Monitoring of macrophage recruitment enhanced by Toll-like receptor 4 activation with MR imaging in nerve injury.

INTRODUCTION: Macrophage recruitment is critical for nerve regeneration after an injury. The aim of this study was to investigate whether ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle-based MRI could be used to monitor the enhanced macrophage recruitment by Toll-like receptor 4 (TLR4) activation in nerve injury. METHODS: Rats received intraperitoneal injections of either lipopolysaccharide (LPS) or phosphate buffered saline (PBS) or no injection (controls) after a sciatic nerve crush injury. After intravenous injection of the USPIOs (LPS and PBS groups) or PBS (control group), MRI was performed and correlated with histological findings. RESULTS: LPS group showed more remarkable hypointense signals on T2*-weighted imaging and lower T2 values in the crushed nerves than PBS group. The hypointense signal areas were associated with an enhanced recruitment of iron-loaded macrophages to the injured nerves. DISCUSSION: USPIO-enhanced MRI can be used to monitor the enhanced macrophage recruitment by means of TLR4 signal pathway activation in nerve injury. Muscle Nerve, 2018.

Assessment of the synergic effect of immunomodulation on nerve repair using multiparametric magnetic resonance imaging.

INTRODUCTION: The immune system plays a pivotal role in nerve injury. The aim of this study was to determine the role of multiparametric magnetic resonance imaging (MRI) in evaluation of the synergic effect of immunomodulation on nerve regeneration in neurotmesis. METHODS: Rats with sciatic nerve neurotmesis and surgical repair underwent serial multiparametric MR examinations over an 8-week period after subepineurial microinjection of lipopolysaccharide (LPS) and subsequent subcutaneous injection of FK506 or subepineurial microinjection of LPS or phosphate-buffered saline (PBS) alone. RESULTS: Nerves treated with immunomodulation showed more prominent regeneration than those treated with LPS or PBS alone and more rapid restoration toward normal T2, fractional anisotropy (FA), and radial diffusivity (RD) values than nerves injected with LPS or PBS. DISCUSSION: Nerves treated with immunomodulation exert synergic beneficial effects on nerve regeneration that can be predicted by T2 measurements and FA and RD values. Muscle Nerve 57: E38-E45, 2018.

DTI metrics can be used as biomarkers to determine the therapeutic effect of stem cells in acute peripheral nerve injury.

PURPOSE: To determine the role of diffusion tensor imaging (DTI) metrics as biomarkers for the therapeutic effects of mesenchymal stem cells (MSCs) in acute peripheral nerve injury. MATERIALS AND METHODS: Forty-four adult rats received subepineurial microinjection of MSCs (n = 22) or phosphate buffered saline (PBS, n = 22) 1 week after the sciatic nerve trunk crush injury. Sequential fat-suppressed T2-weighted imaging, T2 measurement, DTI and sciatic nerve functional assessment were performed at a 3.0 Tesla MR unit over an 8-week follow-up, with histological assessments performed at regular intervals. The sciatic nerve function index, T2 value, and DTI metrics, including fractional anisotropy (FA), axial diffusivity, radial diffusivity (RD), and mean diffusivity values of the distal stumps of crushed nerves were measured and compared between the two groups. RESULTS: Nerves treated with MSCs showed better functional recovery and exhibited more pronounced nerve regeneration compared with nerves treated with PBS. T2 values in nerves treated with MSCs or PBS showed a similar change pattern (P = 0.174), while FA and RD values in nerves treated with MSCs showed more rapid return (one week earlier) to baseline level than nerves treated with PBS (P = 0.045; 0.035). Nerves treated with MSCs had higher FA and lower RD values than nerves treated with PBS during the period from 2 to 3 weeks after surgery (P ≤ 0.0001, 0.004; P = 0.004, 0.006). CONCLUSION: FA and RD values derived from DTI might be used as sensitive biomarkers for detecting the therapeutic effect of stem cells in acute peripheral nerve crush injuries. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:855-862.

Diffusion tensor imaging of symptomatic nerve roots in patients with cervical disc herniation.

RATIONALE AND OBJECTIVES: Cervical disc degeneration can result in nerve root compression and severe symptoms that significantly impair the patient's quality of life. The purpose of this study is to investigate multiple diffusion metrics changes in the diffusion tensor imaging (DTI) of cervical nerve roots and their relationship with the clinical severity of patients with cervical disc herniation. MATERIALS AND METHODS: High directional DTI of the cervical nerve roots was performed in 18 symptomatic patients and 10 healthy volunteers with a 3.0-T magnetic resonance system after a routine cervical disc scanning. The fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the DTI data and compared between the affected and unaffected sides in the same patient and between healthy volunteers and symptomatic patients. The correlation between the side-to-side diffusion metric differences and the clinical International Standards for Neurological Classification of Spinal Cord Injury scores was analyzed. RESULTS: C5-C8 nerve roots were clearly delineated with DTI. The FA, MD, AD, and RD of compressed nerve roots were 0.31 ± 0.091, 2.06 ± 0.536, 2.69 ± 0.657, and 1.75 ± 0.510 mm(2)/s, respectively. Compared to the unaffected side or healthy volunteers, the nerve roots of the affected side showed decreased FA (P < .022) and increased MD (P < .035), AD (P < .047), and RD (P < .012). The clinical International Standards for Neurological Classification of Spinal Cord Injury scores of the patients were negatively correlated with MD (r = -0.57, P = .002), AD (r = -0.451, P = .021), and RD (r = -0.564, P = .003) but not with FA (r = 0.004, P = .984). CONCLUSIONS: DTI can potentially be used to assess microstructural abnormalities in the cervical nerve roots in patients with disc herniation.