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PURPOSE. Studies have shown that a decrease in mammographic density (MD) or lowering of background parenchymal enhancement (BPE) on MRI after initiation of tamoxifen therapy predicts a favorable response in the preventive or adjuvant settings. However, performing serial mammograms poses radiation concerns, while serial MRIs carry high cost as well as risk of multiple Gadolinium doses. Previous studies have shown that tissue sound speed, derived from whole breast ultrasound tomography measurements, is a surrogate biomarker of MD. Ultrasound is ideal for performing serial measurements because it is fast and poses almost no risks. The purpose of this study was to evaluate repeated measures of the sound speed biomarker at 3, 6 and 12-months following tamoxifen initiation. METHOD AND MATERIALS. We performed a case-control comparison involving 74 participants referred by a health professional to undergo tamoxifen therapy (cases) and 150 matched participants with no history of breast cancer (controls). The cases were scanned with ultrasound tomography at baseline (i.e. before start of tamoxifen therapy), and then at 3, 6 and 12 months after tamoxifen initiation. Controls were scanned at baseline and 12 months. In the case group, sound speed was measured pre-treatment in the contralateral breast to avoid potential influences of tumor-related changes on density. In the control group, a single randomized breast was scanned. A pairwise t-test was used to assess differences in sound speed over time and between cases and controls. RESULTS. There was a steady decline in sound speed over the 12-month period for women undergoing tamoxifen therapy (mean(SD): -3.0(8.2) m/s; P=0.001). Furthermore, significant sound speed reductions were observed as early as 4-6 months after tamoxifen initiation (mean(SD): -2.1(6.8) m/s; P=0.008). In contrast, the controls demonstrated no significant change in sound speed over a 12-month period, and the difference between case-control groups was statistically significant (P=0.0009). DISCUSSION. Breast sound speed decreases rapidly after tamoxifen initiation while it remains steady for the control group. These results suggest that sound speed may be a biomarker of response to tamoxifen. Further studies are needed to assess whether this observation can predict clinical response. CONCLUSION. Ultrasound tomography may have utility in monitoring breast sound speed change as a potential biomarker of clinical tamoxifen response. Citation Format: Neb Duric, Mark Sak, Mark Sherman, Ruth Pfeiffer, Sharon Fan, Michael Simon, David Gorski, Teri Albrecht, Haythem Ali, Peter Littrup, Rachel Brem, Gretchen Gierach. Tissue sound speed: A novel imaging biomarker for measuring tamoxifen response [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-11-11.

PURPOSE. Increased mammographic percent density (MPD) is a strong independent risk factor for developing breast cancer. Previous studies have shown that tissue sound speed, derived from ultrasound tomography, is a surrogate biomarker of MPD. We examined associations of sound speed and MPD with breast cancer risk in a case-control study. METHOD AND MATERIALS. We evaluated breast cancer risk associated with sound speed and MPD in a case-control study involving 59 participants with recent breast cancer diagnoses (cases, aged 30-70 years) and 150 participants with no history of breast cancer (controls), who were matched to cases on age, race, and menopausal status. The cases and controls were imaged with both ultrasound tomography (UST) and mammography. In cases, breast density was measured pre-treatment in the contralateral breast to avoid potential influences of tumor-related changes on MPD or sound speed. In controls, a randomly selected breast was imaged. The ultrasound tomography images were used to estimate the volume averaged sound speed of the breast, and the Cumulus software package was applied to mammograms to determine MPD. Odds Ratios (ORs) and 95% Confidence Intervals (CIs), adjusted for matching factors, were calculated for the relation of quartiles of MPD and sound speed with breast cancer risk. OR differences were tested using a bootstrap approach. RESULTS. MPD was associated with elevated breast cancer risk compared to controls, consistent with previous studies, although the trend did not reach statistical significance (OR per quartile=1.28, 95%CI: 0.95, 1.73; ptrend=0.10). In contrast, elevated sound speed was significantly associated with increased breast cancer risk in a dose-response fashion (OR per quartile=1.79, 95%CI: 1.30, 2.48; ptrend=0.0004). The OR-trend for sound speed was statistically significantly different from that observed for MPD (p=0.01). DISCUSSION. Our case-control study showed that increasing quartiles of whole breast sound speed were consistently and more strongly associated with increasing breast cancer risk than quartiles of MPD. These results show promise for UST’s role in breast cancer risk stratification. CONCLUSION. Elevated breast density strongly increases breast cancer risk. UST has the potential to provide a more accurate, non-ionizing method for assessing breast density and its associated breast cancer risk. Citation Format: Mark Sak, Neb Duric, Ruth Pfeiffer, Mark Sherman, Peter Littrup, Michael Simon, David Gorski, Teri Albrecht, Haythem Ali, Rachel Brem, Rachel Brem, Sharon Fan, Gretchen Gierach. Tissue sound speed is more strongly associated with breast cancer risk than mammographic percent density: A comparative case-control study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-28.

Objective To evaluate the combination of tumor volume and sound speed as a potential imaging marker for assessing neoadjuvant chemotherapy (NAC) response. Methods This study was carried out under an IRB-approved protocol (written consent required). Fourteen patients undergoing NAC for invasive breast cancer were examined with ultrasound tomography (UST) throughout their treatment. The volume (V) and the volume-averaged sound speed (VASS) of the tumors and their changes were measured for each patient. Time-dependent response curves of V and VASS were constructed individually for each patient and then as averages for the complete versus partial response groups in order to characterize differences between the two groups. Differences in group means were assessed for statistical significance using t-tests. Differences in shapes of group curves were evaluated with Kolmogorov–Smirnoff tests. Results On average, tumor volume and sound speed in the partial response group showed a gradual decline in the first 60 days of treatment, while the complete response group showed a much steeper decline (P < 0.05). The shapes of the response curves of the two groups, corresponding to the entire treatment period, were also found to be significantly different (P < 0.05). Furthermore, large simultaneous drops in volume and sound speed in the first 3 weeks of treatment were characteristic only of the complete responders (P < 0.05). Conclusion This study demonstrates the feasibility of using UST to monitor NAC response, warranting future studies to better define the potential of UST for noninvasive, rapid identification of partial versus complete responders in women undergoing NAC.

Objectives Ultrasound tomography (UST) is an emerging whole-breast 3-dimensional imaging technique that obtains quantitative tomograms of speed of sound of the entire breast. The imaged parameter is the speed of sound which is used as a surrogate measure of density at each voxel and holds promise as a method to evaluate breast density without ionizing radiation. This study evaluated the technique of UST and compared whole-breast volume averaged speed of sound (VASS) with MR percent water content from noncontrast magnetic resonance imaging (MRI). Materials and Methods Forty-three healthy female volunteers (median age, 40 years; range, 29-59 years) underwent bilateral breast UST and MRI using a 2-point Dixon technique. Reproducibility of VASS was evaluated using Bland-Altman analysis. Volume averaged speed of sound and MR percent water were evaluated and compared using Pearson correlation coefficient. Results The mean standard deviation VASS measurement was 1463 +/- 29 m s(-1) (range, 1434-1542 m s(-1)). There was high similarity between right (1464 +/- 30 m s(-1)) and left (1462 +/- 28 m s(-1)) breasts (P = 0.113) (intraclass correlation coefficient, 0.98). Mean MR percent water content was 35.7% +/- 14.7% (range, 13.2%-75.3%), with small but significant differences between right and left breasts (36.3% +/- 14.9% and 35.1% +/- 14.7%, respectively; P = 0.004). There was a very strong correlation between VASS and MR percent water density (r(2) = 0.96, P < 0.0001). Conclusions Ultrasound tomography holds promise as a reliable and reproducible 3-dimensional technique to provide a surrogate measure of breast density and correlates strongly with MR percent water content.

PURPOSE. Ultrasound tomography (UST) using SoftVue (Delphinus Medical Technologies, Inc.) has the unique ability to provide quantitative whole breast tissue stiffness, including localized measurements on masses. Conversely, handheld ultrasound (HHUS) only provides localized diagnostic information of tissue stiffness, or elasticity. Screening requires global assessment of tissue properties for which HHUS is not suitable, while automated breast ultrasound does not measure stiffness. This study is the first to evaluate imaging of tissue stiffness by SoftVue for common breast masses. METHOD AND MATERIALS. Patients with findings on mammography during the time period of January 2017 to November 2018, were scanned with SoftVue. Patients were selected on the basis of having dense breasts and having either benign or malignant breast masses. All women received standard breast imaging evaluation prior to biopsy. Pathology and/or radiology reports were used as the ground truth for verifying lesion type, which included 195 masses RESULTS. SoftVue demonstrated the ability to measure tissue stiffness throughout the breast and to characterize mass stiffness in all 195 patients. Table 1 lists the average stiffness index for each type of mass. Cysts, fibroadenomas and cancers were found to have mean stiffness indices of (0.10; 95% CI: 0.05 to 0.30), (0.35; 0.25 to 0.77) and (0.60; 0.41 to 1.00) respectively (p DISCUSSION. Masses were characterized using mean stiffness and mean homogeneity of stiffness. Both measures were able to separate the populations of the three types of masses, but the homogeneity texture parameter showed less overlap between benign and malignant masses. Further radiomics analyses of texture features will assure inclusion in a future CAD tool for improved diagnostic performance. During dense breast screening by SoftVue, whole breast tissue stiffness improves cancer conspicuity throughout a breast volume for initial detection during screening, while mass characterization on the basis of stiffness may improve screening specificity, which is not possible with current ultrasound. CONCLUSION. Measuring tissue stiffness throughout the whole breast is not currently available clinically. The study demonstrates that stiffness characterization of lesions derived from whole breast stiffness imaging with UST SoftVue is feasible for future screening of women with dense breasts. Using SoftVue stiffness has the potential to reduce call backs and biopsies, in combination with other parameters, to improve specificity. Table 1Type of MassStiffness index valueStandard deviation95% CIMean HomogeneityStandard Deviation95% CICyst0.100.200.05-0.300.830.050.73 - 0.91FB0.350.240.25-0.770.770.060.65 - 0.85Ca0.610.190.41-1.000.660.090.52 - 0.79 Citation Format: Neb Duric, Peter J Littrup, Cuiping Li, Rachel Brem. Whole breast tissue stiffness and mass characterization by ultrasound tomography [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-02-08.

PURPOSE. Recent analyses of tumor location by breast magnetic resonance (MR) imaging have shown that breast cancers were significantly more likely to be located, at or near the fat-gland interface (FGI). However, these analyses did not include benign masses or coronal evaluations. Ultrasound tomography (UST) is a novel multi-sequence tomographic form of sonography with anatomic and physiologic information that can improve the sensitivity of breast cancer detection, particularly in women with dense breasts. The purpose of this study was to use the native coronal imaging plane of UST SoftVue (Delphinus Medical Technologies, Inc.) to map the locations of cancers, fibroadenomas and cysts, relative to the FGI, in order to facilitate the detection and characterization of breast masses in future UST screening. METHODS AND MATERIALS. Mass location in coronal UST images was determined by a MQSA certified radiologist with extensive UST imaging experience. The relationship of the lesion to the FGI was noted for a total of 427 breast masses (117 cancers, 135 fibroadenomas, 135 cysts and 40 other benign findings), confirmed by biopsy or by hand-held ultrasound for masses that fulfilled all criteria for a simple cyst. The FGI was defined as the circumferential interface between the peripheral fat and parenchyma as determined by examining sound speed (SS) images, which reliably differentiate the much lower SS of fat compared to that of dense tissue. Mass location was placed into three groups: (i) completely surrounded by dense fibroglandular tissue, (ii) completely surrounded by fat or (iii) partially surrounded by both (i.e., the FGI). Lesion locations relative to FGI were compared using the chi-squared test. RESULTS. Cancers were located at the FGI in 93.2% (109/117) of the cases and were surrounded by fat in 6.0% (7/117) or parenchyma in 0.9% (1/117) (p DISCUSSION. Coronal imaging by UST provides reliable circumferential evaluation of the FGI, which can be augmented by axial/sagittal reconstructions as needed for additional confirmation of anterior/posterior aspects of the FGI. Our results confirm the previously reported MRI findings that cancers have a very strong tendency to be located at the FGI and extend these findings by demonstrating that benign masses have a weaker tendency in that regard. With the introduction of UST, our finding that breast cancers occur more frequently at the fat-gland interface may facilitate the conspicuity, rapid search and localization of cancers during screening of women with dense breasts. Perhaps equally important for future specificity of screening women with dense breasts, fibroglandular tissue surrounded only 0.9% of cancers and was much more commonly associated with benign masses. CONCLUSIONS. The native coronal imaging plane by SoftVue UST facilitated detection and localization of cancers, which were much more likely to be found at the FGI (p Table 1Type of massAt FGIIn Dense tissueIn FatCancer109 (93%)1 (1%)7 (6%)Fibroadenoma85 (63%)42 (31%)8 (6%)Cyst39 (29%)93 (69%)3 (2%) Citation Format: Peter Littrup, Mark Sak, Neb Duric, Rachel Brem. Breast cancer development at the fat-gland interface (FGI): Importance of coronal imaging and ultrasound tomography [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-02-05.

Mammographic percent density (MPD) is an independent risk factor for developing breast cancer, but its inclusion in clinical risk models provides only modest improvements in individualized risk prediction, and MPD is not typically assessed in younger women because of ionizing radiation concerns. Previous studies have shown that tissue sound speed, derived from whole breast ultrasound tomography (UST), a non-ionizing modality, is a potential surrogate marker of breast density, but prior to this study, sound speed has not been directly linked to breast cancer risk. To that end, we explored the relation of sound speed and MPD with breast cancer risk in a case-control study, including 61 cases with recent breast cancer diagnoses and a comparison group of 165 women, frequency matched to cases on age, race, and menopausal status, and with a recent negative mammogram and no personal history of breast cancer. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the relation of quartiles of MPD and sound speed with breast cancer risk adjusted for matching factors. Elevated MPD was associated with increased breast cancer risk, although the trend did not reach statistical significance (OR per quartile = 1.27, 95% CI: 0.95, 1.70; ptrend = 0.10). In contrast, elevated sound speed was significantly associated with breast cancer risk in a dose−response fashion (OR per quartile = 1.83, 95% CI: 1.32, 2.54; ptrend = 0.0003). The OR trend for sound speed was statistically significantly different from that observed for MPD (p = 0.005). These findings suggest that whole breast sound speed may be more strongly associated with breast cancer risk than MPD and offer future opportunities for refining the magnitude and precision of risk associations in larger, population-based studies, including women younger than usual screening ages.

ObjectiveTo assess the feasibility of using tissue sound speed as a quantitative marker of breast density.MethodsThis study was carried out under an Institutional Review Board–approved protocol (written consent required). Imaging data were selected retrospectively based on the availability of US tomography (UST) exams, screening mammograms with volumetric breast density data, patient age of 18 to 80 years, and weight less than 300 lbs. Sound speed images from the UST exams were used to measure the volume of dense tissue, the volume averaged sound speed (VASS), and the percent of high sound speed tissue (PHSST). The mammographic breast density and volume of dense tissue were estimated with three-dimensional (3D) software. Differences in volumes were assessed with paired t-tests. Spearman correlation coefficients were calculated to determine the strength of the correlations between the mammographic and UST assessments of breast density.ResultsA total of 100 UST and 3D mammographic data sets met the selection criteria. The resulting measurements showed that UST measured a more than 2-fold larger volume of dense tissue compared to mammography. The differences were statistically significant (P < 0.001). A strong correlation of rS = 0.85 (95% CI: 0.79–0.90) between 3D mammographic breast density (BD) and the VASS was noted. This correlation is significantly stronger than those reported in previous two-dimensional studies (rS = 0.85 vs rS = 0.71). A similar correlation was found for PHSST and mammographic BD with rS = 0.86 (95% CI: 0.80–0.90).ConclusionThe strong correlations between UST parameters and 3D mammographic BD suggest that breast sound speed should be further studied as a potential new marker for inclusion in clinical risk models.

Objectives Some US states have mandated that women be informed when they have dense breasts; however, little is known about how general knowledge about breast density (BD) affects related health decision-making. We examined the effects of BD information and imaging technology information on 138 African–American (AA) and European–American (EA) women's intentions to discuss breast cancer screening with their physicians. Methods Women were randomly assigned to receive BD information and/or imaging technology information via 2 by 2 factorial design, and completed planned behavior measures (e.g., attitudes, intentions) related to BC screening. Results Attitudes mediated the effects of BD information, and the mediation was stronger for AA women compared to EA women. Effects were more robust for BD information compared to imaging technology information. Results of moderator analyses revealed suppressor effects of injunctive norms that were moderated by imaging technology information. Conclusion Information about BD favorably influences women's intentions to engage in relevant breast health behaviors. Stronger attitude mediated-effects for AA women suggest greater scrutiny of BD information. Practice implications Since BD information may influence women's intentions to discuss BC screening, strategies to effectively present BD information to AA women should be investigated given the likelihood of their increased scrutiny of BD information.

Breast density is one of the strongest predictors of breast cancer risk. Women with the densest breasts are four- to six-times more likely to develop cancer compared with those with the lowest densities. Breast density is generally assessed using mammographic imaging; however, this approach has limitations. Magnetic resonance imaging and ultrasound tomography are some alternative imaging modalities that can aid mammography in patient screening and the measurement of breast density. As breast density becomes more commonly discussed, knowledge of the advantages and limitations of breast density as a marker of risk will become more critical. This review article discusses the relationship between breast density and breast cancer risk, lists the benefits and drawbacks of using multiple different imaging modalities to measure density and briefly discusses how breast density will be applied to aid in breast cancer prevention and treatment.

Application of the frequency domain acoustic wave equation on data acquired from ultrasound tomography scans is shown to yield high resolution sound speed images on the order of the wavelength of the highest reconstructed frequency. Using a signal bandwidth of 0.4-1 MHz and an average sound speed of 1500 m s(-1), the resolution is approximately 1.5 mm. The quantitative sound speed values and morphology provided by these images have the potential to inform diagnosis and classification of breast disease. In this study, we present the formalism, practical application, and in vivo results of waveform tomography applied to breast data gathered by two different ultrasound tomography scanners that utilize ring transducers. The formalism includes a review of frequency domain modeling of the wave equation using finite difference operators as well as a review of the gradient descent method for the iterative reconstruction scheme. It is shown that the practical application of waveform tomography requires an accurate starting model, careful data processing, and a method to gradually incorporate higher frequency information into the sound speed reconstruction. Following these steps resulted in high resolution quantitative sound speed images of the breast. These images show marked improvement relative to commonly used ray tomography reconstruction methods. The robustness of the method is demonstrated by obtaining similar results from two different ultrasound tomography devices. We also compare our method to MRI to demonstrate concordant findings. The clinical data used in this work was obtained from a HIPAA compliant clinical study (IRB 040912M1F).

Ultrasound Computer Tomography (USCT) is a promising breast imaging modality under development. Comparison to a standard method like mammography is essential for further development. Due to significant differences in image dimensionality and compression state of the breast, correlating USCT images and X-ray mammograms is challenging. In this paper we present a 2D/3D registration method to improve the spatial correspondence and allow direct comparison of the images. It is based on biomechanical modeling of the breast and simulation of the mammographic compression. We investigate the effect of including patient-specific material parameters estimated automatically from USCT images. The method was systematically evaluated using numerical phantoms and in-vivo data. The average registration accuracy using the automated registration was 11.9mm. Based on the registered images a method for analysis of the diagnostic value of the USCT images was developed and initially applied to analyze sound speed and attenuation images based on X-ray mammograms as ground truth. Combining sound speed and attenuation allows differentiating lesions from surrounding tissue. Overlaying this information on mammograms, combines quantitative and morphological information for multimodal diagnosis.

Ultrasound computed tomography (USCT) holds great promise for breast cancer screening. Waveform inversion-based image reconstruction methods account for higher order diffraction effects and can produce high-resolution USCT images, but are computationally demanding. Recently, a source encoding technique was combined with stochastic gradient descent to greatly reduce image reconstruction times. However, this method bundles the stochastic data fidelity term with the deterministic regularization term. This limitation can be overcome by replacing stochastic gradient descent (SGD) with a structured optimization method, such as the regularized dual averaging (RDA) method, that exploits knowledge of the composition of the cost function. In this work, the dual averaging method is combined with source encoding techniques to improve the effectiveness of regularization while maintaining the reduced reconstruction times afforded by source encoding. It is demonstrated that each iteration can be decomposed into a gradient descent step based on the data fidelity term and a proximal update step corresponding to the regularization term. Furthermore, the regularization term is never explicitly differentiated, allowing non-smooth regularization penalties to be naturally incorporated. The wave equation is solved by use of a time-domain method. The effectiveness of this approach is demonstrated through computer-simulation and experimental studies. The results suggest that the dual averaging method can produce images with less noise and comparable resolution to those obtained by use of stochastic gradient descent.

Hyperthermia is a promising method to enhance chemo- or radiation therapy of breast cancer and the time-temperature profile in the target and surrounding areas is the primary monitoring method. Unlike with thermal ablation of lesions, in hyperthermia there are not good alternative treatment monitoring quantities. However, there is less problem with non-monotonic thermal coefficients of speed of sound used with ultrasonic imaging of temperature. This paper tests a long discussed but little investigated method of imaging temperature using speed of sound and proposes methods of reducing edge enhancement artifacts in the temperature image. Normally, when directly using the speed of sound to reconstruct the temperature image around the tumor, there will be an abnormal bipolar edge enhancement along the boundary between two materials with different speeds of sound at a given temperature. This due to partial volume effects and can be diminished by regularized, weighted deconvolution. An initial, manual deconvolu...

Ultrasound tomography (UST) image segmentation is fundamental in breast density estimation, medicine response analysis, and anatomical change quantification. Existing methods are time consuming and require massive manual interaction. To address these issues, an automatic algorithm based on GrabCut (AUGC) is proposed in this paper. The presented method designs automated GrabCut initialization for incomplete labeling and is sped up with multicore parallel programming. To verify performance, AUGC is applied to segment thirty-two in vivo UST volumetric images. The performance of AUGC is validated with breast overlapping metrics (Dice coefficient (D), Jaccard (J), and False positive (FP)) and time cost (TC). Furthermore, AUGC is compared to other methods, including Confidence Connected Region Growing (CCRG), watershed, and Active Contour based Curve Delineation (ACCD). Experimental results indicate that AUGC achieves the highest accuracy (D=0.9275 and J=0.8660 and FP=0.0077) and takes on average about 4 seconds to process a volumetric image. It was said that AUGC benefits large-scale studies by using UST images for breast cancer screening and pathological quantification.

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.

Women with high breast density are at increased risk of developing breast cancer. Breast density has usually been defined using mammography as the ratio of fibroglandular tissue to total breast area. Ultrasound tomography (UST) is an emerging modality that can also be used to measure breast density. UST creates tomographic sound speed images of the patient’s breast which is useful as sound speed is directly proportional to tissue density. Furthermore, the volumetric and quantitative information contained in the sound speed images can be used to describe the distribution of breast density. The work presented here measures the UST sound speed density distributions of 165 women with negative screening mammography. Frequency distributions of the sound speed voxel information were examined for each patient. In a preliminary analysis, the UST sound speed distributions were averaged across patients and grouped by various patient and density-related factors (e.g., age, body mass index, menopausal status, average mammographic breast density). It was found that differences in the distribution of density could be easily visualized for different patient groupings. Furthermore, findings suggest that the shape of the distributions may be used to identify participants with varying amounts of dense and non-dense tissue.

Ultrasound computed tomography (USCT) holds great promise for improving the detection and management of breast cancer. Because they are based on the acoustic wave equation, waveform inversion-based reconstruction methods can produce images that possess improved spatial resolution properties over those produced by ray-based methods. However, waveform inversion methods are computationally demanding and have not been applied widely in USCT breast imaging. In this work, source encoding concepts are employed to develop an accelerated USCT reconstruction method that circumvents the large computational burden of conventional waveform inversion methods. This method, referred to as the waveform inversion with source encoding (WISE) method, encodes the measurement data using a random encoding vector and determines an estimate of the sound speed distribution by solving a stochastic optimization problem by use of a stochastic gradient descent algorithm. Both computer-simulation and experimental phantom studies are conducted to demonstrate the use of the WISE method. The results suggest that the WISE method maintains the high spatial resolution of waveform inversion methods while significantly reducing the computational burden.

Ultrasound tomography (UST) employs sound waves to produce three-dimensional images of breast tissue and precisely measures the sound speed of breast tissue composition. High breast density is a strong breast cancer risk factor and sound speed is directly proportional to breast density. UST provides a quantitative measure of breast density based on three-dimensional imaging without compression, thereby overcoming the shortcomings of many other imaging modalities. The quantitative nature of the UST breast density measures are tied to an external standard, so sound speed measurement in breast tissue should be independent of specific hardware. The work presented here compares breast sound speed measurement obtained with two different UST devices. The Computerized Ultrasound Risk Evaluation (CURE) system located at the Karmanos Cancer Institute in Detroit, Michigan was recently replaced with the SoftVue ultrasound tomographic device. Ongoing clinical trials have used images generated from both sets of hardware, so maintaining consistency in sound speed measurements is important. During an overlap period when both systems were in the same exam room, a total of 12 patients had one or both of their breasts imaged on both systems on the same day. There were 22 sound speed scans analyzed from each system and the average breast sound speeds were compared. Images were either reconstructed using saved raw data (for both CURE and SoftVue) or were created during the image acquisition (saved in DICOM format for SoftVue scans only). The sound speed measurements from each system were strongly and positively correlated with each other. The average difference in sound speed between the two sets of data was on the order of 1-2 m/s and this result was not statistically significant. The only sets of images that showed a statistical difference were the DICOM images created during the SoftVue scan compared to the SoftVue images reconstructed from the raw data. However, the discrepancy between the sound speed values could be easily handled by uniformly increasing the DICOM sound speed by approximately 0.5 m/s. These results suggest that there is no fundamental difference in sound speed measurement for the two systems and support combining data generated with these instruments in future studies.

Little is known about women’s knowledge of breast density or between-race differences in this knowledge. In the current study, we examined knowledge of breast density and awareness of its role as a breast cancer risk factor among women who had previously taken part in a breast imaging study. Seventy-seven women (54.5 % Black) returned a survey assessing perceptions and accuracy of breast density knowledge, knowledge of one’s own breast density, and breast cancer risk awareness. White women had greater perceived knowledge of breast density compared to Black women; however, differences in the accuracy of definitions of breast density were due to education. Black women were less likely to know how dense their own breasts were. Black and White women both lacked awareness that having dense breast increased breast cancer risk. The results highlight the need to disseminate information regarding breast density to women, while ensuring that the information is equally accessible to both Black and White women.

Women with high breast density have an increased risk of developing breast cancer. Women treated with the selective estrogen receptor modulator tamoxifen for estrogen receptor positive breast cancer experience a 50% reduction in risk of contralateral breast cancer and overall reduction of similar magnitude has been identified among high-risk women receiving the drug for prevention. Tamoxifen has been shown to reduce mammographic density, and in the IBIS-1 chemoprevention trial, risk reduction and decline in density were significantly associated. Ultrasound tomography (UST) is an imaging modality that can create tomographic sound speed images of the breast. These sound speed images are useful because breast density is proportional to sound speed. The aim of this work is to examine the relationship between UST-measured breast density and the use of tamoxifen. So far, preliminary results for a small number of patients have been observed and are promising. Correlations between the UST-measured density and mammographic density are strong and positive, while relationships between UST density with some patient specific risk factors behave as expected. Initial results of UST examinations of tamoxifen treated patients show that approximately 45% of the patients have a decrease in density in the contralateral breast after only several months of treatment. The true effect of tamoxifen on UST-measured density cannot yet be fully determined until more data are collected. However, these promising results suggest that UST can be used to reliably assess quantitative changes in breast density over short intervals and therefore suggest that UST may enable rapid assessment of density changes associated with therapeutic and preventative interventions.

For women with dense breast tissue, who are at much higher risk for developing breast cancer, the performance of mammography is at its worst. Consequently, many early cancers go undetected when they are the most treatable. Improved cancer detection for women with dense breasts would decrease the proportion of breast cancers diagnosed at later stages, which would significantly lower the mortality rate. The emergence of whole breast ultrasound provides good performance for women with dense breast tissue, and may eliminate the current trade-off between the cost effectiveness of mammography and the imaging performance of more expensive systems such as magnetic resonance imaging. We report on the performance of SoftVue, a whole breast ultrasound imaging system, based on the principles of ultrasound tomography. SoftVue was developed by Delphinus Medical Technologies and builds on an early prototype developed at the Karmanos Cancer Institute. We present results from preliminary testing of the SoftVue system, performed both in the lab and in the clinic. These tests aimed to validate the expected improvements in image performance. Initial qualitative analyses showed major improvements in image quality, thereby validating the new imaging system design. Specifically, SoftVue’s imaging performance was consistent across all breast density categories and had much better resolution and contrast. The implications of these results for clinical breast imaging are discussed and future work is described.

We propose a new method for imaging sound speed in breast tissue from measurements obtained by ultrasound tomography (UST) scan- ners. Given the measurements, our algorithm finds a sparse image representation in an overcomplete dictionary that is adapted to the properties of UST images. This dictionary is learned from high reso- lution MRI breast scans using an unsupervised maximum likelihood dictionary learning method. The proposed dictionary-based regular- ization method significantly improves the quality of reconstructed breast UST images. It outperforms the wavelet-based reconstruction and the least squares minimization with lowpass constraints, on both numerical and in vivo data. Our results demonstrate that the use of the learned dictionary improves the image accuracy for up to 4 dB with the exact measurement matrix and for 3.5 dB with the estimated measurement matrix over the wavelet-based reconstruction under the same conditions.

Ultrasound is commonly used as an adjunct to mammography for diagnostic evaluation of suspicions arising from breast cancer screening. As an alternative to conventional sonography that uses hand-held transducers, toroidal array probes that encircle the breast immersed in a water bath have been investigated for ultrasound tomography. In this paper, two sets of experiments performed with a prototype ultrasound scanner on a phantom and a human breast in vivo are used to investigate the effects of diffraction and coherence in ultrasound tomography. Reconstructions obtained with transmission diffraction tomography (TDT) are compared with conventional reflection imaging and computerized ultrasound tomography showing a substantial improvement. The in vivo tests demonstrate that TDT can image the complex boundary of a cancer mass and suggest that it can reveal the anatomy of milk ducts and Cooper's ligaments.

Breast ultrasound tomography is a rapidly developing imaging modality that has the potential to impact breast cancer screening and diagnosis. A new ultrasound breast imaging device (CURE) with a ring array of transducers has been designed and built at Karmanos Cancer Institute, which acquires both reflection and transmission ultrasound signals. To extract the sound-speed information from the breast data acquired by CURE, we have developed an iterative sound-speed image reconstruction algorithm for breast ultrasound transmission tomography based on total-variation (TV) minimization. We investigate applicability of the TV tomography algorithm using in vivo ultrasound breast data from 61 patients, and compare the results with those obtained using the Tikhonov regularization method. We demonstrate that, compared to the Tikhonov regularization scheme, the TV regularization method significantly improves image quality, resulting in sound-speed tomography images with sharp (preserved) edges of abnormalities and few artifacts.

Ultrasound reflection imaging is a promising imaging modality for detecting small, early-stage breast cancers. Properly accounting for ultrasound scattering from heterogeneities within the breast is essential for high-resolution and high-quality ultrasound breast imaging. We develop a globally optimized Fourier finite-difference method for ultrasound reflectivity image reconstruction. It utilizes an optimized solution of acoustic-wave equation and a heterogeneous sound-speed distribution of the breast obtained from tomography to reconstruct ultrasound reflectivity images. The method contains a finite-difference term in addition to the split-step Fourier implementation, and minimizes ultrasound phase errors during wavefield inward continuation while maintaining the advantage of high computational efficiency. The accuracy analysis indicates that the optimized method is much more accurate than the split-step Fourier method. The computational efficiency of the optimized method is one to two orders of magnitude faster than time-reversal imaging using a finite-difference time-domain wave-equation scheme. Our new optimized method can accurately handle ultrasound scattering from breast heterogeneities during reflectivity image reconstruction. Our numerical imaging examples demonstrate that the optimized method has the potential to produce high-quality and high-resolution ultrasound reflectivity images in combination with a reliable ultrasound sound-speed tomography method.

Waveform tomography results are presented from 800 kHz ultrasound transmission scans of a breast phantom, and from an in vivo ultrasound breast scan: significant improvements are demonstrated in resolution over time-of-flight reconstructions. Quantitative reconstructions of both sound-speed and inelastic attenuation are recovered. The data were acquired in the Computed Ultrasound Risk Evaluation (CURE) system, comprising a 20 cm diameter solid-state ultrasound ring array with 256 active, non-beamforming transducers. Waveform tomography is capable of resolving variations in acoustic properties at sub-wavelength scales. This was verified through comparison of the breast phantom reconstructions with x-ray CT results: the final images resolve variations in sound speed with a spatial resolution close to 2 mm. Waveform tomography overcomes the resolution limit of time-of-flight methods caused by finite frequency (diffraction) effects. The method is a combination of time-of-flight tomography, and 2-D acoustic waveform inversion of the transmission arrivals in ultrasonic data. For selected frequency components of the waveforms, a finite-difference simulation of the visco-acoustic wave equation is used to compute synthetic data in the current model, and the data residuals are formed by subtraction. The residuals are used in an iterative, gradient-based scheme to update the sound-speed and attenuation model to produce a reduced misfit to the data. Computational efficiency is achieved through the use of time-reversal of the data residuals to construct the model updates. Lower frequencies are used first, to establish the long wavelength components of the image, and higher frequencies are introduced later to provide increased resolution.

Determining the three-dimensional structure of distant astronomical objects is a challenging task, given that terrestrial observations provide only one viewpoint. For this task, bipolar planetary nebulae are interesting objects of study because of their pronounced axial symmetry due to fundamental physical processes. Making use of this symmetry constraint, we present a technique to automatically recover the axisymmetric structure of bipolar planetary nebulae from two-dimensional images. With GPU-based volume rendering driving a non-linear optimization, we estimate the nebulaýs local emission density as a function of its radial and axial coordinates, and we recover the orientation of the nebula relative to Earth. The optimization refines the nebula model and its orientation by minimizing the differences between the rendered image and the original astronomical image. The resulting model enables realistic 3D visualizations of planetary nebulae, e.g. for educational purposes in planetarium shows. In addition, the recovered spatial distribution of the emissive gas allows validating computer simulation results of the astrophysical formation processes of planetary nebulae.

Our Computerized Ultrasound Risk Evaluation (CURE) system has been developed to the engineering prototype stage and generated unique data sets of both transmission and reflection ultrasound (US). This paper will help define the clinical underpinnings of the developmental process and interpret the imaging results from a similar perspective. The CURE project was designed to incorporate numerous diagnostic parameters to improve upon two major areas of early breast cancer detection. CURE may provide improved tissue characterization of breast masses and reliable detection of abnormal microcalcifications found in some breast cancers and ductal carcinoma in situ (DCIS). Current breast US is limited to mass evaluation, whereas mammography also detects and guides biopsy of malignant calcifications. Screening with CURE remains a distant goal, but improved follow-up of mammographic abnormalities may represent a feasible breakthrough.

We describe the technical design and performance of SoftVue, a breast imaging device based on the principles of ultrasound tomography. SoftVue's imaging sensor is a ring shaped transducer operating at 3 MHz and consisting of 2048 elements. Data acquisition is achieved through 512 receive channels. The transducer encircles the breast, which is immersed in warm water while the patient lies in a prone position. The transducer is translated vertically to acquire data from the entire breast. The acquired data are used to reconstruct images using tomographic inversions. The reconstruction engine is based around a blade-server design that houses multiple CPUs and GPUs. Separate algorithms are used to reconstruct reflection, sound speed, and attenuation images. A patient scan generates a stack of each type of image. The system was designed with the clinical goal of detecting and characterizing breast masses based on their biomechanical and morphological properties. Ongoing clinical studies are being used to assess the performance of the system under realistic clinical settings. Results of the clinical assessment are presented. [The authors acknowledge research support from the National Cancer Institute (5 R44 CA165320-03). Neb Duric and Peter Littrup also acknowledge that they have financial interests in the SoftVue technology.]

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 (rs) 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 (rs = 0.46) and film (rs = 0.56). VASS was negatively associated with nondense area by mammography, both digital (rs = −0.58) and film (rs = −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 rs = −0.06 (p < 0.6) for digital mammography and rs = −0.53 (p < 0.002) for film mammography. For weight, the MPD associations were characterized by rs = −0.53 (p < 0.0001) for digital mammography and −0.38 (p < 0.0001) for film mammography. The association of VASS with age was rs = −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 rs = −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.

Breast density, as assessed by mammography, reflects breast tissue composition. Breast epithelium and stroma attenuate x-rays more than fat and thus appear light on mammograms while fat appears dark. In this review, we provide an overview of selected areas of current knowledge about the relationship between breast density and susceptibility to breast cancer. We review the evidence that breast density is a risk factor for breast cancer, the histological and other risk factors that are associated with variations in breast density, and the biological plausibility of the associations with risk of breast cancer. We also discuss the potential for improved risk prediction that might be achieved by using alternative breast imaging methods, such as magnetic resonance or ultrasound. After adjustment for other risk factors, breast density is consistently associated with breast cancer risk, more strongly than most other risk factors for this disease, and extensive breast density may account for a substantial fraction of breast cancer. Breast density is associated with risk of all of the proliferative lesions that are thought to be precursors of breast cancer. Studies of twins have shown that breast density is a highly heritable quantitative trait. Associations between breast density and variations in breast histology, risk of proliferative breast lesions, and risk of breast cancer may be the result of exposures of breast tissue to both mitogens and mutagens. Characterization of breast density by mammography has several limitations, and the uses of breast density in risk prediction and breast cancer prevention may be improved by other methods of imaging, such as magnetic resonance or ultrasound tomography.

Although mammography is the gold standard for breast imaging, it leads to a high rate of biopsies of benign lesions and a significant false negative rate for women with dense breasts. A clinical breast‐imaging device, based on the principles of ultrasound tomography, is being developed in response to this imaging performance gap. The computed ultrasound risk evaluation (CURE) system has been designed with the clinical goal of providing fast, whole‐breast, operator‐independent imaging, capable of differentiating breast masses. In an initial assessment of its in vivo performance, 50 patients were examined with CURE. The following results were demonstrated: (i) tomographic imaging of breast architecture, (ii) in‐plane spatial resolution of 0.5 mm in reflection and 4 mm in transmission, (iii) imaging of breast masses in reflection and transmission mode (sound speed and attenuation, and (iv) differentiation of breast masses was shown to be feasible. These initial results indicate that operator‐independent, whole‐breast imaging and the detection and characterization of breast masses are feasible. Future studies will focus on improved detection and differentiation of masses with the long‐term goal of improving the specificity of breast exams. [The authors acknowledge financial support from the Karmanos Cancer Institute and the NIH (grant R43 CA108072‐01).]

A complete H-alpha image of the Andromeda Galaxy (M31) is presented allowing the first direct measurement of the total H-alpha luminosity which is (7.3 +/- 2.4) x 10(exp 6) solar luminosity. The H-alpha emission is associated with three morphologically distinct components; a large scale star-forming ring, approximately 1.65 deg in diameter, contributing 66% of the total H-alpha emission, a bright nucleus contributing 6% of the total H-alpha emission with the remaining 28% contributed by a previously unidentified component of extended and filamentary H-alpha emission interior to the star forming ring. The correspondence between the H-alpha image and the Infrared Astronomy Satellite (IRAS) far-infrared high resolution image is striking when both are convolved to a common resolution of 105 arcsec. The close correspondence between the far-infrared and H-alpha images suggests a common origin for the two emissions. The star-forming ring contributes 70% of the far-infrared luminosity of M31. Evidence that the ring emission is energized by high mass stars includes the fact that peaks in the far-infrared emission coincide identically with H II regions in the H-alpha image. In addition, the far-infrared to H-alpha luminosity ratio within the star-forming ring is similar to what one would expect for H II regions powered by stars of spectral types ranging between O9 and B0. The origin of the filamentary H-alpha and far-infrared luminosity interior to the star-forming ring is less clear, but it is almost certainly not produced by high mass stars.

Original article can be found at: http://adsabs.harvard.edu/abs/ Copyright American Astronomical Society. DOI: 10.1086/172780 [Full text of this article is not available in the UHRA]

Ultrasound tomography (UST) is an emerging whole breast 3D imaging technique that obtains quantitative tomograms of speed of sound (as well as other properties) of the entire breast. The measured parameter is the volume averaged speed of sound (VASS) [1,2]. It improves on mammography by measuring density at each voxel and holds promise as a cheap, patient-acceptable, non-ionising radiation method to evaluate density. This study was to evaluate the technique of UST and compare VASS with percentage water density from non-contrast MRI.