Abstract Background Histopathology has demonstrated extensive cortical grey matter (GM) demyelination in multiple sclerosis (MS), and suggests that sulcal folds may be preferentially affected, ...particularly in progressive MS. This has not been confirmed in vivo, and it is not known if it is relevant to clinical status. Objectives To determine sulcal and gyral crown magnetisation transfer ratio (MTR) in MS cortical GM, and the MTR associations with clinical status. Methods We measured sulcal and gyral crown cortical GM MTR values in 61 MS patients and 32 healthy controls. Disability was measured using Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores. Results MTR values were reduced in sulcal and gyral crown regions in all MS subtypes, more so in secondary progressive (SP) MS than relapsing remitting (RR) MS, and similarly in primary progressive (PP) MS and RRMS. Sulcal MTR was lower than gyral crown MTR in controls, PPMS and RRMS patients, but not in SPMS. MTR correlated with clinical status in RRMS and SPMS, but not PPMS. Conclusions Cortical pathology, as reflected by MTR, is present in all MS subtypes and most pronounced in SPMS. A preferential disease effect on sulcal cortical regions was not observed. Cortical MTR abnormalities appear to be more clinically relevant in relapse-onset rather than progressive-onset MS.
Glutamate is the principal excitatory neurotransmitter and is involved in normal brain function. Cognitive impairment is common in multiple sclerosis (MS), and understanding its mechanisms is crucial ...for developing effective treatments. We used structural and metabolic brain imaging to test two hypotheses: (i) glutamate levels in grey matter regions are abnormal in MS, and (ii) patients show a relationship between glutamate concentration and memory performance.
Eighteen patients with relapsing-remitting MS and 17 healthy controls were cognitively assessed and underwent (1)H-magnetic resonance spectroscopy at 3 T to assess glutamate levels in the hippocampus, thalamus, cingulate and parietal cortices. Regression models investigated the association between glutamate concentration and memory performance independently of magnetisation transfer ratio values and grey matter lesions withint he same regions, and whole-brain grey matter volume.
Patients had worse visual and verbal memory than controls. A positive relationship between glutamate levels in the hippocampal, thalamic and cingulate regions and visuospatial memory was detected in patients, but not in healthy controls.
The relationship between memory and glutamate concentration, which is unique to MS patients, suggests the reliance of memory on glutamatergic systems in MS.
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Theimpact of neuroimaging on the study and understanding of dementing illnesses has been enormous. Here we review the main MR structural technical developments applied to Alzheimer’s disease and ...fronto-temporal dementia, two forms of neurodegenerative disorders that have a number of similarities but also several differences. The possibility of detecting increasingly subtle brain changes, together with the need of handling larger and larger data sets, keeping up with the ever expanding aging population, are perhaps the main driving forces behind recent MR technique developments in the field of dementia. The measurement of atrophy is now integrated by more advanced approaches, investigating the alterations of the architecture of brain tissues beyond pure volumetric loss. Brain connectivity is now studied
in vivo
with techniques such as diffusion tensor imaging and tractography. Also, automated methods of subject classification open up new possibilities of rapid and cost-effective diagnosis. The inter-disciplinary efforts are changing the clinical scenario of dementia care from one of helpless defeat to one of promising innovation.
Abstract Advances in technology in recent decades have contributed to rapid developments in non-invasive methods for imaging human anatomy, and advanced imaging methods are now one of the primary ...tools for clinical diagnosis after neurological trauma or disease. Here we review the current and upcoming capabilities of one of the most rapidly developing methods, magnetic resonance imaging (MRI). The underlying theory is introduced so that the reasons for the strengths, weaknesses, and future expectations of this method, can be explained. Current techniques for imaging anatomical changes, inflammation, and changes in white matter, axonal integrity, blood flow and function, are reviewed. Applications for specific purposes of assessing traumatic injury in the brain or spinal cord, and for multiple-sclerosis are also presented, and are used as examples of how the advanced techniques are being used in practice.
We report on a new quantitative magnetization transfer (MT) technique that allows for the in vivo estimation of the macromolecular proton fraction (f) and the bound pool T2 relaxation time (T2b), ...whilst permitting whole brain coverage. In this pilot study, five subjects with multiple sclerosis (MS) and five healthy controls were studied. Both f and T2b were significantly different between MS lesions and normal control white matter (WM). Relationships between f and T1 relaxation time Spearman’s rank correlation coefficient (rs) =-0.97, P <0.001 and f and the magnetization transfer ratio (MTR; rs =0.80, P <0.001) were observed. C ompared with MTR, f and T2b have the potential advantage of relative independence from MT acquisition protocol while offering more pathologically specific information. In particular, f may provide a more direct indication of myelin content in WM.
A large number of mathematical models have been proposed to describe the measured signal in diffusion‐weighted (DW) magnetic resonance imaging (MRI). However, model comparison to date focuses only on ...specific subclasses, e.g. compartment models or signal models, and little or no information is available in the literature on how performance varies among the different types of models. To address this deficiency, we organized the ‘White Matter Modeling Challenge’ during the International Symposium on Biomedical Imaging (ISBI) 2015 conference. This competition aimed to compare a range of different kinds of models in their ability to explain a large range of measurable in vivo DW human brain data. Specifically, we assessed the ability of models to predict the DW signal accurately for new diffusion gradients and b values. We did not evaluate the accuracy of estimated model parameters, as a ground truth is hard to obtain. We used the Connectome scanner at the Massachusetts General Hospital, using gradient strengths of up to 300 mT/m and a broad set of diffusion times. We focused on assessing the DW signal prediction in two regions: the genu in the corpus callosum, where the fibres are relatively straight and parallel, and the fornix, where the configuration of fibres is more complex. The challenge participants had access to three‐quarters of the dataset and their models were ranked on their ability to predict the remaining unseen quarter of the data. The challenge provided a unique opportunity for a quantitative comparison of diverse methods from multiple groups worldwide. The comparison of the challenge entries reveals interesting trends that could potentially influence the next generation of diffusion‐based quantitative MRI techniques. The first is that signal models do not necessarily outperform tissue models; in fact, of those tested, tissue models rank highest on average. The second is that assuming a non‐Gaussian (rather than purely Gaussian) noise model provides little improvement in prediction of unseen data, although it is possible that this may still have a beneficial effect on estimated parameter values. The third is that preprocessing the training data, here by omitting signal outliers, and using signal‐predicting strategies, such as bootstrapping or cross‐validation, could benefit the model fitting. The analysis in this study provides a benchmark for other models and the data remain available to build up a more complete comparison in the future.
The ISBI 2015 ‘White Matter Modeling Challenge’ provided a unique opportunity for a quantitative comparison of diverse models from groups worldwide. Competitors had partial access to data (
|Gmax|=300 mT/m, many Δ) and ranking was based on missing data prediction. Ranking reveals that signal models do not necessarily outperform tissue models. Additionally, assuming a non‐Gaussian noise model provides little benefit, but shows that data preprocessing and signal predicting strategies could benefit the model fitting. With our publicly available data, this analysis provides a benchmark for other future models.
Diffusion tensor magnetic resonance imaging (DT-MRI) provides in vivo information about the pathology of multiple sclerosis lesions. Increases in mean diffusivity (MD) and reductions in fractional ...anisotropy (FA) have been found and may represent axonal disruption. The optic nerve is an ideal structure for study by DT-MRI but previous clinical studies did not obtain the full diffusion tensor necessary to calculate MD and FA. In this study, a technique that was specifically developed to achieve full diffusion tensor measurements from the optic nerve (zonal oblique multislice (ZOOM) echoplanar imaging) was applied to 25 patients with a single unilateral episode of optic neuritis at least one year previously, and 15 controls. The intraorbital nerves were segmented on non-diffusion-weighted images and the regions of interest transferred to MD, FA, and eigenvalue maps to obtain quantitative data. Quantitative visual testing and electrophysiology were also performed. In affected nerves, mean MD and mean orthogonal eigenvalue
λ
⊥ were elevated, and mean FA reduced compared with clinically unaffected contralateral nerves (
P < 0.001) and control nerves (
P < 0.001). The mean principal eigenvalue
λ
\\ was significantly increased in affected nerves compared to contralateral unaffected nerves (
P = 0.04) but not compared to control nerves (
P = 0.13). There was no association of clinical measures of visual function in affected eyes with the DT-MRI parameters but there was a significant correlation of the whole field visual evoked potential (VEP) amplitude with MD (
r = −0.57,
P = 0.006) and
λ
⊥ (
r = −0.56,
P = 0.007). These findings suggest that optic nerve DT-MRI measures provide an indication of the structural integrity of axons.
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