After completing this course, the participant should be able to:
Regina J. Hooley, MD
Assistant Professor of Diagnostic Radiology
Yale School of Medicine
New Haven, CT
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Physicians, sonographers and others who perform and/or interpret ultrasound.
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Estimated Time for Completion: approximately 1 hour
Date of Release and Review: November 28, 2012 and June 16, 2015
Expiration Date: June 16, 2018
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Dr. Regina Hooley discloses no such relationships exist.
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One of the first physical exam skills every physician learns is palpation, which is based on the premise that cancers feel harder than surrounding tissue. Using elastography, tissue stiffness (or hardness) can be measured and converted into an image. The physics behind this principle relies on tissue stiffness quantified by Young's modulus (E or elasticity), determined by calculating the ratio between a uniform compression (stress, s) applied to tissue and the resulting induced tissue deformation (strain, e) (1).
Young's modulus (elasticity) = Stress/Strain or E =s/e
If the amount of force (stress) initially applied to tissue is known, elasticity can be determined. Elasticity (E) is measured in pressure units, pascals, or kilopascals (kPa).
Most cancers feel stiffer on palpation because they have a lower strain value and a higher Young's modulus. Although palpation is inherently subjective, stiffness can be measured with elastography, using a 3-step process:
In clinical practice, the determination of the initial stress applied to the tissue (ie, step 1) poses a significant challenge because the force is usually created by repetitive transducer pressure, which is variable among different operators or even the same operator. The initial stress is also dependent on the angle at which the force is applied.
Ultrasound elastography utilizes either strain or shear-wave elastography. Strain elastography is also known as static or compression elastography. With this technique, gentle repetitive compression is applied to tissue with an ultrasound probe or natural motion (ex. heartbeat or respiration). This results in tissue displacement (strain), which may be measured by tracking longitudinal movement of tissue before and after compression using RF backscatter waveforms or Doppler to identify tissue motion (Fig 1). Strain is greater in soft tissue compared to hard tissue (2, 3), because soft tissue will easily deform when subjected to external pressure.
Strain elastography provides qualitative information. Young's modulus cannot be calculated because the initial stress on the tissue is variable, depending on both the initial transducer pressure and the composition of the underlying tissue. However, strain ratios may be calculated by comparing the strain of a lesion to the surrounding normal tissue (ex. adjacent fat). Soft tissue will have higher strain values than stiff tissue (1).
Shear-wave elastography is also known as transient elastography. This technique also utilizes a gentle initial compression force, usually automatic pulses generated by the ultrasound probe and which induce transversely oriented shear-waves within tissue (Fig 2). The speed of propagation of the shear-waves can be captured by the ultrasound system. This speed is directly proportional to stiffness and Young's modulus using the formula E ? 3 ?v2, where ?=density of tissue (this is a constant in tissue at 1000kg/m3) and v=shear wave propagation velocity(4). Using extremely fast ultrasound acquisition sequences of 5000 frames/sec, the shear-waves and an associated elastogram can be subsequently captured in real-time.
Shear-wave elastography provides quantitative information because elasticity of the tissue can be measured in kPa. Shear-waves travel faster in hard tissue and therefore, hard tissue will greater kPa values compared to soft tissue. With either strain or shear-wave elastography, acoustic information regarding lesion stiffness is converted into a black and white or a color scale image that can also be superimposed on top of a B-mode gray scale image for subsequent analysis.
Multiple studies have shown that ultrasound elastography may provide additional diagnostic information to further characterize breast lesions and has the potential to improve the specificity of low suspicion lesions evaluated with conventional ultrasound. Elastography features including size ratios, shape, homogeneity and quantitative analysis may be complimentary to conventional ultrasound in the comprehensive analysis of breast lesions.
Compared to gray-scale ultrasound, malignant lesions tend to be larger and more irregular on elastography (2,5), likely secondary to stiff peripheral desmoplastic reaction. When measuring lesion size on elastography, careful technique is important in order to avoid false positive results. The lesion should be measured in the exact position on both the elastogram and B-mode image. This can be done with the use of the mirror function available on elastography units, which allows the lesion to be simultaneously visualized with both elastography and B-mode (3).
Malignant lesions also tend to be very heterogeneous and irregularly shaped on elastography, with variable regions of stiffness displayed on the elastogram/color overlay (Fig 3). Irregular lesions with heterogeneous elasticity within the mass and surrounding tissue tend to be malignant (5). Benign lesions tend to have a homogeneous and soft elastogram (Fig 4). Several authors have proposed a grading system using either strain or shear-wave elastography and have proposed a variety of imaging classifications, based on the color pattern (6-8).
Lesion stiffness can also be measured quantitatively with shear wave elastography (stiffness of malignant lesions is generally greater than 80–100 kPa), while fat has relatively low elasticity values near 7 kPa and breast parenchyma have elasticity values ranging from 30-50 kPa (5, 9). However, one must be careful when using kPa in lesion evaluation, as some soft cancers may have low kPA values between 20-80 kPa, similar to benign lesions (5).
Elastography has the potential to differentiate complicated cysts form solid masses. Shear-wave propagation does not occur in cysts and therefore cysts should have elastography values of zero (9) and will appear mostly black or homogeneously blue on the color overlay elastogram (Fig 5). A bull's eye artifact has also been described as a characteristic feature present in benign breast cysts, where central fluid may appear bright with a surrounding dark ring (10). Other investigators also describe a color aliasing artifact that may be present in complicated cysts form solid masses (11), as well as a trilaminar appearance. However, these findings should be used with caution and may only present within cysts evaluated with specific ultrasound units. Moreover, some soft cancers may have a soft elastography appearance (Fig 6).
Elastography has little role in the evaluation of BI-RADS 2, 4C and 5 lesions seen on conventional US. However, elastography has the potential to downgrade BI-RADS 4a lesions to BI-RADS 3, thereby improving the specificity of BIRADS 3 and 4A lesions, including complicated cysts. Berg and colleagues showed that using qualitative shear-wave elastography and color assessment of lesion stiffness, oval shape and a maximum elasticity value of less than 80 kPa could reduce unnecessary biopsy of low-suspicion BI-RADS 4A masses without a significant loss in sensitivity (5). Elastography may also be used to identify oval circumscribed cancers detected on ultrasound and may be used to upgrade a BI-RADS 3 lesion to BI-RADS 4 (Fig 7). Furthermore, elastography feature analysis also has the potential to downgrade BI-RADS 3 lesion to BI-RADS 2 lesions.
Shear-wave elastography may also be complimentary to conventional gray-scale ultrasound by identifying more aggressive invasive ductal carcinomas. The stiffness of cancers with aggressive pathologic features may be higher than the stiffness of cancers with less aggressive pathologic features. In a study of 101 confirmed invasive breast cancers Evans, et al, demonstrated that a high mean stiffness at shear-wave elastography was significantly correlated with high histologic grade, large invasive size, nodal involvement and vascular invasion (12)
Early studies demonstrate promising results in the use of elastography in the analysis of breast lesions seen on conventional ultrasound, although limitations exist. Strain and shear-wave elastography are two separate techniques and imaging features vary across different manufacturers. Some manufacturers provide a black and white elastogram, while others provide a color elastogram. The color coding may be adjusted according to the individual operator's preference. Because there is currently no standard in the color elastogram assignment, stiff lesions may appear red and soft lesions may appear blue, or vice versa.
Inter and intra-observer variability may also be present with both strain and shear-wave elastography particularly because the initial stress applied to the tissue may not be constant. Too much transducer pressure may cause stiffening if surrounding normal tissue and a false positive elastogram (Fig 8). With either strain or shear- wave elastography, gentle pre-compression transducer pressure perpendicular to the lesion is desired for optimal analysis.
With static elastography, variable transducer pressure may be minimized by some manufacturers, requiring the operator to use only very light transducer pressure and instead relying on patient respiration or cardiac pulsations to generate compression on the lesion being analyzed. With shear-wave elastography, initial compression is automatically applied by the ultrasound transducer, thereby also requiring only minimal transducer pressure by the operator. Cosgrove, et al demonstrated that shear-wave elastographymay be more operator independent and reproducible as the compression pulses are generated by the ultrasound transducer (13).
In addition to variability in transducer pressure, which may affect the quality of the elastogram, stiffness of benign and malignant lesions may overlap. For example, some cancers lack a significant desmoplastic reaction and may be soft, resulting in a false negative elastogram (Fig 10). With shear-wave elastography, some cancers may have a mean stiffness of less than 50 kPa (12). Similarly, some benign lesions may appear stiff including hyalinized fibroadenomas, fat necrosis and fibrosis.
Because little data exists regarding the use of elastography in the evaluation of axillary lymph nodes, elastography should be used with caution in the evaluation of these masses. Posterior masses in the breast may be also difficult to evaluate with elastography because the compression force cannot displace tissue deep tissue as much as superficial tissue. Although some investigators have described difficulty in obtaining elastograms in lesions greater than 1 cm deep, in the author's experience, lesions up to 4 cm deep to skin can be adequately evaluated with shear-wave elastography. Finally, very large lesions (> 3cm) may be difficult to evaluate because all of the tissue in the field of view is stiff and normal tissue may not be included for analysis.
Ultrasound elastography is a new tool that has the potential to improve specificity and sensitivity of benign and malignant breast lesions. Radiologists should be familiar with the different types of ultrasound elastography, as it varies across different manufacturers. Currently, there is no universal color-coding standard. Therefore, depending on the manufacturer, stiff lesions may appear red, while soft lesions may appear blue, or vice versa.
Elastography features including size ratios, homogeneity, and lesion stiffness may be helpful to characterize masses seen on conventional breast ultrasound. Careful correlation of B-mode ultrasoound, mammography and elastography is important because not all cancers appear stiff on elastography. If all elastography features are benign, it may be safe to downgrade BI-RADS 4A to 3 or BI-RADS 3 to 2, although large prospective clinical studies are needed for validation.
Future potential applications of elastography include its use in: