A longitudinal study of muscle rehabilitation in the lower leg after cast removal using magnetic resonance imaging and strength assessment

Magnetic resonance imaging (MRI) was used to investigate muscle rehabilitation following cast immobilization. The aim was to explore MRI as an imaging biomarker of muscle function. Sixteen patients completed an eight-week rehabilitation programme following six weeks of cast immobilization for an ankle fracture. MRI of the lower leg was performed at two-week intervals for 14 weeks. Total volume and anatomical cross-sectional areas at 70% of the distance from lateral malleolus to tibial tuberosity (ACSA) were measured for tibialis anterior (TA), medial and lateral gastrocnemius (GM and GL) and soleus (SOL). Pennation angle of muscle fascicules was measured at the same position in GM. Fractional fat/water contents and T2 relaxation times before and after exercise were calculated. Strength was measured as maximum isometric torque developed in plantar- and dorsi-flexion. Torque increased by (mean [SD]) 1.10 (0.32) N m day−1 in males, 0.74 (0.43) N m day−1 in females in plantar-flexion (0.9% of final strength per day), and 0.36 (0.15) N m day−1 in males, 0.28 (0.19) N m day−1 in females in dorsi-flexion (1.1% per day). Neither difference between males and females was significant. Volume and ACSA of muscles recovered by week 14 apart from SOL which was still 6.8% smaller (p = 0.006) than the contralateral leg. T2 peaked at the end of the cast period for TA and SOL, and at week 8 for GM before returning to baseline. Pennation angle recovered rapidly following cast removal. Quantitative MRI can generate markers of muscle biomechanics and indicates that many of these return to baseline within eight weeks of remobilization

Age-related changes in the effects of strength training on lower leg muscles in healthy individuals measured using MRI

BACKGROUND: We previously measured the rate of regaining muscle strength during rehabilitation of lower leg muscles in patients following lower leg casting. Our primary aim in this study was to measure the rate of gain of strength in healthy individuals undergoing a similar training regime. Our secondary aim was to test the ability of MRI to provide a biomarker for muscle function. METHODS: Men and women were recruited in three age groups: 20-30, 50-65 and over 70 years. Their response to resistance training of the right lower leg twice a week for 8 weeks was monitored using a dynamometer and MRI of tibialis anterior, soleus and gastrocnemius muscles at 2 weekly intervals to measure muscle size (anatomical cross-sectional area (ACSA)) and quality (T2 relaxation). Forty-four volunteers completed the study. RESULTS: Baseline strength declined with age. Training had no effect in middle-aged females or in elderly men in dorsiflexion. Other groups significantly increased both plantarflexion and dorsiflexion strength at rates up to 5.5 N m week(-1) in young females in plantarflexion and 1.25 N m week(-1) in young males in dorsiflexion. No changes were observed in ACSA or T2 in any age group in any muscle. CONCLUSION: Exercise training improves muscle strength in males at all ages except the elderly in dorsiflexion. Responses in females were less clear with variation across age and muscle groups. These results were not reflected in simple MRI measures that do not, therefore, provide a good biomarker for muscle atrophy or the efficacy of rehabilitation

Rapid T1 quantification based on 3D phase sensitive inversion recovery

<p>Abstract</p> <p>Background</p> <p>In Contrast Enhanced Magnetic Resonance Imaging fibrotic myocardium can be distinguished from healthy tissue using the difference in the longitudinal <it>T</it>₁relaxation after administration of Gadolinium, the so-called Late Gd Enhancement. The purpose of this work was to measure the myocardial absolute <it>T</it>₁post-Gd from a single breath-hold 3D Phase Sensitivity Inversion Recovery sequence (PSIR). Equations were derived to take the acquisition and saturation effects on the magnetization into account.</p> <p>Methods</p> <p>The accuracy of the method was investigated on phantoms and using simulations. The method was applied to a group of patients with suspected myocardial infarction where the absolute difference in relaxation of healthy and fibrotic myocardium was measured at about 15 minutes post-contrast. The evolution of the absolute <it>R</it>₁relaxation rate (1/<it>T</it>₁) over time after contrast injection was followed for one patient and compared to <it>T</it>₁mapping using Look-Locker. Based on the <it>T</it>₁maps synthetic LGE images were reconstructed and compared to the conventional LGE images.</p> <p>Results</p> <p>The fitting algorithm is robust against variation in acquisition flip angle, the inversion delay time and cardiac arrhythmia. The observed relaxation rate of the myocardium is 1.2 s^-1, increasing to 6 - 7 s^-1after contrast injection and decreasing to 2 - 2.5 s^-1for healthy myocardium and to 3.5 - 4 s^-1for fibrotic myocardium. Synthesized images based on the <it>T</it>₁maps correspond very well to actual LGE images.</p> <p>Conclusions</p> <p>The method provides a robust quantification of post-Gd <it>T</it>₁relaxation for a complete cardiac volume within a single breath-hold.</p

Competition for FcRn-mediated transport gives rise to short half-life of human IgG3 and offers therapeutic potential

Human IgG3 displays the strongest effector functions of all IgG subclasses but has a short half-life for unresolved reasons. Here we show that IgG3 binds to IgG-salvage receptor (FcRn), but that FcRn-mediated transport and rescue of IgG3 is inhibited in the presence of IgG1 due to intracellular competition between IgG1 and IgG3. We reveal that this occurs because of a single amino acid difference at position 435, where IgG3 has an arginine instead of the histidine found in all other IgG subclasses. While the presence of R435 in IgG increases binding to FcRn at neutral pH, it decreases binding at acidic pH, affecting the rescue efficiency—but only in the presence of H435–IgG. Importantly, we show that in humans the half-life of the H435-containing IgG3 allotype is comparable to IgG1. H435–IgG3 also gave enhanced protection against a pneumococcal challenge in mice, demonstrating H435–IgG3 to be a candidate for monoclonal antibody therapies

Gray matter imaging in multiple sclerosis: what have we learned?

At the early onset of the 20th century, several studies already reported that the gray matter was implicated in the histopathology of multiple sclerosis (MS). However, as white matter pathology long received predominant attention in this disease, and histological staining techniques for detecting myelin in the gray matter were suboptimal, it was not until the beginning of the 21st century that the true extent and importance of gray matter pathology in MS was finally recognized. Gray matter damage was shown to be frequent and extensive, and more pronounced in the progressive disease phases. Several studies subsequently demonstrated that the histopathology of gray matter lesions differs from that of white matter lesions. Unfortunately, imaging of pathology in gray matter structures proved to be difficult, especially when using conventional magnetic resonance imaging (MRI) techniques. However, with the recent introduction of several more advanced MRI techniques, the detection of cortical and subcortical damage in MS has considerably improved. This has important consequences for studying the clinical correlates of gray matter damage. In this review, we provide an overview of what has been learned about imaging of gray matter damage in MS, and offer a brief perspective with regards to future developments in this field