J Mammary Gland Biol Neoplasia (2006) 11: 113–123
DOI 10.1007/s10911-006-9018-0
A Review of Breast Ultrasound
Chandra M. Sehgal & Susan P. Weinstein &
Peter H. Arger & Emily F. Conant
Published online: 4 November 2006
# Springer Science + Business Media, Inc. 2006
Abstract Frequent advances in transducer design, elec-
tronics, computers, and signal processing have improved
the quality of ultrasound images to the extent that
sonography is now a major mode of imaging for the
clinical diagnosis of breast cancer. Breast ultrasound is
routinely used for differentiating cysts and solid nodules
with high specificity. In combination with mammography,
ultrasound is used to characterize solid masses as benign or
malignant. There is growing interest in using Doppler
ultrasound and contrast agents for measuring tumor blood
flow and for imaging tumor vascularity. Ease of use and
real-time imaging capability make breast ultrasound a
method of choice for guiding breast biopsies and other
interventional procedures. Breast ultrasound is used in
many forms. B-mode is the most common form of imaging
for the breast, although compound imaging and harmonic
imaging are being increasingly applied to better visualize
breast lesions and to reduce image artifacts. These develop-
ments, together with the formulation of a standardized
lexicon of solid mass features, have improved the diagnos-
tic performance of breast ultrasound. Several approaches
that are currently being investigated to further improve
performance include: (1) computer-aided-diagnosis; (2) the
assessment of tumor vascularity and tumor blood flow with
Doppler ultrasound and contrast agents; and (3) tissue
elasticity imaging. In the future, ultrasound will play a
greater role in differentiating benign from malignant masses
and in the diagnosis of breast cancer.
C. M. Sehgal (*) : S. P. Weinstein : P. H. Arger : E. F. Conant
Silverstein, Department of Radiology, University of Pennsylvania,
3400 Spruce Street, Philadelphia, PA 19104, USA
e-mail: sehgalc@uphs.upenn.edu
Keywords Breast cancer . Ultrasound imaging . Neoplasm .
Sonography
Abbreviations
CAD computer-aided-diagnosis
DCIS ductal carcinoma in situ
ROC receiver operating characteristics
Introduction
Since early attempts in 1953 by Wild and Reid to build a
real-time handheld ultrasound scanner to image breast
lesions [1], ultrasonic imaging has undergone several
transformations, both in instrument design as well as in
clinical applications. In the 1980s, dedicated water bath
scanners using ultrasound-computed tomography (UCT)
gained popularity for imaging the breast [2–7]. These
scanners provided high resolution images in the reflection
and transmission modes, but they did not prove to offer
significant clinical advantages over real-time sonography
due to several factors [8], including the inconvenience of
using water baths for scanning and significant refraction
artifacts in the transmission mode. Today, handheld systems
are predominantly used in clinics for scanning patients.
Modern ultrasound scanners are digital systems. The
scanners digitize the acoustic signal immediately after it is
received by the transducer, and focus and steer the beam
using high speed digital electronics. Unlike early scanners,
which constructed images by a moving single-element trans-
ducer, modern sonographs use a multi-element ultrasound
transducer that does not involve physical movement of the
imaging transducer. The beam is focused and steered
electronically by broadcasting ultrasound from the member
elements of the multi-element array at different times, so that
114
the sound wave from each element arrives at the intended
focal point in the tissue simultaneously.
Modern ultrasound scanners offer various modes of
imaging. The most common mode is grayscale or B-mode
imaging, which uses ultrasound energy scattered by the
tissue back to the transducer for constructing images.
Doppler vascular imaging, on the other hand, uses the
acoustic signal scattered by moving blood to construct
images. There are also modes of imaging that use harmonics
of the echo signal or the shift in echo signal from tissue
motion to construct images. All these imaging modes are
integrated on a single scanner, and users are able to switch
from one mode to another easily. Information on both tissue
architecture and blood flow can thus be obtained in a single
study.
B-Mode Ultrasonography
The most common form of ultrasound imaging used in
breast diagnosis is B-mode ultrasonography [9–11]. It is
based on broadcasting short bursts of ultrasound energy
from transducer elements, then listening to the echoes from
tissues at different depths along the path of ultrasound
propagation. The strength (amplitude) of the echo received
from the tissue is used to control the brightness (B-mode)
of the display monitor. The process of ultrasound pulse
transmission and echo reception is repeated by aiming the
ultrasound pulses in different directions. The echoes
received from all directions are combined to construct a
2D image of the breast. Since each pulse transmission and
echo reception occurs in less than a millisecond, as many as
30 images can be obtained in each second. These images,
when displayed in rapid succession, allow real-time
imaging of the breast.
The brightness of an ultrasonic image represents a
complex combination of sonographic properties of the
tissue and of the ultrasound equipment. In essence, the
equipment adds its own signature to the displayed images.
If we neglect the influence of the equipment, the brightness
of the sonographic image is determined by the size and by
shape of the acoustic inhomogeneities, as well as the
mechanical properties (tissue density and tissue compress-
ibility) of the tissue.
Many factors affect image quality and the ability of an
ultrasound system to display a lesion. They include design
of the transducer (frequency, bandwidth, and aperture),
acoustic properties of the tissues (frequency dependent
attenuation, regional variation in sound speed and tissue
density, and speckle caused by the interference of waves),
signal processing, and the nature of the display monitor.
Because of the complex interactions between various
factors, highly specialized skills are required for interpret-
ing B-mode images.
J Mammary Gland Biol Neoplasia (2006) 11: 113–123
Ultrasound images can reveal different soft tissue layers
within the breast. The skin is highly reflective and appears as a
bright line in the image. Lactiferous ducts are easily seen,
especially when they are dilated. Cooper’s ligaments, sup-
porting glandular structures of the breast, are also commonly
seen as thin echogenic fibers. Fatty tissues cause low-level
echoes and appear dark in the image. Conversely, parenchy-
mal and fibrous tissues reflect ultrasound strongly and appear
bright. The parenchyma to fat ratio varies considerably among
patients, as well as within a patient, depending on her age and
hormone levels. Breast lesions generally appear darker
(hypoechoic) than surrounding tissues.
The main applications of breast ultrasound are (1) to
differentiate between cystic and solid lesions, (2) to
evaluate palpable masses not visible mammographically,
and (3) to evaluate young and pregnant patients with
palpable masses. Some reports have also suggested the use
of ultrasound to determine lymph node status [12–18].
Although simple cysts can be diagnosed with a high
sensitivity of 98–100% [19], the characterization of
complex cysts filled with echogenic fluid can be difficult.
Hogg et al. found that as many as 33% of the lesions
considered to be inderminate were cystic on aspiration [20].
Nightingale et al. proposed the use of ultrasonically
induced acoustic streaming to differentiate fluid-filled and
solid lesions in the breast [21].
Until recently, the use of ultrasound to differentiate
between benign and malignant solid masses and for
screening asymptomatic patients was not recommended.
While ultrasound is still not recommended for screening,
there is growing evidence that it can detect clinically and
mammographically occult cancers [22–24]. These findings
have rekindled interest in using breast ultrasound for
screening breast masses, and there has been a call from
investigators to conduct clinical trials evaluating the efficacy
of breast ultrasound as a screening tool [25]. Furthermore,
computer methods are being developed that analyze acoustic
shadowing for detecting lesions on breast sonograms. Early
results are promising, and, in the future, computerized
approaches may facilitate ultrasound screening [26].
Since the early 1990s, there has been significant progress
in the use of ultrasound imaging for distinguishing
malignant and benign masses [27–30]. It is now common
practice to use sonography to aid in mammographic
diagnosis of solid masses. Several sonographic features
based on margin, shape, and echotexture have been proposed
for the diagnosis of breast nodules [12, 13, 28]. Malignant
nodules are often characterized by poorly defined margins
and irregular borders. Spiculation, angular margins, micro-
lobulations, marked hypoechogenicity, shadowing, duct
extension, and tissue architectural distortion are some of
the common features associated with malignant masses.
Benign lesions, on the other hand, are often well differen-
J Mammary Gland Biol Neoplasia (2006) 11: 113–123
tiated from the surrounding tissue by a well-defined,
circumscribed margin. They tend be round or oval with
gentle bi- or tri-lobulations. Figure 1 shows sonographic
images of malignant and benign breast lesions.
Table 1 describes the performance of individual sono-
graphic features in two different studies using the criteria
originally outlined by Stavros et al. [28]. The results show
that the individual features have high levels of sensitivity,
specificity, positive predictive value (PPV), and accuracy.
Using some of the same features, Arger et al. [31] evaluated
inter-reader variability in diagnosis. Arger et al. concluded
that the interpretations of four different readers were very
similar when standardized descriptions of breast masses
were used for differentiating malignant and benign masses;
the diagnostic performance of individual features was
comparable to the performance reported in the earlier study
by Stavros et al. (Table 1). In another study, Paulinell et al.
added the thickness of the Cooper’s ligament to the
conventional margin, internal echo, and shadowing fea-
tures, concluding that poorly circumscribed margins,
heterogeneous echo pattern, and thickened Cooper’s liga-
ments indicate higher probability of malignancy [30].
More recently, the American College of Radiology has
instituted a lexicon, US-BIRADS, to standardize the
process for reporting breast masses [32–35]. Using the
BI-RADS lexicon, Hong et al. demonstrated that the BI-
RADS features of margin, shape, orientation, lesion
boundary, echo pattern, and posterior acoustic shadowing
were significantly different for malignant and benign
masses [35].
The clinical analysis of breast images is currently almost
exclusively done by a qualitative assessment of lesion features
Figure 1 Sonograms of biopsy proven malignant and benign masses.
(a) The infiltrating ductal carcinoma on the left has an indistinct
margin with an irregular border. The nodule is markedly hypoechoic,
taller-than-wide, and casts a strong shadow. (b) The fibroadenoma on
115
within an image. Variations in human perception of the
images, differences in features used for diagnosis, and, more
fundamentally, a lack of quantitative measurements of the
features used for image analysis are some of the factors that
cause variability in diagnosis by individuals. Consequently,
the final confirmation of benign or malignant diagnosis
usually requires a biopsy. The large number of negative
biopsies results in unnecessary stress and cost to the patient
and the system.
While computer technology has had a tremendous
impact on the design and performance of medical imaging
systems, this technology has not yet been used to improve
the diagnostic performance of individuals reviewing the
images. The development of computer-aided diagnosis
(CAD) could address this limitation and, when used with
routine clinical evaluation, could improve the specificity of
diagnosis. CAD systems apply “intelligent” algorithms that
use mathematically sophisticated classifiers and learning
algorithms to recognize complex patterns in images. When
such systems are successfully implemented, computers can
be increasingly used to help differentiate benign and
malignant tumors. With the wide acceptance of mammo-
graphic CAD and the growing acceptance of magnetic
resonance CAD, interest in ultrasound CAD has also
increased. Several studies on sonographic CAD have
shown that computerized analysis can aid in the interpre-
tation of the images [36–51].
CAD is a multi-step process. It involves identification of
lesions on the image either manually or by computerized
segmentation. Various echo texture and morphometric
(shape and margin) features are extracted from the
segmented masses. Through sophisticated mathematical
the right is well encapsulated and has a sharp, a well-defined margin.
The interior has weak heterogeneous echogenicity. The mass is
shorter-than-wide. Except for the weak shadowing at the edges, due to
refraction, the mass does not have posterior shadowing.
116 J Mammary Gland Biol Neoplasia (2006) 11: 113–123

Table 1 Sensitivity, specificity, PPV, and accuracy of nodule features measured by two independent studies [28, 31].

Feature Sensitivity Specificity PPV (%) Accuracy

[28] [31] [28] [31] [28] [31] [28] [31]

Spiculation 36.0 59 ± 11 99.4 97 ± 5 91.8 97 ± 5 88.8 73 ± 8

Taller than wider 41.6 49 ± 18 98.1 91 ± 4 81.2 90 ± 4 88.7 64 ± 12
Angular margins 83.2 92.0 67.5 90.5
Shadowing 48.8 59 ± 8 94.7 77 ± 1 64.9 82 ± 2 87.1 65 ± 5
Branching pattern 29.6 96.6 64.0 85.5
Hypoechogenicity 68.8 72 ± 10 90.1 86 ± 5 60.1 91 ± 2 87.2 77 ± 6
Calcifications 27.2 96.3 59.6 84.8
Duct extentions 24.8 48 ± 17 95.2 95 ± 5 50.8 95 ± 5 79.3 65 ± 12
Microlobulation 75.2 51 ± 20 83.8 84 ± 3 48.2 82 ± 10 82.4 63 ± 12

In [28] the term ‘markedly hypoechoic’ instead of ‘hypoechogenicity.’ Values quoted in [28] represent mean ± STD of four observers.
PPV Positive predictive value, STD standard deviation

pattern recognition techniques, computers are trained to
assign a probability of malignancy. While there are
considerable differences between studies, the various
approaches described in the literature can be classified into
those that emphasize echo texture [38, 40–44] and those that
use shape and margin features [44–48]. Both approaches
yield comparable diagnostic performance for characterizing
solid masses. The area under the ROC curve, Az, is a metric
that measures diagnostic performance. An Az of 1 represents
perfect performance. For sonographic CAD, Az is between
0.83 and 0.87 for the majority of studies [37, 43–45, 47,
48, 51], with some studies reporting a higher performance
of 0.92 [44] and near perfect values of 0.95–0.98 [46].
Only limited data are available on the diagnostic perfor-
mance of sonographers. In the study by Arger et al. the Az
value for three radiologists ranged between 0.90 and 0.92,
though one radiologist had an Az of 0.97 [31]. In another
study, the Az for radiologists ranged between 0.84 and 0.92
[44]. These data suggest that sonographic CAD computer
performance is comparable to human performance.
Kuo et al. studied the effect of ultrasound scanners on
CAD performance and observed the properties of the
ultrasound scanners did not influence the CAD perfor-
mance significantly [36]. Horsch et al. showed that the
performance of an expert sonographer improved when
CAD was used in the interpretation of sonographic images
of the breast [37]. While the results of sonographic CAD
are encouraging, it is important to note that all studies were
performed on static images using complex and time
consuming off-line analyses. Lack of real-time analysis
has, at least in part, made the widespread application of
sonographic CAD systems impractical. This may change as
manufacturers begin to incorporate CAD as built-in features
on ultrasound scanners.
Microcalcification imaging Mammographically detected
microcalcifications with a diameter on the order of 50 μm
may represent an early cancer, ductal carcinoma in situ
(DCIS). A limitation of breast ultrasound has been its
inability to detect small calcifications. The complex
structure of breast tissue and the grainy noise in the image
due to speckle phenomena often mask microcalcifications,
and their detection with B-mode ultrasound is unreliable.
Compound imaging, discussed below, suppresses speckle
and tissue noise and improves the visibility of breast
calcifications. Also, promising new techniques based on
exciting calcifications by external vibrations [52], or by
radiation force [53], are being developed to better visualize
such microcalcifications. However, the studies to date have
been performed largely using tissue-mimicking phantoms
and excised tissues.
Interventional sonography The absence of radiation, the
real-time nature of the imaging, and the ability to visualize
masses often make B-mode imaging the method of choice
for interventional procedures. Ultrasound is commonly
used for guiding biopsy needles for both aspiration and
core biopsies. Figure 2 shows an example of biopsy
imaging. Ultrasound imaging is also being used for surgical
localization of non-palpable masses, and for the placement
of percutaneous ablation devices such as radiofrequency
electrodes [12, 54].
Compound Imaging
Despite advances, B-mode images contain inherent artifacts
which degrade image quality. Speckle due to interference of
coherent ultrasound waves [55] causes small-scale bright-
ness fluctuations, giving a granular appearance to otherwise
homogeneous tissue. The side lobes and grating lobes of
ultrasound beams result in multi-path reverberations that
often lead to spurious echoes from the tissues. High
J Mammary Gland Biol Neoplasia (2006) 11: 113–123
Figure 2 Sonogram showing an ultrasound-guided core needle
biopsy. The needle (arrow), a strong reflector of ultrasound, is seen
approaching the surface of the target nodule (dotted arrow),
represented by the hypoechoic region in the image.
attenuation of ultrasound by solid masses can cause intense
shadowing and obscure breast anatomy posterior to the
lesion. Also, breast structures like connective tissues and
lactiferous ducts act as specular reflectors and behave as
sound wave mirrors. A small change in the direction of
ultrasound propagation changes the angle of incidence from
normal to oblique, which can dramatically alter the echo
signal from very strong (causing saturation) to very weak
(causing the poor visibility). In addition, because the lateral
edges of breast lesions are parallel to the scan lines, they do
not reflect ultrasound back to the transducer. This makes
the lateral margins and border of subtle lesions often
difficult to detect. Taken together, all these factors reduce
the conspicuity of small lesions and limit the delineation of
the margins of larger lesions.
To decrease the incidence of artifacts, several investi-
gators have proposed the use of compound imaging. In
conventional sonography, ultrasound is transmitted in a
single direction perpendicular to the ultrasound transducer
surface. In compound imaging, multiple views of a given
region of tissue are obtained from different angles. The
different views are combined to form an image. This is
demonstrated in Fig. 3. The different views are obtained by
keeping the ultrasound transducer fixed and steering the
ultrasound beam electronically in off-axis directions within
the plane of imaging. The compound image is updated as
each new frame is acquired, enabling real-time imaging.
This averaging of multiple frames suppresses the artifacts
related to speckle, spurious noise, and shadowing. In
addition, it improves the definition of lesion margins in
the direction orthogonal to the axis of the transducer.
Figure 4 compares conventional B-mode and compound
images of a breast lesion.
117
Several clinical studies have demonstrated the benefits of
compound imaging. Entrekin et al. [56] observed that the
echo amplitude and texture of fat is markedly different from
glandular tissue in compound imaging. The lateral margins
of the lesion were well delineated; the suppression of
speckle revealed punctuated calcifications; the images had
fewer artifacts; and there was better agreement among
observers in identifying lesions. Kwak et al. studied normal
breast structures and abnormal lesions by conventional and
compound imaging [57] and concluded that, compared to
conventional B-mode images, real-time compound images
have better spatial and contrast resolution. In compound
scans the margins of the lesions and their internal
architecture are better delineated. The suppression of
speckle noise by image compounding enhances the visual-
ization of microcalcifications. Kangas et al. observed that
compound imaging increases contrast-to-noise ratio and
lesion signal-to-noise ratio for both benign and malignant
masses by as much as 30–40% [58].
Despite the benefits of compound imaging, conventional
B-mode imaging continues to be the most common
clinically used method. The reason for this is not clear,
but is perhaps related to the users’ familiarity with the
texture of B-mode images, and the fact that the shadowing
suppressed in compound imaging is often used as one of
the features for differentiating benign and malignant
masses. Another potential drawback of compound imaging
is that if the transducer is moved rapidly during scanning,
the frame averaging during compounding can cause motion
blurring.
(a) (b) (c) (d)
Σ
(e)
Figure 3 This figure illustrates the concept of spatial compounding of
ultrasound images. The conventional B-mode image is constructed
with a single scan of the beam generated at 90° to the surface of the
beam as shown in panel (b) of the figure. In compound imaging, three
to nine views are obtained by steering the beam at different angles, as
shown in panels (a), (b) and (c). The frames in panels (a), (b) and (c)
are combined to generate a single frame (e). After displaying
compound image (frame e), the frame (a) is dropped, a new frame
(d) is acquired, and frames (b), (c) and (d) are compounded to form a
new image. Since updating of each compound image requires
acquisition of only one new frame, compound imaging can be
performed in real time, similar to conventional B-mode imaging.
118 J Mammary Gland Biol Neoplasia (2006) 11: 113–123

Figure 4 Images of biopsy-proven DCIS obtained using (a) conven- image. Compound imaging also improves the visualization of
tional B-mode and (b) compound mode. The tumor margin and the suspicious microcalcifications (arrow) which are difficult to identify
internal structure of the lesion are better delineated in the compound in the B-mode image.

Harmonic Imaging
The discussion above focuses on grayscale imaging, in
which the frequency of the signal used to construct images
is the same as the transmitted frequency. Advances in
electronics and in our understanding of tissue-ultrasound
interactions have revealed that transmission of ultrasound
through breast tissues leads to the formation of higher
frequencies. These frequencies are multiples of the trans-
mitted frequencies. For example, ultrasound transmission at
a fundamental frequency of 3 MHz leads to the formation
of harmonics at 6, 9, 12 MHz.... In harmonic imaging, the
fundamental frequency is removed and the residual energy
generated by ultrasound-tissue interactions is used for
constructing images.
Harmonic signals are formed because the speed of sound,
[59, 60]. The technique has been used successfully for
imaging axillary lymph nodes [61] and for evaluating
neoadjuvant chemotherapy responses in breast cancer
patients [62].
Although thus far harmonic imaging has been primarily
used to improve image quality, laboratory studies show that
harmonic signals generated by nonlinear interactions be-
tween the tissues and the ultrasound waves represent tissue
properties different from those represented by B-mode echo
signals [63, 64]. Therefore, harmonic imaging could
provide important new information about tissue in clinical
exams, an area that has not yet been explored.
(a) (c)
c + ∆c
Fundamental

c, is not constant, as commonly assumed in conventional B-

c
mode imaging. Instead, c increases with the particle 123456789111
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velocity of the ultrasound wave. As a result, the high

pressure region of the wave travels faster, whereas the low c - ∆c
f0 2f0 3f0
or negative pressure region of the wave lags behind. This is
demonstrated in Fig. 5. The mismatch between the rate at
which the high and low pressure components of the wave (b) (d)
travel distorts the ultrasound pulse and generates harmonic
frequencies. Harmonic images can be constructed either by
Fundamental

exploiting pulse distortion or by separating the harmonic

signal from the fundamental frequency.
H1

H2

Harmonic imaging makes the ultrasound beam narrower

and suppresses the side bands. The harmonic signal exhibits
less clutter and phase aberration and fewer reverberation
artifacts. All these factors improve the resolution and the
overall quality of the images. For example, harmonic
images of cysts are free of artifacts, simplifying their
diagnosis. Similarly, harmonic imaging also improves the
definition of margins and the detectibility of breast lesions
f0 2f0 3f0
Figure 5 Formation of harmonic signal by nonlinear propagation of
ultrasound. During propagation through the tissue, different points of
the ultrasound pulse (panel a) travel at different sound speeds. The
positive part of the pulse travels faster than the negative part and
distorts the pulse (panel b). The spectrum of the distorted pulse in
panel b, has harmonic signal (panel d). H1 and H2 represent first and
second harmonics.
J Mammary Gland Biol Neoplasia (2006) 11: 113–123
Figure 6 Tumor vessels imaged by Doppler ultrasound. Biopsy proven DCIS (arrows) imaged with (a) color Doppler and (b) power Doppler
ultrasound. The two images show comparable vascularity.
Doppler Ultrasound Imaging without Contrast Agents
Both color and power Doppler imaging have been used to
characterize breast lesions [65–74]. Figure 6 shows
examples of color and power Doppler images. Studies have
consistently reported that tumor blood vessels are visible
with Doppler ultrasound. Cosgrove et al. observed that
while 99% of malignant masses had blood vessels, only 3%
of benign masses showed Doppler signal [65]. Raza and
Baum achieved diagnostic sensitivity and specificity of 68
and 85% using penetrating vessels as indications of
malignancy [67]. However, according to Birdwell et al.
qualitative assessment of images showed no significant
differences in vascularity between malignant and benign
masses [68]; Wilkens et al. also found that Doppler was of
limited value in lesion analysis [73].
Carson et al. used several qualitative measures and
observed that power Doppler features were promising for
characterizing breast lesions [70]. Lee et al. also found
Doppler evaluation helpful in differentiating benign and
malignant masses [72]. Sehgal et al. derived quantitative
measures of tissue vascularity (related to the area covered
by blood vessels per unit area of tumor) from color and
power Doppler images [71]. They observed malignant
masses to be 14 to 54% more vascular than benign masses.
Both types of masses were more vascular than the
surrounding tissues. On average, the benign masses were
2.2 times more vascular than the surrounding tissue, while
malignant masses were five times more vascular. The
regional distribution of tumor vascularity for the two
groups was also different. Whereas tumor vascularity was
equivalent for the core and periphery of the tumor, the
malignant masses had greater vascularity per unit tissue
towards the center of the mass. While the average
vascularity for the malignant and benign groups were
statistically different, there was considerable overlap be-
119
tween the two groups. As a result, the simple assumption
that higher vascularity indicated higher probability of
malignancy resulted in a weak diagnostic performance
(ROC area Az = 0.56−0.65). The diagnostic performance
improved significantly ðAz ¼ 0:85
0:06Þ when the vas-
cularity differences were used in combination with a rule-
based decision tree.
Doppler Imaging with Contrast Agents
The use of contrast agents to enhance tissue structures has
changed the way cross-sectional imaging, such as CT and
MRI, is performed. The development of microbubble-based
contrast agents has raised similar hopes for ultrasound
imaging. The microbubble agents are several orders of
magnitude more echogenic than red blood cells. They do
not extravasate from the blood vessels into the neighboring
tissues. Therefore, the enhancement of the image by these
agents indicates the presence of blood vessels. As described
above, Doppler imaging can directly visualize blood vessels
without using contrast agents. However, several technical
and physiological factors prohibit the visualization of blood
vessels smaller than 100–200 μm. The expectation is that
the use of ultrasound contrast agents will allow the
visualization of smaller vessels (possibly at the capillary
level) with low volume blood blow [75]. Figure 7 shows a
power Doppler image of a breast lesion that appeared
originally to be avascular. The same lesion exhibited
significant vascularity when contrast agent was used.
Kedar et al. observed increased specificity of cancer
characterization from 87.5 to 88.9% [76] with the use of
ultrasound contrast agents. Huber et al. [77], Alamo et al.
[78], and Reiniskainen et al. [79] did not find significant
improvement in tumor characterization by using 2D
imaging and ultrasound contrast agents. However, Forsberg
120
Figure 7 The left panel shows a power Doppler image of a lesion with
a blood vessel (arrows) leading to the nodule. The lesion (dotted circle)
appears avascular. The right panel shows the same lesion after Optison
contrast injection. The relationship between the feeder vessel and the
mass can be better appreciated in the contrast-enhanced image. The
et al. observed that the diagnostic performance, measured
by ROC area under the curve Az, improved substantially
from 0.51 to 0.76 when contrast-enhanced 3D power
Doppler imaging was used instead of 2D contrast-enhanced
power Doppler [80]. Yang et al. also found that tumor
microvessel density measured by immunohistochemical
assay correlated to the number of intratumoral vessels
measured by 2D and 3D contrast-enhanced power Doppler
sonography [81]. The varying results show that the use of
ultrasound contrast agents for differentiating breast masses
is still experimental, and there is yet no accepted method-
ology for either its use or the interpretation of the images.
Tissue Elasticity Imaging: Elastography
and Related Techniques
Over the last decade, there has been an intense effort to
improve the sensitivity and specificity of cancer detection
and of characterization using different imaging modalities.
An area of considerable interest is the use of ultrasound for
imaging tumor elasticity in patients with breast cancer.
Solid tumors are often palpable, indicating that they are
harder than the surrounding tissue. The hope is that
elasticity imaging will facilitate the detection and charac-
terization of these masses. Several excellent reviews are
available on this topic [82–87].
Tissue stiffness or tissue hardness is often described by
Young’s modulus of elasticity, which measures the amount
of longitudinal deformation tissue undergoes in response to
an applied longitudinal force. The Young’s modulus of
elasticity for soft tissue can range from 1 to 100 kPa [88–
91]. While fibroadenomas are only two times stiffer than
normal breast parenchyma, breast cancers can be as much
as 15 times stiffer [88, 90, 91]. The marked difference in
J Mammary Gland Biol Neoplasia (2006) 11: 113–123
contrast-enhanced image shows the nodule (dotted circle) to be vascular.
Although small blood vessels are distributed over the entire mass, there
is greater concentration at the periphery. In the region distal to the feeder
vessels (arrow in the right panel), there is a color blooming artifact
commonly observed in contrast-enhanced power Doppler images.
the elasticity of breast nodules has encouraged several
investigators to develop approaches to image tissue
elasticity or the properties related to it [92–99].
Several different elastography approaches have been
proposed. A common approach for breast imaging involves
sonographic imaging of the tissue before and after gentle
compression. The radiofrequency data from the pre- and post-
compression images are compared to determine tissue
deformation. The compression is often applied freehand by
pressing the transducer on the breast [92–94]. Other ap-
proaches using low frequency fremitus vibrations [12, 95–
97], and acoustic radiation force [98–100] have also been
proposed for breast elasticity imaging with promising results.
Sohn et al. [95–97] used low-frequency vibrations
associated with vocal fremitus to perturb the breast tissue
and Doppler imaging to visualize the vibrations. The
hypothesis is that well-encapsulated benign masses would
displace the surrounding tissue, whereas the infiltrative
nature of the cancers would enable the transmission of
vibrations into the central portion of the mass. Thus,
depending on whether the surrounding tissue or the center
of the mass is enhanced by Doppler imaging during
fremitus, the benign and malignant masses could be
distinguished. Sohn reported 91–93% accuracy by this
method. Schultz et al., however, observed enhancement of
the breast tissue to be significantly influenced by the choice
of imaging parameters [101].
Nightingale et al. proposed the use of radiation force
associated with ultrasound pulses to displace breast tissue for
elastography imaging [98]. The advantage of this approach
is that with some modifications the same transducer can be
used to generate as well as to detect local displacements.
Alizad et al. also proposed the use of radiation force to in-
duce tissue displacement, but instead of measuring the dis-
placement directly, Alizad et al. monitored low-frequency
J Mammary Gland Biol Neoplasia (2006) 11: 113–123
sound waves generated by the impact of ultrasound pulses
on the tissue [99, 100]. The hypothesis is that the signature
of these low-frequency sound waves is directly correlated
to the viscoelastic properties of the tissue.
Although there are several appealing approaches for
elasticity imaging, elastography based on manual compres-
sion of the breast has been adopted by many investigators.
Firm masses show less deformation and appear darker on the
elastograms. Malignant masses known to be stiffer (less
deformation) appear darker in the image compared to the
benign masses. The benign masses on the other hand may
appear brighter, similar, or darker when compared to the
surrounding normal tissue [94]. Comparing the sizes of the
breast lesion on elastograms and conventional B-mode
images revealed an interesting difference between malignant
and benign lesions. Whereas cysts and fibroadenomas are the
same size in the two modes of imaging, carcinomas appear to
be larger on elastograms. This is a significant finding, since
the difference in size can be exploited to differentiate benign
and malignant masses [94]. It is believed that the larger size
of cancers in elastograms indicates that the infiltration of
cancer into the surrounding tissues increases their stiffness.
Conclusions
Breast ultrasound is multimodal and can map blood flow
and mechanical properties of the tissue. Consistent
improvements in image quality over the years have
expanded the role of ultrasound in the detection and
diagnosis of breast pathology, and sonography is routinely
used as an adjunct to X-ray mammography. There are
attempts to combine ultrasound imaging and mammogra-
phy in one instrument to facilitate scanning and to improve
diagnosis [102]. Ultrasound is also a method of choice for
guiding biopsy needles and various therapeutic interven-
tions. We believe that newer techniques will continue to
improve the sensitivity and specificity of breast ultrasound.
Acknowledgments The authors gratefully acknowledge the assis-
tance from Susan M Schultz and Theodore W Cary in preparing this
manuscript. This work was in part supported by NIH grants CA-85424
and CA-87526.
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