Objective quantification of muscle and fat in human dystrophic muscle by magnetic resonance image analysis

Information about changes in muscle composition has to date been primarily restricted to histological examination of biopsy samples or qualitative assessment of images obtained using a variety of techniques (e.g., ultrasound, CT, and MRI). We describe the development of a quantitative method for the analysis of muscle composition using MR T₂ relaxation time mapping and image analysis. This approach provides an objective means of studying muscle and, when used in conjunction with force production measurements, may provide an accurate measure of response to muscle therapy. © 1996 John Wiley & Sons, Inc.     

Muscle–fat MRI: 1.5 tesla and 3.0 tesla versus histology

Introduction: We evaluated muscle/fat fraction (MFF) accuracy and reliability measured with an MR imaging technique at 1.5 Tesla (T) and 3.0T scanner strengths, using biopsy as reference. Methods: MRI was performed on muscle samples from pig and rabbit species (n = 8) at 1.5T and 3.0T. A chemical shift based 2‐point Dixon method was used, collecting in‐phase and out‐of‐phase data for fat/water of muscle samples. Values were compared with MFFs calculated from histology. Results: No significant difference was found between 1.5T and 3.0T (P values = 0.41–0.96), or between histology and imaging (P = 0.83) for any muscle tested. Conclusions: Results suggest that a 2‐point Dixon fat/water separation MRI technique may provide reliable quantification of MFFs at varying field strengths across different animal species, and consistency was established with biopsy. The results set a foundation for larger scale investigation of quantifying muscle fat in neuromuscular disorders. Muscle Nerve 50:170–176, 2014     

Changes in Muscle Thickness and Echo Intensity in Chronic Stroke Survivors: A 2-Year Longitudinal Study

Background and PurposeThe objective of this study was to identify 2-year longitudinal changes in the muscle thickness (MT) and echo intensity (EI) of the abdominal, thigh, and lower limb muscles in chronic stroke survivors.MethodsThis study included 15 chronic stroke survivors aged 74.1±9.9 years. The MT, EI, and subcutaneous fat thickness values of the following muscles on the paretic and nonparetic sides were assessed on transverse ultrasound images: rectus abdominis, external oblique, internal oblique, transversus abdominis, rectus femoris (RF), vastus intermedius, vastus lateralis (VL), vastus medialis, tibialis anterior, gastrocnemius, and soleus. The ultrasound measurements were performed both at baseline and 2 years later.ResultsAfter 2 years, the VL on the paretic side showed a significant decrease in MT (p=0.031) and increase in EI (p=0.002), whereas the RF on the nonparetic side showed a significant decrease in EI (p=0.046). Correlation coefficient analyses showed that changes in MT (r=0.668, p=0.012) and EI (r=0.597, p=0.018) of the VL on the paretic side were significantly associated with a change in the body mass index.ConclusionsThe findings of this longitudinal study suggest that the VL on the paretic side is subject to deteriorations in muscle quantity and quality, and conversely that the RF on the nonparetic side shows an improvement in muscle quality after 2 years in chronic stroke survivors.     

人三角肌肌梭分布的研究

目的 :揭示三角肌的肌梭分布 ,为相关临床应用提供较详尽的形态学资料。 方法 :①用经甲醛固定 1年以内的童尸 3具 (3～ 10a)及成人尸体 2具 (2 5a,4 0a) ,完整取下三角肌 ,采用Sihler’s肌内神经染色法染色其肌内神经。②用经甲醛固定 2年以上的童尸 5具 (2～ 11a) ,在三角肌前亚部、中、后亚部取材 ,组织学HE染色后 ,采用体视学方法进行肌梭密度的研究。 结果 :①三角肌中亚部的肌内神经分支较为丰富。②三角肌的肌梭指数为38.0 2个 / g ,肌梭联合体比例为 13.31%。三角肌中亚部的肌梭密度和肌梭联合体比例与三角肌前、后亚部相比较 ,有统计学意义 (P 0 .0 5 )。中亚部肌腹中部远端的肌梭密度与其近端相比较 ,无显著差异。前亚部的肌梭密度与后亚部相比较 ,无明显差异。结论 :人三角肌三个亚部的肌梭密度不同。三角肌中亚部的肌梭密度和肌梭联合体比例大于前、后两个亚部 ,提示其在肩关节运动的监测和姿势调节中起着重要的作用。对该肌进行活检或病理检查取材研究时应当考虑区分亚部或深浅区。     

Heterogeneity of muscle fat infiltration in children with spina bifida

Children with spina bifida have well recognized functional deficits of muscle, but little is known about the associated changes in muscle anatomy and composition. This study used water-fat magnetic resonance imaging (MRI) to measure fat infiltration in the lower extremity muscles of 11 children with myelomeningocele, the most severe form of spina bifida. MRI measurements of muscle fat fraction (FF) were compared against manual muscle test (MMT) scores for muscle strength. The FF measurements were objective and reliable with mean inter-rater differences of <2% and intraclass correlation coefficients > 0.98. There was a significant inverse relationship between muscle FF and MMT scores (P ≤ 0.001). Surprisingly, however, muscles with negligible strength (MMT 0–1) exhibited a bimodal distribution of FF with one group having FF > 70% and another group having FF < 20%. The MRI also revealed striking heterogeneity amongst individual muscles in the same muscle group (e.g., 4% fat in one participant's lateral gastrocnemius vs. 88% in her medial gastrocnemius), as well as significant asymmetry in FF in one participant with asymmetric strength and sensation. These results suggest that quantitative water-fat MRI may serve as a biomarker for muscle degeneration which may reveal subclinical changes useful for predicting functional potential and prognosis.     

The role of intramuscular nerve repair in the recovery of lacerated skeletal muscles

The repair of lacerated muscle often results in suboptimal recovery. An important cause of poor outcome is denervation of the distal segment. The rabbit medial gastrocnemius muscle laceration model was used to assess whether intramuscular nerve repair resulted in better recovery. Lacerated rabbit muscles were divided into three groups: group A had no muscle repair; group B underwent muscle repair; and group C had muscle repair with intramuscular nerve repair. At 7 months, groups A and B showed significantly greater muscle atrophy, replacement of muscle fiber with scar and adipose tissue, and change of muscle fiber type from a fast-twitch to a slow-twitch pattern compared to group C. A clinical case study subsequently demonstrated feasibility of intramuscular nerve repair; reinnervation of the distal belly led to rapid functional recovery. In conclusion, primary intramuscular nerve repair results in better functional outcomes following repair of lacerated muscles.     

Intramuscular fat infiltration evaluated by magnetic resonance imaging predicts the extensibility of the supraspinatus muscle

Introduction: Rotator cuff (RC) tears result in muscle atrophy and fat infiltration within the RC muscles. An estimation of muscle quality and deformation, or extensibility, is useful in selecting the most appropriate surgical procedure. We determined if noninvasive quantitative assessment of intramuscular fat using MRI could be used to predict extensibility of the supraspinatus muscle. Methods: Seventeen cadaveric shoulders were imaged to assess intramuscular fat infiltration. Extensibility and histological evaluations were then performed. Results: Quantitative fat infiltration positively correlated with histological findings and presented a positive correlation with muscle extensibility (r = 0.69; P = 0.002). Extensibility was not significantly different between shoulders graded with a higher fat content versus those with low fat when implementing qualitative methods. Discussion: A noninvasive prediction of whole‐muscle extensibility may directly guide pre‐operative planning to determine if the torn edge could efficiently cover the original footprint while aiding in postoperative evaluation of RC repair. Muscle Nerve 57 : 129–135, 2018     

Relationship between muscle stress and intramuscular pressure during dynamic muscle contractions

Intramuscular pressure (IMP) has been used to estimate muscle stress indirectly. However, the ability of this technique to estimate muscle stress under dynamic conditions is poorly characterized. Therefore, the purpose of this study was to determine the extent to which IMP is a valid surrogate for muscle stress during dynamic contractions. IMP and muscle stress were compared under steady-state isotonic conditions and during complex dynamic length changes. During concentric contractions the shape of the IMP-velocity curve mimicked the basic shape of the force-velocity curve but with much higher variability. For eccentric contractions, a precipitous drop in IMP was observed despite increased muscle stress. The dissociation between muscle stress and IMP during dynamic contractions was partially explained by sensor movement. When the muscle was not moving, IMP explained 89% +/- 5% of the variance in muscle force. However, when transducer movement occurred the linear relationship between IMP and stress was no longer observed. These findings demonstrate the difficulty in interpreting IMP under dynamic conditions when sensor movement occurs. They also illustrate the need to control transducer movement if muscle stress is to be inferred from IMP measurements such as might be desired during clinical gait testing.     

Guiding intramuscular diaphragm injections using real‐time ultrasound and electromyography

Introduction: We describe a unique method that combines ultrasound and electromyography to guide intramuscular diaphragm injections in anesthetized large animals. Methods: Ultrasound was used to visualize the diaphragm on each side of spontaneously breathing, anesthetized beagle dogs and cynomolgus macaques. An electromyography (EMG) needle was introduced and directed by ultrasound to confirm that the needle entered the muscular portion of the diaphragm, and methylene blue was injected. Injection accuracy was confirmed upon necropsy by tracking the spread of methylene blue. Results: All methylene blue injections were confirmed to have been placed appropriately into the diaphragm. Conclusions: This study demonstrates the feasibility and accuracy of using ultrasound and EMG to guide injections and to reduce complications associated with conventional blind techniques. Ultrasound guidance can be used for clinical EMG of the diaphragm. Future applications may include targeted diaphragm injections with gene replacement therapy in neuromuscular diseases. Muscle Nerve 51 : 287–289, 2015     

Effects of botulinum toxin A therapy and multidisciplinary rehabilitation on lower limb spasticity classified by spastic muscle echo intensity in post-stroke patients

Objectives: The purpose of the present study was to investigate retrospectively the relationship between botulinum toxin type A plus multidisciplinary rehabilitation and muscle echo intensity in post-stroke patients with spasticity. The primary aim was to investigate whether the effects of the intervention on the improvement of spasticity depend on muscle echo intensity, and the secondary aim was to investigate whether the motor function of the lower limbs depends on muscle echo intensity.

Methods: A 12-day inpatient protocol was designed for 102 post-stroke patients with spasticity due to lower limb paralysis. Muscle echo intensity of the triceps surae muscle was measured by ultrasonography, and the patients were categorized into four groups based on Heckmatt scale grades (Grades I–IV).

Results: All four groups classified by the Heckmatt scale showed significant pre-to-post-intervention differences in the knee and ankle modified Ashworth scale scores (p < 0.05). Grades I–III patient groups showed a significant improvement in lower limb motor function following intervention. Grade IV patients did not show a significant improvement in lower limb motor function.

Conclusions: We observed significant improvements in the modified Ashworth scale scores after botulinum toxin type A and multidisciplinary rehabilitation therapy on post-stroke patients with spasticity. Although patients with lower muscle echo intensity demonstrated improvements in motor function, the improvement was poor in those with higher muscle echo intensity.     

Differential effects of nerve, muscle, and fat tissue on regenerating nerve fibers in vivo

Axonal regeneration through silicone tubes was studied using distal nerve stumps, denervated, preatrophied muscle tissue, as well as fat tissue as a target. During the first stage of regeneration, i.e., within 2-3 weeks after surgery, a thin, filamentous structure consisting of fibrin and connective tissue was seen bridging the gap in all systems. Thereafter, this cord obviously served as a guideline for the outgrowth of increasing numbers of axons into distal nerve stumps as well as into muscle tissue, but not into fat tissue. These findings confirm that preatrophied muscle tissue has a similar "neurotrophic" effect on regenerating nerve fibers as distal nerve stumps. The ineffectivity of fat tissue in promoting nerve fiber regeneration could be attributed either to the absence of "neurotrophic factors" or even to an inhibitory effect.     

Sustained focal effects of low-dose intramuscular succinylcholine

We studied low-dose intramuscular succinylcholine in 9 subjects as part as an ongoing investigation of its potential to predict responses to botulinum toxin. We measured compound muscle action potentials (CMAPs) from the extensor digitorum brevis (EDB) muscles in each foot before and after intramuscular injections of 2.5 mg of succinylcholine into the EDB. Succinylcholine reduced mean CMAP amplitudes to 42% of baseline; the maximal reduction occurred at 19 ± 6 (mean standard deviation) minutes. Recovery to 73% of the baseline CMAP amplitude (approximately 50% recovery from block) occurred at 105 ± 49 minutes after injection. Repetitive (train-of-four) stimulation at 2 Hz produced mild CMAP decrements (5–25%), but only during the recovery phase. Varying the succinylcholine concentrations (10, 20, or 50 mg/mL) while holding the total drug dose constant did not change the rate of onset or the extent of block. No systemic complications occurred. We conclude that: (1) 2.5 mg intramuscular succinylcholine can safely induce selective muscle weakness with a time course that differs from intravenously administered succinylcholine; and (2) further clinical studies comparing intramuscular succinylcholine and botulinum toxin are warranted. © 1993 John Wiley & Sons, Inc.     

Quantitative muscle ultrasound versus quantitative magnetic resonance imaging in facioscapulohumeral dystrophy

Introduction: Ultrasound and magnetic resonance imaging (MRI) are non‐invasive methods that can be performed repeatedly and without discomfort. In the assessment of neuromuscular disorders it is unknown if they provide complementary information. In this study we tested this for patients with facioscapulohumeral muscular dystrophy (FSHD). Methods: We performed quantitative muscle ultrasound (QMUS) and quantitative MRI (QMRI) of the legs in 5 men with FSHD. Results: The correlation between QMUS‐determined z‐scores and QMRI‐determined muscle fraction and T1 signal intensity (SI) was very high. QMUS had a wider dynamic range than QMRI, whereas QMRI could detect inhomogeneous distribution of pathology over the length of the muscles. Conclusions: Both QMUS and QMRI are well suited for imaging muscular dystrophy. The wider dynamic range of QMUS can be advantageous in the follow‐up of advanced disease stages, whereas QMRI seems preferable in pathologies such as FSHD that affect deep muscle layers and show inhomogeneous abnormality distributions. Muscle Nerve 50: 968–975, 2014     

Cerebral fat embolism: Use of MR spectroscopy for accurate diagnosis

Cerebral fat embolism (CFE) is an uncommon but serious complication following orthopedic procedures. It usually presents with altered mental status, and can be a part of fat embolism syndrome (FES) if associated with cutaneous and respiratory manifestations. Because of the presence of other common factors affecting the mental status, particularly in the postoperative period, the diagnosis of CFE can be challenging. Magnetic resonance imaging (MRI) of brain typically shows multiple lesions distributed predominantly in the subcortical region, which appear as hyperintense lesions on T2 and diffusion weighted images. Although the location offers a clue, the MRI findings are not specific for CFE. Watershed infarcts, hypoxic encephalopathy, disseminated infections, demyelinating disorders, diffuse axonal injury can also show similar changes on MRI of brain. The presence of fat in these hyperintense lesions, identified by MR spectroscopy as raised lipid peaks will help in accurate diagnosis of CFE. Normal brain tissue or conditions producing similar MRI changes will not show any lipid peak on MR spectroscopy. We present a case of CFE initially misdiagnosed as brain stem stroke based on clinical presentation and cranial computed tomography (CT) scan, and later, MR spectroscopy elucidated the accurate diagnosis.     

Pathology of skeletal muscle and intramuscular nerves in infantile neuroaxonal dystrophy

Summary Biopsies of the biceps muscle and sural nerve were taken from a girl aged 2 years with infantile neuroaxonal dystrophy (INAD).In addition to the typical axonal spheroid bodies in a number of the i. m. nerve fibers, the neuromuscular junctions (NMJs) and motor nerve endings also contained axonal swellings. The sural nerve, except for three dystrophic fibers, was almost completely normal.A teased nerve preparation showed four additional abnormal fibers with focal axonal enlargement similar to those in giant axonal neuropathy (GAN).These results suggest that a biceps muscle biopsy may be more useful than a sural nerve biopsy for the diagnosis of INAD, because the muscle contains abnormal peripheral nerves and NMJs in high frequency.     

Muscle conduction velocity,surface electromyography variables,and echo intensity during concentric and eccentric fatigue

Introduction: Concentric (CON) and eccentric (ECC) contractions may involve different mechanisms related to changes in sarcolemma status and the consequent alteration of action potential transmission along muscle fibers. Methods: Muscle conduction velocity (CV), surface electromyography signal (sEMG), muscle quality, and blood lactate concentrations were analyzed during CON and ECC actions. Results: Compared with ECC, the CON protocol resulted in greater muscle force losses, blood lactate concentrations, and changes in sEMG parameters. Similar reductions in CV were detected in both protocols. Higher echo intensity values were observed 2 days after ECC due to greater muscle damage. Conclusions: The effects of the muscle damage produced by ECC exercise on the transmission of action potentials along muscle fibers (measured as the CV) may be comparable with the effects of hydrogen accumulation produced by CON exercise (related to greater lactate concentrations), which causes greater force loss and change in other sEMG variables during CON than during ECC actions. Muscle Nerve 49 :389–397, 2014