matter tracts may be elucidated and that multiple connections and tract branching are allowed. Maps of connectivity between brain regions are also determined. Four options are described for estimating the degree of connectivity between regions.
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