Functional Connectivity Alterations Reveal Complex Mechanisms Based on Clinical and Radiological Status in Mild Relapsing Remitting Multiple Sclerosis.

Resting state functional MRI (rs-fMRI) has provided important insights into functional reorganization in subjects with Multiple Sclerosis (MS) at different stage of disease. In this cross-sectional study we first assessed, by means of rs-fMRI, the impact of overall T2 lesion load (T2LL) and MS severity score (MSSS) on resting state networks (RSNs) in 62 relapsing remitting MS (RRMS) patients with mild disability (MSSS < 3). Independent Component Analysis (ICA) followed by dual regression analysis confirmed functional connectivity (FC) alterations of many RSNs in RRMS subjects compared to healthy controls. The anterior default mode network (DMNa) and the superior precuneus network (PNsup) showed the largest areas of decreased FC, while the sensory motor networks area M1 (SMNm1) and the medial visual network (MVN) showed the largest areas of increased FC. In order to better understand the nature of these alterations as well as the mechanisms of functional alterations in MS we proposed a method, based on linear regression, that takes into account FC changes and their correlation with T2LL and MSSS. Depending on the sign of the correlation between FC and T2LL, and furthermore the sign of the correlation with MSSS, we suggested the following possible underlying mechanisms to interpret altered FC: (1) FC reduction driven by MS lesions, (2) "true" functional compensatory mechanism, (3a) functional compensation attempt, (3b) "false" functional compensation, (4a) neurodegeneration, (4b) pre-symptomatic condition (damage precedes MS clinical manifestation). Our data shows areas satisfying 4 of these 6 conditions (i.e., 1,2,3b,4b), supporting the suggestion that increased FC has a complex nature that may exceed the simplistic assumption of an underlying compensatory mechanism attempting to limit the brain damage caused by MS progression. Exploring differences between RRMS subjects with short disease duration (MSshort) and RRMS with similar disability but longer disease duration (MSlong), we found that MSshort and MSlong were characterized by clearly distinct pattern of FC, involving predominantly sensory and cognitive networks respectively. Overall, these results suggest that the analysis of FC alterations in multiple large-scale networks in relation to radiological (T2LL) and clinical (MSSS, disease duration) status may provide new insights into the pathophysiology of relapse onset MS evolution.

Deep grey matter MRI abnormalities and cognitive function in relapsing-remitting multiple sclerosis.

Although deep grey matter (GM) involvement in multiple sclerosis (MS) is well documented, in-vivo multi-parameter magnetic resonance imaging (MRI) studies and association with detailed cognitive measures are limited. We investigated volumetric, diffusion and perfusion metrics in thalamus, hippocampus, putamen, caudate nucleus and globus pallidum, and neuropsychological measures, spanning 4 cognitive domains, in 60 relapsing-remitting MS patients (RRMS) (mean disease duration of 5.1 years, median EDSS of 1.5) and 30 healthy controls. There was significantly reduced volume of thalamus, hippocampus and putamen in the RRMS patients, but no diffusion or perfusion changes in these structures. Decreased volume in these deep GM volumes in RRMS patients was associated with a modest reduction in cognitive performance, particularly information processing speed, consistent with a subtle disruption of distributed networks, that subserve cognition, in these patients. Future longitudinal studies are needed to elucidate the influence of deep GM changes on the evolution of cognitive deficits in MS.

The increasing prevalence of multiple sclerosis in New Zealand.

BACKGROUND: New Zealand (NZ) has a high prevalence of multiple sclerosis (MS). Worldwide, the prevalence of MS appears to be increasing. OBJECTIVES: To review all published prevalence studies undertaken in NZ to determine whether the prevalence of MS in NZ is increasing. METHODS: PubMed, Medline, Scopus, Web of Knowledge, EMBASE, AMED and CINAHL were searched to identify studies reporting the prevalence of MS in NZ. Prevalence rates from the National MS Prevalence study in 2006 were compared with earlier prevalence rates for the same regions using Poisson regression. RESULTS: Prevalence rates reported in the earlier regional studies ranged from 23.6 to 68.5/100,000 population; in the same regions in 2006, the range was 47.6-134.2/100,000 population. Prevalence rates were significantly increased in all regions studied except for the Bay of Plenty. The increase in prevalence was seen in both sexes. The sex ratio remained constant over time. CONCLUSIONS: In studies spanning almost 40 years (1968-2006), the prevalence of MS within the same regions of NZ has significantly increased whereas the sex ratio and latitudinal gradient have remained stable.

Reduced grey matter perfusion without volume loss in early relapsing-remitting multiple sclerosis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

A possible clinical tool to depict muscle elasticity mapping using magnetic resonance elastography.

INTRODUCTION: Characterization of muscle elasticity will improve the diagnosis and treatment of muscle disorders. The purpose is to compare the use of magnetic resonance elastography (MRE) and ultrasound elastography (USE) techniques to elucidate the MRE cartography of thigh muscles. METHODS: Both elastography techniques were performed on 5 children and 7 adults. Quantitative (MRE) and qualitative (USE) cartographies of muscle elasticity, as a function of muscle state and age, were obtained with shear waves and manual compression of the ultrasound probe, respectively. RESULTS: Similar cartographies of muscle elasticity were obtained with the 2 methods. The combination of both imaging techniques results in an improved depiction of the physiological changes associated with muscle state and age. CONCLUSIONS: This study demonstrates the feasibility of MRE for use as a clinical tool in the characterization of neuromuscular pathologies and for assessing the efficacy of specific treatments for muscle related diseases.

Cutoff values for alcoholic liver fibrosis using magnetic resonance elastography technique.

BACKGROUND: Due to the lack of cutoff values validated for specific liver diseases, the purpose of this study was to set up specific magnetic resonance elastography (MRE) cutoff values for asymptomatic liver fibrosis in alcoholic patients. METHODS: Ninety patients underwent 3 clinical exams. The liver stiffness was measured locally with the Fibroscan, and globally through cartographies of shear modulus generated with MRE. The Fibroscan method was chosen as the gold standard to classify the fibrosis. The liver score was also obtained with the Fibrometer A, and the diagnostic performance of the methods was analyzed with receiver-operating characteristic (ROC) curves and cutoff values were calculated. RESULTS: Spearman correlation and area under the ROC curve revealed that MRE is a better diagnostic method than the Fibrometer A, to identify various levels of fibrosis. The results showed that the Fibrometer A was adapted for severe fibrosis. The MRE cutoff values are F1:2.20 kPa, F2:2.57 kPa, F3:3.31 kPa, and F4:4 kPa and were not influenced by the glutamic oxaloacetic transaminase level. By using the ultrasound cutoff values attributed for alcoholism, 66% of patients had a similar liver fibrosis diagnosis as the MRE cutoffs. However, both imaging techniques did not provide the same distribution for minor fibrosis. CONCLUSIONS: None of the imaging techniques (Fibroscan, MRE) could replace the gold standard of the biopsy. However, due to the risk and the unnecessary procedure for the present recruited alcoholic patients, the Fibroscan method was chosen as the reference. Since MRE is currently being used as a clinical exam, the present MRE cutoffs could aid clinicians with their diagnosis of liver fibrosis for alcoholism disease.

Characterization of a hyper-viscoelastic phantom mimicking biological soft tissue using an abdominal pneumatic driver with magnetic resonance elastography (MRE).

The purpose of this study was to create a polymer phantom mimicking the mechanical properties of soft tissues using experimental tests and rheological models. Multifrequency Magnetic Resonance Elastography (MMRE) tests were performed on the present phantom with a pneumatic driver to characterize the viscoelastic (µ, η) properties using Voigt, Maxwell, Zener and Springpot models. To optimize the MMRE protocol, the driver behavior was analyzed with a vibrometer. Moreover, the hyperelastic properties of the phantom were determined using compressive tests and Mooney-Rivlin model. The range of frequency to be used with the round driver was found between 60 Hz and 100 Hz as it exhibits one type of vibration mode for the membrane. MRE analysis revealed an increase in the shear modulus with frequency reflecting the viscoelastic properties of the phantom showing similar characteristic of soft tissues. Rheological results demonstrated that Springpot model better revealed the viscoelastic properties (µ=3.45 kPa, η=6.17 Pas) of the phantom and the Mooney-Rivlin coefficients were C(10)=1.09.10(-2) MPa and C(01)=-8.96.10(-3) MPa corresponding to µ=3.95 kPa. These studies suggest that the phantom, mimicking soft tissue, could be used for preliminary MRE tests to identify the optimal parameters necessary for in vivo investigations. Further developments of the phantom may allow clinicians to more accurately mimic healthy and pathological soft tissues using MRE.

Stiffness imaging of the kidney and adjacent abdominal tissues measured simultaneously using magnetic resonance elastography.

To date, non-invasive methods to detect kidney malignancies and mild tumors remain a challenge. The purpose of this study was to establish the proper imaging protocol to determine kidney stiffness and its spatial distribution within the various kidney compartments such as the renal sinus, medulla, and cortex. Here, we have used magnetic resonance elastography (MRE) along with coronal oblique acquisition to simultaneously measure kidney stiffness in comparison with other tissues including the liver, spleen, and psoas.

Analysis of thigh muscle stiffness from childhood to adulthood using magnetic resonance elastography (MRE) technique.

BACKGROUND: Magnetic resonance elastography has been performed in healthy and pathological muscles in order to provide clinicians with quantitative muscle stiffness data. However, there is a lack of data on pediatric muscle. Therefore, the present work studies age-related changes of the mechanical properties. METHODS: 26 healthy subjects composed of 7 children (8-12 years), 9 young adults (24-29 years) and 10 middle-aged adults (53-58 years) underwent a magnetic resonance elastography test. Shear modulus (µ) and its spatial distribution, as well as the attenuation coefficient (α) were measured on the vastus medialis muscle at rest and at contracted conditions (10% and 20% of the maximum voluntary contraction) for each group. FINDINGS: The shear modulus linearly increases with the degree of contraction for young adults while it is maximum at 10% of the maximum voluntary contraction for children (µ_(children_10%)=14.9kPa (SD 2.18)) and middle-aged adults (µ_(middle-aged_10%)=10.42kPa (SD 1.38)). Mapping of shear modulus revealed a diffuse distribution of colors reflecting differences in muscle physiological activity as a function of age. The attenuation coefficient showed a similar behavior for all groups, i.e. a decrease from the relaxed to the contracted states. INTERPRETATION: This study demonstrates that the magnetic resonance elastography technique is sensitive enough to detect changes in muscle mechanical properties for children, middle-aged and young adults and could provide clinicians with a muscle reference data base as a function of age, improving the diagnosis of muscular dystrophy.

Characterization of muscle architecture in children and adults using magnetic resonance elastography and ultrasound techniques.

The purpose of this study is to characterize the muscle architecture of children and adults using magnetic resonance elastography and ultrasound techniques. Five children (8-12 yr) and seven adults (24-58 yr) underwent both tests on the vastus medialis muscle at relaxed and contracted (10% and 20% of MVC) states. Longitudinal ultrasonic images were performed in the same area as the phase image showing the shear wave's propagation. Two geometrical parameters were defined: the wave angle (α(_MRE)) corresponding to the shear wave propagation and the fascicule angle (α(_US)) tracking the path of fascicles. Moreover, shear modulus was measured at different localizations within the muscle and in the subcutaneous adipose tissue. The association of both techniques demonstrates that the shear wave propagation follows the muscle fascicles path, reflecting the internal muscle architecture. At rest, ultrasound images revealed waves propagating parallel to the children fascicle while adults showed oblique waves corresponding to already oriented (α(_US)=15.4±2.54°) muscle fascicles. In contraction, the waves' propagation were in an oblique direction for children (α(_US_10%MVC)=10.6±2.27°, α(_US_20%MVC)=10.2±2.29°) as well as adults (α(_US_10%MVC)=15.4±2.54°, α(_US_20%MVC)=17.2±2.44°). A stiffness variation (1 kPa) was found between the upper and lower parts of the adult VM muscle and a lower stiffness (1.85±0.17 kPa) was measured in the subcutaneous adipose tissue. This study demonstrates the feasibility of the MRE technique to provide geometrical insights from the children and adults muscles and to characterize different physiological media.