Sameer B. Shah

Objective. This meta-analysis aimed to assess the effectiveness of stem cell–seeded conduits compared with autografts and empty conduits in preclinical models of peripheral nerve repair. Methods. A systematic review and meta-analysis was conducted of in vivo preclinical studies published between 2013 and 2024. Endpoints included muscle mass ratio, sciatic function index (SFI), nerve conduction velocity (NCV), compound muscle action potential (CMAP) amplitude, and nerve conduction latency. Studies were further classified by stem cell type, graft material, species, and defect length. Results. Across 30 studies, both stem cell–seeded conduits and autografts outperformed controls across functional and electrophysiological measures. Early improvements (0–3 months) in muscle mass ratio were observed with both stem cell grafts (p = 0.014) and autografts (p = 0.027). SFI improved significantly in both groups at early time points, with stem cell grafts maintaining significance beyond 3 months (p = 0.04). CMAP amplitude showed early gains for both stem cell grafts (p < 0.001) and autografts (p < 0.001), with autografts performing slightly better initially (p = 0.033). NCV improved in both groups early, with stem cell grafts maintaining significance beyond 3 months (p = 0.007). Autografts showed early improvements in latency (p = 0.048), whereas stem cell grafts trended toward benefit without reaching significance. Conclusions. These findings suggest that stem cell–seeded grafts may provide functional benefits similar to autografts in peripheral nerve repair compared with empty conduits. Clinically, this method could be valuable when autografts are unavailable or when harvesting is contraindicated.

When nerves are severed, such as during traumatic injury, an acute injury state is induced, characterized by biological and physical changes in the proximal and distal stumps. Beyond the initial injury phase, over a time frame of weeks to months, nerves that remain unrepaired progressively enter a chronic injury state, characterized by a change in the extracellular matrix structure of the distal stump, the down-regulation of neurotrophic factors and the loss of macrophages’ and Schwann cells’ ability to clear out degraded axons and myelin. There are also potential systemic impacts away from the site of injury, including in end organs such as muscle and bone. The literature suggests that several of these processes may be strongly influenced by innate and adaptive immune system responses, including a major role for complement pathways. This review details evidence in favor of such a possibility, as well as knowledge gaps and areas for future investigation.

Micro-computed tomography (micro-CT) is a commonly used tool for bone evaluation in animal model research. Micro-scale finite element analysis (µFEA) has been proposed to account for different loading scenarios, detailed three-dimensional (3D) bone structure, material properties, and distribution obtained from micro-CT to estimate bone mechanical properties and to predict its potential fracture. The in vivo application of µFEA has been limited to animal models due to the smaller bore size of micro-CT and the long scan time. This narrative review article describes studies that used micro-CT-based µFEA to predict bone mechanical competence, understand bone fracture and remodeling mechanisms, and to evaluate the impacts of the therapeutics, implants, and surgical interventions. Moreover, the concept, limitations, and future potentials of micro-CT-based FEA are discussed.

Magnetization transfer ratio derived from quantitative ultrashort echo time MRI distinguished among rat models of injured and repaired sciatic nerves and correlated with histologic findings.

Objective: Peripheral nerves remain a challenging target for medical imaging, given their size, anatomical complexity, and structural heterogeneity. Quantitative ultrasound (QUS) applies a set of techniques to estimate tissue acoustic parameters independent of the imaging platform. Many useful medical and laboratory applications for QUS have been reported, but challenges remain for deployment in vivo, especially for heterogeneous tissues. Several phenomena introduce variability in attenuation estimates, which may influence the estimation of other QUS parameters. For example, estimating the backscatter coefficient (BSC) requires compensation for the attenuation of overlying tissues between the transducer and the underlying tissue of interest. The purpose of this study is to extend prior studies by investigating the efficacy of several analytical methods of estimating attenuation compensation on QUS outcomes in the human median nerve.Methods: Median nerves were imaged at the volar wrist in vivo and beam‐formed radiofrequency (RF) data were acquired. Six analytical approaches for attenuation compensation were compared: 1–2) attenuation estimated by applying spectral difference method (SDM) and spectral log difference method (SLDM) independently to regions of interest (ROIs) overlying the nerve and to the nerve ROI itself; 3–4) attenuation estimation by applying SDM and SLDM to ROIs overlying the nerve, and transferring these properties to the nerve ROI; and 5–6) methods that apply previously published values of tissue attenuation to the measured thickness of each overlying tissue. Mean between‐subject estimates of BSC‐related outcomes as well as within‐subject variability of these outcomes were compared among the 6 methods.Results: Compensating for attenuation using SLDM and values from the literature reduced variability in BSC‐based outcomes, compared to SDM. Variability in attenuation coefficients contributes substantially to variability in backscatter measurements.Conclusion: This work has implications for the application of QUS to in vivo diagnostic assessments in peripheral nerves and possibly other heterogeneous tissues.

Lower motor neuron (LMN) damage results in denervation of the associated muscle targets and is a significant yet under-appreciated component of spinal cord injury (SCI). Denervated muscle undergoes a progressive degeneration and fibro-fatty infiltration that eventually renders the muscle non-viable unless reinnervated within a limited time window. The distal nerve deprived of axons also undergoes degeneration and fibrosis making it less receptive to axons. In this review, we describe the LMN injury associated with SCI and its clinical consequences. The process of degeneration of the muscle and nerve is broken down into the primary components of the neuromuscular circuit and reviewed, including the nerve and Schwann cells, the neuromuscular junction, and the muscle. Finally, we discuss three promising strategies to reverse denervation atrophy. These include providing surrogate axons from local sources; introducing stem cell-derived spinal motor neurons into the nerve to provide the missing axons; and finally, instituting a training program of high-energy electrical stimulation to directly rehabilitate these muscles. Successful interventions for denervation atrophy would significantly expand reconstructive options for cervical SCI and could be transformative for the predominantly LMN injuries of the conus medullaris and cauda equina.

In this study, we evaluated the utility of using high-frequency ultrasound to non-invasively track the degenerative process in a rat model of peripheral nerve injury. Primary analyses explored spatial and temporal changes in quantitative backscatter coefficient (BSC) spectrum-based outcomes and B-mode textural outcomes, using gray level co-occurrence matrices (GLCMs), during the progressive transition from acute to chronic injury. As secondary analyses, correlations among GLCM and BSC spectrum-based parameters were evaluated, and immunohistochemistry were used to suggest a structural basis for ultrasound outcomes. Both mean BSC spectrum-based and mean GLCM-based measures exhibited significant spatial differences across presurgical and 1-month/2-month time points, distal stumps enclosed proximity to the injury site being particularly affected. The two sets of parameters sensitively detected peripheral nerve degeneration at 1-month and 2-month post-injury, with area under the receiver operating charactersitic curve > 0.8 for most parameters. The results also indicated that the many BSC spectrum-based and GLCM-based parameters significantly correlate with each other, and suggested a common structural basis for a diverse set of quantitative ultrasound parameters. The findings of this study suggest that BSC spectrum-based and GLCM-based analysis are promising non-invasive techniques for diagnosing peripheral nerve degeneration.

Ultrasound (US) is an important imaging tool for skeletal muscle analysis. The advantages of US include point-of-care access, real-time imaging, cost-effectiveness, and absence of ionizing radiation. However, US can be highly dependent on the operator and/or US system, and a portion of the potentially useful information carried by raw sonographic data is discarded in image formation for routine qualitative US. Quantitative ultrasound (QUS) methods provide analysis of the raw or post-processed data, revealing additional information about normal tissue structure and disease status. There are four QUS categories that can be used on muscle and are important to review. First, quantitative data derived from B-mode images can help determine the macrostructural anatomy and microstructural morphology of muscle tissues. Second, US elastography can provide information about muscle elasticity or stiffness through strain elastography or shear wave elastography (SWE). Strain elastography measures the induced tissue strain caused either by internal or external compression by tracking tissue displacement with detectable speckle in B-mode images of the examined tissue. SWE measures the speed of induced shear waves traveling through the tissue to estimate the tissue elasticity. These shear waves may be produced using external mechanical vibrations or internal “push pulse” ultrasound stimuli. Third, raw radiofrequency signal analyses provide estimates of fundamental tissue parameters, such as the speed of sound, attenuation coefficient, and backscatter coefficient, which correspond to information about muscle tissue microstructure and composition. Lastly, envelope statistical analyses apply various probability distributions to estimate the number density of scatterers and quantify coherent to incoherent signals, thus providing information about microstructural properties of muscle tissue. This review will examine these QUS techniques, published results on QUS evaluation of skeletal muscles, and the strengths and limitations of QUS in skeletal muscle analysis.