Bed-rest and exercise remobilization: Concurrent adaptations in muscle glucose and protein metabolism.

BACKGROUND: Bed-rest (BR) of only a few days duration reduces muscle protein synthesis and induces skeletal muscle atrophy and insulin resistance, but the scale and juxtaposition of these events have not been investigated concurrently in the same individuals. Moreover, the impact of short-term exercise-supplemented remobilization (ESR) on muscle volume, protein turnover and leg glucose uptake (LGU) in humans is unknown. METHODS: Ten healthy males (24 ± 1 years, body mass index 22.7 ± 0.6 kg/m2) underwent 3 days of BR, followed immediately by 3 days of ESR consisting of 5 × 30 maximal voluntary single-leg isokinetic knee extensions at 90°/s each day. An isoenergetic diet was maintained throughout the study (30% fat, 15% protein and 55% carbohydrate). Resting LGU was calculated from arterialized-venous versus venous difference across the leg and leg blood flow during the steady-state of a 3-h hyperinsulinaemic-euglycaemic clamp (60 mU/m2/min) measured before BR, after BR and after remobilization. Glycogen content was measured in vastus lateralis muscle biopsy samples obtained before and after each clamp. Leg muscle volume (LMV) was measured using magnetic resonance imaging before BR, after BR and after remobilization. Cumulative myofibrillar protein fractional synthetic rate (FSR) and whole-body muscle protein breakdown (MPB) were measured over the course of BR and remobilization using deuterium oxide and 3-methylhistidine stable isotope tracers that were administered orally. RESULTS: Compared with before BR, there was a 45% decline in insulin-stimulated LGU (P < 0.05) after BR, which was paralleled by a reduction in insulin-stimulated leg blood flow (P < 0.01) and removal of insulin-stimulated muscle glycogen storage. These events were accompanied by a 43% reduction in myofibrillar protein FSR (P < 0.05) and a 2.5% decrease in LMV (P < 0.01) during BR, along with a 30% decline in whole-body MPB after 2 days of BR (P < 0.05). Myofibrillar protein FSR and LMV were restored by 3 days of ESR (P < 0.01 and P < 0.01, respectively) but not by ambulation alone. However, insulin-stimulated LGU and muscle glycogen storage were not restored by ESR. CONCLUSIONS: Three days of BR caused concurrent reductions in LMV, myofibrillar protein FSR, myofibrillar protein breakdown and insulin-stimulated LGU, leg blood flow and muscle glycogen storage in healthy, young volunteers. Resistance ESR restored LMV and myofibrillar protein FSR, but LGU and muscle glycogen storage remained depressed, highlighting divergences in muscle fuel and protein metabolism. Furthermore, ambulation alone did not restore LMV and myofibrillar protein FSR in the non-exercised contralateral limb, emphasizing the importance of exercise rehabilitation following even short-term BR.

Measuring chemical exchange saturation transfer exchange rates in the human brain using a particle swarm optimisation algorithm.

The z-spectrum contains many pools with different exchange rates and T2 values, which can make it difficult to interpret in vivo data and complicates the design of experiments aimed at providing sensitivity to one pool. This work aims to characterise the main pools observable with MRI at 7T in the human brain. To achieve this, we acquired z-spectra at multiple saturation powers in the human brain at 7T. We used simulations to optimise the use of particle swarm optimisation (PSO) to fit these data, validating this approach using further simulations and creatine phantoms. We then used the PSO to fit data from grey and white matter for the pool size, exchange rate, and T2 of five proton pools (magnetisation transfer, amides, amines, nuclear Overhauser enhancement NOE-3.5ppm and NOE-1.7ppm in addition to water). We then devised an approach for using PSO to fit z-spectra while limiting the computational burden, and we investigated the sensitivity of the fit to T2 and k for three overlapping pools. We used this to measure the exchange rate of creatine and to show that it varied with temperature, as expected. In the brain we measured a significantly larger pool size in white matter than in grey matter for the magnetisation transfer pool and the NOE-3.5ppm pool. For all other parameters we found no significant difference between grey and white matter. We showed that PSO can be used to fit z-spectra acquired at a range of B1 to provide information about peak position, amplitude, exchange rate, and T2 in vivo in the human brain. These data could provide more sensitivity to change in some clinical conditions and will also provide key information for further experimental design.

Reduced Myelin Signal in Normal-appearing White Matter in Neuromyelitis Optica Measured by 7T Magnetic Resonance Imaging.

Whether the integrity of normal-appearing white matter (NAWM) is preserved in neuromyelitis optica spectrum disorders (NMOSD) is open to debate. To examine whether the tissue integrity of NAWM in NMOSD is compromised compared to that in healthy controls and patients with multiple sclerosis (MS), we prospectively enrolled 14 patients with NMOSD, 12 patients with MS, and 10 controls for clinical functional assessments and quantitative imaging, including T1 relaxation time (T1) and magnetization transfer ratio (MTR) at 7 Tesla. Cognitive performance on the Paced Auditory Serial Addition Test with a 3-second interstimulus interval (PASAT-3) was significantly lower in the NMOSD compared to the MS group (mean number of correct answers, 34.1 vs. 47.6; p = 0.006), but there were no differences in disease duration or disability. Histograms of T1 and MTR maps of NAWM demonstrated a decreased peak height in patients with NMOSD compared to the healthy controls, but not compared to patients with MS. Using 7T quantitative magnetic resonance imaging (MRI), this study showed that the NAWM in patients with NMOSD is abnormal, with reduced myelin signal; this was not previously observed using MRI at a lower field strength.

Seven-Tesla Magnetization Transfer Imaging to Detect Multiple Sclerosis White Matter Lesions.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion recovery (FLAIR) imaging at 3 Tesla (T) field strength is the most sensitive modality for detecting white matter lesions in multiple sclerosis. While 7T FLAIR is effective in detecting cortical lesions, it has not been fully optimized for visualization of white matter lesions and thus has not been used for delineating lesions in quantitative magnetic resonance imaging (MRI) studies of the normal appearing white matter in multiple sclerosis. Therefore, we aimed to evaluate the sensitivity of 7T magnetization-transfer-weighted (MTw ) images in the detection of white matter lesions compared with 3T-FLAIR. METHODS: Fifteen patients with clinically isolated syndrome, 6 with multiple sclerosis, and 10 healthy participants were scanned with 7T 3-dimensional (D) MTw and 3T-2D-FLAIR sequences on the same day. White matter lesions visible on either sequence were delineated. RESULTS: Of 662 lesions identified on 3T-2D-FLAIR images, 652 were detected on 7T-3D-MTw images (sensitivity, 98%; 95% confidence interval, 97% to 99%). The Spearman correlation coefficient between lesion loads estimated by the two sequences was .910. The intrarater and interrater reliability for 7T-3D-MTw images was good with an intraclass correlation coefficient (ICC) of 98.4% and 81.8%, which is similar to that for 3T-2D-FLAIR images (ICC 96.1% and 96.7%). CONCLUSION: Seven-Tesla MTw sequences detected most of the white matter lesions identified by FLAIR at 3T. This suggests that 7T-MTw imaging is a robust alternative for detecting demyelinating lesions in addition to 3T-FLAIR. Future studies need to compare the roles of optimized 7T-FLAIR and of 7T-MTw imaging.

The z-spectrum from human blood at 7T.

Chemical Exchange Saturation Transfer (CEST) has been used to assess healthy and pathological tissue in both animals and humans. However, the CEST signal from blood has not been fully assessed. This paper presents the CEST and nuclear Overhauser enhancement (NOE) signals detected in human blood measured via z-spectrum analysis. We assessed the effects of blood oxygenation levels, haematocrit, cell structure and pH upon the z-spectrum in ex vivo human blood for different saturation powers at 7T. The data were analysed using Lorentzian difference (LD) model fitting and AREX (to compensate for changes in T1), which have been successfully used to study CEST effects in vivo. Full Bloch-McConnell fitting was also performed to provide an initial estimate of exchange rates and transverse relaxation rates of the various pools. CEST and NOE signals were observed at 3.5 ppm, -1.7 ppm and -3.5 ppm and were found to originate primarily from the red blood cells (RBCs), although the amide proton transfer (APT) CEST effect, and NOEs showed no dependence upon oxygenation levels. Upon lysing, the APT and NOE signals fell significantly. Different pH levels in blood resulted in changes in both the APT and NOE (at -3.5 ppm), which suggests that this NOE signal is in part an exchange relayed process. These results will be important for assessing in vivo z-spectra.

Quantitative analysis of the z-spectrum using a numerically simulated look-up table: Application to the healthy human brain at 7T.

PURPOSE: To develop a method that fits a multipool model to z-spectra acquired from non-steady state sequences, taking into account the effects of variations in T1 or B1 amplitude and the results estimating the parameters for a four-pool model to describe the z-spectrum from the healthy brain. METHODS: We compared measured spectra with a look-up table (LUT) of possible spectra and investigated the potential advantages of simultaneously considering spectra acquired at different saturation powers (coupled spectra) to provide sensitivity to a range of different physicochemical phenomena. RESULTS: The LUT method provided reproducible results in healthy controls. The average values of the macromolecular pool sizes measured in white matter (WM) and gray matter (GM) of 10 healthy volunteers were 8.9% ± 0.3% (intersubject standard deviation) and 4.4% ± 0.4%, respectively, whereas the average nuclear Overhauser effect pool sizes in WM and GM were 5% ± 0.1% and 3% ± 0.1%, respectively, and average amide proton transfer pool sizes in WM and GM were 0.21% ± 0.03% and 0.20% ± 0.02%, respectively. CONCLUSIONS: The proposed method demonstrated increased robustness when compared with existing methods (such as Lorentzian fitting and asymmetry analysis) while yielding fully quantitative results. The method can be adjusted to measure other parameters relevant to the z-spectrum. Magn Reson Med 78:645-655, 2017. © 2016 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.

Relationships between cortical myeloarchitecture and electrophysiological networks.

The human brain relies upon the dynamic formation and dissolution of a hierarchy of functional networks to support ongoing cognition. However, how functional connectivities underlying such networks are supported by cortical microstructure remains poorly understood. Recent animal work has demonstrated that electrical activity promotes myelination. Inspired by this, we test a hypothesis that gray-matter myelin is related to electrophysiological connectivity. Using ultra-high field MRI and the principle of structural covariance, we derive a structural network showing how myelin density differs across cortical regions and how separate regions can exhibit similar myeloarchitecture. Building upon recent evidence that neural oscillations mediate connectivity, we use magnetoencephalography to elucidate networks that represent the major electrophysiological pathways of communication in the brain. Finally, we show that a significant relationship exists between our functional and structural networks; this relationship differs as a function of neural oscillatory frequency and becomes stronger when integrating oscillations over frequency bands. Our study sheds light on the way in which cortical microstructure supports functional networks. Further, it paves the way for future investigations of the gray-matter structure/function relationship and its breakdown in pathology.

Histogram analysis of quantitative T1 and MT maps from ultrahigh field MRI in clinically isolated syndrome and relapsing-remitting multiple sclerosis.

This study used quantitative MRI to study normal appearing white matter (NAWM) in patients with clinically isolated syndromes suggestive of multiple sclerosis and relapsing-remitting multiple sclerosis (RRMS). This was done at ultrahigh field (7 T) for greater spatial resolution and sensitivity. 17 CIS patients, 11 RRMS patients, and 20 age-matched healthy controls were recruited. They were scanned using a 3D inversion recovery turbo field echo sequence to measure the longitudinal relaxation time (T1). A 3D magnetization transfer prepared turbo field echo (MT-TFE) sequence was also acquired, first without a presaturation pulse and then with the MT presaturation pulse applied at -1.05 kHz and +1.05 kHz off resonance from water to produce two magnetization transfer ratio maps (MTR(-) and MTR(+)). Histogram analysis was performed on the signal from the voxels in the NAWM mask. The upper quartile cut-off of the T1 histogram was significantly higher in RRMS patients than in controls (p < 0.05), but there was no difference in CIS. In contrast, MTR was significantly different between CIS or RRMS patients and controls (p < 0.05) for most histogram measures considered. The difference between MTR(+) and MTR(-) signals showed that NOE contributions dominated the changes found. There was a weak negative correlation (r = -0.46, p < 0.05) between the mode of T1 distributions and healthy controls' age; this was not significant for MTR(+) (r = -0.34, p > 0.05) or MTR(-) (r = 0.13, p > 0.05). There was no significant correlation between the median of T1, MTR(-), or MTR(+) and the age of healthy controls. Furthermore, no significant correlation was observed between EDSS or disease duration and T1, MTR(-), or MTR(+) for either CIS or RRMS patients. In conclusion, MTR was found to be more sensitive to early changes in MS disease than T1.

Structural properties of the corticospinal tract in the human brain: a magnetic resonance imaging study at 7 Tesla.

Several fibre tracts can be accurately located using conventional Magnetic Resonance Images (MRI) of the human brain, including the corticospinal tract (CST), which appears as a T (1)-weighted hypointense/T (2)-weighted hyperintense patch in the posterior part of the posterior-limb of the internal capsule (PLIC). Here we use high-field MRI (7T) to assess the quantitative MRI properties of the CST at the PLIC level in 22 healthy young male participants. We used three different imaging modalities: the T (1) and T (2) relaxation times (T (1) and T (2)) and the Magnetization Transfer Ratio (MTR). These measurements obtained in the CST were compared with those in the anterior two-thirds of the PLIC. We observed longer T (1) and T (2) and lower MTR in the CST region compared with the adjacent (control) PLIC region. This effect is consistent with the presence of sparsely distributed, large-diameter fibres described in previous histological studies and, as such, might reflect lower myelin density and/or different morphology of fibres in the CST.