Purpose:To investigate the use of the whole-breast sound speed measurement as a marker of breast density (BD), a known risk factor for breast cancer. Methods: As part of an ongoing study of breast cancer detection, 249 patients were scanned with a clinical prototype that operates on the principles of ultrasound tomography. Typically, 40-100 sound speed tomograms were reconstructed from the scan data, corresponding to the entire volume of the breast of each patient. The data were used to estimate the volume averaged sound speed (VASS) of the breast for each patient. The corresponding mammograms were used to calculate mammographic percent density (MPD) using CUMULUS software. Film mammograms were available for 164 patients while 85 digital mammograms were available for the remaining patients. Standard statistical techniques were used to determine associations of breast sound speed with a variety of mammographic measures such as percent density, area of dense tissue, and area of nondense tissue. Furthermore, associations of breast sound speed with continuous variables such as age and weight and dichotomous variables such as parity and menopausal status were also assessed. Results: VASS was found to be significantly associated with MPD. The Spearman correlation coefficient (r s ) between VASS and MPD was found to be 0.77 and 0.71 for film and digital mammography, respectively. VASS was positively correlated with dense areas by mammography, both digital (r s = 0.46) and film (r s = 0.56). VASS was negatively associated with nondense area by mammography, both digital (r s = −0.58) and film (r s = −0.63). BD by all methods was less in postmenopausal than in premenopausal women. The MPD was lower in the postmenopausal group (by 6.6%, p < 0.08, for the digital group and 7.73%, p < 0.007, for the film group). The VASS was also lower in the postmenopausal group (by 15 m/s, p < 0.001 for the digital group and 8 m/s, p < 0.08, for the film group). The association of MPD with age was characterized with r s = −0.06 (p < 0.6) for digital mammography and r s = −0.53 (p < 0.002) for film mammography. For weight, the MPD associations were characterized by r s = −0.53 (p < 0.0001) for digital mammography and −0.38 (p < 0.0001) for film mammography. The association of VASS with age was r s = −0.33 (p < 0.002) for the digital group and −0.17 (p < 0.03) for the film group. For weight, the relationship was characterized with r s = −0.45 (p < 0.001) for the digital group and −0.37 (p < 0.0001) for the film group. Conclusions: The association between VASS and MPD is strong for both film and digital mammography, suggesting that VASS is a viable measure of breast density. This result sets the stage for future work that will focus on directly testing the association of VASS with breast cancer risk.

A population of 165 women with negative mammographic screens also received an ultrasound tomography (UST) exam at the Karmanos Cancer Institute (KCI) in Detroit, MI. Standard statistical techniques were employed to measure the associations between the various mammographic and UST related density measures and various participant characteristics such as age, weight and height. The Mammographic percent density (MPD) was found to have similar strength associations with UST mean sound speed (Spearman coefficient, rs = 0.722, p < 0.001) and UST median sound speed (rs = 0.737, p < 0.001). Both were stronger than the associations between MPD with two separate measures of UST percent density, a k-means (rs = 0.568, p < 0.001) or a threshold (rs = 0.715, p < 0.001) measure. Segmentation of the UST sound speed images into dense and non-dense volumes showed weak to moderate associations with the mammographically equivalent measures. Relationships were found to be inversely and weakly associated between age and the UST mean sound speed (rs = −0.239, p = 0.002), UST median sound speed (rs = −0.226, p= 0.004) and MPD (rs = −0.204, p= 0.008). Relationships were found to be inversely and moderately associated between BMI and the UST mean sound speed (rs = −0.429, p < 0.001), UST median sound speed (rs = −0.447, p < 0.001) and MPD (rs = −0.489, p < 0.001). The results confirm and strengthen findings presented in previous work indicating that UST sound speed imaging yields viable markers of breast density in a manner consistent with mammography, the current clinical standard. These results lay the groundwork for further studies to assess the role of sound speed imaging in risk prediction.

Purpose: High breast density, as measured by mammography, is associated with increased breast cancer risk, but standard methods of assessment have limitations including 2D representation of breast tissue, distortion due to breast compression, and use of ionizing radiation. Ultrasound tomography (UST) is a novel imaging method that averts these limitations and uses sound speed measures rather than x-ray imaging to estimate breast density. The authors evaluated the reproducibility of measures of speed of sound and changes in this parameter using UST. Methods: One experienced and five newly trained raters measured sound speed in serial UST scans for 22 women (two scans per person) to assess inter-rater reliability. Intrarater reliability was assessed for four raters. A random effects model was used to calculate the percent variation in sound speed and change in sound speed attributable to subject, scan, rater, and repeat reads. The authors estimated the intraclass correlation coefficients (ICCs) for these measures based on data from the authors' experienced rater. Results: Median (range) time between baseline and follow-up UST scans was five (1-13) months. Contributions of factors to sound speed variance were differences between subjects (86.0%), baseline versus follow-up scans (7.5%), inter-rater evaluations (1.1%), and intrarater reproducibility (∼0%). When evaluating change in sound speed between scans, 2.7% and ∼0% of variation were attributed to inter-and intrarater variation, respectively. For the experienced rater's repeat reads, agreement for sound speed was excellent (ICC = 93.4%) and for change in sound speed substantial (ICC = 70.4%), indicating very good reproducibility of these measures. Conclusions: UST provided highly reproducible sound speed measurements, which reflect breast density, suggesting that UST has utility in sensitively assessing change in density. C 2015 American Association of Physicists in Medicine. [http://dx