• Users Online: 145
  • Home
  • Print this page
  • Email this page
Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
Year : 2022  |  Volume : 17  |  Issue : 1  |  Page : 187-195

Role of ultrasonography and strain elastography findings in peripheral nerve sheath tumor: A narrative review

Department of Radiodiagnosis, Jawaharlal Nehru Medical College, Sawangi, Wardha, Maharashtra, India

Date of Submission10-Jan-2022
Date of Decision22-Jan-2022
Date of Acceptance08-Feb-2022
Date of Web Publication25-Jul-2022

Correspondence Address:
Dr. Suresh Vasant Phatak
Department of Radiodiagnosis, Jawaharlal Nehru Medical College, Sawangi (Meghe), Wardha - 442 001, Maharashtra
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jdmimsu.jdmimsu_266_22

Rights and Permissions

Peripheral nerve imaging science is rapidly advancing, for early and robust diagnosis of many ill-health conditions, especially in detection of tumors. Radiological imaging techniques provide dynamic, real-time assessment of anatomy which either can help in diagnosis or prognosis in peripheral nerve disorders. Peripheral nerve tumors are often evaluated with magnetic resonance imaging, although there are many advantages offered with ultrasonography (USG). Strain elastography (SE), another technique, is well known for the diagnosis of soft-tissue tumors and is used to evaluate tissue stiffness. Hard lesions are more resistant to extrinsic compression and show smaller strain, whereas soft lesions show larger strain. The narrative review provides insight in functioning and utility of USG and SE techniques in peripheral nerve sheath tumor diagnosis.

Keywords: Diagnostic ultrasound, neurofibromatosis, peripheral nerve sheath tumor, schwannoma

How to cite this article:
Gowda K B, Mishra GV, Phatak SV, Pavanan A, Dhande RP. Role of ultrasonography and strain elastography findings in peripheral nerve sheath tumor: A narrative review. J Datta Meghe Inst Med Sci Univ 2022;17:187-95

How to cite this URL:
Gowda K B, Mishra GV, Phatak SV, Pavanan A, Dhande RP. Role of ultrasonography and strain elastography findings in peripheral nerve sheath tumor: A narrative review. J Datta Meghe Inst Med Sci Univ [serial online] 2022 [cited 2022 Aug 16];17:187-95. Available from: http://www.journaldmims.com/text.asp?2022/17/1/187/352226

  Introduction Top

In the imaging of peripheral nerves, ultrasonography (USG) is a cost-effective method. USG can identify and assess traumatic, inflammatory, infective, neoplastic, and compressive diseases of the peripheral nerves using modern high-frequency probes with diverse footprints that allow high-resolution imaging at a relatively superficial position. The technique for evaluating nerves by USG, as well as the USG appearances of normal and sick peripheral nerves, is described in this review. A variety of diseases impact peripheral nerves, including trauma, infection, inflammation, benign and malignant tumors, and entrapment neuropathies. With its excellent resolution, USG can identify and characterize various diseases at a low cost. General public unable to afford expensive diagnostic testing, USG remains an underused modality in our nation. The purpose of this review is to acquaint readers with various nerve diseases' USG presentations. Ultrasound (US) elastography is a diagnostic technique for determining tissue and organ elasticity and strain. This review also emphasizes the clinical utility of peripheral nerve US elastography. The peripheral nerves are affected by a variety of disorders and ailments. The nerve resistances are influenced by impingement, surrounding structural pressure, nerve sheath injury, and changed nerve structure. US elastography can be used to determine it. There have been more articles regarding peripheral nerve elastography with disputed messages in the last several years.[1] The annual incidence of peripheral nerve sheath tumor (PNST) is estimated to be 1 per 100,000 people.[2] The peripheral nervous system consists of nerves and ganglia that originate in the brain stem or spinal cord and travel throughout the body to reach their numerous parts. Its function is to provide somatic and autonomic innervation. Axon bundles create peripheral nerves, which are characterized at the microscopic level by myelination mediated by Schwann cells. Endoneurium, perineurium, and epineurium as these layers form the sheath around nerve cell [Figure 1]. The physical and biological variability of tumors that develop or differentiate toward the peripheral nervous system's diverse cell components reflects the anatomical dispersion and histological complexity of the peripheral nervous system. PNST can range from benign to fatal.[3]
Figure 1: Peripheral nerve microanatomy. Individual units are surrounded by epineurium in the peripheral nerve. The nonneoplastic cell components represented, mostly Schwann cells, share phenotypic features with the different nerve sheath malignancies. The perineurial cells that surround individual fascicles exhibit phenotypic overlap with the perineurium's neoplastic cells. The epineurium is populated by a range of mesenchymal cells, and the group of soft-tissue neoplasms that may potentially include the peripheral nerve as a main site has a wide morphological and biological variance.[3] Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884141/bin/nyab021fig1.jpg

Click here to view

  Peripheral Nerve Sheath Tumors Top

Growths in or near the strands of tissue (nerves) that convey information from the brain to the rest of the body are known as peripheral nerve tumors. Nerve tumors of the peripheral nervous system can develop anywhere in the body. Although the vast majority of them are not cancerous (malignant), they can cause discomfort, nerve damage, and loss of function in the afflicted area. PNSTs are generally treated surgically. Sometimes, tumors cannot be incised without affecting neighboring healthy tissue and/or nerves. Other therapies may be advised in certain circumstances. PNSTs come in a variety of shapes and sizes. These tumors could develop within nerves (intraneural tumors) or press against them (extraneural tumors) (extraneural tumors).[4] PNSTs are frequent neoplasms with well-defined characteristics, yet they can be difficult to diagnose at times. Despite the fact that well-defined subgroups of PNSTs were discovered early in the history of surgical pathology, there are still disagreements on how these tumors should be classified and graded. New insights into the nature of PNST have been supplied by advances in molecular biology, which have begun to suggest potential targeted therapy methods.[5] Peripheral nerve tumors induce symptoms and signs due to direct nerve invasion, involvement of neighboring tissues, or mass.[6] With the exception of neurofibromatosis type 1 (NF1) and type 2 (NF2) and schwannomatosis, there are no distinct clinical manifestations that are unique or even particularly diagnostic of a specific nerve tumor.

Symptoms and signs

Patients present for peripheral nerve tumor examination due to a soft-tissue mass, pain, or focal neurologic abnormalities, in the order of frequency.[7] Most benign tumors have a longer lifetime and a gradual rate of advancement, but malignant tumors tend to grow fast in size, degree of discomfort, and neurologic impairment.[7],[8],[9] PNTS symptoms and indicators are resultant of direct effects on the primary nerve or by the tumor pushing on surrounding nerves, blood vessels, or tissues. Although tumor size does not necessarily predict consequences, as the tumor develops, it is more likely to generate signs and symptoms. Peripheral nerve tumor signs and symptoms differ based on where the tumors are located and which organs are impacted. For example underneath skin, it can be visualized as swelling or a bump and there will be numbness, tingling, or pain. In the afflicted region, there is weakness or loss of function, dizziness.[4]


The cause of most peripheral nerve tumors is unknown. Some of them are associated to genetic diseases such as NF1 and NF2 and schwannomatosis. Others are brought on by a faulty gene or triggered by an accident or surgery.[4]

Risk factors

People with the following conditions are more likely to develop peripheral nerve tumors: NF1 and NF2, as well as schwannomatosis tumors form on or near nerves throughout the body in various illnesses. Depending on the location of these tumors, which are typically numerous, they might cause a range of symptoms and indicators. The majority of these tumors are noncarcinomatous. It is reported that exposure to radiation might result in peripheral nerve tumors later in life.[4] Both noncancerous and cancerous peripheral nerve tumors can compress nerves, leading to complications, such as numbness and weakness in the affected area, some of which may be permanent.[4]

Pathologic detection of illness and cancer, including PNSTs, is now being transformed by comprehensive molecular genetic profiling employing high-resolution platforms (PNSTs). Most cases may still be classified using well-defined morphological criteria, however, global methylation profiling.[10] in tumors and next-generation sequencing platforms in tumors and blood[11],[12] may give new diagnostic and prognostic information. PNSTs are significant components of a number of genetic disorders, and pathologic characterization serves as an important diagnostic criterion for clinical follow-up and genetic counseling.

NF1, NF2, schwannomatosis, and Carney complex are the most common of these disorders[13] [Figure 2].
Figure 2: The molecular genetic etiology of nerve sheath cancers is summarized. Nerve tumor syndromes are most commonly caused by germline mutations in the tumor suppressor genes NF1, NF2, SMARCB1, or LZTR1 (schwannomatosis), as well as PRKAR1A (MMNST, in Carney complex). CDKN2A (p16) in atypical neurofibroma/ANNUBP and changes in members of the PRC2 gene family have been linked to tumor growth in NF1 (SUZ12 or EED). The focus of this review is on the principal types of PNST that are likely to be seen in neurosurgical practice [Table 1]. Abbreviations of [Table 1] are mentioned below. Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884141/bin/nyab021fig2.jpg. ANNUBP: Atypical neurofibromatous neoplasms of uncertain biological potential, MPNST: Malignant peripheral nerve sheath tumor, MMNST: Malignant melanotic nerve sheath tumor, NF1: Neurofibromatosis type 1, NF2: Neurofibromatosis type 1, PNST: Peripheral nerve sheath tumor

Click here to view

  Peripheral Nerve Sheath Tumors: Origin and Development Top

Neoplastic proliferations with Schwann cell differentiation describe the most common peripheral nerve sheath malignancies. The Schwann cell, for example, is the major neoplastic cell component of neurofibroma, cytologically distinguished by wavy nuclear outlines and S-100 protein expression.[14],[15],[16] Nonneoplastic peripheral nerve components, such as axons, perineurial cells, fibroblasts, and other inflammatory elements, such as mast cells and lymphocytes, are also seen in neurofibromas. A population of CD34-positive cells with unknown histogenesis is also present.[17],[18]

Schwannomas and neurofibromas are examples of benign PNSTs. Malignant PNST has now become the umbrella term for cancers including malignant schwannoma and neurofibrosarcoma, as, the cell of origin in these tumors is frequently unclear, malignant PNST is the appropriate designation.[19] Neurofibromatosis has been linked to both benign and malignant PNSTs.

  Neurofibromas Top

Neurofibromas most typically afflict people between the ages of 20 and 40, with no gender preference.[20] Neurofibromas account for around 5% of benign soft-tissue neoplasms.[21],[22] There are three forms of neurofibromas: localized, diffuse, and plexiform. The majority of neurofibromas are solitary (localized), accounting for around 90% of all cases.[23],[24] Neurofibromatosis is linked to up to 10% of NF. Comorbidity raises the probability of malignant transformation significantly. Localized neurofibromas are slow-growing neurofibromas that form cutaneous nerves with the occasional involvement of deep-seated bigger nerves. The diffuse subtype is caused by nerves in the head and neck's subcutaneous tissues, and it typically affects children and young adults. Diffuse neurofibromas, unlike the more prevalent focal neurofibroma, are generally ill-defined and extend widely over connective tissue septa and across adipose tissue. Diffuse neurofibroma affects the subcutaneous tissue all the way down to the fascia.[25] When a neurofibroma arises from a deep-seated nerve, it is more likely to cause neurological symptoms, whereas superficial neurofibromas are generally tiny, harmless lumps. On gross inspection and cross-sectional imaging, the plexiform subtype appears as a diffuse tumor with tortuous growth along the branches of the parent nerve, resulting in a serpentine “bag of worms” look. NF1 is characterized by plexiform neurofibromas NF1. Neurofibromas, unlike schwannomas, are tightly linked with their nerve of origin and are not encapsulated on pathologic inspection. As a result, total excision of a neurofibroma necessitates nerve removal.[26]
Table 1: Peripheral nerve tumors relevant to intracranial and paraspinal locations

Click here to view

  Schwannomas Top

Schwannomas affect people between the ages of 20 and 40 and account for around 5% of benign soft-tissue neoplasms.[27],[28] Both men and women are impacted in the same way. The spinal and sympathetic roots of the head and neck, as well as nerves in the flexor surfaces of the upper and lower limbs, are often affected locations (in particular, the ulnar and peroneal nerves). The majority of lesions are isolated and unrelated to NF1. A slow-growing, painless soft-tissue tumor is the most common symptom, unlike with big tumors, pain, and neurologic symptoms. NF1 is linked to around 5% of multiple schwannomas. The most prevalent and well-known hallmark of NF2 is vestibular schwannomas, which cause severe morbidity; dumbbell-shaped schwannomas of the spinal cord are also frequent in NF2. Schwannomas are fusiform masses placed eccentrically close to the afflicted nerve on pathologic examination, and both the schwannoma and the damaged nerve are contained inside a genuine capsule, the epineurium. Schwannomas are mostly made up of Schwann cells. Surgical excision is frequently used to treat schwannoma. The tumor is generally surgically separated from the afflicted nerve, leaving the parent nerve and its function intact. Malignant transformation is exceedingly rare, and recurrence is infrequent.[26] Malignant PNSTs often affect individuals between the ages of 20 and 50, among both the genders, and account for around 5%–10% of all soft-tissue sarcomas.[24],[29] [Figure 3] shows schwannoma in the leg.
Figure 3: Benign tumors can occur in nerves, muscle, and bone. This illustration shows a schwannoma of the tibial nerve in the leg. Source: https://www.mayoclinic.org/-/media/kcms/gbs/patient-consumer/images/2017/06/30/19/10/schwannoma-in-the-leg-8col.jpg

Click here to view

Malignant Peripheral Nerve Sheath Tumors

High-grade malignant spindle cell neoplasms originating in conjunction with nerves, in preexisting Schwann cell neoplasms (most commonly a plexiform neurofibroma), and/or exhibiting a changeable Schwann cell phenotype are all characteristics of malignant peripheral nerve sheath tumor (MPNST) [Figure 4]. They are aggressive tumors with a proclivity for invading surrounding soft tissue and the ability to spread hematogenously. After radiation exposure, MPNST can grow in conjunction with NF1 or appear on its own. MPNST appears as adhering, exophytic lumps under the microscope. They come in a wide range of sizes and consistency, from microscopic changes in a preexisting neoplasm to gigantic tumors. Necrosis and bleeding are quite prevalent. They are generally cellular neoplasms with spindle-shaped cells and tapering nuclei under the microscope. At low power, they exhibit alternating hyper- and hypocellular regions, giving them a streaked look. Mitotic activity is high, and necrosis is common. Perivascular aggregates with herniation inside the vascular lumen are a common occurrence. A limited percentage of MPNSTs are classified as low grade, a term normally reserved for sites of malignant alteration within plexiform neurofibromas in NF1. NF1 is associated with a significant frequency of malignant PNSTs (about 50%). However, malignant PNSTs arise in a limited percentage of NF1 individuals (approximately 5%).[27],[28] A malignant PNST is characterized by a soft-tissue tumor involving the main nerves, as well as pain and neurologic signs. After radiation therapy, a secondary malignant PNST can develop with a latent period of more than 10 years.[27],[28]
Figure 4: MPNSTs are high-grade neoplasms that can emerge from a neurofibroma precursor (asterisks) (a) and are marked by hypercellularity/nuclear atypia (b) and frequent necrosis (c). (d) Epithelioid MPNST is a subtype of MPNST that is distinguished by neoplastic cells with big nuclei and macronuclei. MPNST growing in a preexisting neurofibroma (asterisks) (e) and exhibiting low-grade histology (arrow) (f), including lower cell density and infrequent mitotic figures. MPNSTs often show lower levels of mature Schwann cell markers, such as S100 (g) and SOX10 (h), and may be entirely negative (i). H3K27 trimethylation loss (H3K27me3) is a very unique characteristic. Internal positive control shown underlying endothelial cells (arrows). Source:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884141/bin/nyab021fig8.jpg. MPNST: Malignant peripheralnerve sheath tumor

Click here to view

Ultrasound imaging in peripheral nerve disorders

In the 1940s, US technology was first created for medical usage, with A-mode linear recordings displaying changes in echo intensity as amplitude. A single US pulse is delivered to the tissue, resulting in a one-dimensional linear depiction of reflected US beams as a function of depth. Further technical advancements enabled the creation of B-mode or 2D-mode, which is still used today and involves superimposing numerous linear data channels to form a picture with amplitude indicated as brightness. Prior to the 1980s, however, US was not used on peripheral nerves[30],[31] because of poor image resolution and difficulties distinguishing nerve from other tissues with comparable echogenicity.[32] In 1991, the first study on the diagnostic value of peripheral nerve US in the diagnosis of carpal tunnel syndrome (CTS) was published.[33] Since then, US technology has progressed with the invention of broadband high-frequency linear array transducers, Doppler technology, and postprocessing software programs, all of which have improved US's capacity to detect anatomic and structural anomalies in nerves. Today, neuromuscular USG is progressively and widely employed as an adjuvant to clinical and neurophysiological research in the assessment of Neuromuscular Illness (NMI). NMUS has several advantages, including being a noninvasive, painless, cost-effective, portable, and quick diagnostic that allows for a high-resolution, dynamic evaluation of the whole nerve in real time. As a result, NMUS is regarded as an excellent screening, diagnostic, and monitoring tool. Magnetic resonance neurography (MRN) is an alternative imaging technique that, with the introduction of tractography and diffusion tensor imaging, gives outstanding three-dimensional views of brain architecture as well as functional characteristics.[34],[35] Quantitative approaches, such as muscle fat fraction and nerve size, can also be used to track disease development and could be useful as biomarkers in future treatment trials.[36] MRN, on the other hand, is costly, time-consuming, poorly tolerated in young and claustrophobic persons, limited in availability, and restricted to a prespecified zone in clinical practice. NMUS has better spatial resolution than MRN and can scan extremely tiny nerves; nevertheless, deep neural structures such as the lumbosacral plexus and proximal sciatic nerve, as well as those deep to osseous structures, cannot be visualized. As a result, both NMUS and MRN continue to play a complimentary function; however, the use of each imaging modality must be adapted to the specific clinical circumstance.[37] USG can be used to discover and illustrate the location of damage, differentiate nerve injury in continuity from nerve transection, assess the source of compression, and detect foreign bodies, neuromas, and scarring.[30] The great resolution of USG enables for the examination of tiny nerves such as the digital nerves, which is difficult to do with magnetic resonance imaging (MRI). Furthermore, MRI may be unable to distinguish between neural contusion and nerve damage.[31] Electrodiagnostic investigations do not provide morphologic information such as the location and severity of the damage. As a result, USG plays a critical role in the assessment of patients with suspected nerve damage. Neurilemoma, neurinoma, and malignant PNST are examples of peripheral neurogenic tumors. All neurogenic tumors have similar imaging characteristics. Although it is difficult to distinguish between them, their neurogenic origin can be inferred from their imaging appearances, such as fusiform shape, relationship to the nerve, “split-fat” sign, associated muscle atrophy, and intrinsic imaging characteristics, such as “target sign,” as well as lesion location and typical nerve distribution. The goal of this study is to provide an overview of imaging findings for each kind of PNST, with a focus on distinguishing markers and their correlation with histologic characteristics.[38]

  Ultrasonography's Current and Future Techniques and Approaches Top


The majority of NMUS is done in B- or 2D-mode with a linear array transducer with a frequency range of 15–18 MHz. The morphology, echogenicity, and cross-sectional area (CSA) of the nerve are all evaluated. To discover any abnormalities along the nerve's path, a distal to proximal technique is usually used. Structures should be evaluated in two orthogonal planes, commonly using cross-sectional and longitudinal views, and these pictures recorded as documentation to investigate time trends. When evaluating unilateral illnesses, a comparison with the contralateral nerve is helpful.[37]

Cross-section area

The CSA, which is measured in mm2 and tracked inside the hyperechoic epineurial rim of the nerve with the transducer perpendicular to the nerve, is used to determine the size of the nerve. When employing an oblique view of the nerve, care must be taken to measure a genuine CSA, as CSA is usually overstated. Because of its repeatability and strong inter- and intra-assessor reliability, CSA is the most often employed metric to evaluate anomalies in nerve disorders.[39]


The echogenicity of a peripheral nerve is often documented and changes along the length of the nerve in normal persons, with the proximal portions looking more hypoechoic than the distal segments.[40] The echotexture of the nerve can be assessed semi-quantitatively by calculating the mean grayscale value of a chosen picture, or it can be quantified using thresholding techniques in postprocessing software to calculate the hypoechoic proportion and density of the nerve.[41],[42]

Ultra-high-frequency B-mode

Continuous research and development of US probes and signal processing has resulted in enhanced picture resolution and quantification since its introduction. The Food and Drug Administration authorized the first ultra-high-frequency transducer (Vevo MD ultrasound device, FujiFilm VisualSonics, Toronto, Ontario, Canada) for clinical use in 2016, providing extraordinarily high-resolution imaging of the brain and other structures. This remarkable increase in resolution to 30 m, however, comes at the cost of penetration depth. The 70 MHz probes, in particular, are only capable of imaging superficial structures up to a depth of 3 cm. Despite this restriction, ultra-high-frequency US provides precise information on the size, quantity, and density of fascicles, echogenicity, and intraneural vascularization, allowing substantial insights into interior neural structures. This technique has so far been utilized to gather normative data in the median and ulnar nerves, as well as to assess chronic inflammatory demyelinating polyradiculoneuropathy and spinal muscular atrophy.[43],[44],[45],[46]

Fascicular ultrasound

Smaller brain features, such as individual neuron fascicles, may now be studied in greater detail without improvements in US resolution. Individual nerve fascicle size variation may likely reveal pathogenic clues in peripheral neuropathies, nerve tumors, and nerve trauma. Nerve fascicles are frequently increased in the setting of CSA expansion; however, this is not necessarily uniform.[47] For example, in  Charcot-Marie-Tooth disease More Details type 1A, fascicular size was measured, demonstrating considerable diffuse fascicular expansion across nerves but, more interestingly, nonhomogeneous growth across the fascicles of a single nerve.[48]

Doppler ultrasound

To measure blood flow, B-mode can be used with color or power Doppler. Current noncontrast imaging is unable to identify blood flow in normal nerves, including intraneural and epineural.[49] Surrogates for intraneural blood flow are currently utilized quantitative techniques, such as manual Doppler signal counts or the analysis of Doppler waveforms to determine blood flow velocity. These measurements more accurately reflect hypervascularity rather than a clear increase in blood volume inside the nerve, and due to the sluggish flow within nerves, intraneural blood flow is likely underestimated due to flow velocity detection thresholds.[50] Additional approaches, such as contrast-enhanced ultrasonography and assessment of maximum perfusion intensity, have recently been utilized to more reliably characterize intraneural blood flow.[50],[51]


Another functional approach, US elastography, is gaining popularity as a possible prognostic and monitoring biomarker in neuromuscular disorders. Elastography is a noninvasive technique for measuring tissue stiffness, which can reveal underlying degenerative abnormalities in tissue composition and architecture. The replacement of compliant myelin by diverse less-compliant connective and other tissues tends to enhance stiffness in peripheral neuropathy of all causes.[52] The two main approaches are strain and shear-wave elastography (SWE), which differ in measuring methodology.

Strain elastography

The stiffness of a tissue is measured via strain elastography (SE), which records the displacement of a tissue caused by either physical compression or physiologic tissue movement, such as cardiorespiratory pulsations. The latter approach, known as ambient SE (ASE), is favored for neuromuscular examination because it is more repeatable and accurate in clinical practice than manual compression procedures, which can be difficult to quantify and standardize force.[53]

Shear-wave elastography

SWE, on the other hand, employs a standardized high-intensity acoustic or vibration pulse to generate tissue displacement, resulting in a quantitative assessment of stiffness, with results that are as repeatable and dependable as ASE.[52]

Need for the study

Nerve conduction studies (NCSs) can govern the function of the damaged nerve depending on its location, and MRI has been found to see certain early, preclinical abnormalities in peripheral nerve morphology. However, these tests are costly, cumbersome, and not commonly available; furthermore, they are either invasive (NCS) or need the injection of a contrast agent (MRI), and their sensitivity and specificity are far from ideal.[54],[55],[56],[57] Conventional grayscale USG is increasingly being employed as an auxiliary diagnostic test in patients with suspected peripheral neuropathies due to its lack of invasiveness, greater availability, and cheaper cost. One can identify morphological abnormalities in the afflicted peripheral nerve and calculate its CSA using conventional USG.[58],[59],[60] The former, the older one, is based on operator-induced compression with a transducer to assess tissue displacement and hence its elasticity/stiffness. The result is either given qualitatively as a strain/elasticity ratio between structures, with elastic, intermediate, and stiff tissues colored red, green, and blue, respectively, or semi-quantitatively as a strain/elasticity ratio between structures. The velocity of a transducer-generated shear wave is measured across the tissue of interest and reported as a quantitative quantity in either kilopascals (kPa, as Young modulus) or meters per second (m/s) in the more recently developed SWE.[60] Given the pathophysiology of peripheral neuropathy, which includes a rise in intraneural pressure and edema, ultrasonic elastography appears to be an excellent approach for detecting the early stages of the disease based on changes in the afflicted nerve stiffness. As a result, the goal of this systematic review was to look at the use of SE and SWE in the assessment of peripheral nerves in patients with neuropathy of various causes.

Nerve fibers make up peripheral nerves, which deliver impulses to muscles and govern the body's autonomic nerve activities. The examination of peripheral nerve function is critical for the diagnosis and efficacy assessment of neuromuscular illnesses. Lower extremity ulcers are caused by infections and gangrene, and early identification and treatment of diabetic peripheral neuropathy (DPN) can significantly minimize the development of lower extremity ulcers and amputations, increasing patients' quality of life. There is currently no gold standard for diagnosing peripheral nerve illnesses, which is based mostly on clinical symptoms, signs, neurophysiological testing, quantitative sensory evaluations, and MRI. A neurophysiological test can offer information on the function of neurons, peripheral nerves, neuromuscular junctions, and muscles,[61] but it is intrusive and time-consuming.

Quantitative sensory examination is used to assess the severity of peripheral neurosensory dysfunction, although it is affected by a number of subjective and objective criteria, including analytic software, subject cooperation, and tester expertise. The morphological properties of peripheral nerves may be described by MRI; however, it is vulnerable to physical elements such as bones or internal fixation, as well as greater costs and artifacts. Traditional high-frequency ultrasonography may identify the continuity, thickness, echo intensity, and CSA of peripheral nerves and indicate morphological alterations.[62] Although it is simple and painless, the results can only represent the anatomical properties of peripheral nerves.

US elastography is a biomechanical method that determines the deformation and rebound capacities of tissue based on its structure and composition. This elastic property may be used to assess target tissue when it is exposed to external or internal stimuli, and the resulting value can reflect tissue stiffness.[63] SE is now the most used elastography technology.[64] Acoustic radiation force pulse imaging (ARFI),[65] and SWE are novel approaches for assessing tissue stiffness. It has been used extensively in organs such as the liver, kidney, breast, and thyroid, as well as the musculoskeletal system, which includes muscles and tendons.[64],[66],[67],[68],[69]

Elastography is now being researched for novel uses, such as the detection of peripheral neuropathy, such as DPN and CTS. According to previous studies, disorders including CTS and DPN can induce structural abnormalities, edema inside the nerve fascicle, and a restriction in blood flow, resulting in compression and stiffness of the infected nerve,[70],[71] which can lead to amputation of SWE diagnosis. Simultaneously, preliminary findings from several investigations suggest that SWE can be reliably measured. Indentation testing, reflects the increase in stiffness of nerve tissue.[72] Yet, for such a new technology, there are relatively few studies on SWE of peripheral nerves, especially those addressing the methodology and influencing factors of peripheral nerve SWE in healthy people. The shear wave's propagation velocity in tissue may be reliably measured and computed as follows: E = 3C2, where E stands for Young's modulus, which represents the mechanical characteristics of the tissue, D stands for tissue density, and C stands for shear wave velocity. The quicker the shear wave velocity (SWV) and the higher the Young's modulus value, the tougher the tissue. The abovementioned formula is most commonly used in isotropic, elastic, and spatially homogenous tissues, such as the liver, thyroid, or breast. Anisotropic tissues include muscles, tendons, and peripheral nerves. As a result, extensive research has shown that the SWV is more valuable than Young's modulus value when measuring these anisotropic tissues using SWE.[73],[74]

The quicker the SWV and the higher the Young's modulus value, the tougher the tissue. The abovementioned formula is most commonly used in isotropic, elastic, and spatially homogenous tissues, such as the liver, thyroid, or breast. Anisotropic tissues include muscles, tendons, and peripheral nerves. As a result, extensive research has shown that the SWV is more valuable than Young's modulus value when measuring these anisotropic tissues using SWE. Previous research on SWE of the musculoskeletal system included gender, age, height, weight, and BMI;[60] the stiffness of the median nerve varied in different parts of the body. Skin stiffness differed between men and women, according to the study.[75] At the C6 nerve root, the researchers discovered a substantial inverse relationship between height and weight. Although there have been studies that merely highlight certain difficulties, the effect factors on peripheral nerve elasticity have seldom been examined in depth. However, SWE technology can see, if factors such as location, age, sex, BMI, peripheral nerve thickness, and CSA can affect the stiffness of the median and tibial nerves by measuring the SWV in the healthy population, which could serve as a primary reference and objective evidence for SWE measurement in peripheral nerve disorders.[76] Many forms of peripheral neuropathies can be reliably diagnosed by US elastography, even if the ailment is still asymptomatic. However, it is still unclear if elastographic alterations in nerves precede functional abnormalities detected by nerve conduction investigations. Furthermore, nothing is known regarding the association between peripheral nerve stiffness and the severity of peripheral neuropathy and its underlying disease, while some researches show that such a correlation exists. Large-scale studies, ideally longitudinal ones, are needed to resolve these two concerns.[77]

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Torriani M, Souto SC, Thomas BJ, Ouellette H, Bredella MA. Ischiofemoral impingement syndrome: An entity with hip pain and abnormalities of the quadratus femoris muscle. AJR Am J Roentgenol 2009;193:186-90.  Back to cited text no. 1
Hems TE, Burge PD, Wilson DJ. The role of magnetic resonance imaging in the management of peripheral nerve tumours. J Hand Surg Br 1997;22:57-60.  Back to cited text no. 2
Belakhoua SM, Rodriguez FJ. Diagnostic pathology of tumors of peripheral nerve. Neurosurgery 2021;88:443-56.  Back to cited text no. 3
Rodriguez FJ, Folpe AL, Giannini C, Perry A. Pathology of peripheral nerve sheath tumors: Diagnostic overview and update on selected diagnostic problems. Acta Neuropathol 2012;123:295-319.  Back to cited text no. 5
Mrugala MM, Batchelor TT, Plotkin SR. Peripheral and cranial nerve sheath tumors. Curr Opin Neurol 2005;18:604-10.  Back to cited text no. 6
Baehring JM, Betensky RA, Batchelor TT. Malignant peripheral nerve sheath tumor: The clinical spectrum and outcome of treatment. Neurology 2003;61:696-8.  Back to cited text no. 7
Valeyrie-Allanore L, Ismaili N, Bastuji-Garin S, Zeller J, Wechsler J, Revuz J, et al. Symptoms associated with malignancy of peripheral nerve sheath tumours: A retrospective study of 69 patients with neurofibromatosis 1. Br J Dermatol 2005;153:79-82.  Back to cited text no. 8
Perrin RG, Guha A. Malignant peripheral nerve sheath tumors. Neurosurg Clin 2004;15:203-16.  Back to cited text no. 9
Röhrich M, Koelsche C, Schrimpf D, Capper D, Sahm F, Kratz A, et al. Methylation-based classification of benign and malignant peripheral nerve sheath tumors. Acta Neuropathol 2016;131:877-87.  Back to cited text no. 10
Louvrier C, Pasmant E, Briand-Suleau A, Cohen J, Nitschké P, Nectoux J, et al. Targeted next-generation sequencing for differential diagnosis of neurofibromatosis type 2, schwannomatosis, and meningiomatosis. Neuro Oncol 2018;20:917-29.  Back to cited text no. 11
Carlson ML, Smadbeck JB, Link MJ, Klee EW, Vasmatzis G, Schimmenti LA. Next generation sequencing of sporadic vestibular schwannoma: Necessity of Biallelic NF2 inactivation and implications of accessory non-NF2 variants. Otol Neurotol 2018;39:e860-71.  Back to cited text no. 12
Rodriguez FJ, Stratakis CA, Evans DG. Genetic predisposition to peripheral nerve neoplasia: Diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes. Acta Neuropathol 2012;123:349-67.  Back to cited text no. 13
Perry A, Roth KA, Banerjee R, Fuller CE, Gutmann DH. NF1 deletions in S-100 protein-positive and negative cells of sporadic and neurofibromatosis 1 (NF1)-associated plexiform neurofibromas and malignant peripheral nerve sheath tumors. Am J Pathol 2001;159:57-61.  Back to cited text no. 14
Weiss SW, Langloss JM, Enzinger FM. Value of S-100 protein in the diagnosis of soft tissue tumors with particular reference to benign and malignant Schwann cell tumors. Lab Invest 1983;49:299-308.  Back to cited text no. 15
Chaubal A, Paetau A, Zoltick P, Miettinen M. CD34 immunoreactivity in nervous system tumors. Acta Neuropathol 1994;88:454-8.  Back to cited text no. 16
Carroll SL. Molecular mechanisms promoting the pathogenesis of Schwann cell neoplasms. Acta Neuropathol 2012;123:321-48.  Back to cited text no. 17
Weiss SW, Nickoloff BJ. CD-34 is expressed by a distinctive cell population in peripheral nerve, nerve sheath tumors, and related lesions. Am J Surg Pathol 1993;17:1039-45.  Back to cited text no. 18
Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM, Ilstrup DM. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer 1986;57:2006-21.  Back to cited text no. 19
Resnick D. Soft tissues. In: Bone and Joint Disorders. 3rd ed. Elsevier Health Sciences, Amsterdam; 1995. p. 4491-622.  Back to cited text no. 20
Kransdorf MJ. Benign soft-tissue tumors in a large referral population: Distribution of specific diagnoses by age, sex, and location. AJR Am J Roentgenol 1995;164:395-402.  Back to cited text no. 21
Kransdorf M. Malignant soft-tissue tumors in a large referral population: Distribution of diagnoses by age, sex, and location. Am J Roentgenol 1995;164:129-34.  Back to cited text no. 22
Skovronsky DM, Oberholtzer JC. Pathologic classification of peripheral nerve tumors. Neurosurg Clin N Am 2004;15:157-66.  Back to cited text no. 23
Lassmann H, Jurecka W, Lassmann G, Gebhart W, Matras H, Watzek G. Different types of benign nerve sheath tumors. Light microscopy, electron microscopy and autoradiography. Virchows Arch A Pathol Anat Histol 1977;375:197-210.  Back to cited text no. 24
Peh WC, Shek TW, Yip DK. Magnetic resonance imaging of subcutaneous diffuse neurofibroma. Br J Radiol 1997;70:1180-3.  Back to cited text no. 25
Chee DW, Peh WC, Shek TW. Pictorial essay: Imaging of peripheral nerve sheath tumours. Can Assoc Radiol J 2011;62:176-82.  Back to cited text no. 26
Murphey MD, Smith WS, Smith SE, Kransdorf MJ, Temple HT. From the archives of the AFIP. Imaging of musculoskeletal neurogenic tumors: Radiologic-pathologic correlation. Radiographics 1999;19:1253-80.  Back to cited text no. 27
Stull MA, Moser RP Jr., Kransdorf MJ, Bogumill GP, Nelson MC. Magnetic resonance appearance of peripheral nerve sheath tumors. Skeletal Radiol 1991;20:9-14.  Back to cited text no. 28
Enzinger FM, Weiss SW. Malignant tumors of the peripheral nerves. In: Soft Tissue Tumors. Elsevier publisher, Amsterdam; 2019.  Back to cited text no. 29
Fornage BD. Peripheral nerves of the extremities: Imaging with US. Radiology 1988;167:179-82.  Back to cited text no. 30
Solbiati L, De Pra L, Ierace T, Bellotti E, Derchi LE. High-resolution sonography of the recurrent laryngeal nerve: Anatomic and pathologic considerations. AJR Am J Roentgenol 1985;145:989-93.  Back to cited text no. 31
Gallardo E, Noto Y, Simon NG. Ultrasound in the diagnosis of peripheral neuropathy: Structure meets function in the neuromuscular clinic. J Neurol Neurosurg Psychiatry 2015;86:1066-74.  Back to cited text no. 32
Buchberger W, Schön G, Strasser K, Jungwirth W. High-resolution ultrasonography of the carpal tunnel. J Ultrasound Med 1991;10:531-7.  Back to cited text no. 33
Simon NG, Narvid J, Cage T, Banerjee S, Ralph JW, Engstrom JW, et al. Visualizing axon regeneration after peripheral nerve injury with magnetic resonance tractography. Neurology 2014;83:1382-4.  Back to cited text no. 34
Eppenberger P, Andreisek G, Chhabra A. Magnetic resonance neurography: Diffusion tensor imaging and future directions. Neuroimaging Clin N Am 2014;24:245-56.  Back to cited text no. 35
Morrow JM, Sinclair CD, Fischmann A, Machado PM, Reilly MM, Yousry TA, et al. MRI biomarker assessment of neuromuscular disease progression: A prospective observational cohort study. Lancet Neurol 2016;15:65-77.  Back to cited text no. 36
Carroll AS, Simon NG. Current and future applications of ultrasound imaging in peripheral nerve disorders. World J Radiol 2020;12:101-29.  Back to cited text no. 37
Pilavaki M, Chourmouzi D, Kiziridou A, Skordalaki A, Zarampoukas T, Drevelengas A. Imaging of peripheral nerve sheath tumors with pathologic correlation: Pictorial review. Eur J Radiol 2004;52:229-39.  Back to cited text no. 38
Tagliafico A, Cadoni A, Fisci E, Bignotti B, Padua L, Martinoli C. Reliability of side-to-side ultrasound cross-sectional area measurements of lower extremity nerves in healthy subjects. Muscle Nerve 2012;46:717-22.  Back to cited text no. 39
Simon NG, Cage T, Narvid J, Noss R, Chin C, Kliot M. High-resolution ultrasonography and diffusion tensor tractography map normal nerve fascicles in relation to schwannoma tissue prior to resection. J Neurosurg 2014;120:1113-7.  Back to cited text no. 40
Tagliafico A, Tagliafico G, Martinoli C. Nerve density: A new parameter to evaluate peripheral nerve pathology on ultrasound. Preliminary study. Ultrasound Med Biol 2010;36:1588-93.  Back to cited text no. 41
Boom J, Visser LH. Quantitative assessment of nerve echogenicity: Comparison of methods for evaluating nerve echogenicity in ulnar neuropathy at the elbow. Clin Neurophysiol 2012;123:1446-53.  Back to cited text no. 42
Cartwright MS, Baute V, Caress JB, Walker FO. Ultrahigh-frequency ultrasound of fascicles in the median nerve at the wrist. Muscle Nerve 2017;56:819-22.  Back to cited text no. 43
Vitali S, Rossi P, Aringhieri G, Bocci T, Barloscio D, Santin M, et al. Very-High-Resolution Sonography of Median Nerve: A Comparative Study vs. High-Resolution Sonography in Healthy Subjects. European Congress of Radiology-ECR; 2018.  Back to cited text no. 44
Puma A, Azulay N, Grecu N, Suply C, Panicucci E, Cambieri C, et al. Comparison of high-frequency and ultrahigh-frequency probes in chronic inflammatory demyelinating polyneuropathy. J Neurol 2019;266:2277-85.  Back to cited text no. 45
Regensburger AP, Wagner AL, Hanslik G, Schüssler SC, Fahlbusch FB, Woelfle J, et al. Ultra-high-frequency ultrasound in patients with spinal muscular atrophy: A retrospective feasibility study. Muscle Nerve 2020;61:E18-21.  Back to cited text no. 46
Martinoli C, Schenone A, Bianchi S, Mandich P, Caponetto C, Abbruzzese M, et al. Sonography of the median nerve in Charcot-Marie-Tooth disease. AJR Am J Roentgenol 2002;178:1553-6.  Back to cited text no. 47
Grimm A, Winter N, Rattay TW, Härtig F, Dammeier NM, Auffenberg E, et al. A look inside the nerve – Morphology of nerve fascicles in healthy controls and patients with polyneuropathy. Clin Neurophysiol 2017;128:2521-6.  Back to cited text no. 48
Joy V, Therimadasamy AK, Chan YC, Wilder-Smith EP. Combined Doppler and B-mode sonography in carpal tunnel syndrome. J Neurol Sci 2011;308:16-20.  Back to cited text no. 49
Borire AA, Visser LH, Padua L, Colebatch JG, Huynh W, Simon NG, et al. Utility of maximum perfusion intensity as an ultrasonographic marker of intraneural blood flow. Muscle Nerve 2017;55:77-83.  Back to cited text no. 50
Volz KR, Evans KD, Kanner CD, Dickerson JA. Detection of intraneural median nerve microvascularity using contrast-enhanced sonography: A pilot study. J Ultrasound Med 2016;35:1309-16.  Back to cited text no. 51
Wee TC, Simon NG. Ultrasound elastography for the evaluation of peripheral nerves: A systematic review. Muscle Nerve 2019;60:501-12.  Back to cited text no. 52
Martin MJ, Cartwright MS. A pilot study of strain elastography in the diagnosis of carpal tunnel syndrome. J Clin Neurophysiol 2017;34:114-8.  Back to cited text no. 53
Witt JC, Hentz JG, Stevens JC. Carpal tunnel syndrome with normal nerve conduction studies. Muscle Nerve 2004;29:515-22.  Back to cited text no. 54
Koyuncuoglu HR, Kutluhan S, Yesildag A, Oyar O, Guler K, Ozden A. The value of ultrasonographic measurement in carpal tunnel syndrome in patients with negative electrodiagnostic tests. Eur J Radiol 2005;56:365-9.  Back to cited text no. 55
Andreisek G, Crook DW, Burg D, Marincek B, Weishaupt D. Peripheral neuropathies of the median, radial, and ulnar nerves: MR imaging features. Radiographics 2006;26:1267-87.  Back to cited text no. 56
Dyck PJ, Overland CJ, Low PA, Litchy WJ, Davies JL, Dyck PJ, et al. NPhys Trial Investigators (see Appendix for additional authors). Signs and symptoms versus nerve conduction studies to diagnose diabetic sensorimotor polyneuropathy: Cl vs. NPhys trial. Muscle Nerve 2010;42:157-64.  Back to cited text no. 57
Klauser AS, Halpern EJ, De Zordo T, Feuchtner GM, Arora R, Gruber J, et al. Carpal tunnel syndrome assessment with US: Value of additional cross-sectional area measurements of the median nerve in patients versus healthy volunteers. Radiology 2009;250:171-7.  Back to cited text no. 58
Pastare D, Therimadasamy AK, Lee E, Wilder-Smith EP. Sonography versus nerve conduction studies in patients referred with a clinical diagnosis of carpal tunnel syndrome. J Clin Ultrasound 2009;37:389-93.  Back to cited text no. 59
Bortolotto C, Turpini E, Felisaz P, Fresilli D, Fiorina I, Raciti MV, et al. Median nerve evaluation by shear wave elastosonography: Impact of “bone-proximity” hardening artifacts and inter-observer agreement. J Ultrasound 2017;20:293-9.  Back to cited text no. 60
Kerasnoudis A, Tsivgoulis G. Nerve ultrasound in peripheral neuropathies: A review. J Neuroimaging 2015;25:528-38.  Back to cited text no. 61
Sigrist RM, Liau J, Kaffas AE, Chammas MC, Willmann JK. Ultrasound elastography: Review of techniques and clinical applications. Theranostics 2017;7:1303-29.  Back to cited text no. 62
Park GY, Kwon DR. Application of real-time sonoelastography in musculoskeletal diseases related to physical medicine and rehabilitation. Am J Phys Med Rehabil 2011;90:875-86.  Back to cited text no. 63
Carlsen JF, Ewertsen C, Lönn L, Nielsen MB. Strain elastography ultrasound: An overview with emphasis on breast cancer diagnosis. Diagnostics (Basel) 2013;3:117-25.  Back to cited text no. 64
Nightingale KR, Palmeri ML, Nightingale RW, Trahey GE. On the feasibility of remote palpation using acoustic radiation force. The Journal of the Acoustical Society of America. 2001;110:625-34.  Back to cited text no. 65
Arda K, Ciledag N, Aribas BK, Aktas E, Köse K. Quantitative assessment of the elasticity values of liver with shear wave ultrasonographic elastography. Indian J Med Res 2013;137:911-5.  Back to cited text no. 66
[PUBMED]  [Full text]  
Balleyguier C, Canale S, Ben Hassen W, Vielh P, Bayou EH, Mathieu MC, et al. Breast elasticity: Principles, technique, results: An update and overview of commercially available software. Eur J Radiol 2013;82:427-34.  Back to cited text no. 67
Berg WA, Cosgrove DO, Doré CJ, Schäfer FK, Svensson WE, Hooley RJ, et al. Shear-wave elastography improves the specificity of breast US: The BE1 multinational study of 939 masses. Radiology 2012;262:435-49.  Back to cited text no. 68
Bota S, Bob F, Sporea I, Sirli R, Popescu A. Factors that infuence kidney shear wave speed assessed by acoustic radiation force impulse elastography in patients without kidney pathology. Ultrasound Med Biol 2015;41:1-6.  Back to cited text no. 69
Dikici AS, Ustabasioglu FE, Delil S, Nalbantoglu M, Korkmaz B, Bakan S, et al. Evaluation of the tibial nerve with shear-wave elastography: A potential sonographic method for the diagnosis of diabetic peripheral neuropathy. Radiology 2017;282:494-501.  Back to cited text no. 70
Ghajarzadeh M, Dadgostar M, Sarraf P, Emami-Razavi SZ, Miri S, Malek M. Application of ultrasound elastography for determining carpal tunnel syndrome severity. Jpn J Radiol 2015;33:273-8.  Back to cited text no. 71
Schrier VJ, Lin J, Gregory A, Thoreson AR, Alizad A, Amadio PC, et al. Shear wave elastography of the median nerve: A mechanical study. Muscle Nerve 2020;61:826-33.  Back to cited text no. 72
Bercoff J, Tanter M, Fink M. Supersonic shear imaging: A new technique for soft tissue elasticity mapping. IEEE Trans Ultrason Ferroelectr Freq Control 2004;51:396-409.  Back to cited text no. 73
Gennisson JL, Cornu C, Catheline S, Fink M, Portero P. Human muscle hardness assessment during incremental isometric contraction using transient elastography. J Biomech 2005;38:1543-50.  Back to cited text no. 74
Yang Y, Wang L, Yan F, Xiang X, Tang Y, Zhang L, et al. Determination of normal skin elasticity by using real-time shear wave elastography. J Ultrasound Med 2018;37:2507-16.  Back to cited text no. 75
Bedewi MA, Nissman D, Aldossary NM, Maetani TH, El Sharkawy MS, Koura H. Shear wave elastography of the brachial plexus roots at the interscalene groove. Neurol Res 2018;40:805-10.  Back to cited text no. 76
Zakrzewski J, Zakrzewska K, Pluta K, Nowak O, Miłoszewska-Paluch A. Ultrasound elastography in the evaluation of peripheral neuropathies: A systematic review of the literature. Pol J Radiol 2019;84:e581-91.  Back to cited text no. 77


  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1]


Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  In this article
Peripheral Nerve...
Peripheral Nerve...
Article Figures
Article Tables

 Article Access Statistics
    PDF Downloaded15    
    Comments [Add]    

Recommend this journal