Contrast‐Enhanced Ultrasound and Elastography Imaging of the Neonatal Brain: A Review

Neonates presenting with neurologic symptoms require rapid, noninvasive imaging with high spatial resolution and tissue contrast. Magnetic resonance imaging (MRI) is currently the most sensitive and specific imaging modality for evaluation of neurological pathology. This modality does come with several challenges in the neonatal population, namely, the need to transport a possibly critically sick neonate to the MRI suite and the necessity of the neonate to remain still for a significant length of time, occasionally requiring sedation. Cranial ultrasound has provided radiologists and clinicians with an invaluable imaging modality that allows of rapid, bedside point of care evaluation without ionizing radiation. The major drawback of cranial ultrasound is its lower sensitivity and specificity for subtle/early lesions. Contrast‐enhanced ultrasound (CEUS) and elastography have the potential to improve sensitivity and specificity for a variety of neuropathology but also expand the indications for cranial ultrasound. Goal of this paper is to present and discuss CEUS and elastography for neonatal brain imaging.     

Advanced Pediatric Neurosonography Techniques: Contrast‐Enhanced Ultrasonography,Elastography, and Beyond

Recent technical advances in neurosonography continue broadening the diagnostic utility, sensitivity, and specificity of ultrasound for detecting intracranial abnormalities bed side. The clinical and functional applications of neurosonography have significantly expanded since the 1980s when transcranial Doppler sonography first allowed anatomic and hemodynamic delineation of the intracranial vessels through the thin temporal skull. In the past few years, contrast‐enhanced ultrasonography, elastography, 3D/4D reconstruction tools, and high‐resolution microvessel imaging techniques have further enhanced the diagnostic significance of neurosonography. Given these advances, a thorough familiarity with these new techniques and devices is crucial for a successful clinical application allowing improved patient care. It is essential that future neurosonography studies compare these advanced techniques against the current “gold standard” computed tomography and magnetic resonance imaging to assure the accuracy of their diagnostic potential. This review will provide a comprehensive update on currently available advanced neurosonography techniques.     

Shear wave elastography of the brachial plexus roots at the interscalene groove

Objectives: Sonoelastography is an emerging technology that has been used to evaluate the musculoskeletal system including the brachial plexus of peripheral nerves, which has been only recently considered for study by shear wave elastography. The purpose of this study is to establish the normal sonoelastographic features of the C5–C7 nerve roots of the brachial plexus.

Methods: Forty healthy individuals (21 males and 19 females) were enrolled in the study. Shear wave elastography was used to evaluate the C5–C7 nerve roots of the brachial plexus at the interscalene interval. Normal sonoelastographic values were obtained.

Results: The mean shear elastic modulus of the C5 nerve root was 16.9 kPa (range 5.9–28.8 ± 4.9 standard deviation, SD), 15.7 kPa (range 5.4–26.3 ± 4.3 SD) for the C6 nerve root, and 16 kPa (range 8–29 ± 4.6 SD) for the C7 nerve root. There was a significant statistical difference between both sexes in the elastic modulus at the C6 and C7, but not at the C5 nerve roots. Significant inverse correlation with height was noted at the C6 nerve root. There was no statistical significant difference in tissue stiffness between right- and left-handed subjects, age, and body mass index.

Conclusion: The elastic modulus of the C5–C7 nerve roots has been determined in asymptomatic individuals and can serve as a reference when studying pathological conditions of these structures.

Abbreviations: BMI: body mass index; SWE: shear wave elastography.     

实时组织弹性成像在肌肉萎缩诊断中的应用

目的分析实时组织弹性成像在肌肉萎缩诊断中的应用价值。方法日立公司的HV prieus机器弹性成像程序在受检者右侧肱二头肌处于松弛与紧张状态下分别沿肌束进行实时组织弹性成像检查,根据图像肌肉组织的软硬程度的不同,分析肌肉萎缩和正常肌肉弹性的差别。结果各组松弛状态下肌束实时组织弹性成像图像表现差别不大,紧张状态下肌束实时组织弹性成像图像表现存在显著差异,其诊断肌萎缩肌纤维化的敏感度、特异度、准确度分别为:90.4%、80.0%、80.4%。结论超声弹性成像技术可以作为较客观评价肌肉萎缩的辅助检查方法,使提供常规超声之外的诊断信息成为可能。     

Ultrasound elastography for the evaluation of peripheral nerves: A systematic review

Peripheral nerve disorders are commonly encountered in clinical practice. Electrodiagnostic studies remain the cornerstone of the evaluation of nerve disorders. More recently, ultrasound has played an increasing complementary role in the neuromuscular clinic. Ultrasound elastography is a technique that measures the elastic properties of tissues. Given the histological changes that occur in diseased peripheral nerves, nerve ultrasound elastography has been explored as a noninvasive way to evaluate changes in nerve tissue composition. Studies to date suggest that nerve stiffness tends to increase in the setting of peripheral neuropathy, regardless of etiology, consistent with loss of more compliant myelin, and replacement with connective tissue. The aim of this systematic review is to summarize the current literature on the use of ultrasound elastography in the evaluation of peripheral neuropathy. Limitations of ultrasound elastography and gaps in current literature are discussed, and prospects for future clinical and research applications are raised.     

Viscoelasticity of subcortical gray matter structures

Viscoelastic mechanical properties of the brain assessed with magnetic resonance elastography (MRE) are sensitive measures of microstructural tissue health in neurodegenerative conditions. Recent efforts have targeted measurements localized to specific neuroanatomical regions differentially affected in disease. In this work, we present a method for measuring the viscoelasticity in subcortical gray matter (SGM) structures, including the amygdala, hippocampus, caudate, putamen, pallidum, and thalamus. The method is based on incorporating high spatial resolution MRE imaging (1.6 mm isotropic voxels) with a mechanical inversion scheme designed to improve local measures in pre‐defined regions (soft prior regularization [SPR]). We find that in 21 healthy, young volunteers SGM structures differ from each other in viscoelasticity, quantified as the shear stiffness and damping ratio, but also differ from the global viscoelasticity of the cerebrum. Through repeated examinations on a single volunteer, we estimate the uncertainty to be between 3 and 7% for each SGM measure. Furthermore, we demonstrate that the use of specific methodological considerations—higher spatial resolution and SPR—both decrease uncertainty and increase sensitivity of the SGM measures. The proposed method allows for reliable MRE measures of SGM viscoelasticity for future studies of neurodegenerative conditions. Hum Brain Mapp 37:4221–4233, 2016. © 2016 Wiley Periodicals, Inc.     

Muscle shear modulus measured with ultrasound shear‐wave elastography across a wide range of contraction intensity

Introduction: In this study we examine the repeatability of measuring muscle shear modulus using ultrasound shear‐wave elastography between trials and between days, and the association between shear modulus and contraction intensity over a wide range of intensities. Methods: Shear modulus of the biceps brachii was determined using ultrasound shear‐wave elastography during static elbow flexion (up to 60% of maximal contraction) in healthy young adults. Results: The correspondence of shear modulus was confirmed in phantoms between the manufacturer‐calibrated values and the shear‐wave elastography values. The intraclass correlation coefficient of muscle shear modulus was high: 0.978 between trials and 0.948 between days. Shear modulus increased linearly with elbow flexion torque across contraction intensity, and its slope was associated negatively with muscle strength. Conclusions: Muscle shear modulus measured with ultrasound shear‐wave elastography may be useful for inferring muscle stiffness across a wide range of contraction intensity. In addition, it has high repeatability between trials and between days. Muscle Nerve 50 : 103–113, 2014     

Real‐time visualization of muscle stiffness distribution with ultrasound shear wave imaging during muscle contraction

A stand‐alone ultrasound shear wave imaging technology has been developed to quantify and visualize Young's modulus distribution by remotely applying ultrasound radiation force and tracking the resulting microvibrations in soft tissues with ultrafast ultrasound imaging. We report the first preliminary data that detected the distribution of local muscle stiffness within and between resting and contracting muscles at different muscle lengths with this technology. This technique may assist clinicians in characterizing muscle injuries or neuromuscular disorders. Muscle Nerve, 2010     

Assessment of muscle stiffness using a continuously scanning laser‐Doppler vibrometer

Introduction: A stand‐alone and low‐cost elastography technique has been developed using a single continuously scanning laser Doppler vibrometer. Methods: This elastography technique is used to measure the propagation velocity of surface vibrations over superficial skeletal muscles to assess muscle stiffness. Results: Systematic variations in propagation velocity depending on the contraction level and joint position of the biceps brachii were demonstrated in 10 subjects. Conclusions: This technique may assist clinicians in characterizing muscle stiffness (or tone) changes due to neuromuscular disorders. Muscle Nerve 50 : 133–135, 2014     

Non‐invasive assessment of muscle stiffness in patients with duchenne muscular dystrophy

ABSTRACT: Introduction: Assessment of muscle mechanical properties may provide clinically valuable information for follow‐up of patients with Duchenne muscular dystrophy (DMD) through the course of their disease. In this study we aimed to assess the effect of DMD on stiffness of relaxed muscles using elastography (supersonic shear imaging). Methods: Fourteen DMD patients and 13 control subjects were studied. Six muscles were measured at 2 muscle lengths (shortened and stretched): gastrocnemius medialis (GM); tibialis anterior (TA); vastus lateralis (VL); biceps brachii (BB); triceps brachii (TB); and abductor digiti minimi (ADM). Results: Stiffness was significantly higher in DMD patients compared with controls for all the muscles (main effect for population, P < 0.033 in all cases), except for ADM. The effect size was small (d = 0.33 for ADM at both muscle lengths) to large (d = 0.86 for BB/stretched). Conclusions: Supersonic shear imaging is a sensitive non‐invasive technique to assess the increase in muscle stiffness associated with DMD. Muscle Nerve 51 : 284–286, 2015     

Effect of changes in optic nerve elasticity on central retinal artery blood flow in patients with idiopathic intracranial hypertension

PurposeTo assess changes in central retinal artery (CRA) blood flow by orbital color-coded Doppler ultrasonography in patients with idiopathic intracranial hypertension (IIH) and their relation with optic nerve (ON) elasticity assessed by shear wave elastography (SWE).MethodsThis study was carried out on 68 eyes of patients diagnosed with IIH and 32 eyes of healthy controls. The severity of papilledema in IIH patients was sub-classified into mild and moderate/severe groups. Color-coded Doppler was used to measure peak systolic velocity (PSV), end diastolic velocity (EDV), mean velocity (V_mean) and pulsatility index (PI) of the CRA.ResultsPSV, V_mean, and SWE were significantly higher in patients with IIH than in controls (p = 0.001). The optimal cut-off values of PSV and V_mean for differentiating IIH patients from controls were 11.25 and 6.75 cm/s with AUC 0.81 and 0.785 respectively. AUC was 0.92 and accuracy 91% for combined PSV, V_mean and SWE differentiation between IIH patients and controls. PSV, V_mean and SWE were significantly different between mild versus moderate/severe papilledema (p = 0.001). PSV and V_mean were correlated with papilledema (r = 0.790 and 0.722 respectively) and SWE (r = 0.818 and 0.761 respectively).ConclusionIIH is associated with decreased ON elasticity and reduced CRA blood flow. Individual and combined color-coded Doppler of the CRA and SWE help in diagnosis of IIH. CRA hemodynamic changes are correlated with papilledema severity and with the extent of biomechanical changes in the ON represented by SWE.     

Emerging technologies in neuromuscular ultrasound

Neuromuscular ultrasound is an accepted and valuable element in the evaluation of peripheral nerve and muscle disease. However, ultrasound has several limitations to consider, including operator dependency and lack of a viable contrast agent. Fortunately, new technological advances show promise in resolving these issues. Ultra-high resolution ultrasound enables imaging of the nerve at the fascicular level. Shear wave elastography imaging can provide measures of tissue stiffness that can act as a surrogate measure of nerve and muscle health. Photoacoustic imaging may overcome neuromuscular ultrasound's current lack of contrast agents to detect inflammation and other functional changes within nerve and muscle, while artificial intelligence stands to address operator dependency and improve diagnostic imaging. The basic principles of each of these technologies are discussed along with current research and potential future applications in neuromuscular imaging.     

Evaluation of muscles affected by myositis using magnetic resonance elastography

Introduction: Idiopathic inflammatory myopathies (IIMs, or myositis) represent a group of autoimmune diseases that result in decreased muscle strength and/or endurance. Non‐invasive tools to assess muscle may improve our understanding of the clinical and functional consequences of myopathies and their response to treatment. In this study we examine magnetic resonance elastography (MRE), a non‐invasive technique that assesses the shear modulus (stiffness) of muscle, in IIM subjects. Methods: Nine subjects with active myositis completed the MRE protocol. Participants lay in a positioning device, and scans of the vastus medialis (VM) were taken in the relaxed state and at two contraction levels. Manual inversion was used to estimate the stiffness. Results: A significant reduction in muscle stiffness was seen in myositis subjects compared with healthy controls during the “relaxed” condition. Discussion: The use of non‐invasive technologies such as MRE may provide greater understanding of the pathophysiology of IIM and improve assessment of treatment efficacy. Muscle Nerve, 2011     

Posture‐induced changes in peripheral nerve stiffness measured by ultrasound shear‐wave elastography

Introduction: Peripheral nerves slide and stretch during limb movements. Changes in nerve stiffness associated with such movements have not been examined in detail but may be important in understanding movement‐evoked pain in patients with a variety of different musculoskeletal conditions. Methods: Shear‐wave elastography was used to examine stiffness in the median and tibial nerves of healthy individuals during postures used clinically to stretch these nerves. Results: Shear‐wave velocity increased when limbs were moved into postures that are thought to increase nerve stiffness (mean increase: median nerve = 208% in arm, 236% in forearm; tibial nerve = 136%). There was a trend toward a negative correlation between age and shear‐wave velocity (r = 0.58 for tibial nerve). Conclusions: Shear‐wave elastography provides a tool for examining nerve biomechanics in healthy individuals and patients. However, limb position, age, and effects of nerve tension on neural architecture should be taken into consideration. Muscle Nerve 55 : 213–222, 2017     

Two‐dimensional and shear wave elastography ultrasound: A reliable method to analyse spastic muscles?

Introduction: Few data exist on the feasibility and reliability of measuring muscular atrophy in 2 dimensions (2D) by ultrasonography (US) and elasticity with shear wave elastography (SWE) in spastic muscles. Methods: Fourteen patients with chronic stroke took part in 2 intersession reliability experiments performed with 1‐week intervals between sessions. Pennation angle (PA), muscle thickness (MT), and shear elastic modulus (µ) were measured in spastic gastrocnemius medialis (GM) muscles at rest and at maximal passive stretching in paretic and nonparetic legs. Results: On the paretic side, the coefficient of variation (CV) in GM was 6.30% for MT and 6.40% for PA at rest and was 7.53% and 8.26% for MT and PA, respectively, at maximal passive stretching. The reliability of the µ measurement was good only for GM at rest on the paretic side (CV = 9.86%). Discussion: 2D US associated with SWE shows promise for assessing structural changes in muscles. With some methodological adaptations, this approach could help guide spasticity treatment. Muscle Nerve 57 : 222–228, 2018     

Microscopic magnetic resonance elastography of traumatic brain injury model

Traumatic brain injury (TBI) is a major cause of death and disability for which there is no cure. One of the issues inhibiting clinical trial success is the lack of targeting specific patient populations due to inconsistencies between clinical diagnostic tools and underlying pathophysiology. The development of reliable, noninvasive markers of TBI severity and injury mechanisms may better identify these populations, thereby improving clinical trial design. Magnetic resonance elastography (MRE), by assessing tissue mechanical properties, can potentially provide such marker. MRE synchronizes mechanical excitations with a phase contrast imaging pulse sequence to noninvasively register shear wave propagation, from which local values of tissue viscoelastic properties can be deduced. The working hypothesis of this study is that TBI involves a compression of brain tissue large enough to bring the material out of its elastic range, sufficiently altering mechanical properties to generate contrast on MRE measurements. To test this hypothesis, we combined microscopic MRE with brain tissue collected from adult male rats subjected to a controlled cortical impact injury. Measurements were made in different regions of interest (somatosensory cortex, hippocampus, and thalamus), and at different time points following the injury (immediate, 24 h, 7 days, 28 days). Values of stiffness in the somatosensory cortex were found to be 23-32% lower in the injured hemisphere than in the healthy one, when no significant difference was observed in the case of sham brains. A preliminary in vivo experiment is also presented, as well as alternatives to improve the faithfulness of stiffness recovery.