Detecting age-related changes in skeletal muscle mechanics using ultrasound shear wave elastography.

Aging leads to a decline in muscle mass and force-generating capacity. Ultrasound shear wave elastography (SWE) is a non-invasive method to capture age-related muscular adaptation. This study assessed biceps brachii muscle (BB) mechanics, hypothesizing that shear elastic modulus reflects (i) passive muscle force increase imposed by length change, (ii) activation-dependent mechanical changes, and (iii) differences between older and younger individuals. Fourteen healthy volunteers aged 60-80 participated. Shear elastic modulus, surface electromyography, and elbow torque were measured at five elbow positions in passive and active states. Data collected from young adults aged 20-40 were compared. The BB passive shear elastic modulus increased from flexion to extension, with the older group exhibiting up to 52.58% higher values. Maximum elbow flexion torque decreased in extended positions, with the older group 23.67% weaker. Significant effects of elbow angle, activity level, and age on total and active shear elastic modulus were found during submaximal contractions. The older group had 20.25% lower active shear elastic modulus at 25% maximum voluntary contraction. SWE effectively quantified passive and activation-dependent BB mechanics, detecting age-related alterations at rest and during low-level activities. These findings suggest shear elastic modulus as a promising biomarker for identifying altered muscle mechanics in aging.

Characterization of Muscle Weakness Due to Myasthenia Gravis Using Shear Wave Elastography.

Myasthenia gravis (MG) is often accompanied with muscle weakness; however, little is known about mechanical adaptions of the affected muscles. As the latter can be assessed using ultrasound shear wave elastography (SWE), this study characterizes the biceps brachii muscle of 11 patients with MG and compares them with that of 14 healthy volunteers. Simultaneous SWE, elbow torque and surface electromyography measurements were performed during rest, maximal voluntary contraction (MVC) and submaximal isometric contractions (up to 25%, 50% and 75% MVC) at different elbow angles from flexion to extension. We found that, with increasing elbow angle, maximum elbow torque decreased (p < 0.001), whereas muscle stiffness increased during rest (p = 0.001), MVC (p = 0.004) and submaximal contractions (p < 0.001). Muscle stiffness increased with increasing contraction intensities during submaximal contractions (p < 0.001). In comparison to the healthy cohort, muscle stiffness of MG patients was 2.1 times higher at rest (p < 0.001) but 8.93% lower in active state (75% MVC, p = 0.044). We conclude that (i) increased muscle stiffness shown by SWE during rest might be an indicator of MG, (ii) SWE reflects muscle weakness and (iii) SWE can be used to characterize MG muscle.

Shear wave elastography characterizes passive and active mechanical properties of biceps brachii muscle in vivo.

Mechanical characterization of individual muscles in their in vivo environment is not well studied. Shear wave elastography (SWE) as a non-invasive technique was shown to be promising in quantifying the local mechanical properties of skeletal muscles. This study aimed to investigate the mechanics of the biceps brachii muscle (BB) derived from SWE in relation to elbow joint position and contraction intensity during isometric contraction. 14 healthy, young subjects participated in the study and five different joint positions (60°-180° elbow angle) were investigated. Shear elastic modulus and surface electromyography (sEMG) of the BB and elbow torque were measured simultaneously, both in passive (i.e., resting) and active states during slow, sub-maximal isometric ramp contractions up to 25%, 50%, and 75% of the maximum voluntary contraction. At passive state, the shear elastic modulus of the BB increased with increasing elbow angle (p < 0.001). Maximum elbow flexion torque was produced at 60° and it decreased with increasing elbow angle (p = 0.001). During sub-maximal contractions, both elbow angle (p < 0.001) and contraction intensity (p < 0.001) had significant effects on the shear elastic modulus but only contraction intensity (p < 0.001) affected sEMG amplitude of the BB. Although torque was decreased at extended elbow positions (150°, 180°), higher active shear elastic modulus of BB muscle was found compared to flexed positions (60°, 90°). Linear regression of the BB sEMG amplitude over elbow torque showed good agreement for all joint positions (R2 between 0.69 and 0.89) while the linear agreement between shear elastic modulus of BB and elbow torque differed between flexed (R2 = 0.70 at 60° and R2 = 0.79 at 90°) and extended positions (with the lowest R2 = 0.57 at 150°). We conclude that using SWE, we can detect length-dependent mechanical changes of BB both in passive and active states. More importantly, SWE can be used to characterize active muscle properties in vivo. The present findings have critical importance for developing muscle stiffness as a measure of individual muscle force to validate muscle models and using SWE in clinical diagnostics.

In Vivo Assessment of Shear Wave Propagation in Pennate Muscles Using an Automatic Ultrasound Probe Alignment System.

Goal: Skeletal muscle mechanics can be assessed in vivo using shear wave elastography. However, the impact of pennation angle on shear wave velocity (SWV) remains unclear. This study aims to quantify the effect by automatically aligning the ultrasound probe with muscle fiber orientation. Methods: We propose an automatic ultrasound probe alignment system and compare it to manual and no alignment. SWV of the gastrocnemius medialis muscle of ten volunteers was measured during rest and isometric contractions. Results: The SWV was different between the conditions (p = 0.008). The highest SWV was obtained during the automatic alignment and differences between the conditions were most pronounced during high-level contractions. The automatic system yielded more accurate alignment compared to a manual operator (p = 0.05). Conclusions: The present study indicates that pennation angle affects SWV, hence muscle fiber orientation must be considered to reliably interpret SWV. Using automatic alignment systems allows for more accurate alignment, improving the methodology of ultrasound elastography in skeletal muscles.

Automated Morphometric Analysis of the Hip Joint on MRI from the German National Cohort Study.

PURPOSE: To develop and validate an automated morphometric analysis framework for the quantitative analysis of geometric hip joint parameters in MR images from the German National Cohort (GNC) study. MATERIALS AND METHODS: A secondary analysis on 40 participants (mean age, 51 years; age range, 30-67 years; 25 women) from the prospective GNC MRI study (2015-2016) was performed. Based on a proton density-weighted three-dimensional fast spin-echo sequence, a morphometric analysis approach was developed, including deep learning-based landmark localization, bone segmentation of the femora and pelvis, and a shape model for annotation transfer. The centrum-collum-diaphyseal, center-edge (CE), three alpha angles, head-neck offset (HNO), and HNO ratio along with the acetabular depth, inclination, and anteversion were derived. Quantitative validation was provided by comparison with average manual assessments of radiologists in a cross-validation format. Paired-sample t tests with a Bonferroni-corrected significance level of .005 were employed alongside mean differences and 10th/90th percentiles, median absolute deviations (MADs), and intraclass correlation coefficients (ICCs). RESULTS: High agreement in mean Dice similarity coefficients was achieved (average of 97.52% ± 0.46 [standard deviation]). The subsequent morphometric analysis produced results with low mean MAD values, with the highest values of 3.34° (alpha 03:00 o'clock position) and 0.87 mm (HNO) and ICC values ranging between 0.288 (HNO ratio) and 0.858 (CE) compared with manual assessments. These values were in line with interreader agreements, which at most had MAD values of 4.02° (alpha 12:00 o'clock position) and 1.07 mm (HNO) and ICC values ranging between 0.218 (HNO ratio) and 0.777 (CE). CONCLUSION: Automatic extraction of geometric hip parameters from MRI is feasible using a morphometric analysis approach with deep learning.Keywords: Computer-Aided Diagnosis (CAD), Interventional-MSK, MR-Imaging, Neural Networks, Skeletal-Appendicular, Hip, Anatomy, Computer Applications-3D, Segmentation, Vision, Application Domain, Quantification Supplemental material is available for this article. © RSNA, 2021.

Peripheral Electrical Stimulation Modulates Cortical Beta-Band Activity.

Low-frequency peripheral electrical stimulation using a matrix electrode (PEMS) modulates spinal nociceptive pathways. However, the effects of this intervention on cortical oscillatory activity have not been assessed yet. The aim of this study was to investigate the effects of low-frequency PEMS (4 Hz) on cortical oscillatory activity in different brain states in healthy pain-free participants. In experiment 1, PEMS was compared to sham stimulation. In experiment 2, motor imagery (MI) was used to modulate the sensorimotor brain state. PEMS was applied either during MI-induced oscillatory desynchronization (concurrent PEMS) or after MI (delayed PEMS) in a cross-over design. For both experiments, PEMS was applied on the left forearm and resting-state electroencephalography (EEG) was recording before and after each stimulation condition. Experiment 1 showed a significant decrease of global resting-state beta power after PEMS compared to sham (p = 0.016), with a median change from baseline of -16% for PEMS and -0.54% for sham. A cluster-based permutation test showed a significant difference in resting-state beta power comparing pre- and post-PEMS (p = 0.018) that was most pronounced over bilateral central and left frontal sensors. Experiment 2 did not identify a significant difference in the change from baseline of global EEG power for concurrent PEMS compared to delayed PEMS. Two cluster-based permutation tests suggested that frontal beta power may be increased following both concurrent and delayed PEMS. This study provides novel evidence for supraspinal effects of low-frequency PEMS and an initial indication that the presence of a cognitive task such as MI may influence the effects of PEMS on beta activity. Chronic pain has been associated with changes in beta activity, in particular an increase of beta power in frontal regions. Thus, brain state-dependent PEMS may offer a novel approach to the treatment of chronic pain. However, further studies are warranted to investigate optimal stimulation conditions to achieve a reduction of pain.

A CRISPR/Cas9 mediated point mutation in the alpha 6 subunit of the nicotinic acetylcholine receptor confers resistance to spinosad in Drosophila melanogaster.

Spinosad, a widely used and economically important insecticide, targets the nicotinic acetylcholine receptor (nAChRs) of the insect nervous system. Several studies have associated loss of function mutations in the insect nAChR α6 subunit with resistance to spinosad, and in the process identified this particular subunit as the specific target site. More recently a single non-synonymous point mutation, that does not result in loss of function, was identified in spinosad resistant strains of three insect species that results in an amino acid substitution (G275E) of the nAChR α6 subunit. The causal role of this mutation has been called into question as, to date, functional evidence proving its involvement in resistance has been limited to the study of vertebrate receptors. Here we use the CRISPR/Cas9 gene editing platform to introduce the G275E mutation into the nAChR α6 subunit of Drosophila melanogaster. Reverse transcriptase-PCR and sequencing confirmed the presence of the mutation in Dα6 transcripts of mutant flies and verified that it does not disrupt the normal splicing of the two exons in close vicinity to the mutation site. A marked decrease in sensitivity to spinosad (66-fold) was observed in flies with the mutation compared to flies of the same genetic background minus the mutation, clearly demonstrating the functional role of this amino acid substitution in resistance to spinosad. Although the resistance levels observed are 4.7-fold lower than exhibited by a fly strain with a null mutation of Dα6, they are nevertheless predicated to be sufficient to result in resistance to spinosad at recommended field rates. Reciprocal crossings with susceptible fly strains followed by spinosad bioassays revealed G275E is inherited as an incompletely recessive trait, thus resembling the mode of inheritance described for this mutation in the western flower thrips, Frankliniella occidentalis. This study both resolves a debate on the functional significance of a target-site mutation and provides an example of how recent advances in genome editing can be harnessed to study insecticide resistance.