Our laboratory has focused on the development of ultrasound tomography (UST) for breast imaging. To that end we
have been developing and testing a clinical prototype in the Karmanos Cancer Institute's (KCI) breast center. The
development of our prototype has been guided by clinical feedback from data accumulated from over 300 patients
recruited over the last 4 years. Our techniques generate whole breast reflection images as well as images of the acoustic
parameters of sound speed and attenuation. The combination of these images reveals major breast anatomy, including
fat, parenchyma, fibrous stroma and masses. Fusion imaging, utilizing thresholding, is shown to visualize mass
characterization and facilitates separation of cancer from benign masses. These results indicate that operator-independent
whole-breast imaging and the detection and characterization of cancerous breast masses are feasible using acoustic
tomography techniques.
Analyses of the prototype images suggests that we can detect the variety of mass attributes noted by current ultrasound-BIRADS criteria, such as mass shape, acoustic mass properties and architecture of the tumor environment. These
attributes help quantify current BIRADS criteria (e.g. "shadowing" or high attenuation) and provide greater possibilities
for defining a unique signature of cancer. The potential for UST to detect and characterize breast masses was quantified
using UST measurements of 86 masses from the most recent cohort of patients imaged with the latest version of our prototype. Our preliminary results suggest that the development of a formal predictive model, in support of larger future trials, is warranted.

In-vivo imaging results with ultrasound tomography: Report on an ongoing study at the Karmanos Cancer Institute

PURPOSE
The aim of this study was to differentiate malignant and benign solid breast lesions with a novel ultrasound (US) technique, which measures speed of sound (SoS) using standard US transducers and intrinsic tissue reflections and scattering (speckles) as internal reference.
MATERIALS AND METHODS
This prospective, institutional review board-approved, Health Insurance Portability and Accountability Act-compliant prospective comparison study was performed with prior written informed consent from 20 women. Ten women with histological proven breast cancer and 10 with fibroadenoma were measured. A conventional US system with a linear probe was used for SoS-US (SonixTouch; Ultrasonix, Richmond, British Columbia, Canada). Tissue speckle reflections served as a timing reference for the US signals transmitted through the breasts. Relative phase inconsistencies were detected using plane wave measurements from different angular directions, and SoS images with 0.5-mm resolution were generated using a spatial domain reconstruction algorithm. The SoS of tumors were compared with the breast density of a larger cohort of 106 healthy women.
RESULTS
Breast lesions show focal increments ΔSoS (meters per second) with respect to the tissue background. Peak ΔSoS values were evaluated. Breast carcinoma showed significantly higher ΔSoS than fibroadenomas ([INCREMENT]SoS > 41.64 m/s: sensitivity, 90%; specificity, 80%; area under curve, 0.910) and healthy breast tissue of different densities (area under curve, 0.938; sensitivity, 90%; specificity, 96.5%). The lesion localization in SoS-US images was consistent with B-mode imaging and repeated SoS-US measurements were reproducible.
CONCLUSIONS
Using SoS-US, based on conventional US and tissue speckles as timing reference, breast carcinoma showed significantly higher SoS values than fibroadenoma and healthy breast tissue of different densities. The SoS presents a promising technique for differentiating solid breast lesions.

https://www.zora.uzh.ch/id/eprint/170532/1/document.pdf

Breast Cancer Assessment With Pulse-Echo Speed of Sound Ultrasound From Intrinsic Tissue Reflections: Proof-of-Concept.

Purpose: To explore the feasibility of improving cross-sectional reflection imaging of the breast using refractive and attenuation corrections derived from ultrasound tomography data. Methods: The authors have adapted the planar Kirchhoff migration method, commonly used in geophysics to reconstruct reflection images, for use in ultrasound tomography imaging of the breast. Furthermore, the authors extended this method to allow for refractive and attenuative corrections. Using clinical data obtained with a breast imaging prototype, the authors applied this method to generate cross-sectional reflection images of the breast that were corrected using known distributions of sound speed and attenuation obtained from the same data. Results: A comparison of imagesreconstructed with and without the corrections showed varying degrees of improvement. The sound speed correction resulted in sharpening of detail, while the attenuation correction reduced the central darkening caused by path length dependent losses. The improvements appeared to be greatest when dense tissue was involved and the least for fatty tissue. These results are consistent with the expectation that denser tissues lead to both greater refractive effects and greater attenuation. Conclusions: Although conventional ultrasound techniques use time-gain control to correct for attenuation gradients, these corrections lead to artifacts because the true attenuation distribution is not known. The use of constant sound speed leads to additional artifacts that arise from not knowing the sound speed distribution. The authors show that in the context of ultrasound tomography, it is possible to construct reflection images of the breast that correct for inhomogeneous distributions of both sound speed and attenuation.

Modification of Kirchhoff migration with variable sound speed and attenuation for acoustic imaging of media and application to tomographic imaging of the breast.

Conventional sonography, which performs well in dense breast tissue and is comfortable and radiation-free, is
not practical for screening because of its operator dependence and the time needed to scan the whole breast.
While magnetic resonance imaging (MRI) can significantly improve on these limitations, it is also not
practical because it has long been prohibitively expensive for routine use. There is therefore a need for an
alternative breast imaging method that obviates the constraints of these standard imaging modalities. The
lack of such an alternative is a barrier to dramatically impacting mortality (about 45,000 women in the US per
year) and morbidity from breast cancer because, currently, there is a trade-off between the cost effectiveness
of mammography and sonography on the one hand and the imaging accuracy of MRI on the other. This paper
presents a progress report on our long term goal to eliminate this trade-off and thereby improve breast cancer
survival rates and decrease unnecessary biopsies through the introduction of safe, cost-effective, operatorindependent
sonography that can rival MRI in accuracy.
The objective of the study described in this paper was to design and build an improved ultrasound
tomography (UST) scanner in support of our goals. To that end, we report on a design that builds on our
current research prototype. The design of the new scanner is based on a comparison of the capabilities of our
existing prototype and the performance needed for clinical efficacy. The performance gap was quantified by
using clinical studies to establish the baseline performance of the research prototype, and using known MRI
capabilities to establish the required performance. Simulation software was used to determine the basic
operating characteristics of an improved scanner that would provide the necessary performance. Design
elements focused on transducer geometry, which in turn drove the data acquisition system and the image
reconstruction engine specifications. The feasibility of UST established by our earlier work and that of other
groups, forms the rationale for developing a UST system that has the potential to become a practical, low-cost
device for breast cancer screening and diagnosis.

Breast ultrasound tomography: Bridging the gap to clinical practice

Breast density is one of the strongest predictors of breast cancer risk. Women with the densest breasts are 4 to 6 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.

/pdf/current-and-future-methods-for-measuring-breast-density-a-2br4nio9l1.pdf

Current and future methods for measuring breast density: a brief comparative review

The purpose of this study was to correlate changes in biomechanical properties of breast cancer lesions in response to neoadjuvant chemotherapy. Nine patients were examined repeatedly throughout their treatment, using an experimental prototype based on the principles of ultrasound tomography. The study was HIPAA compliant, approved by the Institutional Review Board, and performed after obtaining the requisite informed consent. Images of reflection, sound speed and attenuation, representing the entire volume of the breast, were reconstructed from the exam data and analyzed for time-dependent changes during the treatment period. It was found that changes in tumor properties could be measured in all cases. Furthermore, changes in sound speed were found to vary strongly from patient to patient. A comparison of the sound speed response curves with pathological findings suggests that complete responders exhibit distinctly different responses as measured by sound speed. These preliminary results were used to define a cut-point for predicting response. Subsequently, a prospective prediction of the treatment response of a new patient was made correctly. We hypothesize that changes in the biomechanical properties of breast cancers, as measured by sound speed, can predict response. Future studies will focus on testing this hypothesis and defining and quantifying markers of response.

Monitoring breast masses with ultrasound tomography in patients undergoing neoadjuvant chemotherapy

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Monitoring breast masses with ultrasound tomography in patients undergoing neoadjuvant chemotherapy