The high DCC values (12–39%) observed in the cysts in this study were due to the decorrelating nature of the noise, artifacts, fluid-debris, and particulate matter in the interior of cysts which move randomly when compressed and thus cannot be tracked using conventional elastography. Due to partial volume averaging, sidelobes, and multiple scattering, cyst edges stayed somewhat correlated between frames, “filling in” the cyst in the DCC image and causing them to appear slightly smaller than in the grayscale image. In larger cysts, this effect had little impact on the overall DCC. This finding might have diagnostic utility, being the reverse of cancers which frequently look larger in elasticity images than in grayscale (Hall et al. 2003
). Lesion depth appeared to impact DCC values more than lesion size, most likely because lower SNR at greater depths reduces the efficacy of speckle tracking. The spotty and random highly correlated regions in the cyst were caused by particulate matter and reverberations which did not completely decorrelate. Sources of the reverberations were often easy to identify in the original grayscale ultrasound image, however, so these regions could be retrospectively removed from the DCC calculations.
The differential correlation coefficients measured in both fibroadenoma and cancer images were significantly lower than in cyst images. This was as expected because in most cases, even hypoechoic solid lesions contain more true speckle than cysts with no discrete solid components. These structures are solid so they have real elastic properties, which keep the speckle correlated. The high variability of DCC values in fibroadenomas is consistent with reports that fibroadenomas exhibit both soft and hard regions in elastograms, which can decorrelate to varying degrees (Hall et al. 2003
The technique we have presented here is similar to the acoustic streaming method investigated by Nightingale et al. (1999)
. That study successfully used high intensity ultrasound to move low level internal echoes in cysts and detect them with Doppler methods to differentiate them from solid lesions. In our case, the force used to produce the deformation in elastograms can cause particles to move in the cyst. Thus, the deformation force is, in some sense, analogous in our method to the radiation force used by Nightingale et al (1999)
and is independent of mechanical index (MI). Our differential correlation coefficient technique may be additionally efficacious in cysts which contain cells that are too large to be moved solely by the energy of the ultrasound beam, such as red blood cells, white blood cells, epithelial cells, and apocrine cells (Stavros 2004
An additional advantage to this technique is that it should be independent of preload. Though tissue elasticity contrast decreases with preload due to the nonlinearity of tissue, the correlation coefficient in a cyst will be low regardless of preload. Any speckle in a cyst is either noise or moves randomly when compressed, independent of the level of pre-compression. This can further be extended to the true statement that any strain measured in a cyst must be noise.
Recall that conventional speckle tracking algorithms used in elasticity imaging maximize correlation coefficient values to estimate displacements after tissue deformation. In this way, differential correlation coefficient values are simultaneously calculated with elastograms without additional computations and strain evaluations of solid masses can be complemented with differential correlation coefficient imaging to determine if a mass is cystic or solid. Since clinical machines capable of performing strain imaging in real time are in clinical use (Janssen et al 2007
, Thomas et al 2007
), differential correlation coefficient images could be simultaneously displayed along with tissue strain in real time.
This preliminary study had several limitations. First, imaging with a mammography-mimicking system limited visualization of breast lesions to the CC view, which some times increased the imaging depth of the lesions. Because ultrasound SNR is low in most breast lesions and decreases with depth, low SNR could cause fibroadenomas and cancers to be mistaken for cysts in the ultrasound images, or to be obscured completely. Additionally, low SNR could dominate decorrelation and greatly increase the DCC in fibroadenomas and cancers. Both of these effects would increase the likelihood of false negatives in this study and were some times emphasized in this study by imaging through the mammographic paddle rather than the position which placed the lesion closest to the transducer. However, use of a horizontal rotational axis as on standard mammographic systems and our combined ultrasound/mammography system or use of free-hand ultrasound, as would generally be done clinically, on a real-time elastography scanner would eliminate this limitation for cases in which the CC mammographic view is not ideal. In addition, freehand scanning would be expected to only increase the amount of available signal in solid masses, thus improving the discrimination between cyst and solid beyond what we have detected. In some sense, we have defined a lower bound for the differentiation between cystic and solid masses.
As a preliminary study, we did not preferentially select any of the lesions for analysis. But future studies could preferentially select human subjects with cancers which are cystic in appearance (round, non-spiculated cancers) and hypoechoic to assess the full utility of this technique. Because some complex cysts can have solid components, future studies should also aspirate and/or biopsy all cysts after imaging in order to fully understand the DCC values in non-simple cysts with only fluid components versus cysts with mixed fluid/solid components.
In this regard, only two of sever simple cysts in this study were aspirated, and although it has not been proven that the remaining five masses were cysts, these masses were deemed benign cysts by our clinical institutional criteria (see Methods section). At our institution, all breast ultrasound is performed by breast imaging sub-specialized radiologists, and we believe this may result in greater specificity or accuracy in determining benign from malignant masses. In our experience, aspirating these cysts would have needlessly inflicted an interventional procedure on these five patients. Further, the five cysts that were not aspirated did not change over a year’s time. Because these cases had 12 month stability and were classified as benign, they are extremely unlikely (<2% risk) to have solid elements (Crystal et al 2003
, Kolb et al 1998). . Thus, the technique appears in this very small sample to be able to distinguish clinically diagnosed benign complex cysts from malignant masses at our institution. However in other settings wherein breast ultrasound is performed by technologists, this differential correlation coefficient imaging can be an independent additional test providing the interpreting radiologist with greater certainty toward distinguishing a non-simple cyst from a solid mass and may indeed offer greater accuracy.
In the future, this technique could be applied with 3D elastography, which should further reduce the correlation coefficient in the cysts while maintaining the background correlation coefficient, causing the overall DCC in cysts to increase. Both the increased kernel size and the increased scanning time inherent in 3D imaging would contribute to these increased values.
Potential clinical implications
The goal of this technique, and of most clinical importance, is whether it can differentiate non-simple cysts from cancerous lesions. This differentiation could result in a reduction of the number of cysts that require aspiration or biopsy and could be especially efficacious in women with multiple lesions. Coupled with the potential to reduce interventions of benign masses is the opportunity to reduce costs and times associated with those procedures: because localized breast sonography is ¼ the cost of cyst aspiration, this could tremendously reduce clinical costs (Hilton et al. 1986
Even with a small subject size (N=18), the DCC differences between cysts and cancers are statistically significant. If a threshold were set based on these values, equal to the mean DCC in the cancer plus three standard deviations, then the cutoff between benign and malignant lesions would be 12.5%. Because the greatest DCC value exhibited by a cancer in this study was 6.7%, no false-negatives would be created with this technique. Only one cyst fell below this threshold (DCC = 12.1%) and though one fibroadenoma in this study fell above this threshold (DCC = 15.4%), there are no negative clinical implications of mischaracterizing a fibroadenoma as a cyst.
Based on this promising preliminary data which suggests the feasibility of this technique, this study will hopefully lead the way toward larger, dedicated clinical trials. Additional factors of cyst characterization, such as signal level and increased through-transmission, could be combined with differential correlation coefficient values for improved cyst identification.