Received: 23 February 2019 Revised: 24 June 2019 Accepted: 29 June 2019

DOI: 10.1002/mus.26624

INVITED REVIEW

Ultrasound elastography for the evaluation of peripheral

nerves: A systematic review

Tze Chao Wee FAFRM(RACP), FFPMANZCA1 | Neil G. Simon PhD, FRACP2

1
Department of Rehabilitation Medicine,
Changi General Hospital, Singapore
2
St Vincent's Clinical School, University of
New South Wales, Darlinghurst, New South
Wales, Australia
Correspondence
Neil Simon, Suite 14a, Northern Beaches
Hospital, Frenchs Forest, NSW, Australia.
Email: neil@nbneuro.com.au
Abstract
Peripheral nerve disorders are commonly encountered in clinical practice. Elec-
trodiagnostic studies remain the cornerstone of the evaluation of nerve disorders.
More recently, ultrasound has played an increasing complementary role in the neuro-
muscular clinic. Ultrasound elastography is a technique that measures the elastic
properties of tissues. Given the histological changes that occur in diseased peripheral
nerves, nerve ultrasound elastography has been explored as a noninvasive way to
evaluate changes in nerve tissue composition. Studies to date suggest that nerve
stiffness tends to increase in the setting of peripheral neuropathy, regardless of etiol-
ogy, consistent with loss of more compliant myelin, and replacement with connective
tissue. The aim of this systematic review is to summarize the current literature on the
use of ultrasound elastography in the evaluation of peripheral neuropathy. Limita-
tions of ultrasound elastography and gaps in current literature are discussed, and
prospects for future clinical and research applications are raised.

KEYWORDS
carpal tunnel syndrome, nerve imaging, peripheral neuropathy, ultrasound elastography

1 | I N T RO D UC T I O N (CSA) proximal to the site of nerve compression. The normal fascicular

Electrodiagnostic studies have been the main diagnostic modality used in
the evaluation of peripheral neuropathy, providing insights into the func-
tion of peripheral nerves and the degree of myelin dysfunction and axonal
loss. In recent years, diagnostic ultrasound has gained traction as a com-
plementary investigation to electrodiagnostic studies. Rapid advancement
in the field of ultrasound, particularly in the development of high fre-
quency transducers, has resulted in improved resolution and image qual-
ity. Many clinically relevant peripheral nerves are located superficially
and, hence, readily accessible for ultrasound examination. Traditionally,
nerves are examined using B mode ultrasound and Doppler examination,
1,2
providing information about structure and vascularity.
Ultrasound has been used as a diagnostic tool for many forms of
peripheral nerve disorders, 3-5
initially focused on evaluation of compres-
sive neuropathies such as carpal tunnel syndrome (CTS), ulnar neuropa-
thy at the elbow (UNE), and fibular neuropathy. Typical findings in
compressive neuropathy include increase in nerve cross-sectional area
architecture seen on B-mode ultrasound of peripheral nerves may be lost
in compressive neuropathy, with associated reduction in nerve
echogenicity. Additional features may be seen such as reduced or exces-
sive nerve mobility, increased vascularity and anomalous anatomical
structures contributing to nerve injury.
Peripheral polyneuropathy has also been extensively evaluated using
standard ultrasound techniques. Ultrasound studies may facilitate diagno-
sis of inflammatory neuropathies such as Guillain-Barré syndrome,
chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal
motor neuropathy (MMN), and multifocal acquired demyelinating sensory
and motor neuropathy (MADSAM).1,3,6-8 Similarly, there are characteristic
ultrasound findings in some hereditary neuropathies, most notably Type
1A Charcot-Marie-Tooth disease, and ultrasound may aid in the process
of distinguishing hereditary neuropathy from CIDP.9 Routine ultrasound
studies do not typically show diagnostic changes in axonal neuropathy,
although some studies have identified correlations between nerve size
and vascularity and functional electrophysiological assessments.10-12

Muscle & Nerve. 2019;1–12. wileyonlinelibrary.com/journal/mus © 2019 Wiley Periodicals, Inc. 1

2 WEE AND SIMON

Beyond conventional B mode ultrasound, ultrasound elastography
techniques provide additional information on the elastic properties of
tissues. Ultrasound elastography as an imaging method to detect
changes in tissue stiffness was first described in the 1990s. 13
It is
known that tissue stiffness is altered in some pathological processes
such as in some tumors and in the presence of an increase in connec-
tive tissue. Ultrasound elastography has predominantly been used for
the evaluation of liver fibrosis and differentiation of malignant and
14,15
benign neoplasms, particularly in the breast. Elastography assess-
ment of hepatic fibrosis is now routine in patients with chronic viral
hepatitis, largely replacing liver biopsy.16 In breast cancer, various
ultrasound elastographic techniques have been used to discriminate
A B
F I G U R E 1 The elastic moduli include Young's modulus (E) and
shear modulus (G).22 A, Young’s modulus measures the effect on a
tissue of longitudinally applied forces. Elastic modulus is sometimes
used synonymously with Young’s modulus. B, Shear modulus is a
measure of the effect on the tissue of a shearwave (whereby a high
intensity pulse generates a secondary (shear) wave that travels
perpendicularly through the tissue)69
between benign and malignant breast tissues, and also for the identifi-
cation of malignant axillary lymph nodes in combination with gray scale
ultrasound.17 There is now increasing interest in the use of ultrasound
elastography for the evaluation of neuromuscular pathologies.18,19
Elastic moduli are used to quantify the differences in tissue elas-
ticity (Figure 1). Essentially elastic moduli measure the relationship
between the stress applied to a tissue and the deformation that
occurs in response to that stress. Calculations of both elastic moduli
assume that the tissue is homogenous and isotropic. This is not the
case in peripheral nerve, which adds a degree of variance to the calcu-
lated values. The shape and boundaries of the imaged tissue will also
impact these measurements.
Ultrasound elastography is broadly divided into strain elastography
and shear wave elastography (SWE), depending on the physical quan-
tity measured (Figure 2). Strain elastography can be further subdivided
based on the method of tissue excitation. The first method of tissue
excitation is manual compression of tissue by means of the transducer
by the sonographer. The degree of manual compression may have sig-
nificant intra and interobserver variation. Mechanical devices have
been developed in an attempt to further standardize the force deliv-
ered to the tissues.20 However, such devices are cumbersome and
mainly limited to research settings. Because the force applied to the
tissues cannot be precisely quantified, rendering standardization diffi-
cult, this technique provides qualitative information that is less useful
for research applications where serial studies are required, but may still
have a role in some clinical applications.
The second method, known as ambient strain elastography, relies
on tissue oscillations induced by vascular pulsations to cause tissue
distortion and then compares two areas to determine a strain ratio.

A B C

Strain elastography using external Strain elastography using internal Shear wave elastography
mechanical force mechanical stimulus (pulsations)

F I G U R E 2 Illustration of the ultrasound elastography techniques used in examination of nerves. A, Strain ultrasound elastography using
external manual compression to produce mechanical excitation. B, Ambient strain ultrasound elastography using cardiovascular pulsations to
produce mechanical excitation. Respiration may also be a form of mechanical excitation (not shown in diagram). Both forms of strain ultrasound
elastography report a ratio showing the deformation of the tissue of interest relative to an index tissue. C, Shear wave elastography (SWE), where
a focused acoustic radiation force is generated by the ultrasound transducer within a region of interest, which leads to the generation of shear
waves and tissue deformation. SWE reports a quantitative output in relation to the elasticity of the tissue such as shear wave velocity
WEE AND SIMON 3

This technique has an advantage compared with conventional strain
elastography using external compression, as it allows a more consis-
tent and reliable examination.21
Third, there is acoustic radiation force impulse (ARFI) strain imaging. In
this technique high intensity sonographic “push pulses” are generated,
causing underlying tissue displacement. Similar to ambient strain elasto-
graphy, ARFI strain imaging provides a more objective and consistent tis-
sue compression compared with compression strain elastography.
Unlike strain elastography, which measures tissue displacement, in
SWE, shear waves are generated after tissue excitation by an ARFI or
by controlled external vibration.22 The shear wave velocity (SWV) is
then measured providing a quantitative assessment of tissue stiffness.
The velocity is related to tissue stiffness with stiffer tissues associated
with faster shear wave propagation. Tissue stiffness may be reported
as SWV in meters/second (m/s) or as shear modulus in kilopascals
(kPA).23 The relationship between shear modulus and SWV is G = ρc2,

F I G U R E 3 Ultrasound shear
wave elastography in carpal tunnel
syndrome. A, A longitudinal B-mode
image of the median nerve at the
carpal tunnel demonstrating a typical
location for elastography
measurement (above the lunate
bone). B, Elastography values in a
normal wrist. C, Demonstrates
increased median nerve stiffness in
mild carpal tunnel syndrome, which is
further increased in severe carpal
tunnel syndrome (D). D, Note that in
severe carpal tunnel syndrome there
is an increase in the stiffness of all of
the contents of the carpal tunnel,
which correlates with increasing
carpal tunnel pressure70
4 WEE AND SIMON
where G is shear modulus, ρ is tissue density (ffi1000 kg/m3) and c is
SWV. Tissue density will vary for different types of soft tissues.
Controlled external vibration is used in transient elastography,
which is an alternative form of SWE that is almost exclusively used
for the assessment of liver fibrosis and has been widely validated for
this.24 The mechanical vibrating device is integrated within the trans-
ducer, which is also used to measure the SWV.
Regardless of the type of ultrasound elastographic techniques used,
the results can be displayed qualitatively as a color elastogram which
shows the relative difference in tissue stiffness within the region of
interest (Figure 3). By convention, red represents greater stiffness while
blue represents lesser stiffness. B mode imaging is used to guide selec-
tion of the region of interest as the elastogram is usually superimposed
on the B mode image. Hence, a good quality B mode image is the basic
starting point for obtaining a good elastographic assessment. The excep-
tion is transient elastography where B mode images are not generated
and thus cannot be used to guide region of interest selection.
A comprehensive review of the physics underlying ultrasound
elastography is beyond the scope of this review but is available
elsewhere. 22
Both strain elastography and SWE have been studied in the field
of neuromuscular research. Study protocols are heterogenous; hence,
comparison of results is challenging. Although SWE has inherent
advantages compared with strain elastography due to its quantitative
results, the choice of technique is often determined by availability of
elastography modes on the ultrasound machines, training, and famil-
iarity with the individual techniques.
This review provides an overview of the various studies on ultra-
sound elastography of peripheral nerves, and the relevance of these
studies to research and clinical practice.
2 | METHODS
Inclusion criteria were publications (including publications ahead of
print) on any form of ultrasound elastography performed on periph-
eral nerves or the brachial plexus, in any language with an English lan-
guage abstract available. Publications from June 2009 up to and
including January 27, 2019 were included. Further articles were iden-
tified by reviewing bibliographies of each included article. Articles
were excluded if they did not pertain to peripheral nerves.
We performed a literature review by a systematic search of
Pubmed and Medline. Search terms included (“elasticity imaging tech-
niques” [MeSH Terms] OR (“elasticity” [All Fields] AND “imaging” [All
Fields] AND “techniques” [All Fields] OR “elasticity imaging tech-
niques” [All Fields] OR “elastography” [All Fields]) AND nerve [All
Fields]. Additional relevant studies not identified in the above search
were detected by reviewing the references of included studies.
A total of 106 publications were identified from the literature sea-
rch and 42 articles were included. Sixty-four publications were
excluded as they were deemed irrelevant by the authors after
reviewing the abstracts. We have also excluded publications in rela-
tion to peripheral nerve tumors and sciatic nerve in patients with back
pain. No further publications were identified from the bibliographies
of included articles. Included studies are summarized in Table 1.
3 | RESULTS
3.1 | CTS and the median nerve
Currently, the majority of studies on ultrasound elastography have focused
on the median nerve at the wrist. Several studies using both strain
elastography and SWE have been published over the last 5 years. Table 1
summarizes the studies of ultrasound elastography in the evaluation of nor-
mal median nerve and CTS. In healthy control subjects, the median nerve is
stiffer at the wrist than the forearm.25,26 However, there was no significant
difference in the elasticity of the median nerve when between each side,
suggesting that contralateral limbs may serve as internal controls.25
Most of the studies in CTS have demonstrated a difference in
nerve stiffness in patients with CTS relative to control wrists, regard-
less of ultrasound elastography techniques (Figure 3).27-40 Relation-
ships between nerve stiffness and electrophysiological measures of
CTS severity were demonstrated in some studies, with increasing
severity of CTS associated with increasing nerve stiffness.27-30 Vari-
ous cutoff values have been proposed for the diagnosis of CTS along
with respective sensitivity and specificity values (Table 2).
Beyond single cutoff values, the ratio between the stiffness of the
median nerve at the carpal tunnel relative to the nerve in the forearm
has been proposed as a more sensitive measure of CTS, akin to the
nerve CSA ratios already commonly used in CTS and ulnar neuropa-
thy.32 A ratio of 1.48 between median nerve stiffness measures at the
wrist and forearm was proposed as a cutoff for the diagnosis of CTS,
yielding a sensitivity of 97.7% and specificity of 100%. It is interesting
that this value approximates the diagnostic cutoff limit of the “swelling
ratio” described when comparing the CSA at the wrist and forearm.
This raises the possibility that elastography and CSA are dependent.
This observation requires specific statistical analysis in future studies.
Ultrasound elastography has also been studied in specific patient
populations with CTS such as pregnancy and hemodialysis (Table 3).
Typically, these studies have identified similar findings to idiopathic
CTS. Relative increase in median nerve stiffness was also found in
patients with systemic sclerosis, leprosy, and acromegaly without
reported clinical CTS, although only one of three studies reported
results of electrodiagnostic studies.41-43 Although the significance of
these studies is difficult to ascertain without baseline elec-
trodiagnostic studies, given that the conditions may all be associated
with peripheral nerve injury, the results suggest that “cutoff” values
for the diagnosis of CTS will differ among patients with other medical
conditions affecting the peripheral nervous system, and should not
necessarily be stand-alone values to be applied blindly.
Nerve ultrasound elastography has also been used to evaluate
changes in the median nerve following decompressive surgery for
CTS. Median nerve stiffness decreases significantly after carpal tunnel
release, associated with reduction in symptoms.20,44 It was also shown
that the elastographic parameters improved more consistently before
changes in nerve morphology, indicating that nerve ultrasound
WEE AND SIMON 5

TABLE 1 Summary of studies on the use of ultrasound elastography in the evaluation of normal median nerve and carpal tunnel syndrome

Author & N (case: Region/ Elastography Imaging

publication year Study type controls) diagnosis technique plane Key findings
Zhu et al25 2018 Observational 40 Median nerve at the Shear wave Longitudinal Good consistency in evaluating
wrist and forearm healthy median nerve in
in normal subjects. normal subjects.
Bedewi et al26 Observational 20 Median nerve at the Shear wave Axial Median nerve is stiffer at the
2019 wrist and forearm wrist compared to the
in normal subjects. forearm in normal subjects.
Greening and Cross-sectional 26 Tibial and median Shear wave Longitudinal Increased stiffness of the
Dilley56 2017 nerves in healthy median and tibial nerves in
subjects. postures that result in
stretching of the nerves.
Cingoz et al27 Prospective 59:18 CTS Shear wave Longitudinal SWE is a potential modality to
2018 case control diagnose CTS and
differentiate mild from
moderate and severe CTS.
Zhang et al28 Prospective 72:46 CTS Shear wave Longitudinal Difference in SWV of mild to
2017 case control moderate vs. severe CTS.
Excellent interobserver
agreement for SWV
measurements.
Arslan et al29 Prospective 96:21 CTS Shear wave Axial Difference in SWV between
2018 case control controls and different CTS
severity. Excellent
interobserver agreement for
SWV measurements.
Kantarci et al30 Prospective 60:36 CTS Shear wave Longitudinal Difference in SWV of mild to
2014 case control moderate vs. severe CTS.
Excellent interobserver
agreement for SWV
measurements.
Orman et al31 Prospective 74:45 CTS Strain Axial Increased median nerve
2013 case control stiffness in CTS. No
difference between CTS
severity groups.
Paluch et al32 Prospective 87:34 CTS Shear wave Longitudinal Proposed to use ratio of SWE
2018 case control value of median nerve at
wrist to forearm instead of a
SWE cut off value.
Kesikburun Case report 1 CTS Strain Longitudinal Median nerve stiffer on the
et al33 2016 symptomatic side.
Martin et al21 Prospective 18:28 CTS Ambient strain Axial and Used ambient strain
2017 case control longitudinal elastography. Reliable, but
no difference in control vs.
CTS patients.
Yoshii et al34 Prospective 35:30 CTS Strain Axial Cyclic compression device
2017 case control used. Median nerve in CTS
patients stiffer than control.
Yoshii et al35 Prospective 38:60 CTS Strain Axial Cyclic compression device used
2015 case control to measure strain and
pressure applied. Best
diagnostic variable is
pressure/strain ratio.
Miyamoto et al36 Prospective 43:44 CTS Strain Axial Combined strain ratio and CSA
2014 case control improved diagnostic
accuracy. Good
interobserver agreement.
(Continues)
6 WEE AND SIMON

TABLE 1 (Continued)

Author & N (case: Region/ Elastography Imaging

publication year Study type controls) diagnosis technique plane Key findings
Tatar et al37 Prospective 35:36 CTS Strain Axial Strain elastography
2016 case control discriminated patients with
mild, mild to moderate, and
severe from controls.
Ghajarzadeh Prospective 60:44 CTS Strain Axial Used pixel counts on
et al38 2015 case control elastogram to establish color
indices showing a difference
between control and CTS.
Liao et al39 2015 Prospective 16:10 CTS Strain Axial Quantified and mapped
case control mechanical behavior of
median nerve, flexor tendons
and flexor retinaculum of
control and CTS patients.

Abbreviations: CTS, carpal tunnel syndrome; SWE, shear wave elastography; SWV, shear wave velocity.

TABLE 2 Cutoff values in median nerve elasticity in the diagnosis of carpal tunnel syndrome

n Severity

Study C CTS Cutoff Mild Moderate Severe Sen Spe PPV NPV
Kantarci et al30 2014 36 60 40.4kPa 55.1kPa+/−12.9 101.4kPa+/−26.7 93.3 88.9 93.3 88.9
Cingoz et al27 2018 18 59 38.25kPa 44.0kPa 82.0kPa 78.6 62.5 88.8 43.4
(32.5-59.5) (64.0-95.5)
Paluch et al32 2018 34 87 79kPa NA 96.6 100 100 91.9
28
Zhang et al 2017 46 72 3.0m/s 3.25m/s +/−0.41 5.24m/s+/−0.55 83.3 91.3 93.8 77.8
Arslan et al29 2018 21 96 3.23m/s 3.65m/s+/−0.53 4.01m/s+/−0.68 5.09m/s+/−0.57 81 82 95.1 50

Note: Note that direct comparison of the results is not valid given the differences in technique used (refer to Table 1).
C, controls; CTS, carpal tunnel syndrome; NA, not available; NPV, negative predictive value; PPV, positive predictive value; Sen, sensitivity; Spe, specificity.

elastography may be a more sensitive measure of nerve recovery than
CSA.20 Similar changes were identified after treatment with low level
laser energy and splinting.45 As such, median nerve ultrasound
elastography may be a potential objective measure useful to deter-
mine the effectiveness of CTS treatments in clinical practice and clini-
cal trial design. There is a distinct advantage in having an objective
measure to determine treatment effect given the prominent influence
of the surgical placebo effect on measures of clinical response. How-
ever, with any observation performed before and after an interven-
tion, it is critical to confirm the reproducibility of the techniques being
used, particularly in the case of strain elastography techniques.
It is relevant to consider whether performing elastography in addi-
tion to standard ultrasound imaging enhances the diagnostic evalua-
tion of patients with CTS. Elastography improved the diagnostic
accuracy of ultrasound studies when used in combination with con-
studies are typically around 70-80% sensitive for the diagnosis of UNE,
and adding in B-mode ultrasound assessments increases the diagnostic
sensitivity. There is presently only sparse data regarding the use of ultra-
sound elastography as a diagnostic modality in UNE. Like CTS, the stud-
ies have shown increased nerve stiffness at the site of injury but a
relationship between the severity of ulnar neuropathy and ultrasound
elastography values was not established.46,47 Increased nerve stiffness
has also been identified in patients with ulnar neuropathy in Guyon’s
canal at the wrist.48 Based on currently published data, the role of
elastography in the diagnosis of ulnar neuropathy remains unclear.
3.3 | Peripheral polyneuropathy
Evaluation of peripheral polyneuropathy is a common reason for

ventional B mode ultrasound. 36,37

Second, elastography may contrib- referral to the clinical neurophysiology laboratory. Electrodiagnostic

ute to the sonographic grading of severity of the CTS, which may be
of relevance to treatment selection.
3.2 | Ulnar neuropathy
UNE is traditionally more difficult to confirm than CTS, and further clinic
based diagnostic tools would be welcome. Detailed electrodiagnostic
studies are generally effective at detecting large-fiber peripheral neu-
ropathies. B-mode ultrasound studies are useful to identify inflamma-
tory and some genetic etiologies of peripheral polyneuropathy;
however, standard ultrasound studies add less value in patients with
axonal neuropathy.1 Axonal neuropathies are associated with loss of
myelinated axons and relative increase in intraneural connective tis-
sue. As such, serial measurement of nerve stiffness using ultrasound
T A B L E 3 Summary of studies on the use of ultrasound elastography in the evaluation of carpal tunnel syndrome/median nerve in relation with other conditions or following therapeutic
intervention

Author & N (case: Elastography

WEE AND SIMON

publication year Study type controls) Region/diagnosis technique Imaging plane Key findings
41
Ogur et al 2015 Prospective case 30:25 CTS in pregnant women Strain Longitudinal Stiffness of median nerve varies along the
control carpal tunnel, greater at the middle and
distal carpal tunnel. Higher in pregnant CTS
than pregnant controls.
Xin et al42 2017 Prospective case 49:22 CTS in hemodialysis. Strain Axial Higher strain ratio in patients with CTS
control compared to controls. Combined strain
ratio and CSA increases sensitivity of CTS
diagnosis.
Aslan et al62 2018 Prospective case 24:24 Median nerve in post stroke patients with Shear wave Longitudinal Chronic flexed wrist posture may cause
control (contralateral flexed wrist posture. median nerve compression and atrophy
wrist with increased stiffness. Excellent
serve as interobserver agreement.
control)
Burulday et al43 2018 Prospective case 30:40 Median nerve and acromegaly. Strain and Axial and Increased median nerve stiffness in
control shear wave longitudinal acromegaly.
Nogueira-Barbosa Prospective case 18:18 Median nerve and leprosy Strain Axial Increased median nerve stiffness in leprosy.
et al44 2017 control Moderate intraobserver and fair
interobserver agreement.
Yagci et al45 Prospective case 47:53:38a Systemic sclerosis versus idiopathic CTS and Strain Axial Increased median nerve stiffness in systemic
2017 control healthy volunteers. sclerosis. No significant difference between
CTS and controls.
Yoshii et al20 Cross-sectional 22 CTS post carpal tunnel release. Strain Axial Nerve swelling and stiffness may recover post
2017 carpal tunnel release with recovery of
elasticity more consistent.
Asadov et al46 2018 Prospective case 43:33 CTS post steroid injection. Strain Axial Carpal tunnel strain ratio improved post
control treatment but not median nerve strain
ratio. Strain ratio different in group
benefitting from treatment.
Tezcan et al47 Retrospective case 19:18 CTS post low level energy laser. Strain Axial Stiffness and CSA of the median nerve
2018 control decrease after low-level laser therapy for
CTS.
Aslan et al53 2018 Prospective case 25:32 Median and posterior tibial nerves in Shear wave Axial and Median and posterior tibial nerves are stiffer
control adolescents with T1DM. longitudinal in adolescents with T1 DM without DPN.
Interobserver agreement better in
longitudinal axis.

Abbreviations: CSA, cross-sectional area; CTS, carpal tunnel syndrome; DM, diabetes mellitus; DPN, diabetic peripheral neuropathy.
a
Systemic sclerosis:CTS:controls.
7
8 WEE AND SIMON

TABLE 4 Summary of studies on the use of ultrasound elastography in the evaluation of diabetic polyneuropathy

Author & N (case: Region/ Elastography Imaging

publication year Study type controls) diagnosis technique plane Key findings
Dikici et al51 Prospective 40:20 Tibial nerve in patients Shear wave Longitudinal Diabetic patients with DPN
2017 case with DM. had stiffer tibial nerve than
control those without DPN and
controls. SWE had better
sensitivity and specificity
than CSA.
Jiang et al52 Prospective 70:20 Tibial nerve in patients Shear wave Longitudinal Able to distinguish DPN
2018 case with Type 2 DM. patients with abnormal NCS
control from early DPN patients
with normal NCS. Excellent
inter and intraobserver
agreement.
Aslan et al53 Prospective 25:32 Median and posterior Shear wave Axial and Median and posterior tibial
2018 case tibial nerves in longitudinal nerves stiffer in adolescents
control adolescents with with T1 DM without DPN.
T1 DM without Interobserver agreement
DPN. better in longitudinal axis.
Ishibashi et al54 Prospective 198:29 Tibial nerve in Strain Able to distinguish subclinical
2016 case patients with DM. DPN from DPN.
control Elastography better than
CSA to identify DPN.

Abbreviations: CSA, cross-sectional area; DM, diabetes mellitus; DPN, diabetic peripheral neuropathy; NCS, nerve conduction studies.

elastography may provide an additional means to measure the pro-
gression of peripheral neuropathy (Table 4).
Using SWE, patients with type 2 diabetes mellitus with clinical dia-
betic peripheral neuropathy (DPN), with or without electrodiagnostic
evidence of peripheral neuropathy, demonstrated greater stiffness of
the tibial nerve at the ankle compared with diabetic patients without
49-52
DPN and normal subjects. The increase in nerve stiffness was
greater as the severity of neuropathy increased.52 Of interest, there is
increased tibial nerve stiffness in diabetic patients without DPN
suggesting that elastography may be able to detect DPN before it
becomes evident clinically or on nerve conduction studies.
These studies reflect the potential of SWE to detect both clinical
DPN and subclinical DPN that was not evident on standard elec-
trodiagnostic studies. Ultrasound elastography has potential as a
screening tool for early DPN in both type 1 and type 2 diabetes
mellitus, and has the advantage of less discomfort and potentially a
shorter examination time compared with a standard electrodiagnostic
examination. However, ultrasound elastography is not currently rec-
ommended as a standalone tool to diagnose DPN. The diagnosis of
DPN should be made in the appropriate clinical context, supported by
relevant clinical examination and neurophysiological findings.
seen in more distal nerve trunks. As such, echotextural analysis is limited
and detecting pathology is limited to identifying focal or diffuse nerve
enlargement. SWE findings in electrodiagnostically confirmed brachial
plexopathy in patients with breast cancer after radiotherapy
(RT) showed a marked increase in stiffness in the irradiated brachial
plexus relative to the un-irradiated contralateral plexus.53
Overall, performing ultrasound elastography on the brachial plexus is
technically challenging due to the nature of the anatomy of the area. The
reliability and reproducibility is accordingly low.55 Prominent vascular
structures and respiratory movements may potentially contribute to vari-
ability in results. However, the results above demonstrate the potential
clinical applications of ultrasound elastography in brachial plexopathy.
4 | DISCUSSION
This systematic review has analyzed the role of ultrasound
elastography as a tool to study peripheral nerves both in healthy and
disease states. In many areas, application of the technique is in its
infancy, although there appear to be emerging roles in the evaluation
of peripheral polyneuropathy and entrapment neuropathy.

4.1 | Challenges and technical factors

3.4 | Brachial plexus
There have been limited studies on the use of ultrasound elastography
to evaluate the brachial plexus.53-55 Ultrasound elastography is of
potential interest in brachial plexus pathology as there are limitations of
B-mode ultrasound in this region. Specifically, the normal brachial plexus
is relatively hypoechoic and does not usually show the fascicular pattern
4.1.1 | The effect of limb positioning
Several studies examined the effect of limb position on nerve ultra-
sound elastography.56-59 For example, median nerve stiffness can
change substantially (greater than 200%) with various positions of the
upper limb joints. The position in which the median nerve is thought
WEE AND SIMON
to be under least tension is with the shoulder abducted to 30 degrees,
elbow flexed to 90 degrees, and the wrist in maximum flexion. Maxi-
mum tension appears when the shoulder is abducted to 90 degrees
with maximum wrist and elbow extension.56 Similar influences of
lower limb positioning on tibial nerve elastography have been identi-
fied in most studies, although the magnitude of nerve stiffness change
is less. The lowest stiffness is seen with the hip and foot in the neutral
position and the knee slightly flexed, and the highest stiffness is seen
with the hip in maximum flexion, knee at maximum extension, and
ankle at maximum dorsiflexion.56-58
Overall, these studies are important because they contribute to
our understanding of the effect of biomechanical forces of perineural
tissues on nerve excursion during movements. Given these findings in
healthy subjects, it is likely that chronic limb posture associated with
disease (such as contracture or spasticity) may have an impact on
nerve stiffness and hence elastography results. This has been con-
firmed in poststroke patients with chronic flexed wrist posture where
the median nerve stiffness on the affected side was significantly
increased compared with the unaffected side.60 The authors postu-
lated that spastic flexion of the wrist had the potential to compress
the median nerve within the carpal tunnel, resulting in chronic ische-
mia and fibrosis of the median nerve, thus leading to increase in nerve
stiffness.
Limb position is also known to influence results of nerve conduc-
tion studies.61 As such, like in other diagnostic studies, consistent limb
positioning is an important methodological consideration in studies of
nerve ultrasound elastography.
4.1.2 | The effect of different anatomic regions
Upon commencing ultrasound elastography studies, it quickly
becomes apparent that the values obtained from nerves vary in differ-
ent anatomic regions. This may relate to the structures surrounding
the nerve or the propensity to recurrent subclinical injury at sites of
compression. Similar variation can be seen on B-mode ultrasound
studies at common sites of nerve compression.62
The number of studies on peripheral nerve ultrasound elastography
have increased over the past few years. However, it is difficult to com-
pare results across different studies due to differences in elastographic
techniques used. To apply results to clinical practice or clinical trials, a
standardized and uniform excitatory force is required, such as is used in
SWE. While strain elastography may still provide satisfactory results,
additional rigor regarding the choice of technique is required.
4.1.3 | The effect of ultrasound machine transducers
It is unclear at this point whether results are comparable across
machines made by different manufacturers even when similar tech-
niques are used as the results from studies of elasticity of tissue phan-
63-65
toms (ultrasound models with standardized elasticity) were mixed.
The use of different transducers within the same ultrasound machine
can result in a statistically different ultrasound elastography results using
63
phantoms for image acquisitions set at the same depth. One study
9
found that different machines yielded different SWV when the same
elastographic phantom was used.63 The differences were also present at
different acquisition depths and when different transducers were used.
On the other hand, another study demonstrated minimal variability
across imaging method/transducer combinations, imaging depths and
operators.65 Although only 2 ultrasound systems were included in this
study, which may limit the generalization of the study, the chosen sys-
tems are widely used in clinical and research settings.
With respect to reliability, studies of peripheral nerve elastography
have demonstrated excellent inter- and intra-observer agreement when
SWE was used in the examination of median nerve in normal subjects.25
In disease states, similar inter- and intra-observer agreement was also
reported in studies using SWE in patients with CTS and
DPN. 27,28,40,49,50
However, technical factors, such as the degree of pres-
sure applied through the probe, the angle of insonation, and the amount
of gel under the probe all affect elastography studies. As such, a careful
approach in the clinic is needed to translate the excellent inter- and
intra-observer agreement seen in controlled research setting into clinical
practice.
4.1.4 | The effect of transducer orientation
Some authors reported ultrasound elastography assessment with the
nerve in axial orientation while others used the longitudinal view.
Authors have commented that it was more difficult to obtain reliable
results when performing ultrasound elastography on nerves in the
axial view in their preliminary studies,25,56,66 which is also the experi-
ence of our own laboratory. Elastography values tend to be higher
when taken in longitudinal axis compared with transverse axis.51
4.1.5 | Other technical considerations and artifacts
Caution is also required regarding “bone-proximity” hardening arti-
facts.67 This is an artifact that occurs when the region of interest is
adjacent to a bone that affects even propagation of shear wave
resulting in unreliable readings. An increasing median nerve stiffness
was demonstrated as measurements were taken from the mid-fore-
arm, carpal tunnel inlet, and carpal tunnel outlet.67 This finding has
implications for the reliability of nerve ultrasound elastography results
of nerve running in close proximity to bones such as the median nerve
in the carpal tunnel and ulnar nerve at the cubital tunnel.
Besides bone, other structures adjacent to the peripheral nerve
may influence the elastographic parameters obtained using SWE if
they are included in the selected region of interest. Specifically, fluid-
containing structures such as blood vessels and cysts will be associ-
ated with signal drop out on elastograms. Stiff tissues such as tendons
and ligaments may contaminate regions of interest and, hence, artifi-
cially elevate measurements. For this reason, regions of interest must
be carefully selected to only include peripheral nerve tissue. It has also
not yet been established whether the region of interest should
exclude the epineurium, as is done with CSA measurements on B-
mode ultrasound.
10
Furthermore, the size of the region of interest may influence the
resulting values. While this has not been specifically studied in periph-
eral nerves, studies of breast lesions indicate that a smaller region of
interest may result in the best diagnostic performance.68
Finally, there are many technical considerations in performing
ultrasound elastography, such as transducer pressure and patient
positioning, which may all influence the final results.
4.2 | Recommendations for further research
Several technical factors still need to be resolved. Specifically, the
reliability of nerve ultrasound elastography using the various tech-
niques needs to be established. There is significant regional variabil-
ity in the ultrasound elastography of peripheral nerves, and as such
further studies on healthy control subjects are required to delineate
the nature of normal nerve stiffness in various anatomical regions.
The optimal methodology of ultrasound elastography requires broad
refinement.
Further studies comparing different ultrasound machine manufac-
turers are required to ascertain whether values are comparable between
systems.
With respect to the various clinical scenarios, most work has been
undertaken in CTS. Further studies of other compressive neuropathies
are required to confirm the relevance of ultrasound elastography out-
side CTS. In addition, further studies are needed to replicate the origi-
nal CTS studies given the concerns about artifactual increase in
ultrasound elastography values at the wrist and the influence of
closely associated structures described above.
There have been only limited studies in patients with peripheral
polyneuropathy, and it would be of relevance to both clinical prac-
tice and clinical trial design to examine nerves in patients with axo-
nal neuropathy and compare them with patients with inflammatory
and hereditary demyelinating neuropathies, as well as correlating
the findings with other diagnostic techniques and clinical severity
scales.
5 | CO NC LUSIO NS
Nerve ultrasound elastography is a new and rapidly developing field.
It has shown potential to add value to conventional ultrasound studies
but requires more work to be undertaken to develop it as a reliable
and useful technique. The role of ultrasound elastography in the eval-
uation of peripheral nerve disorders is yet to be clearly defined
although it appears to be promising as an adjunct to other diagnostic
studies and as a potential measure of treatment response. Further-
more, well-designed studies are required to advance applications of
the technique to peripheral nerve disorders.
Ethical Publication Statement: We confirm that we have read the
Journal’s position on issues involved in ethical publication and affirm
that this report is consistent with those guidelines. None of the
authors has any conflicts of interest to disclose.
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How to cite this article: Wee TC, Simon NG. Ultrasound
elastography for the evaluation of peripheral nerves: A
systematic review. Muscle Nerve. 2019;1–12. https://doi.org/
10.1002/mus.26624