REVIEW ARTICLE
Progress in the Application
of Ultrasound Elastography for
Brain Diseases
Jianyi Liao, MD, Huihui Yang, MD, Jinsui Yu, MD, Xiaowen Liang, MD, Zhiyi Chen, PhD
Received January 27, 2020, from the Depart-
ment of Ultrasound Medicine, Laboratory of
Ultrasound Molecular Imaging, Third Affili-
ated Hospital of Guangzhou Medical Univer-
sity, Guangzhou, China. Manuscript accepted
for publication April 8, 2020.
This work was supported by the Research
Projects of National Natural Science Founda-
tion of China (No. 81971621, No. 81671707),
the Natural Science Foundation of Guangdong
Province (No. 2019A1515012212), Major
Research Projects of Universities in Guangdong
Province (2019KZDZX1032), the Research
Fund for Lin He’s Academician Workstation
of New Medicine and Clinical Translation,
Scientific and Technological Livelihood
Projects of Liwan District (201904003) and
the Youth Foundation of the Third Affiliated
Hospital of Guangzhou Medical University
(grant 2017Q10).
Address correspondence to Zhiyi Chen,
PhD, Department of Ultrasound Medicine,
Laboratory of Ultrasound Molecular Imag-
ing, Third Affiliated Hospital of Guangzhou
Medical University, No.63 Duobao road,
510150 Guangzhou, China.
E-mail: zhiyi_chen@gzhmu.edu.cn
Abbreviations
ARFI, acoustic radiation force impulse;
HIE, hypoxic ischemic encephalopathy;
MCA, middle cerebral artery; MRI, mag-
netic resonance imaging; ROI, region of
interest; SWE, shear wave elastography;
TBI, traumatic brain injury; US, ultra-
sound; VTQ, virtual touch tissue
quantification
doi:10.1002/jum.15317
© 2020 by the American Institute of Ultrasound in Medicine | J Ultrasound Med 2020; 9999:1–12 | 0278-4297 | www.aium.org
Ultrasound (US) can be used to evaluate the brain structure and nervous system
damage. Patients with neurologic symptoms need rapid, noninvasive imaging with
high spatial resolution and tissue contrast. Magnetic resonance imaging is currently
the most sensitive and specific imaging method for evaluating neuropathologic
conditions. This approach does present some challenges, such as the need to trans-
port patients who may be seriously ill to the magnetic resonance imaging suite and
the need for patients to remain for a considerable time. Cranial US provides a very
valuable imaging method for clinicians, which can make a rapid diagnosis and eval-
uation without ionizing radiation. The main disadvantage of cranial US is its low
sensitivity and specificity for subtle/early lesions. In recent years, with the rapid
development of anatomic and functional US technology, the practicability of US
diagnosis and intervention has been greatly improved. Ultrasound elastography
may have the potential to improve the sensitivity and specificity of various cranial
nerve conditions. Ultrasound elastography has received considerable critical atten-
tion, and an increasing number of studies have recognized its critical role in
evaluating brain diseases. At present, US elastography has been applied to the eval-
uation of traumatic brain injury, ischemic stroke, intraoperative brain tumors, and
hypoxic ischemic encephalopathy. The latest animal experiments and human clini-
cal trial developments in the applications of US elastography for brain diseases are
summarized in this review.
Key Words—brain; shear wave elastography; ultrasound elastography
T he latest development of neurosonographic technology
continues to broaden the accuracy, sensitivity, and specificity
of ultrasound (US) in the diagnosis of intracranial abnorm-
alities. Since the 1980s, when transcranial Doppler US was first
allowed to describe the anatomy and hemodynamics of the thin part of
the skull, the clinical and functional application of neurosonography
has expanded substantially.1 Because of its high convenience, high
efficiency, bedside capability, and lack of radiation, US has become a
useful tool for brain examinations. Compared with magnetic
resonance imaging (MRI), its limitations include operator experience,
lack of quantification, and lower prognoses. In the past few years,
contrast-enhanced US, US elastography, and ultrafast Doppler
imaging have enhanced diagnostic importance in brain diseases.2,3
With the progress of these technologies, full familiarity with these new
technologies and devices is very important for successful clinical
applications and improvements in prognoses. Contrast-enhanced US
can be used to show different degrees of brain injury, such as cerebral
hemorrhage, hypoxic ischemic brain injury, cerebral infarction, and
Liao et al—Ultrasound Elastography for Brain Diseases
other diseases.1 It has important prognostic relevance to
clearly show the evolution of hyperperfusion or
reperfusion after injury. However, contrast-enhanced
US requires additional contrast agents, and at the same
time, the peripheral vein needs to be punctured, which
entails an invasive examination. Ultrafast Doppler
imaging is a high-spatial and -temporal resolution
imaging method for cerebral vascular anatomy and
hemodynamic information mapping,3 but it fails to show
extravascular lesions, such as cerebral hemorrhage,
periventricular leukomalacia, changes in brain parench-
yma, and hydrocephalus. Ultrasound elastography is a
noninvasive imaging technology, which does not need
an additional contrast agent. It is another functional US
technology, which can quantify tissue hardness and
reflect the tissue composition or structure, edema, injury,
and perfusion.2 Ultrasound elastography plays an
important role in traumatic brain injury (TBI), brain
tumors, ischemic stroke, and hypoxic ischemic encepha-
lopathy (HIE).2 This review will provide a comprehen-
sive update on US elastographic techniques currently
available in animal and clinical trials.
Ultrasound elastography is a US imaging modality
that evaluates the elasticity and stiffness of soft tissue.
Given that elasticity is an important physiologic charac-
teristic, the distribution of the internal elastic modulus
is closely related to the biological characteristics of an
organism.3 The elastic value of tissue reflects the orga-
nizational hardness, which is related to the tissue’s
molecular composition and pathologic tissue struc-
tures.4,5 Compared with conventional US imaging
modalities, US elastography estimates altered soft
tissue elasticity for accurate visualization of various
pathologic conditions. An increasing number of studies
using US elastography to investigate cranial diseases
have been conducted in recent years.6–9
Principles of US Elastography
In recent years, the development of noninvasive
methods to evaluate the mechanical properties of tis-
sues based on elastography has received substantial
attention. These techniques exploit various pathologic
changes in the soft tissue elasticity to generate qualita-
tive and quantitative information that can be used for
diagnostic purposes. Ultrasound elastography was first
proposed by Ophir et al10 in 1991 and can be used to
2 J Ultrasound Med 2020; 9999:1–12
medically define both the stiffness of a tissue and dis-
placement (strain) in response to an applied force.4
According to the latest European guidelines, US
elastography is divided into 2 categories: quasistatic
(compressive) elastography and dynamic shear wave
elastography (SWE).11,12 Quasistatic elastic imaging
mainly includes real-time tissue elastic imaging,
whereas dynamic SWE includes transient elasto-
graphy, acoustic radiation force impulse (ARFI) imag-
ing, and SWE. The main principle of US elastography
is measurement of tissue deformation in response to
external compression. Changes in elasticity and tissue
deformation caused by compression are measured,
processed, and finally displayed in real time on color-
coded elastic maps. The fundamental method of US
elastography is to apply an external or internal
(including its own) dynamic or static stimulus to a
tissue. Based on physical rules, such as elasticity and
biomechanics, the tissue will produce a response, such
as displacement, strain, and speed, which vary
depending on the distribution of the tissue.
Quasistatic elasticity imaging reflects the relative
hardness of a tissue. The basic principle is that con-
stant pressure acts on the surface of the object to
cause tissue deformation. Tissue strain information is
obtained by collecting radiofrequency echo informa-
tion before and after applying pressure. A new gener-
ation of real-time tissue elastic imaging technology
has enabled detection of the deformation of liver
tissue caused by cardiac beat compression and uses
tissue diffusion quantitative analysis technology to
analyze the elastic image. Real-time tissue elastic
imaging is a semiquantitative elastographic technique
that measures the ratio between lesion tissue and nor-
mal parenchyma; however, the ratio is relative and
does not represent an absolute value of the viscoelas-
tic parameter. Notably, the quality of a quasistatic
elastographic scan depends largely on the operator’s
experience and skill level. In contrast, dynamic SWE
reflects the absolute stiffness (Young’s modulus) of a
tissue. Transient elastography is a commonly used
1-dimensional method. The main principle of tran-
sient elastography is that the vibration axis of the US
transducer emits a low-frequency elastic wave that
propagates in tissue. At the same time, the US trans-
ducer transmits a US beam to track the propagation
of the elastic wave and measure its velocity, subse-
quently displaying the hardness value in the image.13

The physician can accurately assess the hardness of
the tissue based on the image information. Dynamic
elastography defines the elasticity of the tissue by
measuring the propagation velocity of the shear wave.
A stiffer tissue corresponds to higher shear wave
velocity.14 Acoustic radiation force impulse imaging is
a tissue-based mechanical excitation technique that
propagates shear waves away from the excitation
region by providing local pulsed acoustic radiation
forces; the tissue response of the displacement is used
to generate an elasticity map and produce an elastic
diagram.15 The SWE principle is as follows: the US
transducer emits focused acoustic radiation pulses
into the body tissue, causing longitudinal displace-
ment of tissues at different depths at almost the exact
same time, eventually producing shear waves
(Figure 1). The tissue elasticity maps are displayed in
real time after ultra–high-speed imaging and color
coding, and Young’s modulus values of the tissue are
quantitatively analyzed.
The speed of shear wave propagation depends on
the stiffness of the tissue.16 At present, the shear wave
imaging system usually uses the equation E = 3q(cs)2 to
calculate the Young’s modulus, where q represents
the tissue density, and cs represents the shear wave
velocity.16,17 Most commercial suppliers provide
Figure 1. Schematic diagram of brain imaging using US shear
wave imaging. A shear wave (green) propagates perpendicular to
a compressed wave (blue) to image the brain tissue.
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Liao et al—Ultrasound Elastography for Brain Diseases
automated computing systems that convert kilopascals
to meters per second and meters per second to kilopas-
cals. Most US systems display the stiffness values in kilo-
pascals and meters per second in tabular form.
Generally, a tissue with a larger elastic modulus (ie,
greater hardness) produces a lower response, such as a
smaller amplitude or higher velocity, which US imaging
in combination with digital signal-processing or digital
image-processing techniques uses to organize and evalu-
ate the tissue. The internal response is evaluated to
reflect differences in mechanical properties, such as the
elastic modulus within the tissue structure. Ultrasound
elastography allows the user to identify areas where
lesions have developed in organs that are not generally
evident via conventional US. The data obtained from
elastographic examinations increase the likelihood of
identifying early lesions and an accurate analysis.5
Application Progress
Ultrasound elastography is a noninvasive technique
for measuring tissue stiffness. As more clinicians
and researchers have determined that many disease
processes affect tissue stiffness, the application of
these technologies has grown considerably, providing
new imaging goals for disease biology. Many clinical
applications of US elastography are rapidly develop-
ing. Ultrasound equipment with elastographic options
can more accurately image and evaluate the proper-
ties of lesions located in many organs, such as the
breast, thyroid, testis, prostate, lymph nodes, and
brain tissue.3,18–23 The progress of US elastography
applied to brain tissue is reviewed below.
Normal Performance of Cranial US
Elastography
With the continuous advancement of US instrumen-
tation, many US devices are available on the market
that include elastic imaging technology that can mea-
sure the shear wave velocity and tissue stiffness in a
region of interest (ROI; Figure 2). A seminal study
by Macé et al24 applied SWE to live rat brains and
found that the dynamic shear modulus values of brain
tissue ranged from 2 to 25 kPa (an average of
12 kPa), and they quantified these measurements
3
Liao et al—Ultrasound Elastography for Brain Diseases
across different anatomic regions. At the same time,
the reproducibility of this technique was found to be
favorable, and a similar spatial distribution of elastic
properties was observed in all rats.
Recently, several scholars have applied US
elastography to neonatal brains, showing that full-term
newborn brains show greater hardness than those of
preterm neonates. Kim et al9 performed strain elastic-
ity imaging on 21 healthy neonates. Compared with
the white matter around the ventricle, the caudate
nucleus, and the subcortical white matter, the cerebral
cortex gray matter showed higher elasticity, and the
caudate nucleus was less elastic than the white matter
around the lateral ventricle. Compared with the sub-
cortical white matter, the periventricular white matter
showed higher elasticity Furthermore, the corrected
gestational age was positively correlated with cortical
gray matter scores, and the correlation was almost per-
fect. Virtual Touch tissue quantification (VTQ; Sie-
mens Medical Solutions, Mountain View, CA) is a
kind of acoustic radiation elastography and a new tis-
sue characterization technology. Its advantage is that it
can quantitatively detect the viscoelasticity of tissue in
a specific area and display it with corresponding indica-
tors. The US transducer emits thrust pulses to the ROI
where elastic detection is required and collects subtle
Figure 2. Two-dimensional shear wave imaging of the parietal lobe of the neonatal brain. Two-dimensional shear wave imaging was per-
formed on the parietal lobes of neonates, and the Young’s modulus of elasticity and shear wave velocity were measured.
4 J Ultrasound Med 2020; 9999:1–12
changes in longitudinal compression and lateral vibra-
tion after the tissue is stressed. The shear wave velocity
of the tissue elasticity around the tissue in the ROI is
quickly calculated. Another study used VTQ of the
ARFI to assess tissue elasticity in neonates of different
gestational ages.25 Acoustic radiation force impulse
examinations were performed in 41 neonates with dif-
ferent gestational ages without brain injuries, and VTQ
was used to quantify the hardness of the gray and
white matter tissues. Researchers were able to establish
baseline VTQ values in the gray and white matter
brain regions of preterm and term neonates.25 In addi-
tion, the study found that VTQ (high elasticity) was
significantly higher in term neonates than that in pre-
term neonates. Presumably, this increase in elasticity is
directly related to the increase in myelination during
normal brain development. At the same time, the
report stated that no adverse events directly related to
ARFI were found in the study.25 Albayrak and Kasap26
included 44 full-term and 39 preterm neonates in their
study and measured SWE of the white matter around
the thalamus and occipital periventricular regions. The
Pearson correlation coefficient was used to determine
the relationship between gestational age and the stiff-
ness of the thalamus and periventricular white matter.
The results of the study showed that the hardness

values of the thalamus and ventricular white matter
brain parenchyma were significantly lower in the pre-
term neonate group than those in the term group. In
addition, the research team also found that the per-
iventricular white matter hardness values of both
groups were lower than those of the thalamic stiffness.
According to the characteristics of the receiver operat-
ing characteristic curve, the optimal cutoff values for
determining prematurity were an average thalamic
hardness of less than 8.28 kPa and a periventricular
white matter hardness of less than 6.59 kPa. In that
study, the hardness of the brain parenchyma of pre-
term neonates (measured in the thalamic and per-
iventricular white matter) was significantly lower than
that in the term neonate group. In addition, a signifi-
cant positive correlation was found between gestational
age at birth and hardness values. This study showed
that using 2-dimensional SWE can differentiate
between the brain stiffness values of preterm infants
and term neonates, and the results could be used as a
reference standard for evaluating neonatal brain
stiffness.
In another study, Ertl et al27 recruited 108 healthy
patients as research participants. All participants were
divided into groups by age: 20 to 40, 40 to 60, and
older than 60 years. The results of 2-dimensional
Figure 3. Summary of image processing in a sample rat brain. A, Shear wave imaging mode. B, Two-dimensional grayscale imaging mode.
C, The scale of the shear wave image of the brain was readjusted to 0 to 35 kPa to enhance the contrast. D, The area of interest was manu-
ally selected to avoid the skull and artifacts. E and F, Hematoxylin–eosin and cresyl violet staining representing corresponding brain tissue
sections, respectively. Reproduced with permission from Xu et al.7
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Liao et al—Ultrasound Elastography for Brain Diseases
SWE with a trans-septal window on parenchymal
elasticity showed that the left-side value was 3.34 kPa
and the right-side value was 3.33 kPa. They found no
correlation between elasticity values and body mass
index or sex. However, they observed a high correla-
tion between elasticity values and age. Obtaining the
normal range of cranial brain values by US
elastography is conducive to comparing lesion tissues
with normal tissues, which will be beneficial for com-
parative evaluations of subsequent brain disease
development. It is important to note that the specific
values of the elastic modulus are still different because
of the differences in the conditions set by multiple
instrument agents. More research is needed to obtain
more representative data.
Traumatic Brain Injury
Traumatic brain injury is a common brain disease.
Traumatic brain injury refers to a series of injuries in
the brain caused by external forces.28–30 It is a major
global cause of death and disability, affecting millions
of patients each year. The annual incidence of TBI is
estimated to be 295 per 100,000.31 In the United
States alone, approximately 1.5 million patients
5
Liao et al—Ultrasound Elastography for Brain Diseases
currently receive TBI treatment. Every year, 50,000
people die of brain trauma, which has a huge emo-
tional and economic impact on society.32 The pattern
of acute head trauma varies widely. Symptoms may be
present with primary and secondary conditions, includ-
ing brain swelling, diffuse axonal injury, and mild to
moderate TBI. Traumatic brain injury is one of the
major causes of death and severe disability in
populations younger than 45 years. Therefore, an accu-
rate assessment is particularly important for clinical
evaluation of traumatic injuries, treatment selection,
and prognostic evaluation in patients with TBI.33–35
Regarding basic research on TBI, biomechanical
research must accurately evaluate mathematical models
of brain tissue mechanical parameters. Due to limited
intracranial spatial resolution, US imaging has tradi-
tionally been used less frequently for TBI analyses
compared with other conventional imaging modalities.
However, the development of new US techniques,
such as contrast-enhanced US, microvascular imaging,
and elastography, has substantially improved its capa-
bilities. These advances in US imaging provide TBI
imaging researchers and clinicians with new opportuni-
ties for clinical monitoring and understanding of the
pathologic mechanisms of TBI. In one study, Xu et al7
constructed TBI models in mice and rats and used
SWE to image them 24 hours after injury or immedi-
ately after injury, measuring and comparing the hemi-
spheric stiffness values, and performed comprehensive
analyses in conjunction with brain histologic examina-
tions (Figure 3). The results showed that the stiffness
values of the cerebral hemispheres of the pseudo-TBI
rodents were consistent. Twenty-four hours after TBI,
the relative brain tissue stiffness values of the mice and
rats decreased ipsilaterally and contralaterally, respec-
tively, relative to each other and compared with those
of the pseudo-TBI rodents. The absolute tissue elastic-
ity of the rats increased, whereas the increase was not
significant in mice. This study showed that differences
in rodent hemispheric stiffness values 24 hours after
mild TBI may reflect the observed edema and hemor-
rhage on the same side of the TBI and the known
decrease in cerebral blood flow in the cerebral hemi-
sphere. If these results are validated, then SWE may
serve as a method to detect adverse changes in the
brain fluid content after mild TBI. If new US technol-
ogy is further developed, then SWE may play an
important role in the detection and diagnosis of TBI.
6 J Ultrasound Med 2020; 9999:1–12
The lack of adequate acoustic imaging windows has
prevented imaging experts and clinicians from using
US as a first-line, routine assessment tool in patients
with TBI. The information provided by the new US
technology complements traditional imaging tech-
niques. Due to the important inherent advantages of
US (such as cost-effectiveness, portability, rapid avail-
ability, and lack of radiation), US imaging of the brain
will play an important role in the future treatment of
patients with TBI.
Brain Tumors
Abnormal tissue is known to have different mechanical
properties than normal tissue. This feature is widely
used by clinicians to detect tumors or lesions in accessi-
ble organs by manual palpation. Although direct “palpa-
tion” of the brain during certain neurosurgical
procedures is feasible, this technique is extremely lim-
ited. Quantitative assessments of brain elasticity in the
body will be of great interest for many applications in
neurology and neurosurgery. For diagnosis, a brain elas-
ticity examination can help improve tumor detection.
In neurosurgery, real-time brain elastography can pro-
vide new intraoperative tools for lesion location and
edge assessment. The elastographic method uses
changes in soft tissue elasticity caused by specific patho-
logic or physiologic processes.36 For example, com-
pared with normal surrounding or nearby tissues, many
solid tumors have different mechanical properties.
Compared with normal brain elasticity, significant dif-
ferences in the elasticity of tumor tissues have been
described, with the tumor tissues being harder than
normal tissue. In addition, low-grade gliomas are signifi-
cantly harder than high-grade gliomas. Low-grade glio-
mas are hypothesized to be harder than high-grade
gliomas because high-grade malignancies tend to have
greater central necrosis, resulting in decreased tissue
stiffness.8 With the advancement of neurosurgery from
traditional open surgical approaches to minimally inva-
sive procedures, US imaging has become widely used in
neurosurgery. Compared with computed tomography
and MRI, intraoperative US images not only display the
size and shape of a tumor but also provide more
detailed information regarding the inside of the tissue.
In 2005, Scholz et al37 used vibrography techniques to
compare brain tumors with normal brain tissue and
 Liao et al—Ultrasound Elastography for Brain Diseases

evaluated tumor stiffness. This pioneering study
showed that normal brain tissue and brain tumors are
sufficiently flexible to be detected and distinguished.
Chauvet et al8 used SWE to evaluate different brain
tumors during surgery. Sixty-three patients were
included and classified on the basis of 4 main types of
tumors: meningiomas, low-grade gliomas, high-grade
gliomas, and metastases. The Young’s modulus mea-
sured by SWE provided new insights for differentiating
brain tumors: the Young’s modulus values of brain
tumors in the 4 subgroups were 33.1  5.9 kPa,
23.7  4.9 kPa, 11.4  3.6 kPa, and 16.7  2.5 kPa,
respectively. Normal brain tissue is characterized by a
repeatable average stiffness of 7.3  2.1 kPa. In addi-
tion, the stiffness of low-grade gliomas was different
from that of high-grade gliomas, whereas normal brain
stiffness was very different from that of low-grade glio-
mas. Multiple studies have shown significant differences
in the elasticity values of the most common types of
brain tumors. Neurosurgeons can use the information
available from intraoperative SWE to predict diagnosis
and guide resection. More specifically, stiffness mea-
surements can help surgeons quantitatively distinguish
between high- and low-grade gliomas. This differentia-
tion is very important because the tumor grade is sub-
stantially associated with the prognosis and treatment
strategy. The use of SWE can reduce the risk of mis-
takes in the intraoperative assessment of the grade, facil-
itate classification, and clarify the best intraoperative
strategy.
Ischemic Stroke
Ischemic stroke is one of the more common diseases
in neurology. Reduced cerebral blood flow after
stroke causes ischemia in the ipsilateral cerebral hemi-
sphere, cerebral edema, and increased intracranial
pressure and occurs in the contralateral hemi-
sphere.38,39 Xu et al6 used SWE to measure the hemi-
spheric elastic modulus in transient ischemic injury
models of male C57BL/6 mice. Elastic images of the

Figure 4. Summary of stroke image processing in a mouse with 72-hour MCA occlusion. A, Shear wave elastography. B, Two-dimensional
grayscale image. C, Analysis of brain hemisphere area hardness: manual selection of ROIs to avoid skulls and artifacts, including one in the
right hemisphere (dark blue). In the visible region, the shear modulus is low. D, Corresponding triphenyl tetrazolium chloride histologic
specimen from the same mouse showing damage in the right hemisphere, distinguished by white areas. This damage is related to the loca-
tion of the low shear modulus observed in the elastoplastic image. Reproduced with permission from Xu et al.6

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Liao et al—Ultrasound Elastography for Brain Diseases
murine brains were collected 24 and 72 hours after
middle cerebral artery (MCA) occlusion. The shear
modulus values of the ipsilateral and contralateral
hemispheres of these mice were measured and com-
pared with the corresponding values of control ani-
mals (Figure 4). The results showed that the shear
modulus of the ipsilateral hemisphere was significantly
decreased, and the shear modulus of the contralateral
hemisphere was significantly increased 24 hours after
induction of ischemic stroke compared with those in
the control animals. A significant difference was
observed between the ipsilateral and contralateral
shear modulus values at 24 and 72 hours after infarc-
tion. The results suggest that the difference between
the hemispheric mean values of the intracerebral shear
modulus of stroke-affected animals at 24 and 72 hours
after stroke may reflect the initial formation of cere-
bral edema and cerebral blood flow occurring on the
same side of the ischemic infarct. A transient increase
in intracranial pressure and an initial reduction in
blood flow with subsequent development of contralat-
eral hemispheric edema have been described. Martín
et al40 induced transient cerebral ischemia in adult
male Sprague Dawley rats to assess brain shear wave
velocity at 1, 2, 4, and 7 days after induction
Figure 5. Schematic diagram of the neonatal cranial US scan pro-
cedure. The US transducer was placed at the anterior sacral area
of the neonate to image the intracranial structure and identify
lesions.
8 J Ultrasound Med 2020; 9999:1–12
compared to that in control animals. On the seventh
day after the onset of cerebral ischemia, the shear
wave velocity in the occluded MCA region changed
from 3.5 m/s in normal brain tissue to 2 m/s. Over
time, the decrease in the shear wave velocity caused
reduced tissue elasticity due to brain tissue damage.
In the MCA occlusion region, the shear wave velocity
decreased linearly after the first day. On the second,
fourth, and seventh days, the shear wave velocity was
significantly lower than that of the control animals. In
the contralateral hemisphere of the MCA occlusion
region, no evidence of changes in brain tissue elastic-
ity was found at any time after ischemia. The conse-
quence of stroke is necrotic liquefaction of the brain
tissue, but this mechanism occurs in the microstruc-
ture of the tissue. However, necrotic liquefaction can-
not be detected directly by SWE. Shear wave
elastography only measures changes in tissue elasticity
at the macroscopic scale. An increase in the water
concentration may be observed in the edematous tis-
sue, and even if the water is inelastic, the propagation
of the shear wave will be slowed, since the moisture
content is lower than that of the wavelength
(λ ≈ 4 mm) in the brain tissue. Therefore, US
elastography provides a potential method to detect
and evaluate subtle changes in the brain after ischemic
stroke. With continuous research, US elastography is
expected to provide useful information for clinically
relevant diagnosis and treatment.
Neonatal Hypoxic Ischemic
Encephalopathy
With the progression of perinatal medical technology,
the success rate for rescue of critically preterm neo-
nates has generally improved, but the incidence of
abnormalities of the nervous system in the short and
long terms is high. Early diagnosis and treatment of
different types of brain injury in preterm neonates
warrant exploration.41,42 As preterm neonates with
brain damage often lack specific neurologic symptoms
and signs, an auxiliary examination plays an important
role in the diagnosis of brain damage. The commonly
used diagnostic imaging methods are US imaging,
computed tomography, and MRI. Computed tomog-
raphy can diagnose HIE, but it is radioactive; the res-
olution of MRI is relatively high, but neonates need

to be transported to a specific examination room over
a long distance. In the diagnosis of neonatal brain dis-
eases, US has been widely used because of its nonin-
vasive, economical, simple, easily confirmed, and
highly repeatable operations (Figure 5).43
Hypoxic ischemic encephalopathy is a brain dis-
ease caused by hypoxia and ischemia during the perina-
tal period, which not only threaten the lives of
neonates but also represent important influencing fac-
tors of brain injury sequelae.44 Therefore, understand-
ing how to diagnose early neonatal HIE and intervene
in a timely manner has considerable clinical impor-
tance and is also the focus of extensive research locally
and abroad. The acoustic radiation force imaging tech-
nique can sensitively and quickly detect changes in the
brain tissue elasticity of neonates, especially premature
neonates, after ischemia and hypoxia and may play an
important role in the diagnosis of early neonatal brain
injury. Several studies have used acoustic radiation
force pulse imaging techniques to evaluate the hard-
ness of human neonatal brain parenchyma. Chen
et al45 examined neonates for HIE in preterm and full-
term groups. Measurements were performed at the
bilateral parietal lobe, thalamus, and cerebral falx. Com-
pared with full-term neonates without HIE, preterm
neonates without HIE had higher values of parietal lobe
hardness. Compared with term neonates with HIE, the
right thalamus and bilateral parietal lobes of preterm
neonates with HIE had higher elasticity values. For neo-
nates, cranial US is one of the most effective screening
tools for diagnosing brain diseases. Currently, cranial US
is a routine imaging modality for assessing preterm neo-
nates and any neonates suspected of having brain dam-
age. Given that neonatal rats with varying degrees of
hypoxic ischemic brain injury have different tissue elas-
ticity values, elastographic techniques can be applied in
the newborn brain.46 According to the latest research
findings, several neonatal cases have been identified in
which increased brain edema was associated with pro-
gressive hypoxic ischemic brain injury. The shear wave
velocity and brain stiffness were found to be increased.
This phenomenon requires further research to verify its
reproducibility before clinical application.1 A large num-
ber of biochemical and neural tissue changes occur after
injury, and flow changes, microvascular damage, tissue
regeneration and reorganization, and the potential con-
tribution of cytokines and inflammatory cells to such
brain tissue elasticity changes should be considered/
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Liao et al—Ultrasound Elastography for Brain Diseases
explored. Further research will be required to establish
normative data and to understand how this technique
distinguishes normal and pathologic states in the brain.
In summary, US elastography still requires many well-
designed studies to confirm its value in brain disease
analysis. The research that is presently available is quite
encouraging, and this method will likely become increas-
ingly popular and widely accepted in the next few years.
Safety of US Elastography
As discussed, 2-dimensional SWE has been widely
applied in other parenchymal tissues without any asso-
ciated risks and is currently recommended by relevant
guidelines.47–49 In addition, experimental animal stud-
ies also provide valid data for brain tissues. In neuro-
surgery studies, no side effects have been reported in
research conducted based on the ALARA (as low as
reasonably achievable) principle.50 According to early
animal data, SWE in the newborn brain is also safe.
A recent study showed that after experiments on the
brains of newborn mice, no effects on their learning
and memory or histologic changes in the brain paren-
chyma were observed. A Western blot analysis of pro-
teins expressed in the brains of neonatal mice revealed
that interference in an important pathway (the pho-
sphoinositide 3-kinase–protein kinase B–mammalian
target of rapamycin pathway) occurred with US imag-
ing lasting longer than 30 minutes. The main role of
this pathway is to regulate expansion of the nervous
system during development. However, the research
team assumed that the damage could be repaired with
continued growth.51 When 2-dimensional SWE is used
to evaluate the neonatal brain, the total scan time
should be more carefully monitored. Brain US
elastography has also shown a good safety profile. No
obvious immediate or late-stage adverse reactions have
been reported in the current literature.
Advantages and Limitations
Due to its advantages of objectivity, noninvasiveness,
convenience, and rapid development, US elastography
has become an important research focus in the field of
US medicine. As a new method to reflect the character-
istics of the mechanical properties of tissues,
9
Liao et al—Ultrasound Elastography for Brain Diseases
elastography can provide information concerning tissue
elasticity that cannot be acquired by conventional imag-
ing modalities, expanding the diagnostic range of con-
ventional US and compensating for its inadequacies.
The echo signal received by the US transducer compli-
cates identification of different tissues with the same
acoustic impedance; nevertheless, tissue elastography
can distinguish their differences. With its wide applica-
tion in clinical practice, the unique application value
advantages of elastography are increasingly apparent
compared with the traditional imaging examinations.
Ultrasound elastography of the adult brain is more diffi-
cult to perform because the skull attenuates sound
waves. To obtain accurate elastic parameters, the skull
generally must be opened. Nevertheless, in neonates,
the anterior fontanel is not completely closed, which is
conducive to sound window penetration and to imple-
mentation of brain US elastography. However, several
deficiencies in the effective acquisition of elastographic
data remain. Ultrasound elastography results may still
vary according to the type of device used and
elastographic parameter calculation methods, and
elastographic image quality can also be affected by mul-
tiple factors, such as the transducer frequency, radio-
frequency sampling rate, and bandwidth.52,53 However,
in clinical applications, measurement of the shear wave
velocity has been found to be affected by many factors,
such as respiratory motion, heart motion, and the depth
of the ROI, which leads to a decrease in the accuracy of
the measurement results.11 Under the same forces, a
deeper position of the measured object corresponds to
a higher elasticity grade and increased hardness of the
object. One possible explanation is that a deeper loca-
tion of an object corresponds to greater difficulty in pro-
ducing deformation. When real-time tissue elastography
is used to evaluate brain lesions, the elastic images are
easily disturbed by peripheral pressure. When this pres-
sure is increased, the corresponding tissues will show
marked displacement, which will lead to deviations in
the diagnosis of the lesions. The traditional elastic
strain imaging technique either uses a transducer to
compress the tissue or depends on the intrinsic motion
of the tissue (e.g., heart motion and breathing motion).
However, the imaging effect is limited by the depth
and position of the image, and artifacts are easily pro-
duced. When using acoustic radiation elastography to
diagnose neonatal brain diseases, although the influ-
ence of external factors such as the applied pressure on
10
imaging can be reduced, corresponding safety prob-
lems may remain. Larger study populations are
required for long-term tracking, identification, and
analysis. Notably, the measurement results obtained
from different commercially available US systems may
differ. Researchers and clinicians should contact the
specific manufacturer regarding the critical values for
developing specific elastographic applications.
Summary and Prospects
In summary, as a new emerging technology, US
elastography not only expands the diagnostic scope of
conventional US but also enriches information con-
cerning treatment efficacy. This technology can identify
the nature of lesions and reduce the rate of missed
diagnoses and misdiagnoses. Ultrasound elastography
provides a new method for clinical diagnosis of brain
diseases and increases the effectiveness of modern US
technology. With the advancement of science and tech-
nology, improved computing methods, continuous
improvement of elastographic imaging equipment, and
continuous development of clinical application skills,
US elastography is expected to overcome the existing
deficiencies of traditional US and will likely become
more useful for brain disease analysis. Although the
application of US elastography in brain imaging is still
at an early stage, the current research in animal models
and human experiments is tremendously promising
and exciting. As a standard brain-imaging aid, US
elastography is an effective approach that can enhance
diagnostic and prognostic evaluations of patients with
various neurologic diseases. To further explore the field
of cerebral elasticity, a standardized cerebral US elastic-
ity imaging process must be established through multi-
center studies. In the future, the technology can be
applied for early diagnosis and therapeutic evaluations
of cerebral hemorrhage, periventricular leukomalacia,
HIE, hydrocephalus, and other conditions.
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