磁共振弹性图

磁共振弹性图(magnetic resonance elastography,MRE)利用磁共振成像(MRI)技术,测量由外力引起的组织内部质点位移空间分布,以此为输入对弹性力学的逆问题进行求解,从而获得组织弹性系数的空间分布图。介绍了M RE的成像原理,综述其各种成像手段以及MRE在医学上的应用和前景。     

In vivo elasticity measurements of extremity skeletal muscle with MR elastography

MR elastography (MRE) has been shown to be capable of non-invasively measuring tissue elasticity even in deep-lying regions. Although limited studies have already been published examining in vivo muscle elasticity, it is still not clear over what range the in vivo elasticity values vary. The present study intends to produce further information by examining four different skeletal muscles in a group of 12 healthy volunteers in the age range of 27-38 years. The examinations were performed in the biceps brachii, the flexor digitorum profundus, the soleus and the gastrocnemius. The average shear modulus was determined to be 17.9 (+/- 5.5), 8.7 (+/- 2.8), 12.5 (+/- 7.3) and 9.9 (+/- 6.8) kPa for each muscle, respectively. To ascertain the reproducibility of the examination, the stiffness measurements in two volunteers were repeated seven times for the biceps brachii. These examinations yielded a mean shear modulus of 11.3 +/-.7 and 13.3 +/- 4.7 kPa for the two subjects. For elasticity reconstruction, an automated reconstruction algorithm is introduced which eliminates variation due to subjective manual image analysis. This study yields new information regarding the expected variation in muscle elasticity in a healthy population, and also reveals the expected variability of the MRE technique in skeletal muscle.     

Magnetic resonance elastography with guided pressure waves

Magnetic resonance elastography aims to non-invasively and remotely characterize the mechanical properties of living tissues. To quantitatively and regionally map the shear viscoelastic moduli in vivo, the technique must achieve proper mechanical excitation throughout the targeted tissues. Although it is straightforward, ante manibus, in close organs such as the liver or the breast, which practitioners clinically palpate already, it is somewhat fortunately highly challenging to trick the natural protective barriers of remote organs such as the brain. So far, mechanical waves have been induced in the latter by shaking the surrounding cranial bones. Here, the skull was circumvented by guiding pressure waves inside the subject's buccal cavity so mechanical waves could propagate from within through the brainstem up to the brain. Repeatable, reproducible and robust displacement fields were recorded in phantoms and in vivo by magnetic resonance elastography with guided pressure waves such that quantitative mechanical outcomes were extracted in the human brain.     

姜黄素减轻小鼠深部组织压力性损伤

目的评价姜黄素(Cur)对缺血-再灌注所致小鼠深部组织压力性损伤(DTPI)创面愈合的影响。方法将小鼠随机分为对照组(Con)、模型组(Mod)、姜黄素4和8 mg/kg干预组(Cur 4,Cur 8),每组10只。磁铁压迫法构建深部组织损伤模型,每隔48 h于创面注射姜黄素,拍照观察伤口愈合情况。HE染色观察伤口愈合病理改变,realtime PCR检测肿瘤坏死因子(TNF-α)、白介素-6(IL-6)、白介素-10(IL-10)、血管内皮生长因子(VEGF-α)、转化生长因子-β(TGF-β)的mRNA表达;Western blot检测VEGF-α、TGF-β、Stat3、p-Stat3蛋白的表达。结果与对照组相比,模型组伤口逐渐恶化,病理学改变明显。与模型组相比,Cur 8组伤口愈合明显加快(P<0.05);Cur 8组炎性细胞浸润减少,新生血管密度增多。Cur 8组TNF-α、IL-6的mRNA表达量均低于模型组,IL-10、VEGF-α和TGF-β表达量均高于模型组(P<0.05);Cur 8组VEGF-α、TGF-β、p-Stat3蛋白表达水平均高于模型组(P<0.05)。结论姜黄素可减轻小鼠缺血-再灌注所致的DTPI,其机制可能与抑制炎性反应及促进血管再生有关。     

BOLD MRI mapping of transient hyperemia in skeletal muscle after single contractions

Transient increases in signal intensity (DeltaSI, peak 2.6 +/- 0.6 %, mean +/- SE, n = 14) were observed in axial, gradient-echo, echo-planar magnetic resonance images acquired at 1.5 T from human anterior tibialis muscle following single, 1 s duration, isometric ankle dorsiflexion contractions. The magnitude of the MRI-measured DeltaSI was not significantly different using TR of 2000 vs 500 ms, or using spin-echo vs gradient-echo echo-planar pulse sequences. However, DeltaSI measured by gradient-echo sequences was significantly greater at 3 vs 1.5 T (3.8 +/- 0.8 vs 1.6 +/- 0.2 %, n = 5). The time course of the transient DeltaSI (peak at 7.9 +/- 0.4 s after each contraction, decay with half-time of 4.6 +/- 0.6 s) was comparable to the time course of the transient increase in relative heme saturation (13 +/- 2 %, n = 5) measured after single contractions in another group of subjects by near-infrared spectroscopy (peak at 9.3 +/- 0.5 s, decay with half-time 6.2 +/- 0.8 s, n = 8). Simulations of intravascular and extravascular blood-oxygenation level-dependent (BOLD) effects in muscle suggested that intravascular BOLD makes a major contribution to the transient changes, although other factors such as increased vascular volume or increased muscle cell T2 may also contribute. The transients can be exploited for muscle functional imaging analogous to BOLD-based brain functional imaging, and might provide an index of peripheral vascular function.     

Macrophage activation and skeletal muscle healing following traumatic injury

Following injury to different tissues, macrophages can contribute to both regenerative and fibrotic healing. These seemingly contradictory roles of macrophages may be related to the markedly different phenotypes that macrophages can assume upon exposure to different stimuli. We hypothesized that fibrotic healing after traumatic muscle injury would be dominated by a pro‐fibrotic M2a macrophage phenotype, with M1 activation limited to the very early stages of repair. We found that macrophages accumulated in lacerated mouse muscle for at least 21 days, accompanied by limited myofibre regeneration and persistent collagen deposition. However, muscle macrophages did not exhibit either of the canonical M1 or M2a phenotypes, but instead up‐regulated both M1‐ and M2a‐associated genes early after injury, followed by down‐regulation of most markers examined. Particularly, IL‐10 mRNA and protein were markedly elevated in macrophages from 3‐day injured muscle. Additionally, though flow cytometry identified distinct subpopulations of macrophages based on high or low expression of TNFα, these subpopulations did not clearly correspond to M1 or M2a phenotypes. Importantly, cell therapy with exogenous M1 macrophages but not non‐activated macrophages reduced fibrosis and enhanced muscle fibre regeneration in lacerated muscles. These data indicate that manipulation of macrophage function has potential to improve healing following traumatic injury. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Value of whole breast magnetic resonance elastography added to MRI for lesion characterization

The purpose of this work was to assess the diagnostic value of magnetic resonance elastography (MRE) in addition to MRI to differentiate malignant from benign breast tumors, and the feasibility of performing MRE on the whole breast. MRE quantified biomechanical properties within the entire breast (50 slices) using an 11 min acquisition protocol at an isotropic image acquisition resolution of 2 × 2 × 2 mm³. Fifty patients were included. Finally, 43 patients (median age 52) with a suspect breast lesion detected by mammography and/or ultrasound were examined by MRI and MRE at 1.5 T. The viscoelastic parameters, i.e. elasticity (G_d), viscosity (G_l), the magnitude of the complex shear modulus , and the phase angle , were measured via MRE and correlated with MRI Breast Imaging—Reporting and Data System (BI‐RADS) score, histological type, and histological grade. Stroma component and angiogenesis were also correlated with viscoelastic properties. In the 43 lesions, G_d decreased and y increased with the MRI BI‐RADS score (p_Gd = 0.02, p_y = 0.002), whereas (G_l) and y were increased in malignant lesions (p_Gl = 0.045, p_y = 0.0004). The area under the curve increased from 0.84 for MRI BI‐RADS alone to 0.92 with the MRI BI‐RADS and y (AUC increase +0.08; 95% CI (?0.003; 0.16)). Lesion characterization using the y parameter increased the diagnostic accuracy. The phase angle y was found to have a significant role (p = 0.01) in predicting malignancy independently of the MRI BI‐RADS. Interestingly, histological analysis showed no correlation between viscoelastic parameters and percentage and type of stroma, CD34 quantification of vessels, or histological grade. The combination of MRE and MRI improves the diagnostic accuracy for breast lesions in the studied cohort. In particular, the phase angle y was found to have a significant role in predicting malignancy in addition to BI‐RADS.     

Structural response of skeletal muscle mitochondria to experimental deep hypothermia

Bulletin of Experimental Biology and Medicine -     

Magnetic resonance elastography of the lumbar back muscles: A preliminary study

Back pain is associated with increased lumbar paraspinal muscle (LPM) stiffness identified by manual palpation and strain elastography. Recently, magnetic resonance elastography (MRE) has allowed the stiffness of muscle to be characterized noninvasively in vivo, providing quantitative 3D stiffness maps (elastograms). The aim of this study was to characterize the stiffness (shear modulus, SM) of the LPM (multifidus and erector spinae) using MRE. MRE of the lumbar region was performed on seven adults in supine position. MRE was acquired in three muscular states: relaxed with outstretched legs, stretched with passive pelvis flexion, and contracted with outstretched legs and tightened trunk muscles. The mean SM was measured within a region of interest manually defined in the multifidus, erector spinae, and the entire paraspinal compartment. The intermuscular difference and the effects of stretching and contraction were assessed by ANOVA and t‐tests. At rest, the mean SM of the paraspinal compartment was 1.6 ± 0.2 kPa. It increased significantly with stretching to 1.65 ± 0.3 kPa, and with contraction to 2.0 ± 0.7 kPa. Irrespective of muscular state, the erector spinae was significantly stiffer than the multifidus. The multifidus underwent proportionally higher stiffness changes from rest to contraction and stretching. MRE can be used to measure the stiffness of the LPM in different muscular states. We hypothesize that, irrespective of posture, the erector spinae behaves as semi‐rigid beam, and ensures permanent stiffness of the spine. The multifidus behaves as an adaptable muscle that provides segmental flexibility to the spine and tunes the spine stiffness. Clin. Anat. 31:514–520, 2018. © 2018 Wiley Periodicals, Inc.     

CTGF/CCN-2 over-expression can directly induce features of skeletal muscle dystrophy

Muscular dystrophies are diseases characterized by muscle weakness together with cycles of degeneration and regeneration of muscle fibres, resulting in a progressive decrease of muscle mass, diminished muscle force generation and an increase in fibrosis. Fibrotic disorders are the endpoint of many chronic diseases in different tissues, where accumulation of the extracellular matrix (ECM) occurs. Connective tissue growth factor CTGF/CCN2, which is over-expressed in muscular dystrophies, plays a major role in many progressive scarring conditions. To test the hypothesis that CTGF might not only contribute conversion of already damaged muscle into scar tissue, but that it could by itself also directly contribute to skeletal muscle deterioration, we evaluated the effect of CTGF over-expression in tibialis anterior muscle of wild-type mice, using an adenovirus containing the CTGF mouse sequence (Ad-mCTGF). CTGF over-expression induced extensive skeletal muscle damage, which was followed by a massive regeneration of the damaged muscle, as evidenced by increased embryonic myosin and fibres with centrally located nuclei. It also induced strong fibrosis with increased levels of fibronectin, collagen, decorin and α-smooth muscle actin (α-SMA). Moreover, CTGF over-expression caused a decrease of the specific isometric contractile force. Strikingly, when CTGF over-expression stopped, the entire phenotype proved to be reversible, in parallel with normalization of CTGF levels. Thus, CTGF not merely acts downstream of muscle injury but also contributes directly to the deterioration of skeletal muscle phenotype and function. Moreover, normalization of expression levels led to spontaneous reversal of the CTGF-induced phenotype and to full recovery of muscle structure. These observations underscore the importance of CTGF in the pathophysiology of muscular dystrophies and suggest that targeting CTGF might have significant potential in the development of novel therapies for Duchenne muscular dystrophy and related diseases.     

Assessing the variability of 23Na MRI in skeletal muscle tissue: Reproducibility and repeatability of tissue sodium concentration measurements in the lower leg at 3 T

The goal of this study was to evaluate the reproducibility and repeatability of tissue sodium concentration (TSC) measurements using ²³Na MRI in skeletal muscle tissue. ²³Na MRI was performed at 3 T on the right lower leg of eight healthy volunteers (aged 28 ± 4 years). The examinations were repeated at the same site after ~ 22 weeks to assess the variability over a medium‐term period. Additionally, they were scanned at a second site shortly before or shortly after the first visit (within 3 weeks) to evaluate the inter‐site reproducibility. Moreover, we analysed the effect of B₀ correction on the variability. Coefficients of variations (CVs) from mean TSC values as well as Bland–Altman plots were used to assess intra‐site repeatability and inter‐site reproducibility. In phantom measurements, the B₀ correction improved the quantitative accuracy. We observed differences of up to 4.9 mmol/L between the first and second visit and a difference of up to 3.7 mmol/L between the two different sites. The CV for the medium‐term repeatability was 15% and the reproducibility CV was 9%. The Bland–Altman plots indicated high agreement between the visits in all muscle regions. The systematic bias of ?0.68 mmol/L between site X and Y (P = 0.03) was slightly reduced to ?0.64 mmol/L after B₀ correction (P = 0.04). This work shows that TSC measurements in healthy skeletal muscle tissue can be performed with good repeatability and reproducibility, which is of importance for future longitudinal or multicentre studies.     

Magnetic resonance elastography of the lungs: A repeatability and reproducibility study

Lung diseases are one of the leading causes of death worldwide, from which four million people die annually. Lung diseases are associated with changes in the mechanical properties of the lungs. Several studies have shown the feasibility of using magnetic resonance elastography (MRE) to quantify the lungs' shear stiffness. The aim of this study is to investigate the reproducibility and repeatability of lung MRE, and its shear stiffness measurements, obtained using a modified spin echo‐echo planar imaging (SE‐EPI) MRE sequence. In this study, 21 healthy volunteers were scanned twice by repositioning the volunteers to image right lung both at residual volume (RV) and total lung capacity (TLC) to assess the reproducibility of lung shear stiffness measurements. Additionally, 19 out of the 21 volunteers were scanned immediately without moving the volunteers to test the repeatability of the modified SE‐EPI MRE sequence. A paired t‐test was performed to determine the significant difference between stiffness measurements obtained at RV and TLC. Concordance correlation and Bland–Altman's analysis were performed to determine the reproducibility and repeatability of the SE‐EPI MRE‐derived shear stiffness measurements. The SE‐EPI MRE sequence is highly repeatable with a concordance correlation coefficient (CCC) of 0.95 at RV and 0.96 at TLC. Similarly, the stiffness measurements obtained across all volunteers were highly reproducible with a CCC of 0.95 at RV and 0.92 at TLC. The mean shear stiffness of the lung at RV was 0.93 ± 0.22 kPa and at TLC was 1.41 ± 0.41 kPa. TLC showed a significantly higher mean shear stiffness (P = 0.0004) compared with RV. Lung MRE stiffness measurements obtained using the SE‐EPI sequence were reproducible and repeatable, both at RV and TLC. Lung shear stiffness changes across respiratory cycle with significantly higher stiffness at TLC than RV.     

CB2R orchestrates fibrogenesis through regulation of inflammatory response during the repair of skeletal muscle contusion

Skeletal muscle injuries repair typically is an overlapping event between inflammation and tissue repair. Our previous study has demonstrated that activation of cannabinoid receptor type 2 (CB2R) by JWH-133 alleviates fibrosis in the repair of rat skeletal muscle contusion. Meanwhile, accumulated data show that CB2R stimulation exerts anti-inflammatory property in sepsis and cystitis. However, the effects of CB2R on inflammatory cytokines in response to the repair of skeletal muscle contusion are still unknown. In this study, we used selective agonist or antagonist of CB2R to observe the role of CB2R on inflammation and fibrogenesis during the repair of contused skeletal muscles in rats. Our results revealed that treatment with Gp1a, a selective CB2R agonist, significantly decreased the infiltration of neutrophils and macrophages, the expression of pro-inflammatory cytokines MCP-1, TNF-α, IL-1β and IL-6, the expression of pro-fibrotic cytokines IL-4, IL-13, TGF-β and P-Smad3 while increased anti-fibrotic cytokine IL-10 production as compared with Vehicle. The opposite results were observed in the CB2R inhibition group with AM630. Our study demonstrated that CB2R orchestrates fibrogenesis through regulation of inflammatory response during the repair of skeletal muscle contusion.     

Simultaneous multislice rapid magnetic resonance elastography of the liver

To design and validate a rapid Simultaneous Multi‐slice (SMS) Magnetic Resonance Elastography technique (MRE), which combines SMS acquisition, in‐plane undersampling and an existing rapid Magnetic Resonance Elastography (MREr) scheme to allow accelerated data acquisition in healthy volunteers and comparison against MREr. SMS‐MREr sequence was developed by incorporating SMS acquisition scheme into an existing MREr sequence that accelerates MRE acquisition by acquiring data during opposite phases of mechanical vibrations. The MREr sequence accelerated MRE acquisition by acquiring data during opposite phases of mechanical vibrations. Liver MRE was performed on 23 healthy subjects using MREr and SMS‐MREr sequences, and mean stiffness values were obtained for manually drawn regions of interest. Linear correlation and agreement between MREr‐ and SMS‐MREr‐based stiffness values were investigated. SMS‐MREr reduced the scan time by half relative to MREr, and allowed acquisition of four‐slice MRE data in a single 17‐second breath‐hold. Visual comparison suggested agreement between MREr and SMS‐MREr elastograms. A Pearson's correlation of 0.93 was observed between stiffness values derived from MREr and SMS‐MREr. Bland–Altman analysis demonstrated good agreement, with ?0.08 kPa mean bias and narrow limits of agreement (95% CI: 0.23 to ?0.39 kPa) between stiffness values obtained using MREr and SMS‐MREr. SMS can be combined with other fast MRE approaches to achieve further acceleration. This pushes the limit on the acceleration that can be achieved in MRE acquisition, and makes it possible to conduct liver MRE exams in a single breath‐hold.     

大鼠骨骼肌卫星细胞的原代培养和鉴定

目的采用组织块培养技术探索大鼠骨骼肌卫星细胞的原代培养方法。方法以成年SPF级Sprague-Dawley大鼠为研究对象,采用组织块培养法获取大鼠骨骼肌卫星细胞,并与C2C12成肌细胞进行比较,对两种细胞进行形态学研究及采用免疫荧光和免疫组织化学法测定两种细胞α-actin蛋白和Desmin蛋白的表达及分布,从而对骨骼肌卫星细胞进行鉴定。结果通过组织块培养法获取的细胞增殖旺盛,分化良好。免疫细胞荧光和免疫组织化学实验结果显示,α-actin蛋白和Desmin蛋白在两种细胞胞浆中均有分布。结论用组织块培养法获取的骨骼肌卫星细胞具有良好的增殖与分化能力,用此种方法可培养出高纯度的骨骼肌卫星细胞。     

Relationship between functional deficit and severity of experimental fast-strain injury of rat skeletal muscle

We developed a rat model of fast-strain muscle injury to examine the relationship between functional deficit and the degree of muscle damage. A single fast strain was applied to the right plantaris (Plt) muscle of adult male rats. A tetanic contraction was induced by stimulating the sciatic nerve. Three types of strain injuries were produced by manipulating the timing of strain and contraction conditions, including applying the strain at: (1) the shortening phase (SP), (2) the full contraction phase (FCP) during tetanic contraction and (3) when the muscle is not contracting, i.e. non-contraction (NC). The contralateral Plt muscle was used as the control. Morphological and functional analysis were performed and the severity of strain injury was estimated by measuring [³H]thymidine labelling 48 h after the strain was applied. The results show a significant decrease in tension output in all three groups at 5 min after strain application (P<0.01). The functional deficit lasted for 3 weeks in the NC group, while rats of the SP and FCP groups showed recovery 1 week after strain. Increased uptake of [³H]thymidine was similar in SP and FCP groups, but 3.5-fold higher in NC than in SP and FCP groups (P<0.01). Histological analysis revealed an increase in the size of interstitial spaces of the muscle in NC compared to SP and FCP groups (P<0.05). Our results suggest that the contraction of muscle fibres limits the severity of connective tissue damage, and that muscle damage accompanied by disruption of the muscle connective tissue network requires a relatively longer recovery time. Electronic Publication     

Quantification of skeletal muscle mitochondrial function by 31P magnetic resonance spectroscopy techniques: a quantitative review

Magnetic resonance spectroscopy (MRS) can give information about cellular metabolism in vivo which is difficult to obtain in other ways. In skeletal muscle, non‐invasive ³¹P MRS measurements of the post‐exercise recovery kinetics of pH, [PCr], [Pi] and [ADP] contain valuable information about muscle mitochondrial function and cellular pH homeostasis in vivo, but quantitative interpretation depends on understanding the underlying physiology. Here, by giving examples of the analysis of ³¹P MRS recovery data, by some simple computational simulation, and by extensively comparing data from published studies using both ³¹P MRS and invasive direct measurements of muscle O₂ consumption in a common analytical framework, we consider what can be learnt quantitatively about mitochondrial metabolism in skeletal muscle using MRS‐based methodology. We explore some technical and conceptual limitations of current methods, and point out some aspects of the physiology which are still incompletely understood.     

Nrf2 augments skeletal muscle regeneration after ischaemia–reperfusion injury

Skeletal muscles harbour a resident population of stem cells, termed satellite cells (SCs). After trauma, SCs leave their quiescent state to enter the cell cycle and undergo multiple rounds of proliferation, a process regulated by MyoD. To initiate differentiation, fusion and maturation to new skeletal muscle fibres, SCs up‐regulate myogenin. However, the regulation of these myogenic factors is not fully understood. In this study we demonstrate that Nrf2, a major regulator of oxidative stress defence, plays a role in the expression of these myogenic factors. In both promoter studies with myoblasts and a mouse model of muscle injury in Nrf2‐deficient mice, we show that Nrf2 prolongs SC proliferation by up‐regulating MyoD and suppresses SC differentiation by down‐regulating myogenin. Moreover, we show that IL‐6 and HGF, both factors that facilitate SC activation, induce Nrf2 activity in myoblasts. Thus, Nrf2 activity promotes muscle regeneration by modulating SC proliferation and differentiation and thereby provides implications for tissue regeneration.Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.