Regional patterns of grey matter atrophy and magnetisation transfer ratio abnormalities in multiple sclerosis clinical subgroups: A voxel-based analysis study.

In multiple sclerosis (MS), demyelination and neuro-axonal loss occur in the brain grey matter (GM). We used magnetic resonance imaging (MRI) measures of GM magnetisation transfer ratio (MTR) and volume to assess the regional localisation of reduced MTR (reflecting demyelination) and atrophy (reflecting neuro-axonal loss) in relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS)

Grey and White Matter Magnetisation Transfer Ratio Measurements in the Lumbosacral Enlargement: A Pilot In Vivo Study at 3T

Magnetisation transfer (MT) imaging of the central nervous system has provided further insight into the pathophysiology of neurological disease. However, the use of this method to study the lower spinal cord has been technically challenging, despite the important role of this region, not only for motor control of the lower limbs, but also for the neural control of lower urinary tract, sexual and bowel functions. In this study, the feasibility of obtaining reliable grey matter (GM) and white matter (WM) magnetisation transfer ratio (MTR) measurements within the lumbosacral enlargement (LSE) was investigated in ten healthy volunteers using a clinical 3T MRI system. The mean cross-sectional area of the LSE (LSE-CSA) and the mean GM area (LSE-GM-CSA) were first obtained by means of image segmentation and tissue-specific (i.e. WM and GM) MTR measurements within the LSE were subsequently obtained. The reproducibility of the segmentation method and MTR measurements was assessed from repeated measurements and their % coefficient of variation (%COV). Mean (± SD) LSE-CSA across 10 healthy subjects was 59.3 (± 8.4) mm2 and LSE-GM-CSA was 17.0 (± 3.1) mm2. The mean intra- and inter-rater % COV for measuring the LSE-CSA were 0.8% and 2.3%, respectively and for the LSE-GM-CSA were 3.8% and 5.4%, respectively. Mean (± SD) WM-MTR was 43.2 (± 4.4) and GM-MTR was 40.9 (± 4.3). The mean scan-rescan % COV for measuring WM-MTR was 4.6% and for GM-MTR was 3.8%. Using a paired t-test, a statistically significant difference was identified between WM-MTR and GM-MTR in the LSE (p<0.0001). This pilot study has shown that it is possible to obtain reliable tissue-specific MTR measurements within the LSE using a clinical MR system at 3T. The MTR acquisition and analysis protocol presented in this study can be used in future investigations of intrinsic spinal cord diseases that affect the LSE

ZOOM or Non-ZOOM? Assessing spinal cord diffusion tensor imaging protocols for multi-centre studies

The purpose of this study was to develop and evaluate two spinal cord (SC) diffusion tensor imaging (DTI) protocols, implemented at multiple sites (using scanners from two different manufacturers), one available on any clinical scanner, and one using more advanced options currently available in the research setting, and to use an automated processing method for unbiased quantification. DTI parameters are sensitive to changes in the diseased SC. However, imaging the cord can be technically challenging due to various factors including its small size, patient-related and physiological motion, and field inhomogeneities. Rapid acquisition sequences such as Echo Planar Imaging (EPI) are desirable but may suffer from image distortions. We present a multi-centre comparison of two acquisition protocols implemented on scanners from two different vendors (Siemens and Philips), one using a reduced field-of-view (rFOV) EPI sequence, and one only using options available on standard clinical scanners such as outer volume suppression (OVS). Automatic analysis was performed with the Spinal Cord Toolbox for unbiased and reproducible quantification of DTI metrics in the white matter. Images acquired using the rFOV sequence appear less distorted than those acquired using OVS alone. SC DTI parameter values obtained using both sequences at all sites were consistent with previous measurements made at 3T. For the same scanner manufacturer, DTI parameter inter-site SDs were smaller for the rFOV sequence compared to the OVS sequence. The higher inter-site reproducibility (for the same manufacturer and acquisition details, i.e. ZOOM data acquired at the two Philips sites) of rFOV compared to the OVS sequence supports the idea that making research options such as rFOV more widely available would improve accuracy of measurements obtained in multi-centre clinical trials. Future multi-centre studies should also aim to match the rFOV technique and signal-to-noise ratios in all sequences from different manufacturers/sites in order to avoid any bias in measured DTI parameters and ensure similar sensitivity to pathological changes

Blood Oxygenation Level-Dependent Response to Multiple Grip Forces in Multiple Sclerosis: Going Beyond the Main Effect of Movement in Brodmann Area 4a and 4p

This study highlights the importance of looking beyond the main effect of movement to study alterations in functional response in the presence of central nervous system pathologies such as multiple sclerosis (MS). Data show that MS selectively affects regional BOLD (blood oxygenation level dependent) responses to variable grip forces (GF). It is known that the anterior and posterior BA 4 areas (BA 4a and BA 4p) are anatomically and functionally distinct. It has also been shown in healthy volunteers that there are linear (first order, typical of BA 4a) and nonlinear (second to fourth order, typical of BA 4p) BOLD responses to different levels of GF applied during a dynamic motor paradigm. After modeling the BOLD response with a polynomial expansion of the applied GFs, the particular case of BA 4a and BA 4p were investigated in healthy volunteers (HV) and MS subjects. The main effect of movement (zeroth order) analysis showed that the BOLD signal is greater in MS compared with healthy volunteers within both BA 4 subregions. At higher order, BOLD-GF responses were similar in BA 4a but showed a marked alteration in BA 4p of MS subjects, with those with greatest disability showing the greatest deviations from the healthy response profile. Therefore, the different behaviors in HV and MS could only be uncovered through a polynomial analysis looking beyond the main effect of movement into the two BA 4 subregions. Future studies will investigate the source of this pathophysiology, combining the present fMRI paradigm with blood perfusion and nonlinear neuronal response analysis

Fast and reproducible in vivo T1 mapping of the human cervical spinal cord

PURPOSE: To develop a fast and robust method for measuring T1 in the whole cervical spinal cord in vivo, and to assess its reproducibility. METHODS: A spatially nonselective adiabatic inversion pulse is combined with zonally oblique-magnified multislice echo-planar imaging to produce a reduced field-of-view inversion-recovery echo-planar imaging protocol. Multi- inversion time data are obtained by cycling slice order throughout sequence repetitions. Measurement of T1 is performed using 12 inversion times for a total protocol duration of 7 min. Reproducibility of regional T1 estimates is assessed in a scan-rescan experiment on five heathy subjects. RESULTS: Regional mean (standard deviation) T1 was: 1108.5 (±77.2) ms for left lateral column, 1110.1 (±83.2) ms for right lateral column, 1150.4 (±102.6) ms for dorsal column, and 1136.4 (±90.8) ms for gray matter. Regional T1 estimates showed good correlation between sessions (Pearson correlation coefficient = 0.89 (P value < 0.01); mean difference = 2 ms, 95% confidence interval ± 20 ms); and high reproducibility (intersession coefficient of variation approximately 1% in all the regions considered, intraclass correlation coefficient = 0.88 (P value < 0.01, confidence interval 0.71-0.95)). CONCLUSIONS: T1 estimates in the cervical spinal cord are reproducible using inversion-recovery zonally oblique-magnified multislice echo-planar imaging. The short acquisition time and large coverage of this method paves the way for accurate T1 mapping for various spinal cord pathologies. Magn Reson Med, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Feasibility of in vivo multi-parametric quantitative magnetic resonance imaging of the healthy sciatic nerve with a unified signal readout protocol

Magnetic resonance neurography (MRN) has been used successfully over the years to investigate the peripheral nervous system (PNS) because it allows early detection and precise localisation of neural tissue damage. However, studies demonstrating the feasibility of combining MRN with multi-parametric quantitative magnetic resonance imaging (qMRI) methods, which provide more specific information related to nerve tissue composition and microstructural organisation, can be invaluable. The translation of emerging qMRI methods previously validated in the central nervous system to the PNS offers real potential to characterise in patients in vivo the underlying pathophysiological mechanisms involved in a plethora of conditions of the PNS. The aim of this study was to assess the feasibility of combining MRN with qMRI to measure diffusion, magnetisation transfer and relaxation properties of the healthy sciatic nerve in vivo using a unified signal readout protocol. The reproducibility of the multi-parametric qMRI protocol as well as normative qMRI measures in the healthy sciatic nerve are reported. The findings presented herein pave the way to the practical implementation of joint MRN-qMRI in future studies of pathological conditions affecting the PNS

Imaging outcomes for trials of remyelination in multiple sclerosis.

Trials of potential neuroreparative agents are becoming more important in the spectrum of multiple sclerosis research. Appropriate imaging outcomes are required that are feasible from a time and practicality point of view, as well as being sensitive and specific to myelin, while also being reproducible and clinically meaningful. Conventional MRI sequences have limited specificity for myelination. We evaluate the imaging modalities which are potentially more specific to myelin content in vivo, such as magnetisation transfer ratio (MTR), restricted proton fraction f (from quantitative magnetisation transfer measurements), myelin water fraction and diffusion tensor imaging (DTI) metrics, in addition to positron emission tomography (PET) imaging. Although most imaging applications to date have focused on the brain, we also consider measures with the potential to detect remyelination in the spinal cord and in the optic nerve. At present, MTR and DTI measures probably offer the most realistic and feasible outcome measures for such trials, especially in the brain. However, no one measure currently demonstrates sufficiently high sensitivity or specificity to myelin, or correlation with clinical features, and it should be useful to employ more than one outcome to maximise understanding and interpretation of findings with these sequences. PET may be less feasible for current and near-future trials, but is a promising technique because of its specificity. In the optic nerve, visual evoked potentials can indicate demyelination and should be correlated with an imaging outcome (such as optic nerve MTR), as well as clinical measures

A call to action: Improving urban green spaces to reduce health inequalities exacerbated by COVID-19

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordHealth is not equally distributed across society; there are avoidable, unfair, systematic differences in health between population groups. Some of these same groups (older people, BAME communities, those with some non-communicable diseases (NCDs)) may be particularly vulnerable to risk of exposure and severe COVID-19 outcomes due to co-morbidities, structural vulnerabilities, and public-facing or health and social care jobs among other factors. Additionally, some of the restrictions designed to reduce SARS-CoV-2 spread impact specifically on these same groups by limiting their activity and access to preventive or health promotion services. Greenspaces, accessed with social distancing, may mitigate some of the predicted negative health effects of COVID-19 restrictions. Maintaining or increasing publicly accessible urban greenspaces, particularly for marginalised groups, is reflected in the Sustainable Development Goals, and its importance amplified in the COVID-19 pandemic. Urban greenspaces should be considered a public health and social investment and a chance to rebalance our relationship with nature to protect against future pandemics. By investing in urban public greenspaces, additional benefits (job/food creation, biodiversity promotion, carbon sequestration) may coincide with health benefits. Realising these requires a shift in the balance of decision making to place weight on protecting, enhancing and providing more appropriate greenspaces designed with local communities. The current pandemic is a reminder that humanity placing too many pressures on nature has damaging consequences. COVID-19 economic recovery programs present an opportunity for sustainable transformation if they can be leveraged to simultaneously protect and restore nature and tackle climate change and health inequalities