Diffusion Tensor Imaging: Techniques and Applications for Peripheral Nerve Injury.

ABSTRACT: Peripheral nerve injuries (PNIs) represent a complex clinical challenge, necessitating precise diagnostic approaches for optimal management. Traditional diagnostic methods often fall short in accurately assessing nerve recovery as these methods rely on the completion of nerve reinnervation, which can prolong a patient's treatment. Diffusion tensor imaging (DTI), a noninvasive magnetic resonance imaging (MRI) technique, has emerged as a promising tool in this context. DTI offers unique advantages including the ability to quantify nerve recovery and provide in vivo visualizations of neuronal architecture. Therefore, this review aims to examine and outline DTI techniques and its utility in detecting distal nerve regeneration in both preclinical and clinical settings for peripheral nerve injury.

In-Vivo MRI in Rodents: A Protocol for Optimal Animal Positioning.

ABSTRACT: Magnetic resonance imaging (MRI) is a potentially powerful novel peripheral nerve diagnosis technique. To determine its validity, in-vivo preclinical studies are necessary. However, when using a rodent model, positioning rats and achieving high-resolution images can be challenging. We present a short report that outlines an optimal protocol for positioning rats for in-vivo MRI acquisition. Female Sprague-Dawley rats with sciatic nerve injury were induced into anesthesia using 4% isoflurane in oxygen and maintained at 1.5%. Rats were placed into a plexiglass cradle in a right lateral recumbent position, and a surface coil was placed over the left leg. Respiration rate and body temperature were monitored throughout the scan. Our protocol was successful as rats were able to undergo MRI scanning safely and efficiently. There were no adverse reactions, and clear images of the left sciatic nerve were obtained. Animal positioning took 30 minutes, and 5 different acquisitions were obtained in 2 hours. The total time from anesthesia induction to recovery was under 3 hours. Given the increasing interest in MRI diagnostic techniques, we hope this report aids other researchers studying peripheral nerve injury imaging in rat models.

Consecutive assessment of recovery after peripheral nerve injury of the sciatic nerve within the same rat using PET/MRI.

BACKGROUND: Positron emission tomography (PET) has been reported as effective in diagnosing peripheral nerve injury (PNI). However, there is a lack of studies evaluating different degrees of PNI using PET within the same individual to reduce errors due to interindividual differences. PURPOSE: To evaluate the recovery process in the same rat after sciatic nerve injury using PET/magnetic resonance imaging (MRI). MATERIAL AND METHODS: Crushing nerve injuries were induced in the left sciatic nerves of six male rats, preserving the right ones. The degree of nerve damage was measured at one, two, three, four, and five weeks postoperatively using three assessment methods: paw withdrawal threshold test (RevWT); PET (SUVR); and MRI (MRSIR). All the representing values of each method are presented as ratio values of the right and left sides in each rat. RESULTS: Significant gradual recovery of all rats was observed over time in all the methods. No significant differences in RevWT and MRSIR were observed between before and more than four weeks after injury, whereas a significant difference in SUVR was still observed between before and five weeks after injury (P = 0.0007). The parameters of all methods decreased significantly over time (P = 0.000, all), and the explanatory power was significant in RevWT, SUVR, and MRSIR. CONCLUSION: PET and MRI could be valuable non-invasive techniques for diagnosing neuropathic pain resulting from PNI. PET/MRI would be expected to be a more accurate and informative diagnostic tool for PNI than MRI alone.

High Resolution MRI Confirms Torsional Injury as Mechanism for Combined Ankle and Common Fibular (Peroneal) Nerve Injuries.

Common fibular nerve (CFN) injury due to ankle fracture is an underreported complication. The authors have proposed that torsional injury to the ankle can be translated along the interosseous membrane (IOM), producing tension on the CFN at the fibular neck. A 23-year-old woman presented to our clinic for left foot drop. Three months prior, the patient sustained a fall with left ankle inversion injury while running. She was diagnosed with a minor ankle fracture and placed in an orthopaedic boot. Unfortunately, her swelling worsened and one week later the patient was diagnosed with foot drop, which was further corroborated with EMG studies showing severe CFN injury localizing to the fibular neck. Because of the lack of recovery, she underwent decompression of the CFN. She experienced immediate symptomatic relief. High resolution imaging in this case supports our previous mechanism for indirect trauma to the ankle resulting in CFN injury. (Journal of Surgical Orthopaedic Advances 33(1):053-055, 2024).

Neuromuscular ultrasound findings in gunshot wounds.

INTRODUCTION/AIMS: A spectrum of peripheral nerve injuries is associated with gunshot wounds (GSWs). Due to Wallerian degeneration, distal nerve lesions may go undetected on electrodiagnostic (EDX) testing. In patients with GSW undergoing high-resolution ultrasound (HRUS) for evaluation of neurological deficits, we have observed distal nerve morphological changes, but these have not been systematically studied. The aim of this study was to characterize changes on HRUS in nerves at and distal to gunshot injuries and to identify the frequency with which these changes occur. METHODS: A retrospective cohort study was performed on patients referred for HRUS with peripheral nerve injuries from GSW. The primary injured nerve(s) were assessed along with distal segments of the same nerve and those of adjacent nerves. Findings were also compared to EDX studies. RESULTS: Twenty-two of the 28 nerves injured proximally by GSW were evaluated distally and of these, 68% showed abnormal ultrasound findings, including enlarged cross sectional area (59%), fascicular enlargement (50%), and decreased nerve echogenicity (59%). In 17 patients, adjacent nerves were evaluated and 8 of the patients (47%) showed abnormalities in at least one distal adjacent nerve, including enlarged cross sectional area (41%), fascicular enlargement (41%), and decreased nerve echogenicity (35%). DISCUSSION: This study demonstrated morphological changes at the site of the GSW but also in distal nerve segments including nerve enlargement, fascicular enlargement, and changes in nerve echogenicity. The complementary use of HRUS with EDX was highlighted in evaluation of GSW victims to assess the extent of peripheral nerve injury.

Evaluation of peripheral nerve injury according to the severity of damage using 18F-FDG PET/MRI in a rat Model of sciatic nerve injury.

OBJECTIVES: We ascertained that the PET scan may be a valuable imaging modality for the noninvasive, objective diagnosis of neuropathic pain caused by peripheral nerve injury through the previous study. This study aimed to assess peripheral nerve damage according to severity using18F-FDG PET/MRI of the rat sciatic nerve. METHODS: Eighteen rats were divided into three groups: 30-second (G1), 2-minute (G2), and 5-minute (G3) crushing injuries. The severity of nerve damage was measured in the third week after the crushing injury using three methods: the paw withdrawal threshold test (RevWT), standardized uptake values on PET (SUVR), and intensity analysis on immunohistochemistry (IntR). RESULTS: There were significant differences between G1 and G3 in both SUVR and IntR (p = 0.012 and 0.029, respectively), and no significant differences in RevWT among the three groups (p = 0.438). There was a significant difference in SUVR (p = 0.012), but no significant difference in IntR between G1 and G2 (p = 0.202). There was no significant difference between G2 and G3 in SUVR and IntR (p = 0.810 and 0.544, respectively). DISCUSSION: Although PET did not show results consistent with those of immunohistochemistry in all respects, this study demonstrated that PET uptake tended to increase with severe nerve damage. If this research is supplemented by further experiments, PET/MRI can be used as an effective diagnostic modality.

Iatrogenic "overshoot" nerve injuries: imaging features.

OBJECTIVE: Describe features of iatrogenic "overshoot" nerve injuries on ultrasound and MRI, which occur when an instrument passes through the bone and injures the nerve after it penetrates the opposite cortex. MATERIALS AND METHODS: After a keyword search of the radiology database at a tertiary care orthopedic hospital from January 2016 to December 2022, those fulfilling the inclusion criteria of (1) instrumentation through the bone during surgery, (2) acute neuropathy immediately after surgery, (3) nerve injury confirmed on electrodiagnostics, and (4) imaging consistent with overshoot nerve injury were included. Imaging studies were retrospectively evaluated to determine primary and secondary signs of an overshoot nerve injury. RESULTS: Six patients (3 females, mean age 26.7 (range 10-49) years) had nerve injury fitting the mechanism of injury: 3 injuries to the radial nerve during fixation of distal humerus fractures, 1 tibial nerve and 1 superficial peroneal nerve injury during fixation of tibial fractures, and 1 posterior interosseous nerve injury during biceps tendon repair. Ultrasounds were performed in all while 4 also had MRI. Secondary signs included (1) cortical defect adjacent to injured nerve (n=2); (2) scar extending from bone to injured nerve (n=2); (3) screw tip pointing to injured nerve (n=1, 4) tract in bone on MRI from previous instrumentation pointing to injured nerve (n=2). CONCLUSION: In addition to primary signs such as laceration or neuroma, secondary signs of "overshoot" nerve injury include cortical defect, scar extending to nerve, screw tip pointing to nerve, and linear tract in the bone on MRI.

The role of preoperative ultrasound in the management of peripheral nerve injuries.

BACKGROUND: Peripheral nerve injury refers to any damage or trauma to the nerves located outside the central nervous system. Ultrasonography is a reliable, cheap, and minimally invasive method in clinical practice to give physicians useful information about nerve injury. OBJECTIVES: to assess the power of ultrasound in determining the presence, localization, and extent of neural damage in patients with clinical evidence of peripheral nerve lesions before surgery. METHODS: This cross-sectional study was conducted on 78 patients (56 females and 22 males, aged from 9 to 52 years) who had different pathologies including entrapment, tumoral, post-traumatic, and post-surgical nerve injuries at the Neurosurgery and Physical Medicine, Rheumatology, and Rehabilitation Departments, Tanta University Hospitals. All studied patients had preoperative evaluation; neurological examination, electrodiagnostic studies, and sonographic examinations with linear array transducers (frequencies ranging from 7.5 to 16 MHz). RESULTS: The most common pathological condition was entrapment neuropathy (39 patients) (50%). Ultrasound complemented the electrodiagnostic studies by determining the site of entrapment manifested by increased mean maximum cross-sectional area of the nerve proximal to the site of entrapment and nerve hypoechogenicity. In post-traumatic and iatrogenic neuropathies (35 patients) (44.9%), the ultrasound finding revealed neuroma in continuity in nine cases (11.5%), complete neurotmesis with stump neuroma in eighteen patients (23.1%), and eight cases (10.3%) showed perineural adhesion. In all cases, the nerve was hypoechoic at the site of injury. The presence of hyperechoic fibrous tissue could indicate perineural adhesion and the necessity for neurolysis. This study also included three (3.8%) cases had schwannoma, and one case (1.3%) had neurofibroma. Ultrasound was used to confirm the diagnosis by determining the tumor's size and vascular supply. CONCLUSIONS: Ultrasonography is a diagnostic and surgical planning tool that is becoming more and more useful for the management of peripheral nerve injuries. Its high resolution and real-time capability provide safe and cost-effective scans that aid in determining the extent of injuries. For patients with peripheral nerve injuries, ultrasound is advised to be added to the routine clinical and neurophysiological evaluation. It is also advised to use ultrasound as a first-line imaging modality for tumors thought to be of nerve origin.

Quantitative evaluation of rat sciatic nerve degeneration using high-frequency ultrasound.

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.

[Choosing the right imaging for the diagnostics and assessment of the course of peripheral nerve injuries]. / Die Wahl der richtigen Bildgebung zur Diagnostik und Verlaufsbeurteilung peripherer Nervenverletzungen.

BACKGROUND: Nerve injuries are a frequent problem in routine clinical practice and require intensive interdisciplinary care. OBJECTIVE: The current status of imaging to confirm the diagnosis of nerve injuries is described. The role of high-resolution ultrasound and magnetic resonance imaging (MRI) in the diagnostics and follow-up of peripheral nerve injuries is elaborated. MATERIAL AND METHODS: Review of the current state of imaging to confirm the diagnosis of nerve injuries. RESULTS: Depending on the suspected site of damage, the primary domain of magnetic resonance (MR) imaging (MR neurography) is injuries in the region of the spine, nerve roots, brachial plexus and lumbar plexus, pelvis and proximal thigh. In contrast, in other peripheral nerve lesions of the extremities the advantages of high-resolution nerve ultrasound in a dynamic setting predominate. The MR neurography is indicated here, especially in the frequent bottleneck syndromes and only in very isolated and selected cases. CONCLUSION: In addition to a correct anatomical assignment, the timely decision for a possible intervention and the appropriate concomitant treatment are an important basis for a favorable prognosis of nerve injuries. Imaging techniques should therefore be used early in the diagnostics and follow-up controls of peripheral nerve injuries.

Fluorescence imaging of peripheral nerve function and structure.

Peripheral nerve injuries are common and can cause catastrophic consequences. Although peripheral nerves have notable regenerative capacity, full functional recovery is often challenging due to a number of factors, including age, the type of injury, and delayed healing, resulting in chronic disorders that cause lifelong miseries and significant financial burdens. Fluorescence imaging, among the various techniques, may be the key to overcome these restrictions and improve the prognosis because of its feasibility and dynamic real-time imaging. Intraoperative dynamic fluorescence imaging allows the visualization of the morphological structure of the nerve so that surgeons can reduce the incidence of medically induced injury. Axoplasmic transport-based neuroimaging allows the visualization of the internal transport function of the nerve, facilitating early, objective, and accurate assessment of the degree of regenerative repair, allowing early intervention in patients with poor recovery, thereby improving prognosis. This review briefly discusses peripheral nerve fluorescent dyes that have been reported or could potentially be employed, with a focus on their role in visualizing the nerve's function and anatomy.

Imaging Peripheral Nerve Injuries of the Lower Extremities: What Surgeons Need to Know.

Peripheral nerve injury is a common sequela of lower extremity trauma. Injuries to lower extremity nerves range from contusions and stretch injuries that will often resolve without interventions to traumatic disruptions requiring surgical procedures, including neurolysis, repair or even nerve grafting. While clinical examination and tools such as electromyography will often help to localize the site of injury, imaging is a critical tool in determining the extent and degree of nerve injury in the setting of trauma. Modalities such as ultrasound and radiography are often useful, but MRI is considered the primary imaging modality for assessing the extent and degree of nerve injury. Specialized techniques such as MR neurography tailored to the needs of individual patients can provide important and detailed information in support of clinical decision making and presurgical planning. In this paper, we will review the anatomy of peripheral nerves of the lower extremity, mechanisms of injury affecting nerves and provide guidance for the use of MRI correlated with validated classification systems in assessing injuries affecting the nerves of the lower extremities.

Characterizing peroneal nerve injury clinicoradiological patterns with MRI in patients with sciatic neuropathy and foot drop after total hip replacement.

OBJECTIVE: Sciatic nerve injury following total hip arthroplasty (THA) predominantly affects the peroneal division of the sciatic nerve, often causing a foot drop. This can result from a focal etiology (hardware malposition, prominent screw, or postoperative hematoma) or nonfocal/traction injury. The objective of this study was to compare the clinicoradiological features and define the extent of nerve injury resulting from these two distinct mechanisms. METHODS: Patients who developed a postoperative foot drop within 1 year after primary or revision THA with a confirmed proximal sciatic neuropathy based on MRI or electrodiagnostic studies were retrospectively reviewed. Patients were divided into two cohorts: group 1 (focal injury), including patients with an identifiable focal structural etiology, and group 2 (nonfocal injury), including patients with a presumed traction injury. Patient demographics, clinical examinations, subsequent surgeries, electrodiagnostic study results, and MRI abnormalities were noted. The Student t-test was used to compare time to onset of foot drop and time to secondary surgery. RESULTS: Twenty-one patients, treated by one surgeon, met inclusion criteria (8 men and 13 women; 14 primary THAs and 7 revision THAs). Group 1 had a significantly longer time from THA to the onset of foot drop, with a mean of 2 months, compared with an immediate postoperative onset in group 2 (p = 0.02). Group 1 had a consistent pattern of localized focal nerve abnormality on imaging. In contrast, the majority of patients in group 2 (n = 11) had a long, continuous segment of abnormal size and signal intensity of the nerve, while the other 3 patients had a segment of less abnormal nerve in the midthigh on imaging. All patients with a long continuous lesion had Medical Research Council grade 0 dorsiflexion prior to secondary nerve surgeries compared with 1 of 3 patients with a more normal midsegment. CONCLUSIONS: There are distinct clinicoradiological findings in patients with sciatic injuries resulting from a focal structural etiology versus a traction injury. While there are discrete localized changes in patients with a focal etiology, those with traction injuries demonstrate a diffuse zone of abnormality within the sciatic nerve. A proposed mechanism involves anatomical tether points of the nerve acting as points of origin and propagation for traction injuries, resulting in an immediate postoperative foot drop. In contrast, patients with a focal etiology have localized imaging findings but a highly variable time to the onset of foot drop.

Spatio-temporally deciphering peripheral nerve regeneration in vivo after extracellular vesicle therapy under NIR-II fluorescence imaging.

Extracellular vesicles (EVs) show potential as a therapeutic tool for peripheral nerve injury (PNI), promoting neurological regeneration. However, there are limited data on the in vivo spatio-temporal trafficking and biodistribution of EVs. In this study, we introduce a new non-invasive near-infrared fluorescence imaging strategy based on glucose-conjugated quantum dot (QDs-Glu) labeling to target and track EVs in a sciatic nerve injury rat model in real-time. Our results demonstrate that the injected EVs migrated from the uninjured site to the injured site of the nerve, with an increase in fluorescence signals detected from 4 to 7 days post-injection, indicating the release of contents from the EVs with therapeutic effects. Immunofluorescence and behavioral tests revealed that the EV therapy promoted nerve regeneration and functional recovery at 28 days post-injection. We also found a relationship between functional recovery and the NIR-II fluorescence intensity change pattern, providing novel evidence for the therapeutic effects of EV therapy using real-time NIR-II imaging at the live animal level. This approach initiates a new path for monitoring EVs in treating PNI under in vivo NIR-II imaging, enhancing our understanding of the efficacy of EV therapy on peripheral nerve regeneration and its mechanisms.

Ultrasound of peripheral nerve injury.

Nerve injury in children is important to recognize early given the greater chance for recovery. Both children and adults have better outcomes the sooner nerve injuries are recognized and repaired. Children have even better functional results after surgical repair, thought to be related to their neural plasticity. Ultrasound is a powerful diagnostic tool for grading and mapping peripheral nerve injury and is complementary to electromyography and nerve conduction studies. Nerve injuries can be classified into low and high grade with ultrasound adding essential prognostic information and aiding in patient management. High-grade nerve injuries likely require surgical intervention. This article will review nerve anatomy and injury grading systems that radiologists can learn quickly in order to accurately communicate with their clinical partners. A practical approach to describe the sonographic appearance of nerve injury will be discussed. This article will show radiologists how the added value of ultrasound for peripheral nerve injury can directly affect clinical management.

Value of ultrasound assessment for traumatic nerve injury of the upper limb.

AIM OF WORK: The type of traumatic peripheral nerve injury is a key factor for determining optimal treatment. Proper assessment of peripheral nerve injury facilitates appropriate treatment, significantly affects prognosis, and reduces disabilities. This study evaluated ultrasonography (US) to assess upper limb traumatic nerve injuries and compared the US with electrodiagnostic studies as the gold standard. MATERIALS AND METHODS: Participants were 69 adults (57 [83%] men, 12 [17%] women; mean age 36.3 ± 13.5 years) with a total of 96 peripheral nerve injuries (duration of 1 month-3 years). High-frequency US examinations and electro-physiologic studies confirmed upper limb peripheral nerve injury. RESULTS: Nerve discontinuation was diagnosed in 15 (15.6%) nerves; the cross-sectional area was increased in 33 (34.4%) nerves. Of 96 injuries, 54 (56.3%) were median, 24 (25%) were ulnar, and 18 (18.8%) were radial nerves. No statistically significant difference was found between US and electro-physiologic studies for nerve injury diagnosis (p = 0.054). CONCLUSION: No significant differences were found between US and electro-physiologic studies for diagnosis of nerve injuries; however, US was valuable to assess surrounding tissue and supplied muscles. The capabilities to detect nerve injury and associated distal muscular, vascular, and other regional structures position the US as a complementary diagnostic tool.

Ninj2 regulates Schwann cells development by interfering laminin-integrin signaling.

Rationale: Myelin sheath is an important structure to maintain normal functions of the nerves. Nerve Injury-Induced Protein 2 (Ninj2) was found upregulated in Schwann cells (SC) upon injury. However, whether and how Ninj2 plays a role in myelination remain unknown. Methods: In this study, we use transmission electron microscope imaging, immunofluorescent imaging, and behavioral tests to show the effects of Ninj2 on myelination and remyelination in peripheral nervous system (PNS) of SC-specific Ninj2 knockout mice (Dhhcre/+;Ninj2fl/fl ). For mechanism studies, we use RNA-Seq analysis to show the Ninj2-related pathways, and co-immunoprecipitation/mass-spectrometry to identify the Ninj2-interacting proteins in SCs. Furthermore, we evaluate the effect of integrin inhibitor GRGDSP during remyelination. Results: Ninj2 negatively regulates SC development. Ninj2-deficient mice exhibit precocious myelination phenotype, as well as the accelerated remyelination process after sciatic nerve injury. Loss of Ninj2 promotes myelination by promoting SC proliferation to augment its population. Mechanistically, Ninj2 interacted with ITGB1 on SC membrane, which inhibits laminin-integrin signaling. Removal of Ninj2 induces the activity of laminin-integrin signaling, resulting in the improved myelination in the Dhhcre/+;Ninj2fl/fl mice. Inhibition of laminin-integrin signaling by integrin inhibitor GRGDSP sufficiently delays the remyelination process in the Dhhcre/+;Ninj2fl/fl mice with sciatic nerve injury. Conclusion: Our study found Ninj2 as a negative regulator in the network controlling myelination in the PNS.