Learning objectives. Performance of ultrasound. Many advantages of ultrasound. Elastography for evaluation of breast masses

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1 Elastography for evaluation of breast masses Learning objectives List physical principles of elastography imaging of the breast List different types of elastography imaging of the breast State results of current research into elastography The challenge of breast cancer detection Worldwide, >1,000,000 new cases each year In US, 275,000 new cases, 41,000 deaths (2006) Nearly 1 million breast biopsies performed each year Screening mammography reduces mortality Mammography limitations Sensitivity approx 85%, less in dense tissue PPV of biopsy approx 20-25% in USA The challenge of breast cancer detection Proliferation of many breast imaging modalities Hope is to improve on mammography Increase sensitivity and/or increase specificity Goal of any breast imaging test Find early stage clinically significant cancer Have minimal intrusion and minimal impact on women s lives Many advantages of ultrasound Non-invasive and well tolerated by patients Lesions identified on US are easy to biopsy No injection, no ionizing radiation Equipment is inexpensive and mobile Clear advantages to using US technologies for characterization of masses Performance of ultrasound As adjunct to mammography and palpation Huge impact by excluding simple cysts from biopsy Low specificity beyond simple cysts Screening: In trials with expert sonographers cancer detection , biopsy rate 2-3x mammo overall PPV 10-11% No known impact on mortality Screening with conventional US adds to burden of biopsies for women, with no proven benefit Limited specificity for characterization of solid masses Excellent NPV for malignancy Stavros criteria (1995): <2% malignancy 1

2 Possible impact of using elastography to characterize breast masses Downgrade BI-RADS 3 and BI-RADS 4a that are definitely benign Upgrade BI-RADS 3 that are malignant Confidently identify cysts Impact: Significantly decrease benign biopsies and aspirations No change or even increase in cancer detection Using elastography to characterize breast masses Deform tissue in some way, then observe tissue response Based on principles of tissue elasticity, benign vs. malignant The original elastography: Clinical palpation Apply mechanical pressure (palpation) Subjectively assess resulting deformation of tissue Compares relative stiffness of lesion with surrounding tissue Limitations: subjective, limited sensitivity, specificity, and reproducibility The original elastography: Clinical palpation Apply mechanical pressure (palpation) Subjectively assess resulting deformation of tissue Compares relative stiffness of lesion with surrounding tissue Limitations: subjective, limited sensitivity, specificity, and reproducibility Elastography: Ultrasound Palpation US palpation: apply manual pressure with transducer and simply observe degree of deformation A fibroadenoma without compression (A). The fibroadenoma with manual compression (B) by the transducer. Garra, Ultrasound Quarterly 23(4), 2007 Elastography: quantitative methods Quantitative techniques for assessing tissue elasticity Less subjective than manual palpation Apply force to tissue Different types of elastography use different sources Internal or external manual compression vibration high intensity US pulse Measure tissue displacement induced by this force and estimate tissue stiffness Can use US, MRI, optical imaging Performing Elastography 2

3 Types of elastography Static elastography Static elastography: initial apparatus Shear wave elastography Photograph of a transducer mounted in a motorized holder attached to a mammographic compression paddle with cutout for needle localization. The transducer assembly can be pivoted away from the cutout to allow a craniocaudal mammographic examination for localization. Garra et al Radiology, 1997 Ultrasound elastograms: initial work Fibroadenoma. Note bright (soft) signal on elastogram Fibroadenoma. Note dark (firm) signal on elastogram. Static Elastography Most commonly used method for breast Manual pressure applied with transducer Tissue deformation is measured Lesion size Computer aided analysis of continuous images Spatial correlation Phase shift tracking Combined autocorrelation method Analysis of measured tissue strain is generated Garra et al, Radiology 1997 Static Elastography Requires light pressure with transducer to maintain linear (proportional) relationship between pressure and tissue strain Higher pressure manifests non linear properties of tissue elasticity Therefore results are somewhat user dependent Techniques for analysis of tissue deformation: Computer aided analysis of continuous US images obtained with probe compression Transverse continuous US images of a malignant breast lesion. The computer-delineated margin is the white outline. Computer calculates the values for the three features of strain contour difference, shift distance, and area difference and the value for one feature of shape solidity. Transverse continuous US images of a benign breast lesion. The computer-delineated margin is the white outline. Computer calculated the values for the three features of strain contour difference, shift distance, and area difference and the value for the one feature of shape solidity. Moon et al,

4 Techniques for analysis of tissue deformation Lesion size comparison technique Measure size of lesion on B mode image Measure size of lesion after strain Grade lesion using ratio of pre to post strain diameters Lesion size comparison technique Fibroadenoma, before strain Fibroadenoma, after strain from Regner et al, 2006 Lesion size comparison technique Lesion size comparison technique: FA Fibroadenoma, equal size on 2D and strain image IDC, larger size on strain image than 2D Regner, 2006 From Burnside et al, Differentiating Benign from Malignant Solid Breast Masses with US Strain Imaging. Radiology 2007 Invasive ductal carcinoma Pitfalls in lesion size comparison technique From Burnside et al, Differentiating Benign from Malignant Solid Breast Masses with US Strain Imaging. Radiology 2007 Measurements obtained from static B mode image; Interobserver variability in size assessment affects calculated ratio Regner et al,

5 Pitfalls in lesion size comparison technique Techniques for analysis of tissue deformation Combined autocorrelation method Displays elasticity relative to the average strain of tissue within a region of interest Images obtained before and after application of pressure are processed comparing amplitude of signals from within this ROI Strain distribution reconstructed as an elasticity image Measurements obtained from static B mode image; Interobserver variability in size assessment Regner 2006 Combined autocorrelation method Elasticity image displayed as a color map Lesion is graded based on this image Each pixel of the elasticity image is assigned one of 256 specific colors, depending on the magnitude of strain Greatest strain (softest tissue) is red No strain (hardest tissue) is blue Average strain is green; breast tissue considered average strain Grading lesions Grade 1: uniformly green, even strain throughout, indistinguishable from background tissue From Grade 1, fibroadenoma Static elastography: Elastography Grade 1 Cho et al,

6 Grading lesions Grade 2, fibroadenoma Grade 2, mosaic of blue and green but mostly green: strain (soft) in most of the lesion Static elastography: Elastography Grade 2 Grading lesions Grade 3: strain (soft) only at the periphery, no strain in the middle Cho et al, 2008 Grade 3, LCIS Static elastography: Elastography Grade 3 Cho et al,

7 Grading lesions Grade 4, IDC Grade 4: no strain in the lesion but strain in the surrounding tissue Static elastography: Elastography Grade 4 Grading lesions Grade 5: All blue, no strain in lesion or in surrounding tissue Cho et al, 2008 Grade 5, IDC Static elastography: Elastography Grade 5 Cho

8 Similar low suspicion (4a) US appearance: elastography could avoid a biopsy and still detect the cancer Incorporating elastography into US assessment of masses Decrease the rate of intervention for benign lesions Maintain or increase cancer detection rate Mosaic B9 E score 1: FA Blue suspicious, E score 4, IDC Zhi et al, 2007 Similar suspicious US appearance: elastography could avoid a biopsy and still detect the cancer Interpretation with conventional ultrasound Blue, E score 4: IDC Mosaic, E score 2, FA Zhi et al, 2007 Interpretation clearcut Simple cysts: benign Highly suspicious features: biopsy Probably benign (BI-RADS 3) 2% malignant: can we identify these cancers Interpretation nonspecific Non simple cysts, low suspicion masses (BI- RADS 4a) Avoid biopsy without missing cancer Straightforward interpretation elastography not necessary Obvious cyst Obvious suspicious Potential for elastography Obviate short interval follow up Obviate biopsy of B- 4a masses Confirm a cyst when features are non simple Identify BI-RADS 3 that are cancer 8

9 Results of clinical trials Elasticity scores of 111 lesions Conventional US standard of care: NPV 98% Clinical trials range 80-96% Elastography adds specificity but decreases sensitivity Benign lesions Malignant lesions 5/52 had score of 2 Most authors used cutoff of 3-4 as threshold for biopsy: not sensitive enough for current practice Sohn et al, 2009 From Itoh et al, Radiology 2006 Results of elastography series 1997, Garra: 1/11 cancers with false negative score (false negative 9.1%) 2006, Regner: 5/52 cancers false negative (false negative rate 9.6%) 2005, Moon: false negative rate 10% 2007 Zhi: 296 lesions: 26/87 cancers false negative 2009 Fleury: 270 masses, 6/44 cancers false negative Most authors used cutoff of 3-4 as threshold for biopsy Results of elastography series if threshold for biopsy is varied 2008 Tohno: 489 lesions, 121 cancer 27/121 false negative at threshold /121 false negative at threshold 2-3 5/121 false negative at threshold Itoh: 111 lesions, 52 cancer 7/52 false negative at threshold 3-4 5/52 false negative at threshold 2-3 0/52 false negative at threshold 1 Cho 2008: 100 masses, 17 cancer 5/17 false negative at threshold 3-4 3/17 false negative at threshold 2-3 0/17 false negative at threshold 1-2 Analysis of benign (light blue) and malignant (dark blue) elastography scores Analysis of benign (light blue) and malignant (dark blue) elastography scores score 1 score 2 score 3 score 4 score score 1 score 2 score 3 score 4 score 5 Cho et al, 2008: Total 100 lesions, 17 malignant and 83 benign Itoh et al, 2006 Total 111 lesions, 52 malignant and 59 benign 9

10 Analysis of benign (light blue) and malignant (dark blue) elastography scores BI-RADS 3 and 4a lesions score 1 score 2 score 3 score 4 score 5 Very low rate of malignancy (0-10%) Threshold used in clinical trials results in too many false negatives to be useful for these low risk lesions Can elastography score 1 combined with low suspicion appearance eliminate malignancy Tohno et al, 2008 Total 489 lesions, 121 malignant and 391 benign Elastography score by BI-RADS category Elastography score 1 Potential to eliminate biopsy and follow up for low suspicion mass (BI-RADS 3, 4a) Tohno et al: 3% of E 1 masses were malignant Potential for elastography Obviate short interval follow up Obviate biopsy of B-4a masses Confirm a cyst when features are non simple Identify BI-RADS 3 that are cancer Cho et al, 2008 Characterization of complicated non simple cysts High resolution US scanners increasing number of non simple cysts Difficult to distinguish from solid masses Very low rate of malignancy Characterization of complicated non simple cysts Static elastography Deform tissue with external compression Transient shear wave imaging Deform tissue with a high intensity US pulse transmitted by the US transducer Complicated cyst DCIS 10

11 Static elastography of cysts Static elastography of cysts Cysts can be either relatively stiff (as for a distended balloon) or soft Similar variation as clinical exam Appearance on strain images is not predictable Varies with amount of compression used and with level of distension of cyst Transient shear wave elastography Tissue deformation created by a high intensity US pulse transmitted by the US transducer Transient shear wave elastography Allows quantitative evaluation of tissue elasticity Benign: kpa, malignant >100 and even >180kPa. Normal tissue: 3 kpa for fat, 45 kpa for glandular Schematic presentation of shear wave elasticity imaging. A shear wave excitation transducer as well as various imaging transducers and detection sensors are shown. Other imaging modalities, such as magnetic resonance imaging, also can be used to detect shear waves Sarazyan et al 1998 Tanter et al, 2008 Characterization of complicated cysts: Transient shear wave elastography Shear waves do not propagate in fluid Cysts do not contain an elastic modulus value May allow confident identification of non simple cysts, and prevent misdiagnosis of solid mass as cyst No propagation of shear wave is detected, which is consistent with a liquid content of the area. Right B-mode image corresponds to one of the flat transmit B-mode images acquired during the ultrafast acquisition. Left B-mode image corresponds to the conventional B-mode image (transmit and receive focus) acquired just before switching into the ultrafast mode. Tanter et al,

12 Characterization of complicated cysts: Transient shear wave elastography Potential for elastography Obviate short interval follow up Obviate biopsy of B-4a masses Confirm a cyst when features are non simple Identify BI-RADS 3 that are cancer Interpreted as solid on B-mode, SSI shows no shear wave detected within mass consistent with a cyst. Tanter et al, 2008 Detecting malignancies among BIRADS 3 masses <2% malignant Therefore require large numbers of these masses Few investigators correlated elastography score with BI-RADS category Few had enough BI-RADS 3 masses Elastography score by BI-RADS category BI-RADS 3 None were malignant But only 27 in study Need much larger number of masses to determine if elastography scores will make a difference to final outcome Cho et al, 2008 Potential for elastography Obviate short interval follow up Obviate biopsy of B- 4a masses Confirm a cyst when features are non simple Identify BI-RADS 3 that are cancer Potential for elastography for assessment of breast masses Downgrade BI-RADS 3 and BI-RADS 4a that are definitely benign Upgrade BI-RADS 3 that are malignant Confidently identify non simple cysts Impact: Significantly decrease benign biopsies No change or even increase in cancer detection 12

13 Elastography in current clinical practice Requires trials with much larger series of patients Determine false negative rate at different elastography scores Validate ability to downgrade BI-RADS 3, 4a Evaluate ability to upgrade BI-RADS 3 masses More studies must correlate elastography score, BI-RADS category, and pathology outcome Summary Ultrasound has limited specificity for most solid masses and many non simple cysts Elastography for assessment of breast masses Utilizes principles of tissue stiffness Could increase specificity, decrease benign biopsies Research trials have been too small to confidently establish false negative rate 13