Noninvasive diffusion MRI to determine the severity of peripheral nerve injury.

OBJECTIVE: Primary repair of peripheral nerves is recommended following transection; however, patient management following repair is challenged by a lack of biomarkers to nerve regeneration. Previous studies have demonstrated that diffusion magnetic resonance imaging (MRI) may provide viable biomarkers of nerve regeneration in injury models; though, these methods have not been systematically evaluated in graded partial transections and repairs. METHODS: Ex vivo diffusion MRI was performed in fixed rat sciatic nerve samples 4 or 12 weeks following partial nerve transection and repair (25% cut = 12, 50% cut = 12 and 75% cut = 11), crush injuries (n = 12), and sham surgeries (n = 9). Behavioral testing and histologic evaluation were performed in the same animals and nerve samples for comparison. RESULTS: Diffusion tractography provided visual characterizations of nerve damage and recovery consistent with the expected degree of injury within each cohort. In addition, quantitative indices from diffusion MRI correlated with both histological and behavioral evaluations, the latter of indicated full recovery for sham and crush nerves and limited recovery in all partially transected/repaired nerves. Nerve recovery between 4 and 12 weeks was statistically significant in partial transections 50% and 75% depth cuts (p = 0.043 and p = 0.022) but not for 25% transections. INTERPRETATION: Our findings suggest that DTI can i) distinguish different degrees of partial nerve transection following surgical repair and ii) map spatially heterogeneous nerve recovery (e.g., due to collateral sprouting) from 4 to 12 weeks in partially transected nerves.

Reconstruction of Upper Third Ear Defects: Utility of a Limited Tanzer Reduction.

BACKGROUND: Large ear defects (>3 cm) present a significant reconstructive challenge and often require extensive operations, which can lead to donor-site morbidity and contour abnormalities. Through our case series, we propose a limited Tanzer reduction, a novel modification of the well-recognized Tanzer technique, as a potential reconstructive option for traumatic and oncologic upper third ear defects. METHODS: We retrospectively reviewed patients who underwent planned ear reconstruction for large ear defects (>3 cm) at a university center by a single surgeon (WPT) over a five-year period. Demographics, complications, and need for revision surgery were recorded. A satisfaction survey was also completed. RESULTS: Five patients met our inclusion criteria as they underwent ear reconstruction with the limited Tanzer reduction. All reconstructions followed oncologic resection for cutaneous malignancy. The mean follow-up was 760.2 days. No complications were encountered, and no revisions were required. All cases had good aesthetic outcomes. The satisfaction survey revealed no self-image distortion or social obstacles following the reconstruction. CONCLUSION: The proposed limited Tanzer reduction technique was shown to be a safe, viable, functionally and aesthetically pleasing option for the reconstruction of large defects of the ear and thus should be part of the armamentarium of the reconstructive surgeon.

Comparison of Telfa Rolling and a Closed Washing System for Autologous Fat Processing Techniques in Postmastectomy Breast Reconstruction.

BACKGROUND: The purpose of this study was to compare the commonly used fat grafting techniques-Telfa rolling and a closed washing system-in breast reconstruction patients. METHODS: Consecutive patients undergoing fat grafting were retrospectively reviewed and grouped by technique. Patients with less than 180 days of follow-up were excluded. Demographics, operative details, and complications were compared using univariate analysis with significance set at p < 0.05. RESULTS: Between January of 2013 and September of 2017, 186 women underwent a total of 319 fat grafting procedures. There was no difference in demographics, number of procedures performed, volume of fat grafted, and number of days after reconstruction that fat grafting was performed between groups (p > 0.05). Telfa rolling patients had longer operative times for second fat grafting procedures (implant exchange often completed prior) [100.0 minutes (range, 60.0 to 150.0 minutes) versus 79.0 minutes (range, 64.0 to 94.0 minutes); p = 0.03]. Telfa rolling breasts had more palpable masses requiring imaging (26.0 percent versus 14.4 percent; p = 0.01) and an increased incidence of fat necrosis (20.6 percent versus 8.0 percent; p < 0.01). The closed washing system was found to be an independent predictor of decreased rates of imaging-confirmed fat necrosis (OR, 0.29; p = 0.048). There was no difference in fat necrosis excision or cancer recurrence between the groups. CONCLUSION: The closed washing system was independently associated with decreased rates of imaging-confirmed fat necrosis compared to Telfa rolling without an increase in other complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Author Correction: Probabilistic Assessment of Nerve Regeneration with Diffusion MRI in Rat Models of Peripheral Nerve Trauma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Diffusion Magnetic Resonance Imaging Predicts Peripheral Nerve Recovery in a Rat Sciatic Nerve Injury Model.

BACKGROUND: Nerve regeneration after an injury should occur in a timely fashion for function to be restored. Current methods cannot monitor regeneration prior to muscle reinnervation. Diffusion tensor imaging has been previously shown to provide quantitative indices after nerve recovery. The goal of this study was to validate the use of this technology following nerve injury via a series of rat sciatic nerve injury/repair studies. METHODS: Sprague-Dawley rats were prospectively divided by procedure (sham, crush, or cut/repair) and time points (1, 2, 4, and 12 weeks after surgery). At the appropriate time point, each animal was euthanized and the sciatic nerve was harvested and fixed. Data were obtained using a 7-Tesla magnetic resonance imaging system. For validation, findings were compared to behavioral testing (foot fault asymmetry and sciatic function index) and cross-sectional axonal counting of toluidine blue-stained sections examined under light microscopy. RESULTS: Sixty-three rats were divided into three treatment groups (sham, n = 21; crush, n = 23; and cut/repair, n = 19). Fractional anisotropy was able to differentiate between recovery following sham, crush, and cut/repair injuries as early as 2 weeks (p < 0.05), with more accurate differentiation thereafter. More importantly, the difference in anisotropy between distal and proximal regions recognized animals with successful and failed recoveries according to behavioral analysis, especially at 12 weeks. In addition, diffusion tension imaging-based tractography provided a visual representation of nerve continuity in all treatment groups. CONCLUSIONS: Diffuse tensor imaging is an objective and noninvasive tool for monitoring nerve regeneration. Its use could facilitate earlier detection of failed repairs to potentially help improve outcomes.

Diffusion Tensor Tractrography Visualizes Partial Nerve Laceration Severity as Early as 1 Week After Surgical Repair in a Rat Model Ex Vivo.

BACKGROUND: Previous studies in our laboratory have demonstrated that a magnetic resonance imaging method called diffusion tensor imaging (DTI) can differentiate between crush and complete transection peripheral nerve injuries in a rat model ex vivo. DTI measures the directionally dependent effect of tissue barriers on the random diffusion of water molecules. In ordered tissues such as nerves, this information can be used to reconstruct the primary direction of diffusion along fiber tracts, which may provide information on fiber tract continuity after nerve injury and surgical repair. METHODS: Sprague-Dawley rats were treated with different degrees of partial transection of the sciatic nerve followed by immediate repair and euthanized after 1 week of recovery. Nerves were then harvested, fixed, and scanned with a 7 Tesla magnetic resonance imaging to obtain DTIand fiber tractography in each sample. Additional behavioral (sciatic function index, foot fault asymmetry) and histological (Toluidine blue staining) assessments were performed for validation. RESULTS: Tractography yielded a visual representation of the degree of injury that correlated with behavioral and histological evaluations. CONCLUSIONS: DTI tractography is a noninvasive tool that can yield a visual representation of a partial nerve transection as early as 1 week after surgical repair.

Sciatic nerve injury model in rabbits: What to expect.

Rabbits are commonly used for sciatic nerve injuries larger than 1.5 cm. This report provides insight into risks and benefits associated with using rabbit models in sciatic nerve injury models and proposes interventions that researchers can use to prevent experimental complications. Fifty-six rabbits from a sciatic nerve injury study that involved a 40 mm sciatic nerve injury were analyzed to examine postoperative complication rates. Autophagy of the phalanges and plantar pressure ulcer development were the most common and serious complications faced. These complications led to 23.2% (n = 13) of rabbits not being used for data in the original experiment due to euthanasia outside of intended postoperative time points. This increased the cost needed to complete the experiment by $25,038.44. It is our recommendation that alternative models be used instead of rabbits for sciatic nerve injuries. If rabbits must be used, a treatment protocol for preventing autophagy and pressure ulcers is outlined below.

Probabilistic Assessment of Nerve Regeneration with Diffusion MRI in Rat Models of Peripheral Nerve Trauma.

Nerve regeneration after injury must occur in a timely fashion to restore function. Unfortunately, current methods (e.g., electrophysiology) provide limited information following trauma, resulting in delayed management and suboptimal outcomes. Herein, we evaluated the ability of diffusion MRI to monitor nerve regeneration after injury/repair. Sprague-Dawley rats were divided into three treatment groups (sham = 21, crush = 23, cut/repair = 19) and ex vivo diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI) was performed 1-12 weeks post-surgery. Behavioral data showed a distinction between crush and cut/repair nerves at 4 weeks. This was consistent with DTI, which found that thresholds based on the ratio of radial and axial diffusivities (RD/AD = 0.40 ± 0.02) and fractional anisotropy (FA = 0.53 ± 0.01) differentiated crush from cut/repair injuries. By the 12th week, cut/repair nerves whose behavioral data indicated a partial recovery were below the RD/AD threshold (and above the FA threshold), while nerves that did not recover were on the opposite side of each threshold. Additional morphometric analysis indicated that DTI-derived normalized scalar indices report on axon density (RD/AD: r = -0.54, p < 1e-3; FA: r = 0.56, p < 1e-3). Interestingly, higher-order DKI analyses did not improve our ability classify recovery. These findings suggest that DTI may provide promising biomarkers for distinguishing successful/unsuccessful nerve repairs and potentially identify cases that require reoperation.

Applied Bioengineering in Tissue Reconstruction, Replacement, and Regeneration.

IMPACT STATEMENT: The use of autologous tissue in the reconstruction of tissue defects has been the gold standard. However, current standards still face many limitations and complications. Improving patient outcomes and quality of life by addressing these barriers remain imperative. This article provides historical perspective, covers the major limitations of current standards of care, and reviews recent advances and future prospects in applied bioengineering in the context of tissue reconstruction, replacement, and regeneration.

Diffusion tensor tractography to visualize axonal outgrowth and regeneration in a 4-cm reverse autograft sciatic nerve rabbit injury model.

BACKGROUND: Diffusion tensor tractography (DTT) has recently been shown to accurately detect nerve injury and regeneration. This study assesses whether 7-tesla (7T) DTT imaging is a viable modality to observe axonal outgrowth in a 4 cm rabbit sciatic nerve injury model fixed by a reverse autograft (RA) surgical technique. METHODS: Transection injury of unilateral sciatic nerve (4 cm long) was performed in 25 rabbits and repaired using a RA surgical technique. Analysis of the nerve autograft was performed at 3, 6, and 11 weeks postoperatively and compared to normal contralateral sciatic nerve, used as control group. High-resolution DTT from ex vivo sciatic nerves were obtained using 3D diffusion-weighted spin-echo acquisitions at 7-T. Total axons and motor and sensory axons were counted at defined lengths along the graft. RESULTS: At 11 weeks, histologically, the total axon count of the RA group was equivalent to the contralateral uninjured nerve control group. Similarly, by qualitative DTT visualization, the 11-week RA group showed increased fiber tracts compared to the 3 and 6 weeks counterparts. Upon immunohistochemical evaluation, 11-week motor axon counts did not significantly differ between RA and control; but significantly decreased sensory axon counts remained. Nerves explanted at 3 weeks and 6 weeks showed decreased motor and sensory axon counts. DISCUSSION: 7-T DTT is an effective imaging modality that may be used qualitatively to visualize axonal outgrowth and regeneration. This has implications for the development of technology that non-invasively monitors peripheral nerve regeneration in a variety of clinical settings.

Burn wounds in the young versus the aged patient display differential immunological responses.

BACKGROUND: Individuals in the geriatric age range are more prone than younger individuals to convert their partial thickness thermal burns into full thickness injuries. We hypothesized that this often observed clinical phenomenon is strongly related to differential local injury responses mediated by the immune system. MATERIALS & METHODS: Skin samples from areas with partial thickness thermal burns were obtained during routine excision and grafting procedures between post burn days 2-6. Tissue samples were grouped by age ranges with young patients defined as <30 years of age or aged patients defined as >65. Formalin fixed samples were used to confirm depth of burn injury and companion sections were homogenized for multiplex analysis using a Luminex platform. Immunohistochemical staining was used to quantify total macrophage numbers as well as the M1 and M2 subpopulations. RESULTS: Our analysis includes samples derived from 11 young subjects (mean age=23) and 3 aged subjects (mean age=79.2). Our initial survey of analytes examined 31 cytokines/chemokines. Twelve were excluded from consideration as they were present in concentrations either above or below the optimal detection range. Two analytes emerged as candidate molecules with significant differences between the young and the aged patient responses to burn injury. EGF levels were on average 21.69pg/ml in young vs 14.87pg/ml in aged (p=0.032). RANTES/CCL5 levels were on average 14.86pg/ml in young vs 4.26pg/ml in aged (p=0.026). Elevated macrophage numbers were present within wounds of younger patients compared to the old (p<0.01), with a higher concentration of the M1 type in the elderly (p>0.05). CONCLUSION: Our study has identified at least 2 well known cytokines, CCL5 (RANTES) and EGF, which are differentially regulated in response to burn injury by young versus aged burn victims. Evidence suggests that a proinflammatory environment can explain the high conversion rate from partial to full thickness burns. Our data suggest the need for future studies at the point of injury (cutaneous targets) that may be modulated by post burn release of cytokines/chemokines.