RESEARCH ARTICLE

Copyright 2013 American Scientic Publishers

All rights reserved
Printed in the United States of America

Journal of Medical Imaging and

Health Informatics
Vol. 3, 114, 2013

Ultrasound Diagnosis of Breast Cancer

Yufeng Zhou
School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore
Ultrasound is a popular imaging modality for its safety and low cost. Its role in the diagnosis of breast cancer
is discussed, and its performance is then compared those of mammography (gold standard) and MRI. Besides
conventional B-mode and color or power Doppler ultrasound images, latest development of acoustic radiation
force impulse (ARFI) and supersonic shear imaging and their application in breast diagnosis are introduced.

Keywords: Breast Cancer, Sonography, Magnetic Resonance Imaging, Doppler Ultrasound, Acoustic
Radiation Force Impulse Imaging, Supersonic Shear Imaging.

1. SONOGRAPHY IN BREAST
CANCER DIAGNOSIS
Ultrasound (US) is becoming a popular clinical diagnosis modality in the past decades with the major advances in transducer,
electrical circuit, digital signal processing, and system control,
and has already been applied to large varieties of diseases
because of its uniqueness of low cost, exibility, non-invasion,
and non-ionization. US has the ability to image and evaluate
patients internal anatomy structure and physiology in real-time
with astounding clarity. Therefore, it makes signicant contributions to healthcare.
The breast examination by US started from 1951 with an optimistic opinion that US would replace mammography eventually
in detecting breast cancer.1 However, with more comprehensive
studies, it illustrates that US is only valid for the discrimination
between cysts and solid masses. The performance of US depends
on the size, number, location, and properties of the lesions, the
operation skills, and the system specications (i.e., resolution and
frequency).
The diagnosis of cysts is clinically and socially important for
remarkable reduction on the number of breast biopsies and early
therapy, particularly for those non-palpable ones. Aspiration or
biopsy is not required to simple cysts,2 which reduces the healthcare cost, anxiety and discomfort of patients during with surgery.
However, for palpable masses, aspiration is advocated due to its
less expense, availability at many centers, and often accompanies
with therapy, but not much desirable for many women due to
its discomfort. US is the appropriate method of lesion diagnosis
with accuracy of 96100% if it is not palpable and applicable
for aspiration.25 A simple cyst usually has smooth walls, sharp
anterior and posterior borders, no internal echoes, and posterior
enhancement (Fig. 1). Using a gel or uid offset and aligning
the target to the focal region with better resolution could dene
the anterior wall, especially for supercial lesions. In comparison, posterior enhancement is mostly inconsistent. The smallest
J. Med. Imaging Health Inf. Vol. 3, No. 2, 2013

detectable cysts in the breast depends on the type, location, breast

size, and US system, and are usually 23 mm.4 Scanning the
lesion carefully in two projections and discriminating wall irregularities are useful in nding intracystic tumors.3 6 Occasionally, inappropriate equipment setting (i.e., time compensated gain
(TCG), locations of focal point(s), or brightness), technical limitation (i.e., low driving frequency of transducer, inherent noise
in beam forming, or poor resolution), or missing subtle changes
by the operator may result in diagnostic error.
However, it is hard to judge whether a visible mass is benign
or malignant in the sonography because of the similar features.
Only circumscribed masses, such as a cyst, require differential US diagnosis (Fig. 2). A mass with stellate or spiculated
borders as well as a circumscribed mass contains suspicious
micro-calcications does not require US for further evaluation.
However, calcium deposition inside a cyst is easily mistaken as
micro-calcications because of the similar granular appearance.7
Both benign and malignant breast masses may be partially or
completely obscured by the normal tissue. When a palpable mass
is not visible in the mammography, US will be applied to determine whether it is cystic or solid. Because all solid masses may
not be visible in the sonography even in dense breasts, the falsenegative detection of breast cancer is about 25%.8 A palpable
mass that is invisible in both mammography and sonography
strongly needs biopsy histology (Fig. 3).
Occasionally, diffuse mastitis does not have an appropriate
response to antibiotics, which suggests abscess formation. Therefore, mammography may not be appropriate for pain and edema
of the breast and will not display a discrete abscess cavity
with inammation-induced higher density. US is an alternative
approach for diagnosing and guidance of surgical drainage of
abscesses, which have various sonographic characteristics, such
as irregular hypoechoic or anechoic cavities, occasional uiduid or uid-debris levels, posterior enhancement, distortion on
surrounding, and overlying skin thickening (Fig. 4).

2156-7018/2013/3/001/014

doi:10.1166/jmihi.2013.1157

RESEARCH ARTICLE
(a)

J. Med. Imaging Health Inf. 3, 114, 2013

(b)

(c)

Fig. 1. A palpable lesion in the left upper inner quadrant of breast shown in (a) oblique and (b) craniocaudal mammograms (arrows), and (c) a simple cyst
in the transverse sonogram (arrows) with smooth borders, no internal echoes, posterior enhancement, and lateral shadows from the smoothly curved walls.

US seems a more sensitive imaging modality for positive axillary lymph nodes in the breast cancer that is commonly involved
but rarely evaluated than physical examination and axillary mammography with compression.9 The capability of metastatic nodes
by US and physical examination are 72.7% and 45.4%, respectively, with equal specicities of these two techniques (97.3%)
in a study of 60 patients.10 Furthermore, US has success in the

(a)

guidance of ne-needle aspiration of cyst, biopsy of solid masses,

preoperative needle, and wire localization.1113
Fibroadenomas are smoothly round, oval, or lobulated lesions
with homogeneous internal echoes and posterior enhancement
while carcinomas are irregular solid masses with internal echoes
and attenuated brightness.1415 Therefore, their US images have
certain overlaps, and accurate determination is possible with

(b)

Fig. 2. A 3-cm palpable broadenoma found by biopsy is shown in (a) oblique mammogram (arrows) and (b) the longitudinal sonogram as a well-outlined,
slightly lobulated, and homogeneous solid mass (arrows).

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J. Med. Imaging Health Inf. 3, 114, 2013

(a)

(b)

(c)

Fig. 3. False-negative (a) oblique and (b) craniocaudal mammograms with moderate density but no discrete mass and (c) the longitudinal sonogram of a
4-cm palpable mass in the lower inner quadrant of the right breast, which was revealed as ductal carcinoma in biopsy.

conventional sonography.3 1619 Ratios of the length to the anteroposterior diameter of the cancer and broadenomas are signicantly different, and the oblong conguration in broadenomas
is more apparent in supercial position.20
US has been implemented in screening breast cancer, particularly those with dense tissue, in Japan, Europe, and Australia. However, its inability of detecting all types of breast
cancers and a substantial number of non-palpable cancers who
are visible and invisible at mammography, respectively, prevents US being a valuable screening modality because of its
unacceptably high false-negative rate, (0.347% with mean of
20.7%), which may be even higher for small and clinically occult
cancers.21 Most importantly, US detection of a signicant number
of non-palpable carcinomas with good-quality negative mammograms is not always satisfactory. In addition, US has a remarkable false-positive rate in asymptomatic patients because of the

shadowing produced by many normal structures22 and similar

sonographic features between fat lobules and solid tumors.23 US
diagnosis is unable to exclude malignancy and identify an underlying reason for the asymmetric broglandular tissue, but mammography and physical examination.8
In summary, sonography at high quality and high frequency
used in a judicious manner is a valuable tool in the clinics. Sonography is applied to the evaluation of circumscribed lesions found
in the mammography, palpable masses invisible in the mammography, and a cyst is in the differential diagnosis. The need
for biopsy on a simple cyst could be eliminated after the US
diagnosis. Otherwise, a biopsy or mammographic follow-up is
required no matter of the sonography results, in which US provides not much clinically useful information and, subsequently, is
not suggested.4

Fig. 4. Longitudinal sonogram of (a) a mastitis and large area of induration that has an irregular abscess cavity with echoes and posterior enhancement, and
(b) a severe mastitis with multiple small (3-9 mm) scattered abscesses (solid arrows), thick skin (open arrows), high echogenicity, structure distortion, and a
sharp interface between normal and abnormal tissue (curved arrow).

RESEARCH ARTICLE
2. COMPARISON OF MAMMOGRAPH,
SONOGRAPHY AND MRI
The diagnostic sonography in the breast has been investigated
for at least 30 years.1 Sonography did not detect any proven
cancers that were missed by mammography. Mammography was
found superior in detecting 97% of the 64 pathologically conrmed cancers, while sonography can only seek 58% of them.
Mammography detected more than 90% in all cancer categories,
including those amenable to cure, but the value for sonography
is only 48% (40% of the non-palpable malignancies and 8% of
the cancers smaller than 1 cm that did not yet spread to axillary
lymph nodes). Tumor size and axillary lymph node status are
the most important prognostic indicators for breast cancer, and
the mammography done far outperformed sonography in detecting the smallest cancers and those that did not yet spread to
axillary nodes. A major factor limiting the ability of sonography for non-palpable breast cancers seems to be its inability to
image the micro-calcications (individual particles 0.20.5 mm).
Mammography-positive sonography-negative cancers usually are
small, non-palpable, and have not yet spread to axillary lymph
nodes, whereas very rare sonography-positive mammographynegative cancers are always detectable by physical examination
and more likely to have metastasized. Therefore, upgrading to
state-of-the-art mammography is preferred to improving the cancer detection ability rather than purchasing an US system.24
The role of sonography in breast diagnosis is an ongoing
investigation.25 US is a widely accepted method for discriminating cysts from solid masses and guiding interventional procedures. Sensitivities and accuracy of the US in the discrimination
between benign and malignant breast nodules are not high
enough to reply on, and its value in comparison or addition to
mammography is still in debate.26 Thus, US is not recommended
as a screening tool due to the failure in establishing its efcacy.27
US was performed to detect
(1) circumscribed lesions (possible cysts),
(2) palpable lesions visible in mammography,
(3) palpable lesions not visible in mammography, and
(4) non-palpable lesions visible in mammography in a 2-year
prospective study of 4,811 cases.
As a result, 1,103 cases (23%) were reclassied their suspicion
levels of malignancy.25
US can achieve a certain improvement in breast cancer diagnosis as an adjunct to mammography. Although it not very dramatic
for the total cohort of patients, such an improvement was considerable for the subgroup of patients, especially among the young
patients with low sensitivity of mammography. Mammographic
classication based on a relatively high threshold for biopsy provides US opportunity of increasing sensitivity. If further advances
are achieved in US diagnosis, especially for diffusely growing
cancers, a further acceptance of US in the breast cancer diagnosis
is expected.25
Young breasts, despite low occurrence, are more sensitive to
radiation so that the limited exposure is desired. US imaging
is usually performed in the initial study. No further evaluation is necessary for a cyst. If the mass is solid or invisible in
sonography, at least one mammogram will be obtained to seek
micro-calcications. Although mammography allows detection of
almost all palpable masses, adequate positioning may not be possible for very deep lesions adjacent to the chest wall or in a
4

J. Med. Imaging Health Inf. 3, 114, 2013

slim woman with a mass at the extreme periphery of the breast.

Altogether, US is not a substitute for mammography, nor does a
negative sonogram rule out carcinoma.4

3. DIAGNOSIS OF MICROCALCIFICATION
The identication of micro-calcication (i.e., smaller than
0.5 mm) on mammography has been widely studied and is indispensable in the early detection of breast cancer.12 3545% of
discovery of non-palpable breast cancers depends on the presence of clusters of micro-calcication on mammography.2 Microcalcications are brighter reectors than the surrounding breast
parenchyma without an acoustic shadow in sonography.6 In a
study of 89 tumors found in 84 patients, micro-calcications
were visible in 44 breast cancers using high resolution ultrasound
(HRUS, 49%), 40 cancers using X-ray mammography (XRM)
(45%) and 46 breast cancers on histology (53%).28 HRUS has
the sensitivity of 95%, specicity of 87.8%, and accuracy of
91% in the detection of micro-calcication. The corresponding
values for histology are 80%, 71.4% and 75.3%, respectively.
Therefore, US is a sensitive and reliable diagnosis modality
for micro-calcication in breast cancer presented within a mass
lesion.28 HRUS detected micro-calcication in 6 cancers that
were negative on XRM, among them 4 were positive on histology. These false positives may be due to the requirement of
sufcient deposition of calcium phosphate for the identication
of micro-calcications for XRM but not necessary for US. In
addition, XRM is a survey of the entire breast, whilst US is
tomographic and its multi-section analysis may increase detection accuracy.28
Calcications that occur within masses are more visible on US,
which is partially because most malignant solid nodules provide
a great echogenicity. In contrast, sonography for benign calcications with many hyperechoic and heterogeneous bers are less
reliable. Hence, malignant are more visible in the sonography
than benign calcications. Although the sensitivity of sonography for calcications is lower than that of mammography, sonographically visible calcications within a solid mass have high
possibility of malignant.29
The different types of ductal carcinoma in situ (both comedo
and non-comedo) correlate with mammographic patterns of
micro-calcications and the latter inconsistent foci of microcalcications. Malignant micro-calcications within ductal carcinoma in situ and microscopically invasive ductal carcinoma,
which do not have associated sonographically demonstrable
masses, are difcult to identify on US.28

4. DIAGNOSIS OF LYMPH NODE

METASTASES
The presence of axillary lymph node metastases in breast cancer
is an important symptom in assessing prognosis and determining
the treatment plan. Axillary staging is conventionally performed
by axillary lymph node dissection. The use of sonography in
detecting metastases is feasible and would reduce the number of
false-negatives at sentinel node biopsy.30
In the studies including palpable and non-palpable nodes,
if the size (>5 mm) or node visibility in sonography was
used as the criterion for positivity, sensitivity varying between
66.1% (95% condence interval: 52.677.9%) and 72.7% (49.8
89.3%), with no heterogeneity between them, including both

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J. Med. Imaging Health Inf. 3, 114, 2013

(a)

(b)

(c)

Fig. 5. Extensive clustered pleomorphic micro-calcication within a large area of (a) increased soft tissue density, highly suspicious of malignancy in mammogram, (b) multiple bright echogenic spots (small white arrows) within a large markedly hypoechoic mass lesion in sonography, corresponding to the
mammographic ndings of micro-calcication, and (c) inltrative ductal carcinoma with micro-calcications (arrows) in H&E histology with magnication of 125.

gold standard of axillary lymph node dissection and sentinel

node biopsy. However, the variation of specicity is from 44.1%
(34.354.3%) to 97.9% (88.799.9%), and heterogeneity is found
between the results.30 If the lymph node morphology was used
for positivity, variations of sensitivity and specicity are from
between 54.7% (41.767.2%) and 80.4% (73.986.2%) to 92.3%
(74.999.1%) and 97.1% (9099.6%), respectively. Whist in the
studies, including only non-palpable nodes, if the node size in
sonography (>5 mm) or its visibility was used as a criterion for
positivity, sensitivity varies from 48.8% (39.658%) to 87.1%
(76.194.3%) and specicity from 55.6% (44.766.3%) to 97.3%
(86.199.9%). If the node morphology was used as the criterion for positivity, variations of sensitivity and specicity were
from 26.4% (15.340.3%) and 88.4% (82.193.1%) to 75.9%
(56.489.7%) and 98.1% (90.199.9%), respectively. In the US
guided biopsy, the sensitivity varies between 43.5% (3354.7%)
and 94.9% (88.598.3%) and specicity between 96.9% (91.3
99.4%) and 100% (96.2100%), although sensitivity is reduced
because it is necessary to visualize the node or to fulll the sonographic criteria for malignancy.
Therefore, sonography is moderately sensitive and specic in
the diagnosis of axillary metastases in breast cancer. However,
it cannot be used as a sole method for decision, whether to perform axillary lymph node dissection. When suspicious metastatic
axillary nodes are found, a US guided biopsy can be performed,
which increases the specicity (100% vs. 96.5% use of sonography alone) at the cost of certain aggression and extra resources.
Subsequently, about half of the axillae with metastases would be
detected with a high specicity (96.5%) and a good sensitivity
(48.4%), and then those positive patients would undergo axillary

lymph node dissection. The remaining negative would be candidates for sentinel node biopsy, which improves the negative
predictive value of the sentinel node biopsy because of the lower
prevalence of metastases and thereby increases the certainty of
sonography-based diagnosis.30

5. SURVEILLANCE OF WOMEN AT HIGH

FAMILIAL RISK FOR BREAST CANCER
Breast cancer susceptibility gene (BRCA) mutation carriers, who
exhibit adverse histopathologic features of biologic aggressiveness, has a lifetime risk for up to 6580% to develop breast
cancers rather than sporadic ones.31 A comparative cohort study
was carried out to investigate the effectiveness of mammography, US, and MRI in 529 women with increased familial risk.32
Annual conventional mammography was performed with at least
two views (medio-lateral oblique and cranio-caudals) per breast,
and additional or spot compression views where appropriate.
Diagnoses were coded according to the Breast Imaging Reporting and Data system (BI-RADS) diagnostic categories. Breast
ultrasound was performed with 7.5- to 13-MHz probes. Standard contrast-enhanced MRI of both entire breasts was performed
on a 1.5 T system after injection of 0.1 mmol/kg gadopentetate
dimeglumine.
43 breast cancers were identied in the total cohort (34 invasive, 9 ductal carcinoma in situ). Overall sensitivity of diagnostic
imaging was 93% (40 of 43); overall node-positive rate was 16%,
and one interval cancer occurred (1 of 43, or 2%). In the analysis by modality, sensitivity was low for mammography (33%)
and US (40%) or the combination of both (49%). MRI offered
5

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J. Med. Imaging Health Inf. 3, 114, 2013

Fig. 6. (A) Mammogram and (B) sonogram of suggestive of cancer (arrowhead) on a 53-year-old patient with a family history of breast cancer and personal
history of benign breast biopsy on the left breast revealed no clinical ndings. (C) MRI showed only scar tissue on the left (arrowhead), but revealed a
suspicious lesion in the right breast (long arrow), which was an invasive ductal cancer, pT1b, G3, N0, M0 by biopsy. Absence of cancer in the left breast was
conrmed by 4-year follow-up.

a much higher sensitivity (91%). The sensitivity of mammography in the higher-risk groups was 25%, compared to 100%
for MRI. Specicity of MRI (97.2%) was equivalent to that of
mammography (96.8%).33 Mammography, either alone or combined with sonography, seems insufcient for diagnosis of early
breast cancer in patients who are at increased familial risk with
or without BRCA mutation. If MRI is used for surveillance, a
signicantly higher sensitivity, specicity, and positive predictive
value (PPV) could be achieved for diagnosis of intraductal and
invasive familial or hereditary cancer at a more favorable stage.33
Indeed, not even half of all cancers were prospectively diagnosed
with a combination of mammography and sonography, whereas
breast MRI alone diagnosed 91% (39 of 43). However, MRI is
still an investigational technique for surveillance and screening of
asymptomatic women with normal conventional diagnosis. Apart
from cost, the most important reason of breast MRI is low PPV,
low specicity, and allegedly low sensitivity for ductal carcinoma
in situ (DCIS). However, MRI has the highest sensitivity for invasive as well as intraductal cancers, which was not achieved at the
expense of similar specicity as that of mammography.33 Combined with mammography, sonography can compensate some but
not all the shortcomings of mammography with a substantial
number of false-positive diagnoses. In comparison to surveillance
by MRI, mammography was of limited and US of no additional
value. US screening may, however, be useful in the long interval
between the annual surveillances.33
6

Altogether, surveillance with MRI allows an earlier diagnosis of familial breast cancer and has better performance than
mammography or the combination of mammography with highfrequency sonography.

6. DOPPLER ULTRASOUND
The well-known phenomenon of tumor angiogenesis is associated with an increase in malignancy.34 35 These abnormalities included tumor stains, irregular large caliber vessels, and
either prolonged or rapid emptying of vessels presumably due
to blood pooling, leaky vessels, and/or arterio-venous shunts.
Among the established breast diagnosing techniques, mammography and sonography have undisputed contributions. However,
no adequate information on the growth pattern and the prognosis
of breast humps are available. Doppler US has been investigated
to differentiate benign lesion from malignant solid breast masses
from their different Doppler characteristics, (i.e., symmetric signals in normal tissue, no signals in cysts, and higher maximum
systolic and end-diastolic pressures in malignant tumors)3638
with high sensitivity and specicity despite considerable overlap
in the benign and malignant types.39 40 Highly sensitive color
Doppler on even minute tumor vessels could map the tumor
blood ow both quantitatively and qualitatively.
Color Doppler in 2 of 39 malignant breast disease patients
with the tumor size of 0.68.0 cm (median 2.0 cm) did not
show any vascularity. In comparison, no blood vessels were

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found in 10 of 73 benign masses (0.34.7 cm with the median

of 1.4 cm). In patients with puerperal mastitis, abscess, phylloides tumor, and haemangioma, vascularization was extremely
high. Benign and malignant breast lesions have signicantly different Doppler US features. There is a remarkable overlap of
carcinoma and benign tumor in peak ow velocity.41 The discrepancies between reported studies may be related to the US
system and the scanning techniques.42 The accuracy for smaller
blood vessels, especially for poorly vascularized masses, could
be improved using a high-frequency and high-resolution system. Furthermore, color Doppler may also be able to reduce the
number of biopsy and histological evaluations for patients with
suspicious mammograms.41
In another prospective study, the color Doppler ow images of
55 proven breast cancers were performed, and 82% of them were
classied on a three-level scale of vascularity (minimal: 14%,
moderate: 29%, marked: 53%), suggesting its clinical potential
use. 4% of the ow images had no detectable ow. 69% of the
normal breasts had moderate or marked vascularity (minimal:
28%, moderate: 41%, marked: 28%), and 3% were avascular.
Because of poor distinction between normal tissues and cancer,
more sensitive Doppler methods are required for the low vessel
ow that is rather specic for malignancy.
Power Doppler sonography has advantages over color Doppler
type with high sensitivity in the detection of vascular ow. Power
Doppler ndings were considered positive when at least one
vessel was associated with the solid breast mass (Fig. 7). In
one study comprising 176 breast cancers in 176 patients (2791
years, mean std: 56 15 years), 65% and 10% of the cases
were invasive ductal carcinoma and invasive lobular carcinoma,

respectively.43 Among them, 73% showed vascularity and 27%

showed no vascularity on power Doppler sonography. The sizes
of the lesions in which power Doppler sonography revealed vessels and no vessels were 780 (21 15) mm and 355 (14
14) mm, respectively (p < 001); however, these two categories
overlapped. Tumor vascularity revealed by power Doppler sonography correlated strongly with detection of lymph node involvement and lymphatic vascular invasion with sensitivities of 93%
and 90%, but low specicities of 32% and 35%, respectively.
More importantly, patients with breast cancer in whom vessels were not revealed by power Doppler sonography were also
unlikely to have lymph node involvement and lymphatic vascular invasion with negative predictive values of 90% and 87%,
respectively.
In conclusion, Doppler US could detect moderately small vessels around and within tumors, even if they were too small to be
displayed on conventional B-mode images. Although only cancer patients were involved, the presence of similar vessels in the
normal breast indicates Doppler imaging as a technique with a
presumably higher specicity but much lower sensitivity.

7. ACOUSTIC RADIATION FORCE

IMPULSE IMAGING
The limitations of palpation and biopsy as well as CT, MRI,
and US imaging require a noninvasive, cost-effective, safe, and
accurate modality for detecting changes in tissue pathology. Several groups have developed elasticity-based imaging modality in
order to exploit the relationship between pathology and tissues
mechanical properties.

(a)

(b)

(c)

(d)

Fig. 7. Patterns of tumor vascularity in breast cancer revealed by power Doppler sonography. (a) penetrating, irregularly branching prominent vessels,
(b) peripheral and penetrating vessels, (c) few central vessels, and (d) no vessels.

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Acoustic radiation force is due to the momentum transfer from

the propagation of acoustic waves to the dissipative medium.44
The absorption is in the direction of wave propagation, whereas
the reection depends on the angular scattering properties of the
target.45 Under plane-wave assumptions, the generated radiation
force in the tissue is.44 46
F =

2I
c

(1)

where F is a force per unit volume,  is tissue attenuation, I is

the acoustic intensity, and c is the sound speed of tissue.
Acoustic radiation force impulse (ARFI) imaging, a novel transient elastography method, generates radiation force inside the
tissue, detects the consequent localized displacements by correlating the ultrasonic echoes, and then estimate the mechanical
properties of target.47 All tissues are inherently viscoelastic and
response differently to mechanical excitation, on the order of ten
micrometers, which can be monitored both spatially and temporally and is inversely proportional to local tissue stiffness. The
tissue volume exposed to radiation force is determined by the
focal characteristics of the transmitting transducer, and the temporal prole of the force is dependent on transmitted pulse shape,
usually with the duration less than 1 ms. In this method, a single
diagnostic transducer is used both to apply localized radiation
forces inside the tissue and to track the resulting tissue displacements, which guarantees good alignment and ease of real-time
implementation. ARFI imaging has many potential advantages,
such as identifying and characterizing a wide variety of soft tissue lesions, atherosclerosis, plaque, and thrombosis in clinics.
There is good correlation between the ARFI image and the
matched B-mode image in the breast at the depth of 525 mm
(Fig. 8(a)). In the ARFI image, the boundary of an infected
lymph node as a palpable lesion appears stiffer than its interior
and the tissue above it (i.e., smaller displacements). The oval
structure in the B-mode image immediately above and to the left
of the lesion (upper arrow) is outlined as a softer region of tissue
than its surroundings in the ARFI image. The transient response
to ARFI excitation depends on tissue structure and mechanical
properties. In Figure 8(b) the region of tissue spanning 1318 mm
moves further, and exhibits a later peak displacement than the
others, which is slightly darker in the matched B-mode image.

Peak displacements of ARFI images range from 5 to 13 m

in vivo, and the lesion in the B-mode image exhibits a stiff
outer boundary and a softer interior in the matched ARFI image
(Fig. 9). Core biopsy of this lesion demonstrated an infected
lymph node with a more liquid abscessed component. While
these ndings are circumstantial, they do suggest potential correlation between the clinical pathology and the ARFI image.
The discrepancy of the brightness in the B-mode image and
detected stiffness indicates no direct relationship between them
as expected.
There is no speckle in the ARFI images. Thus, the traditionally dened speckle SNR of a conventional US imaging system
is in general lower than that of the ARFI imaging system. Comparison of the contrast of the ARFI and B-mode images yields
variable results. The applied radiation force and resulting tissue
displacements are predominantly in the direction of wave propagation. With the current imaging geometry, only these axial displacements are tracked, and the anticipated error is 0.14 m.48
While useful information might be derived from the lateral displacement, tracking of such small lateral displacements (<1 m)
is extremely challenging. The increase in displacement estimation error with depth rather than the decreased SNR does not
degrade image quality.49 The resolution of an ARFI imaging system depends on transducer specications and conguration, the
number and location of pushing beam, spatial relationship of
pushing locations and tracking beams, and the pulse length and
kernel size in the tracking algorithm as well as the tissue property itself, and is at least comparable to that in the conventional
B-mode imaging.
The acoustic energy required to generate detectable displacements in vivo is large (<1,000 W/cm2 in situ), but its duration is
short (0.7 ms in each pushing location). So the radiation forceinduced displacement in soft tissue is detectable while maintaining a temperature increase below 1  C.50 51 Altogether, the
operating parameters of ARFI imaging are safe, and will not
result in an increased risk to the patient.
In summary, ARFI imaging is feasible in vivo for the diagnosis of breast. Differences in displacement maps are correlated
with tissue structure as observed in the matched B-mode images.
The transient response of tissue varied with tissue type and its

Fig. 8. (a) ARFI image of tissue displacement at 0.8 ms (right), and matched B-mode image (left) in an in vivo female breast. The transducer is located at
the top of the images, and the colorbar scale is microns. (b) Displacement through time at different depths in the center of the ARFI image (0 mm laterally).

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Fig. 9.

RESEARCH ARTICLE

ARFI images at times of (a) 0.4 ms, (b) 1.2 ms, (c) 2.1 ms, and (d) 3.0 ms in the in vivo female breast (the same dataset as shown in Fig. 8).

visco-elastic behavior. Although these ndings are preliminary,

they present several opportunities for ARFI imaging with a considerable clinical promise.

8. SUPERSONIC SHEAR IMAGING

Supersonic shear imaging (SSI) is another transient elastography approach and combines the remote palpation of the ARFI
technique and the ultrafast echographic imaging approach, which
provides a quantitative elasticity map with less dependence on
operator in comparison to static elastography.52 53 The initial

Fig. 10. Generation of a conical shear wave front propagating in the imaging plane of the echographic probe.

clinical investigation illustrates its potential as an adjunct for

sonography.
SSI generates a remote radiation force by focused ultrasonic
beams as ARFI. Consequently, a transient shear wave will be
formed by the remote tissue vibration. Several pushing beams
at increasing depths are transmitted to generate a quasi-plane
shear wave front that propagates throughout the region-of-interest
(Fig. 10). After that, successive raw radiofrequency (RF) data
is acquired at an ultrafast frame rate (2,000 frames/s). Contrary
to conventional sonography formed using line-by-line scanning,
ultrafast echoic images are achieved by transmitting a single
quasi-plane ultrasonic wave which has slight diffraction along the
transducer elevation direction and then performing the imaging
process (i.e., beam forming, array signal processing) only in the
receiving mode. Because of the memory limit, only 128 successive ultrafast echoic images can be stored at a total duration of
30 ms.54 55
3 successive SSI sequences were performed to locate the lesion
(Fig. 11). The rst SSI sequence was performed using pushing

Fig. 11. Protocol of quantitative elastography for a lesion located in the

center using the SSI method. Three SSI sequences are performed. The rst
SSI sequence corresponds to a pushing line along the central line of the
ultrasound image. The second and third SSI sequences correspond to two
successive pushing lines located on the right and left edges of the image.
These three pushing modes enable the nal recovery of a quantitative elasticity map over the entire ultrasound region.

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J. Med. Imaging Health Inf. 3, 114, 2013

Fig. 12. Comparison between the B-mode ultrasound and the elasticity image obtained in the SSI with colorbar presenting the shear wave speed (09 m/s,
E = 0240 kPa) with the delineation between soft fatty tissues (7 kPa) and breast parenchyma (30 kPa) in normal breast tissue.

beams centered along the central line, which allowed elasticity

imaging on both left and right parts. Then, the second and third
SSI sequences were performed with a left and a right pushing
line, respectively, and allow elasticity imaging in the middle of
the imaging plane.
In the initial clinical trial, a total of 15 lesions were assessed
quantitatively for its elasticity at an image window of 38
44 mm2 . The elasticity map displays the local shear wave speed
cs on a color scale ranging from 09 m/s with the corresponding
Youngs Modulus, E = 3cs2 , ranging from 0240 kPa. Elasticity maps exhibit good concord with the spatial heterogeneities
and structures in normal breast tissue and provide quantitative
highlighting for benign and malignant lesions. In general, benign
solid and malignant lesions in that study had a mean Youngs
modulus of 4580 kPa and 100 kPa (in some cases >180 kPa),

respectively. It is known, however, that some cancers such as the

mucinous subtype can be rather soft, and some mature broadenomas can be extremely stiff.
8.1. Normal Breast Tissue
The quantitative elasticity in normal breast tissue clearly delineated the different structures of breast. Youngs modulus ranged
between 3 kPa for fatty tissues to 45 kPa in the parenchyma.
Figure 12 compares the US gray scale and Youngs modulus
image, which presents a brous mass (benign lesion corresponding to a brocystic disease). The Youngs modulus is easily
recovered in the normal breast tissue areas. There is nice delineation between fatty tissue (7 kPa) and breast parenchyma
(4050 kPa) on both the US grayscale and elasticity images.
These characteristic values were found in all healthy patients.55

Fig. 13. Comparison between B-mode ultrasound and quantitative elasticity map in the SSI mode for inltrating ductal carcinoma grade III. Hypoechoic lesion
with indistinct margins, slightly posterior shadowing classied as BI-RADS category 5.

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RESEARCH ARTICLE

Fig. 14. Comparison between B-mode ultrasound and quantitative elasticity map in the SSI for small (5-mm diameter) hypoechoic lesion classied as BI-RADS
category 5, which is difcult to detect on B-mode ultrasound. The elasticity map clearly delineates a small and stiff region (165 kPa), which was conrmed
by biopsy exam as an inltrating ductal carcinoma grade III.

8.2. Malignant Lesions

A typical example of a BI-RADS category 5 lesion and its corresponding elasticity map is shown in Figure 13. The B-mode
US depicted a 10-mm hypoechoic mass with indistinct margins
and posterior shadowing, which strongly indicates a high suspicion of malignancy and is conrmed in the pathologic diagnosis
as an inltrating ductal adenocarcinoma (grade III with a high
mitotic activity). SSI clearly exhibits higher stiffness of the lesion
with mean elasticity value of 150175 kPa and better delineation
of the lesion margins than B-mode US images. The lesion size
measured on the elasticity map was conrmed by the pathologic
analysis (8 10 mm). In addition, the Youngs modulus image
in the SSI enables a satisfactory discrimination between fatty tissues (5 kPa), breast parenchyma (40 kPa), and lesion location
(170 kPa) in the resolution of roughly 1.5 mm.
The potential ability of the SSI for the guided percutaneous procedures (core biopsies or ne needle aspirations) with

clinically satisfactory location precision was illustrated in

Figure 14 for a small, slightly hypoechoic nodular lesion with
indistinct contours measuring 5 mm, which was classied as
BIRADS category 4. This lesion is rather difcult to discriminate on B-mode US because of its low echogenicity contrast
in comparison to the normal parenchyma after local anesthesia,
thus necessitating multiple sampling. In comparison, the elasticity map clearly delineates a small and stiff region (165 kPa)
and properly depicted margins with an average 5 mm diameter.
This lesion size was conrmed after biopsy by the pathologist.
8.3. Benign Solid Lesions
SSI was also able to detect benign solid lesions such as broadenomas or brocystic disease changes. In all cases, these lesions
were detected on the elasticity mapping as rather soft structures with mean Youngs modulus <80 kPa for, whereas malignant lesions exhibited mean elasticity >100 kPa. A hypoechoic,

Fig. 15. Comparison between B-mode ultrasound and quantitative elasticity map in the SSI for hypoechoic, homogeneous, lobular-shaped lesion classied as
BI-RADS category 4, which was diagnosed as brocystic disease by biopsy and has comparable elasticity with the surrounding healthy tissues (E:1227 kPa).

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J. Med. Imaging Health Inf. 3, 114, 2013

(a)

(b)

Fig. 16. Comparison between B-mode image and quantitative elasticity map in the SSI of (a) hypoechoic lesions with lobulated margins, discretely reinforcing
ultrasound beam, classied as BI-RADS category 4, which was diagnosed as a cyst containing inammatory cells and debris in ne-needle aspiration, and
(b) another patient with a benign cyst nodule.

homogenous, lobular-shaped lesion classied as BI-RADS category 4 can be observed in Figure 15. SSI describes structures with different elasticity in good concord with the structures
depicted in the B-mode image, but comparable elasticity with the
surrounding healthy tissues (E:815 kPa). Biopsy was performed
under US guidance and led to a histologic diagnosis in favor of
brocystic disease.
8.4. Benign Cysts
SSI was also useful in the diagnosis of cystic lesions.
Figure 16(a) corresponds to hypoechoic lesions with lobulated
margins and a discretely reinforced US beam, which was classied as BI-RADS category 4. Fine-needle aspiration was performed under US guidance, and a yellow-colored liquid was
evacuated, which led to a histologic examination as a cyst containing inammatory cells and debris. The SSI elasticity map
provided local Youngs modulus in healthy surrounding tissues
except in the lesion, which is consistent with the fact that shear
waves do not propagate in liquids. All data corresponding to nonpropagating shear waves are intrinsically ltered by the imaging post processing algorithm. Two reasons for this ltering can
be evoked. First, the strong acoustic streaming induced in the
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liquid can lead to a de-correlation of the successive US data.

Second, the strong modication of the shear displacement versus
the propagation direction yields to a de-correlation of shear displacement time proles at neighboring locations, resulting in a
false time-of-ight estimation. This de-correlation can be in both
cases ltered, leading to an absence of Youngs modulus estimation in the liquid. Figure 16(b) corresponds to another more
clearly hypo-echoic cystic lesion which is identied as a liquid
area surrounded by soft tissues in the SSI.
In summary, quantitative mapping of breast tissue elasticity is
feasible in vivo using the SSI approach. Discrimination between
breast fat and parenchyma and identication of malignant lesion,
benign solid lesion, cystic lesions are feasible, reliable, and
clearly visible. This novel imaging modality is signicantly less
operator dependent than static elastography as the mechanical
excitation that interrogates breast tissues is induced by the system itself. It could have a potential in clinics for breast lesion
diagnosis.

9. CONCLUSION
High-frequency high-quality sonography system has signicant
technical improvements with high resolution, great contrast, large

J. Med. Imaging Health Inf. 3, 114, 2013

dynamic range, less speckle noise, high frame rate, and multiple ultrasound imaging modality (i.e., color Doppler and realtime three-dimensional scanning) in the past decades. Although
digital signal/image processing techniques aided the automated
tumor/cancer detection and enhanced the outcome, the superiority of state-of-the-art mammography over sonography has
been shown in a variety of clinical studies. However, in the
detection and diagnosis of benign lesions, for example, a distinction between cystic and solid masses, mammography is not
necessarily the preeminent examination, and sonography is the
useful procedure of choice. Meanwhile, development of novel
ultrasound-based elastography, especially the transient type that
generates remote pushing force to the target, enables the detection of the mechanical properties of tissue, which has higher
sensitivity, specicity and contrast than the conventional B-mode
ultrasound images. Although the preliminary results are very
promising, its role in breast cancer diagnosis will be carried out
in multiple and randomized clinic centers and then be compared
with mammography for performance evaluation.

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Received: 10 December 2012. Revised/Accepted: 12 January 2013.

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