Test-retest reproducibility of in vivo magnetization transfer ratio and saturation index in mice at 9.4 Tesla

Background: Magnetization transfer saturation (MTsat) imaging was developed to reduce T1 dependence and improve specificity to myelin compared to the widely used MT ratio (MTR), while maintaining a feasible scan time. Knowledge of MTsat reproducibility is necessary to apply MTsat in preclinical neuroimaging. Purpose: To assess the test-retest reproducibility of MTR and MTsat in the mouse brain at 9.4 T and calculate sample sizes required to detect various effect sizes. Study Type: Prospective. Animal Model: C57Bl/6 Mouse Model (6 females and 6 males, aged 12 to 14 weeks). Field Strength/Sequence: Magnetization Transfer Imaging at 9.4 T. Assessment: All mice were scanned at two timepoints (5 days apart). MTR and MTsat maps were analyzed using mean region of interest (ROI), and whole brain voxel-wise analysis. Statistical Tests: Bland Altman plots assessed biases between test and retest measurements. Test retest reproducibility was evaluated via between and within-subject coefficients of variation (CV). Sample sizes required were calculated (at a 95 % significance level and power of 80 %), given various minimum detectable effect sizes, using both between and within-subject approaches. Results: Bland Altman plots showed negligible biases between test and retest sessions. ROI based and voxel-wise CVs revealed high reproducibility for both MTR (ROI: CVs < 8 %) and MTsat (ROI: CVs < 10 %). With a sample size of 6, changes on the order of 15% can be detected in MTR and MTsat, both between and within subjects, while smaller changes (6 to 8 %) require sample sizes of 10 to 15 for MTR, and 15 to 20 for MTsat. Data Conclusion: MTsat exhibits comparable reproducibility to MTR, while providing sensitivity to myelin with less T1 dependence than MTR. Our findings suggest both MTR and MTsat can detect moderate changes, common in pathologies, with feasible preclinical sample sizes. Keywords: magnetization transfer ratio, magnetization transfer saturation, reproducibility, preclinical rodent imaging

A New Type of Super-Sparse Matrix Converter with Γ Source and Its Characteristics Analysis

To solve the problem of low voltage transmission in ultra sparse matrix converter (USMC), a novel ultra sparse matrix converter (USMC) is proposed. The new USMC topology contains of a Γ source boost circuit in the DC link. By increasing the output voltage of DC link, the inverter stage can output higher voltage, thus widening the range of voltage transmission ratio. Furthermore, combined with the SVPWM modulation strategy, the voltage transfer ratio of the new USMC topology is derived, which lays a theoretical foundation for the application of USMC. Finally, Matlab / Simulink simulation results verify the correctness and feasibility of the topology.

Assessing Lumbar Plexus and Sciatic Nerve Damage in Relapsing-Remitting Multiple Sclerosis Using Magnetisation Transfer Ratio

Background: Multiple sclerosis (MS) has traditionally been regarded as a disease confined to the central nervous system (CNS). However, neuropathological, electrophysiological, and imaging studies have demonstrated that the peripheral nervous system (PNS) is also involved, with demyelination and, to a lesser extent, axonal degeneration representing the main pathophysiological mechanisms.Aim: The purpose of this study was to assess PNS damage at the lumbar plexus and sciatic nerve anatomical locations in people with relapsing-remitting MS (RRMS) and healthy controls (HCs) in vivo using magnetisation transfer ratio (MTR), which is a known imaging biomarker sensitive to alterations in myelin content in neural tissue, and not previously explored in the context of PNS damage in MS.Method: Eleven HCs (7 female, mean age 33.6 years, range 24-50) and 15 people with RRMS (12 female, mean age 38.5 years, range 30-56) were recruited for this study and underwent magnetic resonance imaging (MRI) investigations together with clinical assessments using the expanded disability status scale (EDSS). Magnetic resonance neurography (MRN) was first used for visualisation and identification of the lumbar plexus and the sciatic nerve and MTR imaging was subsequently performed using identical scan geometry to MRN, enabling straightforward co-registration of all data to obtain global and regional mean MTR measurements. Linear regression models were used to identify differences in MTR values between HCs and people with RRMS and to identify an association between MTR measures and EDSS.Results: MTR values in the sciatic nerve of people with RRMS were found to be significantly lower compared to HCs, but no significant MTR changes were identified in the lumbar plexus of people with RRMS. The median EDSS in people with RRMS was 2.0 (range, 0-3). No relationship between the MTR measures in the PNS and EDSS were identified at any of the anatomical locations studied in this cohort of people with RRMS.Conclusion: The results from this study demonstrate the presence of PNS damage in people with RRMS and support the notion that these changes, suggestive of demyelination, maybe occurring independently at different anatomical locations within the PNS. Further investigations to confirm these findings and to clarify the pathophysiological basis of these alterations are warranted.

Rollover Prevention Control for Autonomous Electric Road Sweeper

This paper presents a method to prevent the rollover of autonomous electric road sweepers (AERS). AERS have an articulated frame steering (AFS) mechanism. Moreover, the heights of the center of gravity of the front and rear bodies are high. As such, they are prone to rolling over at low speeds and at small articulation angles. A bicycle model with a nonlinear tire model was used as a vehicle model for AERS. Using that vehicle model, path tracking and speed controllers were designed in order to follow a predefined path and speed profile, respectively. To check the rollover propensity of AERS, load transfer ratio (LTR) based the rollover analysis was completed. Based on the results of the analysis, a rollover prevention scheme was proposed. To validate the proposed scheme, a simulation was conducted using a U-shaped path under constant speed conditions. From the simulation, it was shown that the proposed scheme is effective in preventing AERS from rolling over.

Cross-education and detraining effects of eccentric vs. concentric resistance training of the elbow flexors

Background Unilateral resistance training increases the strength of the contralateral non-trained homologous muscles known as the cross-education effect. We tested the hypothesis that unilateral eccentric resistance training (ET) would induce greater and longer-lasting cross-education effect when compared with concentric resistance training (CT). Methods Young (20–23 y) participants were allocated to ET (5 males, 4 females) or CT (5 males, 4 females) group that performed unilateral progressive ET or CT of the elbow flexors, twice a week for 5 weeks (10 sessions) followed by a 5-week detraining, and control group (7 males, 6 females) that did not perform any training. Maximum voluntary isometric contraction torque of the elbow flexors (MVIC), one-repetition maximum of concentric dumbbell curl (1-RM), and biceps brachii and brachialis muscle thickness (MT) were measured from the trained and non-trained arms before, several days after the last training session, and 5 weeks later. A ratio between the trained and non-trained arms for the change in MVIC or 1-RM from pre- to post-training (cross-body transfer ratio) was compared between ET and CT groups. Results The control group did not show significant changes in any variables. Both ET and CT increased (P < 0.05) MVIC (22.5 ± 12.3 % vs. 26.0 ± 11.9 %) and 1-RM (28.8 ± 6.6 % vs. 35.4 ± 12.9 %) of the trained arm without a significant difference between groups. MVIC was maintained after detraining for ET but returned to the baseline for CT, and 1-RM was maintained after detraining for both ET and CT. For the non-trained arm, MVIC (22.7 ± 17.9 % vs. 12.2 ± 10.2 %) and 1-RM (19.9 ± 14.6 % vs. 24.0 ± 10.6 %) increased similarly (P > 0.05) after ET and CT, and MVIC returned to the baseline after detraining, but 1-RM was maintained for both groups. An increase (P < 0.05) in MT was found only after ET for the trained arm (7.1 ± 6.1 %). The cross-body transfer ratio for MVIC was greater (P < 0.05) for ET (90.9 ± 46.7 %) than CT (49.0 ± 30.0 %). Conclusions These results did not support the hypothesis and showed similar changes in the most of the variables between ET and CT for the trained and non-trained arms, and strong cross-education effects on MVIC and 1-RM, but less detraining effect after ET than CT on MVIC of the trained arm. Trial registration University Hospital Medical Information Network Clinical Trials Registry (UMIN000044477; Jun 09, 2021).

Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study

Background: The envelope protein of human endogenous retrovirus W (HERV-W-Env) is expressed by macrophages and microglia, mediating axonal damage in chronic active MS lesions. Objective and Methods: This phase 2, double-blind, 48-week trial in relapsing-remitting MS with 48-week extension phase assessed the efficacy and safety of temelimab; a monoclonal antibody neutralizing HERV-W-Env. The primary endpoint was the reduction of cumulative gadolinium-enhancing T1-lesions in brain magnetic resonance imaging (MRI) scans at week 24. Additional endpoints included numbers of T2 and T1-hypointense lesions, magnetization transfer ratio, and brain atrophy. In total, 270 participants were randomized to receive monthly intravenous temelimab (6, 12, or 18 mg/kg) or placebo for 24 weeks; at week 24 placebo-treated participants were re-randomized to treatment groups. Results: The primary endpoint was not met. At week 48, participants treated with 18 mg/kg temelimab had fewer new T1-hypointense lesions ( p = 0.014) and showed consistent, however statistically non-significant, reductions in brain atrophy and magnetization transfer ratio decrease, as compared with the placebo/comparator group. These latter two trends were sustained over 96 weeks. No safety issues emerged. Conclusion: Temelimab failed to show an effect on features of acute inflammation but demonstrated preliminary radiological signs of possible anti-neurodegenerative effects. Current data support the development of temelimab for progressive MS. Trial registration: CHANGE-MS: ClinicalTrials.gov: NCT02782858, EudraCT: 2015-004059-29; ANGEL-MS: ClinicalTrials.gov: NCT03239860, EudraCT: 2016-004935-18

Surface-in pathology in multiple sclerosis: a new view on pathogenesis?

While multiple sclerosis can affect any part of the CNS, it does not do so evenly. In white matter it has long been recognized that lesions tend to occur around the ventricles, and grey matter lesions mainly accrue in the outermost (subpial) cortex. In cortical grey matter, neuronal loss is greater in the outermost layers. This cortical gradient has been replicated in vivo with magnetization transfer ratio and similar gradients in grey and white matter magnetization transfer ratio are seen around the ventricles, with the most severe abnormalities abutting the ventricular surface. The cause of these gradients remains uncertain, though soluble factors released from meningeal inflammation into the CSF has the most supporting evidence. In this Update, we review this ‘surface-in’ spatial distribution of multiple sclerosis abnormalities and consider the implications for understanding pathogenic mechanisms and treatments designed to slow or stop them.