Dr. Grajo is a Diagnostic Radiology Resident at the University of South Florida, Tampa, FL, and Dr. Barr is a Radiologist at Southwoods Radiology, Radiology Consultants Inc., Youngstown, OH.
One out of every 8 women will develop breast cancer during their
lifetime. Currently, the best method of treating breast cancer involves
early detection. Physicians have used palpation for many years as a way
to detect lumps or nodules in the female breast. In fact, regular breast
self-examinations (BSE) and clinical breast examinations (CBE) have
long been used to detect breast nodules in their earliest stages of
development. Although the effects of BSE on mortality rates from breast
cancer are debatable, CBE still exists as a standard screening protocol
for breast cancer in women. As an adjunct to direct manual palpation,
physicians have utilized ultrasonography to visualize lesions in breast
tissue. Lesion features are frequently characterized based on shape,
echogenicity, shadowing, margin irregularity, and microlobulation.1-3
Ultrasound has been extremely important because of its ability to help
differentiate cystic breast lesions from solid lesions. This provides
the clinician with useful insight into the possible benignity or
malignancy of a given lesion.
Over the past two decades, various new methods have been developed to sonographically evaluate the stiffness of a lesion.4-11 These
methods offer the potential to quantify the formerly qualitative-only
measurement of tissue stiffness; therefore, allowing for increased
differentiation of cystic and solid breast lesions. With the use of
standard ultrasound equipment and new “elasticity imaging” (EI)
software, the trained clinician can now noninvasively differentiate
benign and malignant breast lesions with high sensitivity and
specificity. Although the standard of care for the diagnosis of breast
cancer still involves biopsy, elastography has the potential to
significantly reduce the number of biopsies of benign breast lesions.12,13
This would help to alleviate anxiety in many patients and to decrease
the related high healthcare costs in the United States (U.S.). This
article will review the physics behind the elastographic technique, the
utility of elasticity imaging in clinical practice, the implications of
EI on patient care, and possible advances in elastography in the near
Defining the technique
also referred to as elastography, offers great potential to characterize
cystic and solid breast lesions using a combination of standard
ultrasound imaging and innovative software technology. There are 2 main
categories of elasticity imaging: compression, or “strain,”
elastography, and shear wave elastography. Strain elastography is a
qualitative method that measures stiffness based on soft-tissue
distortion caused by minimal manual compression. Conversely, shear wave
elastography is a quantitative method that relies on the principles of
Young’s modulus to measure the speed of low-frequency shear wave
transmission through soft tissue. In the authors’ lab, minimal manual
compression is utilized, usually provided by the patient’s respiratory
cycle and cardiac rebound, to produce strain images. This article
describes this method.
Like conventional B-mode sonographic
imaging, EI differentiates cystic breast lesions from solid breast
lesions. An artifact that occurs with some manufacturers’ equipment has
been reported to characterize cystic lesions with high accuracy. The
technology can also further characterize solid lesions that contain both
benign and malignant elements. In such cases, the clinician can
aspirate or biopsy the various elements in a lesion with the guidance of
the elasticity software. This allows for obtaining appropriate breast
tissue more accurately and helps to provide the pathologist with
information regarding the likely composition of the specimen.
characterizing the composition of breast lesions, EI offers the
potential to differentiate benign lesions from malignant with high
sensitivity and specificity. The technique is based on the differing
physical properties of benign and malignant lesions, as described by
clinicians throughout the literature. It has long been reported that
benign lesions tend to be “softer,” with more mobility within the breast
parenchyma, while malignant lesions tend to be “harder,” with a
propensity for remaining firmly fixed within the tissue.14,15
The theory behind elastography is that cancerous and noncancerous
lesions will demonstrate differing amounts of tissue motion relative to
the normal surrounding breast parenchyma when minimal pressure is
applied. The ability to differentiate soft and hard lesions allows the
clinician to utilize EI to predict the benignity or malignancy of breast
lesions. This would potentially lead to a significant decrease in the
number of benign breast biopsies and, therefore, reduce the overall cost
The physics of elastography
is performed with a standard high-frequency ultrasound probe. The
returning radiofrequency signals are analyzed in real time with the
standard B-mode algorithm and the EI algorithm. The EI algorithm
analyzes the stiffness of a lesion compared to the compressibility of
its surrounding tissue, much like measuring the degree of stiffness of a
marble suspended within a bowl of gelatin. In this model, external
compression will cause the gelatin, and not the marble, to change shape.
The computer analyzes this degree of deformation to determine if the
lesion is soft or hard. Both the standard B-mode image and the EI image
are displayed in real time. The EI algorithm is sensitive for a 0.1%
strain and uses temporal persistency strategy to enhance the descriptive
pattern in the elastogram. Using this technique in the breast, the
elastography contrast for cancerous and noncancerous lesions is between
1000% and 5000%, as opposed to the tissue contrast of 1% to 100% between
cancerous and noncancerous lesions using conventional imaging
techniques, such as ultrasound, mammography, and magnetic resonance
imaging (MRI).16 Motion is provided by patient breathing and
cardiac rebound. If additional compression is required, slow minimal
palpation with the probe can be applied. In patients with small breasts,
the patient may have to hold her breath to limit motion. The
sonographer must ensure that the lesion remains in the image plane
during the compression cycle. It is important to have the probe and
lesion perpendicular to the scanning table. We record a short clip that
demonstrates both the compression and release stages. The best image is
selected by cine review for subsequent measurements.
performing an ultrasound on a patient with a known breast lesion(s),
both the standard B-mode image and the elastogram are displayed
side-by-side (Figure 1). We can then directly compare the relative
stiffness of a lesion based on its elastic properties in relation to the
surrounding tissue. In our study, we set the ultrasound machine to
display “soft lesions” as white and “hard lesions” as black. This gives
us immediate insight into the relative stiffness of any lesion within
the breast parenchyma. It is important to emphasize that the
elastographic technique provides the clinician only with the relative
stiffness of breast lesions within the surrounding tissue. Therefore,
lesions will exhibit varying shades of gray in fatty breast tissue as
opposed to dense breast tissue. To obtain an appropriate dynamic range
for interpretation, we try to include fatty tissue, normal dense breast
tissue, and the lesion in the field of view. This limits our ability to
utilize EI in a mass screening protocol.
By displaying the B-mode
sonographic image and the elastogram side-by-side, we can also directly
compare the relative dimensions of the lesions in both image displays.
We then predict the benignity or malignancy of the breast lesion based
on size of the lesion in the elasticity image compared to its size in
the B-mode display. Either length or area of the lesion in the greatest
dimension can be utilized to measure the magnitude of the lesion. If the
lesion appears smaller on the elastogram based on direct measurement,
it is characterized as benign. If the lesion measures equally or larger
on the elastogram compared to the B-mode image, the lesion is deemed to
be malignant. In our initial study, we determined that EI is able to
correctly differentiate benign and malignant breast lesions with very
high sensitivity and specificity.17-19
Clinical utility of breast elasticity imaging
imaging offers the potential to characterize various breast lesions in
great detail and to provide the sonographer with an extremely helpful
adjunct to the standard ultrasound examination. The elastographic
technique is entirely noninvasive and adds only a few minutes to the
conventional sonographic exam. It augments the value of the sonogram and
allows for immediate interpretation of results. In addition,
elastography provides the clinician with detailed characterization of
the cystic or solid breast lesion that may not be readily appreciated on
B-mode imaging. For example, lesions that appear to be solid on B-mode
imaging may actually be complicated cysts when imaged with elastographic
software. In the authors’ clinical study, 4% of all lesions that
appeared solid on B-mode were actually complicated cysts when viewed as a
strain image.20 These lesions can be easily aspirated, negating the need for subsequent biopsy.
clinician can rapidly predict the benignity or malignancy of breast
lesions with EI software and standard B-mode imaging techniques. In the
authors’ clinical study, the size of the breast lesion on the B-mode and
the elasticity image was directly compared. The lesion was determined
as likely to be benign or malignant based on the ratio of the lesion’s
size on the strain image compared to its size on B-mode image. If the
ratio is <1, the lesion appears smaller on the elastogram. We predict
that this lesion is most likely going to be benign when biopsied for
pathologic correlation. On the other hand, the lesion is likely to be
malignant if it appears larger on the elastogram compared to the
standard B-mode image. The resulting ratio produced from direct
measurement would be ≥1. Direct measurement of the lesion’s size in both
the B-mode image and the elastogram can be measured in seconds. In
fact, the size discrepancy between the images is sometimes so drastic
that it can simply be “eyeballed” to immediately determine a relative
ratio. Although biopsy of all lesions is still the standard of care for
diagnosing breast lesions, the information garnered from the
elastographic technique can augment the information that the radiologist
can provide the pathologist. If the authors’ results can be duplicated
on a large-scale, multicenter basis, it is hoped, then the initial
determination of a breast lesion’s nature can lead to a decrease in the
number of benign breast biopsies.
Appearance of benign lesions
our experience with EI, benign lesions appear smaller on strain images
compared to the corresponding B-mode image (Figures 2 and 3). This is
based on the relative elasticity of a breast lesion within its
surrounding parenchyma. If a lesion demonstrates stiffness similar to
normal dense breast tissue, it is more likely to be benign (Figure 4).
In our lab, we also display soft structures as white, which further
demarcates areas of increased elasticity. Of particular interest is the
easy identification of both simple and complicated cysts with
compression elastography. We have shown that cystic lesions demonstrate a
“bull’s-eye” artifact, featuring a dark structure with both central and
posterior bright foci (Figure 5).21 The identification of
lesions as benign cystic lesions on elastography can lead to direct
aspiration of symptomatic lesions and avoidance of biopsy for
complicated cysts, which may otherwise appear suspicious on standard
B-mode imaging. In lesions with both cystic and solid components,
elasticity can help guide biopsy to obtain the most useful specimen.
Appearance of malignant lesions
to their increased stiffness, malignant lesions appear the same or
larger on the elastogram when compared to the B-mode image. In our
center, these malignant lesions appear dark on the strain images and may
demonstrate adjacent areas of tissue invasion that would not be
appreciated on B-mode. In the authors’ experience, we can predict
malignancy based on the real-time elastogram with high confidence.
Furthermore, a recent retrospective review has shown the potential to
determine the aggressiveness of malignant lesions and predict the grade
of these tumors via EI. Limited data analysis has demonstrated that more
aggressive malignancies, such as invasive ductal carcinomas (Figures 6
and 7) and invasive lobular carcinomas (Figure 8), will exhibit higher
elasticity/B-mode (E/B) ratios compared to mucinous carcinomas or ductal
carcinoma in situ (DCIS), for example. Moreover, initial results
demonstrate that higher grades of IDC correlate with higher E/B ratios
in a statistically significant fashion.22 This observation
could have important implications for the radiologist’s ability to
characterize breast lesions, such as in classification according to the
BIRADS system. With the use of elastography, one may be able to
downgrade or upgrade BIRADS 3 and 4A lesions. Further validation and
standardization of this technique is required.
imaging has demonstrated the ability to differentiate benign and
malignant breast lesions with high sensitivity and specificity. Numerous
imagers have utilized various forms of the elastographic technique,
including color elastography, strain ratio measurements, and, most
recently, shear wave technology, to characterize an array of breast
lesions. In our practice, the authors have produced very favorable
results with compression elasticity images utilizing simple cardiac and
respiratory cycles to provide the appropriate degree of compression for
the production of strain images. The appropriate degree of compression
is, in fact, a critical aspect of reproducing these favorable results.
Applying excessive manual compression to breast tissue will compact the
parenchyma and make fat appear harder, skewing the interpretation of the
strain image. The concept of applying only minimal compression, termed
“pre-compression,” is of vital importance in obtaining accurate and
reproducible strain images.
EI can be particularly helpful when
working up complicated breast lesions. Some lesions may contain both
benign and malignant-appearing components, making it difficult to decide
where to biopsy within the lesion. Because of the distinction between
“soft” and “hard” lesions provided by elastography, the clinician can
direct the biopsy needle to the more suspicious components within a
particular breast lesion. The hard component of the lesion can be
biopsied, while the soft component can be aspirated with FNA. This will
subsequently lead to direct needle placement and increased biopsy
accuracy. It will also enhance pathologic diagnosis, as the radiologist
can provide the pathology lab with more detailed information along with
the specimen itself.
Over the last several years, we have
conducted both single-center and multicenter trials to demonstrate the
effectiveness of compression elasticity imaging in differentiating
benign and malignant breast lesions. With strain elastography, it is
often difficult to interpret the elastogram in cases where a benign
lesion (eg, fibroadenoma, fibrocystic change) lies within a background
of dense breast tissue. The elastographic properties are similar and it
is difficult to determine the boundaries of the lesion. Shear wave
imaging will be helpful in these cases. We believe that strain
elastography can have several implications for the future of breast
imaging. These include a decrease in number of benign biopsies, a
reduction in the costs of lesion work-up, incorporation into the BIRADS
classification system, and possibly the prediction of breast cancer
grade. Additionally, the elastographic technique can help direct needle
biopsy and provide useful diagnostic information to the pathologist. As
such, EI may prove to be an important adjunct to standard B-mode
sonography in the evaluation of a breast lesion.
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Grajo JR, Peterson CM, Barr RG. Does the EI/B-mode length ratio predict breast cancer tumor grade? Proceedings of the Ninth International Conference on the Ultrasonic Measurement and Imaging of Tissue Elasticity. 2010.