2-D Slicewise Waveform Inversion of Sound Speed and Acoustic Attenuation for Ring Array Ultrasound Tomography Based on a Block LU Solver.

Ultrasound tomography is an emerging imaging modality that uses the transmission of ultrasound through tissue to reconstruct images of its mechanical properties. Initially, ray-based methods were used to reconstruct these images, but their inability to account for diffraction often resulted in poor resolution. Waveform inversion overcame this limitation, providing high-resolution images of the tissue. Most clinical implementations, often directed at breast cancer imaging, currently rely on a frequency-domain waveform inversion to reduce computation time. For ring arrays, ray tomography was long considered a necessary step prior to waveform inversion in order to avoid cycle skipping. However, in this paper, we demonstrate that frequency-domain waveform inversion can reliably reconstruct high-resolution images of sound speed and attenuation without relying on ray tomography to provide an initial model. We provide a detailed description of our frequency-domain waveform inversion algorithm with open-source code and data that we make publicly available.

Breast Tomographic Ultrasound: The Spectrum from Current Dense Breast Cancer Screenings to Future Theranostic Treatments.

This review provides unique insights to the scientific scope and clinical visions of the inventors and pioneers of the SoftVue breast tomographic ultrasound (BTUS). Their >20-year collaboration produced extensive basic research and technology developments, culminating in SoftVue, which recently received the Food and Drug Administration's approval as an adjunct to breast cancer screening in women with dense breasts. SoftVue's multi-center trial confirmed the diagnostic goals of the tissue characterization and localization of quantitative acoustic tissue differences in 2D and 3D coronal image sequences. SoftVue mass characterizations are also reviewed within the standard cancer risk categories of the Breast Imaging Reporting and Data System. As a quantitative diagnostic modality, SoftVue can also function as a cost-effective platform for artificial intelligence-assisted breast cancer identification. Finally, SoftVue's quantitative acoustic maps facilitate noninvasive temperature monitoring and a unique form of time-reversed, focused US in a single theranostic device that actually focuses acoustic energy better within the highly scattering breast tissues, allowing for localized hyperthermia, drug delivery, and/or ablation. Women also prefer the comfort of SoftVue over mammograms and will continue to seek out less-invasive breast care, from diagnosis to treatment.

Sound Speed Estimation for Distributed Aberration Correction in Laterally Varying Media.

Spatial variation in sound speed causes aberration in medical ultrasound imaging. Although our previous work has examined aberration correction in the presence of a spatially varying sound speed, practical implementations were limited to layered media due to the sound speed estimation process involved. Unfortunately, most models of layered media do not capture the lateral variations in sound speed that have the greatest aberrative effect on the image. Building upon a Fourier split-step migration technique from geophysics, this work introduces an iterative sound speed estimation and distributed aberration correction technique that can model and correct for aberrations resulting from laterally varying media. We first characterize our approach in simulations where the scattering in the media is known a-priori. Phantom and in-vivo experiments further demonstrate the capabilities of the iterative correction technique. As a result of the iterative correction scheme, point target resolution improves by up to a factor of 4 and lesion contrast improves by up to 10.0 dB in the phantom experiments presented.

A Forward Model Incorporating Elevation-Focused Transducer Properties for 3-D Full-Waveform Inversion in Ultrasound Computed Tomography.

Ultrasound computed tomography (USCT) is an emerging medical imaging modality that holds great promise for improving human health. Full-waveform inversion (FWI)-based image reconstruction methods account for the relevant wave physics to produce high spatial resolution images of the acoustic properties of the breast tissues. A practical USCT design employs a circular ring-array comprised of elevation-focused ultrasonic transducers, and volumetric imaging is achieved by translating the ring-array orthogonally to the imaging plane. In commonly deployed slice-by-slice (SBS) reconstruction approaches, the 3-D volume is reconstructed by stacking together 2-D images reconstructed for each position of the ring-array. A limitation of the SBS reconstruction approach is that it does not account for 3-D wave propagation physics and the focusing properties of the transducers, which can result in significant image artifacts and inaccuracies. To perform 3-D image reconstruction when elevation-focused transducers are employed, a numerical description of the focusing properties of the transducers should be included in the forward model. To address this, a 3-D computational model of an elevation-focused transducer is developed to enable 3-D FWI-based reconstruction methods to be deployed in ring-array-based USCT. The focusing is achieved by applying a spatially varying temporal delay to the ultrasound pulse (emitter mode) and recorded signal (receiver mode). The proposed numerical transducer model is quantitatively validated and employed in computer simulation studies that demonstrate its use in image reconstruction for ring-array USCT.

Optimal transmit apodization for the maximization of lag-one coherence with applications to aberration delay estimation.

Phase aberration is one of the major sources of image degradation in medical ultrasound imaging. One of the earliest and simplest techniques to correct for phase aberration involves nearest-neighbor cross correlation to estimate delays between neighboring receive channels and the compensation of aberration delays in a delay-and-sum beamformer. The main challenge is that neighboring receive channels may not have sufficient signal correlation to accurately estimate the aberration delays. Although algorithms such as the translating transmit aperture or the common midpoint gather are designed to perfectly maximize signal correlations between received signals, these algorithms require the use of different transmit apertures for each received signal. Instead, this work proposes the use of a single globally-applicable transmit apodization function that optimizes the lag-one coherence based on the van Cittert-Zernike theorem. For the application to phase aberration correction, it is shown across 20 different zero-mean Gaussian-random aberrators that the proposed optimal apodization function reduces the estimation error in the aberration delay profile from 22.85% to 15.72%.

A forward model incorporating elevation-focused transducer properties for 3D full-waveform inversion in ultrasound computed tomography.

Ultrasound computed tomography (USCT) is an emerging medical imaging modality that holds great promise for improving human health. Full-waveform inversion (FWI)-based image reconstruction methods account for the relevant wave physics to produce high spatial resolution images of the acoustic properties of the breast tissues. A practical USCT design employs a circular ring-array comprised of elevation-focused ultrasonic transducers, and volumentric imaging is achieved by translating the ring-array orthogonally to the imaging plane. In commonly deployed slice-by-slice (SBS) reconstruction approaches, the three-dimensional (3D) volume is reconstructed by stacking together two-dimensional (2D) images reconstructed for each position of the ring-array. A limitation of the SBS reconstruction approach is that it does not account for 3D wave propagation physics and the focusing properties of the transducers, which can result in significant image artifacts and inaccuracies. To perform 3D image reconstruction when elevation-focused transducers are employed, a numerical description of the focusing properties of the transducers should be included in the forward model. To address this, a 3D computational model of an elevation-focused transducer is developed to enable 3D FWI-based reconstruction methods to be deployed in ring-array-based USCT. The focusing is achieved by applying a spatially varying temporal delay to the ultrasound pulse (emitter mode) and recorded signal (receiver mode). The proposed numerical transducer model is quantitatively validated and employed in computer-simulation studies that demonstrate its use in image reconstruction for ring-array USCT.

Separation of mainlobe and sidelobe contributions to B-mode ultrasound images based on the aperture spectrum.

Purpose: Isolating the mainlobe and sidelobe contribution to the ultrasound image can improve imaging contrast by removing off-axis clutter. Previous work achieves this separation of mainlobe and sidelobe contributions based on the covariance of received signals. However, the formation of a covariance matrix at each imaging point can be computationally burdensome and memory intensive for real-time applications. Our work demonstrates that the mainlobe and sidelobe contributions to the ultrasound image can be isolated based on the receive aperture spectrum, greatly reducing computational and memory requirements. Approach: The separation of mainlobe and sidelobe contributions to the ultrasound image is shown in simulation, in vitro, and in vivo using the aperture spectrum method and multicovariate imaging of subresolution targets (MIST). Contrast, contrast-to-noise-ratio (CNR), and speckle signal-to-noise-ratio are used to compare the aperture spectrum approach with MIST and conventional delay-and-sum (DAS) beamforming. Results: The aperture spectrum approach improves contrast by 1.9 to 6.4 dB beyond MIST and 8.9 to 13.5 dB beyond conventional DAS B-mode imaging. However, the aperture spectrum approach yields speckle texture similar to DAS. As a result, the aperture spectrum-based approach has less CNR than MIST but greater CNR than conventional DAS. The CPU implementation of the aperture spectrum-based approach is shown to reduce computation time by a factor of 9 and memory consumption by a factor of 128 for a 128-element transducer. Conclusions: The mainlobe contribution to the ultrasound image can be isolated based on the receive aperture spectrum, which greatly reduces the computational cost and memory requirement of this approach as compared with MIST.

Feasibility of ultrasound tomography-guided localized mild hyperthermia using a ring transducer: Ex vivo and in silico studies.

BACKGROUND: As of 2022, breast cancer continues to be the most diagnosed cancer worldwide. This problem persists within the United States as well, as the American Cancer Society has reported that ∼12.5% of women will be diagnosed with invasive breast cancer over the course of their lifetime. Therefore, a clinical need continues to exist to address this disease from a treatment and therapeutic perspective. Current treatments for breast cancer and cancers more broadly include surgery, radiation, and chemotherapy. Adjuncts to these methods have been developed to improve the clinical outcomes for patients. One such adjunctive treatment is mild hyperthermia therapy (MHTh), which has been shown to be successful in the treatment of cancers by increasing effectiveness and reduced dosage requirements for radiation and chemotherapies. MHTh-assisted treatments can be performed with invasive thermal devices, noninvasive microwave induction, heating and recirculation of extracted patient blood, or whole-body hyperthermia with hot blankets. PURPOSE: One common method for inducing MHTh is by using microwave for heat induction and magnetic resonance imaging for temperature monitoring. However, this leads to a complex, expensive, and inaccessible therapy platform. Therefore, in this work we aim to show the feasibility of a novel all-acoustic MHTh system that uses focused ultrasound (US) to induce heating while also using US tomography (UST) to provide temperature estimates. Changes in sound speed (SS) have been shown to be strongly correlated with temperature changes and can therefore be used to indirectly monitor heating throughout the therapy. Additionally, these SS estimates allow for heterogeneous SS-corrected phase delays when heating complex and heterogeneous tissue structures. METHODS: Feasibility to induce localized heat in tissue was investigated in silico with a simulated breast model, including an embedded tumor using continuous wave US. Here, both heterogenous acoustic and thermal properties were modeled in addition to blood perfusion. We further demonstrate, with ex vivo tissue phantoms, the feasibility of using ring-based UST to monitor temperature by tracking changes in SS. Two phantoms (lamb tissue and human abdominal fat) with latex tubes containing varied temperature flowing water were imaged. The measured SS of the water at each temperature were compared against values that are reported in literature. RESULTS: Results from ex vivo tissue studies indicate successful tracking of temperature under various phantom configurations and ranges of water temperature. The results of in silico studies show that the proposed system can heat an acoustically and thermally heterogenous breast model to the clinically relevant temperature of 42°C while accounting for a reasonable time needed to image the current cross section (200 ms). Further, we have performed an initial in silico study demonstrating the feasibility of adjusting the transmit waveform frequency to modify the effective heating height at the focused region. Lastly, we have shown in a simpler 2D breast model that MHTh level temperatures can be maintained by adjusting the transmit pressure intensity of the US ring. CONCLUSIONS: This work has demonstrated the feasibility of using a 256-element ring array transducer for temperature monitoring; however, future work will investigate minimizing the difference between measured SS and the values shown in literature. A hypothesis attributes this bias to potential volumetric average artifacts from the ray-based SS inversion algorithm that was used, and that moving to a waveform-based SS inversion algorithm will greatly improve the SS estimates. Additionally, we have shown that an all-acoustic MHTh system is feasible via in silico studies. These studies have indicated that the proposed system can heat a tumor within a heterogenous breast model to 42°C within a narrow time frame. This holds great promise for increasing the accessibility and reducing the complexity of a future all-acoustic MHTh system.

Rapid Reductions in Breast Density following Tamoxifen Therapy as Evaluated by Whole-Breast Ultrasound Tomography.

PURPOSE: Women whose mammographic breast density declines within 12-18 months of initiating tamoxifen for chemoprevention or adjuvant treatment show improved therapeutic responses compared with those whose density is unchanged. We tested whether measuring changes in sound speed (a surrogate of breast density) using ultrasound tomography (UST) could enable rapid identification of favorable responses to tamoxifen. METHODS: We evaluated serial density measures at baseline and at 1 to 3, 4 to 6, and 12+ months among 74 women (aged 30-70 years) following initiation of tamoxifen for clinical indications, including an elevated risk of breast cancer (20%) and diagnoses of in situ (39%) or invasive (40%) breast carcinoma, enrolled at Karmanos Cancer Institute and Henry Ford Health System (Detroit, MI, USA). For comparison, we evaluated an untreated group with screen negative mammography and frequency-matched on age, race, and menopausal status (n = 150), at baseline and 12 months. Paired t-tests were used to assess differences in UST sound speed over time and between tamoxifen-treated and untreated patients. RESULTS: Sound speed declined steadily over the 12 month period among patients receiving tamoxifen (mean (SD): -3.0 (8.2) m/s; p = 0.001), whereas density remained unchanged in the untreated group (mean (SD): 0.4 (7.1) m/s; p = 0.75 (relative change between groups: p = 0.0009)). In the tamoxifen group, we observed significant sound speed reductions as early as 4-6 months after tamoxifen initiation (mean (SD): -2.1 (6.8) m/s; p = 0.008). Sound speed reductions were greatest among premenopausal patients (P-interaction = 0.0002) and those in the middle and upper tertiles of baseline sound speed (P-interaction = 0.002). CONCLUSIONS: UST can image rapid declines in sound speed following initiation of tamoxifen. Given that sound speed and mammographic density are correlated, we propose that UST breast imaging may capture early responses to tamoxifen, which in turn may have utility in predicting therapeutic efficacy.

Multicenter Study of Whole Breast Stiffness Imaging by Ultrasound Tomography (SoftVue) for Characterization of Breast Tissues and Masses.

We evaluated whole breast stiffness imaging by SoftVue ultrasound tomography (UST), extracted from the bulk modulus, to volumetrically map differences in breast tissues and masses. A total 206 women with either palpable or mammographically/sonographically visible masses underwent UST scanning prior to biopsy as part of a prospective, HIPAA-compliant multicenter cohort study. The volumetric data sets comprised 298 masses (78 cancers, 105 fibroadenomas, 91 cysts and 24 other benign) in 239 breasts. All breast tissues were segmented into six categories, using sound speed to separate fat from fibroglandular tissues, and then subgrouped by stiffness into soft, intermediate and hard components. Ninety percent of women had mammographically dense breasts but only 11.2% of their total breast volume showed hard components while 69% of fibroglandular tissues were softer. All smaller masses (<1.5 cm) showed a greater percentage of hard components than their corresponding larger masses (p < 0.001). Cancers had significantly greater mean stiffness indices and lower mean homogeneity of stiffness than benign masses (p < 0.05). SoftVue stiffness imaging demonstrated small stiff masses, mainly due to cancers, amongst predominantly soft breast tissues. Quantitative stiffness mapping of the whole breast and underlying masses may have implications for screening of women with dense breasts, cancer risk evaluations, chemoprevention and treatment monitoring.

The Potential Role of the Fat-Glandular Interface (FGI) in Breast Carcinogenesis: Results from an Ultrasound Tomography (UST) Study.

This study explored the relationship between the extent of the fat-glandular interface (FGI) and the presence of malignant vs. benign lesions. Two hundred and eight patients were scanned with ultrasound tomography (UST) as part of a Health Insurance Portability and Accountability Act (HIPAA)-compliant study. Segmentation of the sound speed images, employing the k-means clustering method, was used to help define the extent of the FGI for each patient. The metric, α, was defined as the surface area to volume ratio of the segmented fibroglandular volume and its mean value across patients was determined for cancers, fibroadenomas and cysts. ANOVA tests were used to assess significance. The means and standard deviations of α for cancers, fibroadenomas and cysts were found to be 4.0 ± 2.0 cm-1, 3.1 ± 1.7 cm-1 and 2.3 ± 0.9 cm-1, respectively. The differences were statistically significant (p < 0.001). The separation between the groups increased when α was measured on only the image slice where the finding was most prominent, with values for cancers, fibroadenomas and cysts of 5.4 ± 3.6 cm-1, 3.6 ± 2.3 cm-1 and 2.4 ± 1.5 cm-1, respectively. Of the three types of masses studied, cancer was associated with the most extensive FGIs, suggesting a potential role for the FGI in carcinogenesis, a subject for future studies.

The Fat-glandular Interface and Breast Tumor Locations: Appearances on Ultrasound Tomography Are Supported by Quantitative Peritumoral Analyses.

OBJECTIVE: To analyze the preferred tissue locations of common breast masses in relation to anatomic quadrants and the fat-glandular interface (FGI) using ultrasound tomography (UST). METHODS: Ultrasound tomography scanning was performed in 206 consecutive women with 298 mammographically and/or sonographically visible, benign and malignant breast masses following written informed consent to participate in an 8-site multicenter, Institutional Review Board-approved cohort study. Mass locations were categorized by their anatomic breast quadrant and the FGI, which was defined by UST as the high-contrast circumferential junction of fat and fibroglandular tissue on coronal sound speed imaging. Quantitative UST mass comparisons were done for each tumor and peritumoral region using mean sound speed and percentage of fibroglandular tissue. Chi-squared and analysis of variance tests were used to assess differences. RESULTS: Cancers were noted at the FGI in 95% (74/78) compared to 51% (98/194) of fibroadenomas and cysts combined (P < 0.001). No intra-quadrant differences between cancer and benign masses were noted for tumor location by anatomic quadrants (P = 0.66). Quantitative peritumoral sound speed properties showed that cancers were surrounded by lower mean sound speeds (1477 m/s) and percent fibroglandular tissue (47%), compared to fibroadenomas (1496 m/s; 65.3%) and cysts (1518 m/s; 84%) (P < 0.001; P < 0.001, respectively). CONCLUSION: Breast cancers form adjacent to fat and UST localized the vast majority to the FGI, while cysts were most often completely surrounded by dense tissue. These observations were supported by quantitative peritumoral analyses of sound speed values for fat and fibroglandular tissue.

Determinants of the reliability of ultrasound tomography sound speed estimates as a surrogate for volumetric breast density.

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.

Breast ultrasound tomography versus MRI for clinical display of anatomy and tumor rendering: preliminary results.

OBJECTIVE: The objective of our study was to determine the clinical display thresholds of an ultrasound tomography prototype relative to MRI for comparable visualization of breast anatomy and tumor rendering. SUBJECTS AND METHODS: Thirty-six women were imaged with MRI and our ultrasound tomography prototype. The ultrasound tomography scan generated reflection, sound-speed, and attenuation images. The reflection images were fused with the components of the sound-speed and attenuation images that achieved thresholds to represent parenchyma or solid masses using an image arithmetic process. Qualitative and quantitative comparisons of MRI and ultrasound tomography clinical images were used to identify anatomic similarities and optimized thresholds for tumor shapes and volumes. RESULTS: Thresholding techniques generated ultrasound tomography images comparable to MR images for visualizing fibrous stroma, parenchyma, fatty tissues, and tumors. In 25 patients, tumors were cancerous and in 11, benign. Optimized sound-speed thresholds of 1.46±0.1 and 1.52±0.03 km/s were identified to best represent the extent of fibroglandular tissue and solid masses, respectively. An arithmetic combination of attenuation images using a threshold of 0.16±0.04 dB/cm (mean±SD) further characterized benign from malignant masses. No significant difference in tumor volume was noted between benign or malignant masses by ultrasound tomography or MRI (p>0.1) using these universal thresholds. CONCLUSION: Ultrasound tomography is able to image and render breast tissues in a manner comparable to MRI. Using universal ultrasound tomography threshold values for rendering the size and distribution of benign and malignant tissues appears feasible without IV contrast material.

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

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 images reconstructed 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.

In vivo breast sound-speed imaging with ultrasound tomography.

We discuss a bent-ray ultrasound tomography algorithm with total-variation (TV) regularization. We have applied this algorithm to 61 in vivo breast datasets collected with our in-house clinical prototype for imaging sound-speed distributions in the breast. Our analysis showed that TV regularization could preserve sharper lesion edges than the classic Tikhonov regularization. Furthermore, the image quality of our TV bent-ray sound-speed tomograms was superior to that of the straight-ray counterparts for all types of breasts within BI-RADS density categories 1 through 4. Our analysis showed that the improvements for average sharpness (in the unit of (m x s)(-1)) of lesion edges in our TV bent-ray tomograms are between 2.1 to 3.4-fold compared with the straight ray tomograms. Reconstructed sound-speed tomograms illustrated that our algorithm could successfully image fatty and glandular tissues within the breast. We calculated the mean sound-speed values for fatty tissue and breast parenchyma as 1422 +/- 9 m/s (mean +/- SD) and 1487 +/- 21 m/s, respectively. Based on 32 lesions in a cohort of 61 patients, we also found that the mean sound-speed for malignant breast lesions (1548 +/- 17 m/s) was higher, on average, than that of benign ones (1513 +/- 27 m/s) (one-sided p<0.001). These results suggest that, clinically, sound-speed tomograms can be used to assess breast density (and therefore, breast cancer risk), as well as detect and help differentiate breast lesions. Finally, our sound-speed tomograms may also be a useful tool to monitor the clinical response of breast cancer patients to neo-adjuvant chemotherapy.

An improved automatic time-of-flight picker for medical ultrasound tomography.

OBJECTIVE AND MOTIVATION: Time-of-flight (TOF) tomography used by a clinical ultrasound tomography device can efficiently and reliably produce sound-speed images of the breast for cancer diagnosis. Accurate picking of TOFs of transmitted ultrasound signals is extremely important to ensure high-resolution and high-quality ultrasound sound-speed tomograms. Since manually picking is time-consuming for large datasets, we developed an improved automatic TOF picker based on the Akaike information criterion (AIC), as described in this paper. METHODS: We make use of an approach termed multi-model inference (model averaging), based on the calculated AIC values, to improve the accuracy of TOF picks. By using multi-model inference, our picking method incorporates all the information near the TOF of ultrasound signals. Median filtering and reciprocal pair comparison are also incorporated in our AIC picker to effectively remove outliers. RESULTS: We validate our AIC picker using synthetic ultrasound waveforms, and demonstrate that our automatic TOF picker can accurately pick TOFs in the presence of random noise with absolute amplitudes up to 80% of the maximum absolute signal amplitude. We apply the new method to 1160 in vivo breast ultrasound waveforms, and compare the picked TOFs with manual picks and amplitude threshold picks. The mean value and standard deviation between our TOF picker and manual picking are 0.4 micros and 0.29 micros, while for amplitude threshold picker the values are 1.02 micros and 0.9 micros, respectively. Tomograms for in vivo breast data with high signal-to-noise ratio (SNR) ( approximately 25 dB) and low SNR ( approximately 18 dB) clearly demonstrate that our AIC picker is much less sensitive to the SNRs of the data, compared to the amplitude threshold picker. DISCUSSION AND CONCLUSIONS: The picking routine developed here is aimed at determining reliable quantitative values, necessary for adding diagnostic information to our clinical ultrasound tomography device--CURE. It has been successfully adopted into CURE, and allows us to generate such values reliably. We demonstrate that in vivo sound-speed tomograms with our TOF picks significantly improve the reconstruction accuracy and reduce image artifacts.

Novel approach to evaluating breast density utilizing ultrasound tomography.

Women with high mammographic breast density have a four- to fivefold increased risk of developing breast cancer compared to women with fatty breasts. Many preventative strategies have attempted to correlate changes in breast density with response to interventions including drugs and diet. The purpose of this work is to investigate the feasibility of assessing breast density with acoustic velocity measurements with ultrasound tomography, and to compare the results with existing measures of mammographic breast density. An anthropomorphic breast tissue phantom was first imaged with our computed ultrasound tomography clinical prototype. Strong positive correlations were observed between sound speed and material density, and sound speed and computed tomography number (Pearson correlation coefficients= 0.87 and 0.91, respectively). A cohort of 48 women was then imaged. Whole breast acoustic velocity was determined by creating image stacks and evaluating the sound speed frequency distribution. The acoustic measures of breast density were evaluated by comparing these results to two mammographic density measures: (1) qualitative estimates determined by a certified radiologist using the BI-RADS Categorical Assessment based on a 1 (fatty) to 4 (dense) scale, and (2) quantitative measurements via digitization and computerized analysis of archival mammograms. A one-way analysis of variance showed that a significant difference existed between the mean values of sound speed according to BI-RADS category, while post hoc analyses using the Scheffé criterion for significance indicated that BI-RADS 4 (dense) patients had a significantly higher sound speed than BI-RADS 1, 2, and 3 at an alpha level of 0.05. Using quantitative measures of breast density, a direct correlation between the mean acoustic velocity and calculated mammographic percent breast density was demonstrated with correlation coefficients ranging from 0.75 to 0.89. The results presented here support the hypothesis that sound speed can be used as an indicator of breast tissue density. Noninvasive, nonionizing monitoring of dietary and chemoprevention interventions that affect breast density are now possible.

Detection of breast cancer with ultrasound tomography: first results with the Computed Ultrasound Risk Evaluation (CURE) prototype.

Although mammography is the gold standard for breast imaging, its limitations result in a high rate of biopsies of benign lesions and a significant false negative rate for women with dense breasts. In response to this imaging performance gap we have been developing a clinical breast imaging methodology based on the principles of ultrasound tomography. The Computed Ultrasound Risk Evaluation (CURE) system has been designed with the clinical goals of whole breast, operator-independent imaging, and differentiation of breast masses. This paper describes the first clinical prototype, summarizes our initial image reconstruction techniques, and presents phantom and preliminary in vivo results. In an initial assessment of its in vivo performance, we have examined 50 women with the CURE prototype and obtained the following results. (1) Tomographic imaging of breast architecture is demonstrated in both CURE modes of reflection and transmission imaging. (2) In-plane spatial resolution of 0.5 mm in reflection and 4 mm in transmission is achieved. (3) Masses > 15 mm in size are routinely detected. (4) Reflection, sound speed, and attenuation imaging of breast masses are demonstrated. These initial results indicate that operator-independent, whole-breast imaging and the detection of breast masses are feasible. Future studies will focus on improved detection and differentiation of masses in support of our long-term goal of increasing the specificity of breast exams, thereby reducing the number of biopsies of benign masses.

Development of ultrasound tomography for breast imaging: technical assessment.

Ultrasound imaging is widely used in medicine because of its benign characteristics and real-time capabilities. Physics theory suggests that the application of tomographic techniques may allow ultrasound imaging to reach its full potential as a diagnostic tool allowing it to compete with other tomographic modalities such as x-ray computer tomography, and MRI. This paper describes the construction and use of a prototype tomographic scanner and reports on the feasibility of implementing tomographic theory in practice and the potential of ultrasound (US) tomography in diagnostic imaging. Data were collected with the prototype by scanning two types of phantoms and a cadaveric breast. A specialized suite of algorithms was developed and utilized to construct images of reflectivity and sound speed from the phantom data. The basic results can be summarized as follows. (i) A fast, clinically relevant US tomography scanner can be built using existing technology. (ii) The spatial resolution, deduced from images of reflectivity, is 0.4 mm. The demonstrated 10 cm depth-of-field is superior to that of conventional ultrasound and the image contrast is improved through the reduction of speckle noise and overall lowering of the noise floor. (iii) Images of acoustic properties such as sound speed suggest that it is possible to measure variations in the sound speed of 5 m/s. An apparent correlation with x-ray attenuation suggests that the sound speed can be used to discriminate between various types of soft tissue. (iv) Ultrasound tomography has the potential to improve diagnostic imaging in relation to breast cancer detection.