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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., (© 2022 American Association of Physicists in Medicine.)

We have investigated limited angle transmission tomography to estimate speed of sound (SOS) distributions for breast cancer detection. That requires both accurate delineations of major tissues, in this case by segmentation of prior B-mode images, and calibration of the relative positions of the opposed transducers. Experimental sensitivity evaluation of the reconstructions with respect to segmentation and calibration errors is difficult with our current system. Therefore, parametric studies of SOS errors in our bent-ray reconstructions were simulated. They included mis-segmentation of an object of interest or a nearby object, and miscalibration of relative transducer positions in 3D. Close correspondence of reconstruction accuracy was verified in the simplest case, a cylindrical object in homogeneous background with induced segmentation and calibration inaccuracies. Simulated mis-segmentation in object size and lateral location produced maximum SOS errors of 6.3% within 10 mm diameter change and 9.1% within 5 mm shift, respectively. Modest errors in assumed transducer separation produced the maximum SOS error from miscalibrations (57.3% within 5 mm shift), still, correction of this type of error can easily be achieved in the clinic. This study should aid in designing adequate transducer mounts and calibration procedures, and in specification of B-mode image quality and segmentation algorithms for limited angle transmission tomography relying on ray tracing algorithms., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A photoacoustic volume imaging (PAVI) system was designed to study breast cancer detection and diagnosis in the mammographic geometry in combination with automated 3-D ultrasound (AUS). The goal of the work described here was to validate the design and evaluate its performance in human breast tissues for non-invasive imaging of deeply positioned structures covering such geometry. The good penetration of near-infrared light and high receiving sensitivity of a broad-bandwidth, 572-element, 2-D polyvinylidene fluoride (PVDF) array at a low center frequency of 1 MHz were used with 20 channel simultaneous acquisition. Pseudo-lesions filled with dilute blood were imaged in three human breast specimens at various depths up to 49 mm. With near-infrared light illumination and 256-sample averaging, the extrapolated maximum depth in imaging a 2.4-mm blood-rich lesion with a 3-dB contrast-to-noise ratio in a compressed breast was 54 mm. Three-dimensional photoacoustic volume image stacks of the breasts were co-registered with 3-D ultrasound image stacks, suggesting for the first time that PAVI, based on the intrinsic tissue contrast, can visualize tissue interfaces other than those with blood, including the inner skin surface and connective tissue sheets. With the designed system, PAVI revealed satisfactory imaging depth and sensitivity for coverage of the entire breast when imaged from both sides in the mammographic geometry with mild compression., (Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to retrospectively evaluate the effect of 3-dimensional automated ultrasound (3D-AUS) as an adjunct to digital breast tomosynthesis (DBT) on radiologists' performance and confidence in discriminating malignant and benign breast masses., Methods: Two-view DBT (craniocaudal and mediolateral oblique or lateral) and single-view 3D-AUS images were acquired from 51 patients with subsequently biopsy-proven masses (13 malignant and 38 benign). Six experienced radiologists rated, on a 13-point scale, the likelihood of malignancy of an identified mass, first by reading the DBT images alone, followed immediately by reading the DBT images with automatically coregistered 3D-AUS images. The diagnostic performance of each method was measured using receiver operating characteristic (ROC) curve analysis and changes in sensitivity and specificity with the McNemar test. After each reading, radiologists took a survey to rate their confidence level in using DBT alone versus combined DBT/3D-AUS as potential screening modalities., Results: The 6 radiologists had an average area under the ROC curve of 0.92 for both modalities (range, 0.89-0.97 for DBT and 0.90-0.94 for DBT/3D-AUS). With a Breast Imaging Reporting and Data System rating of 4 as the threshold for biopsy recommendation, the average sensitivity of the radiologists increased from 96% to 100% (P > .08) with 3D-AUS, whereas the specificity decreased from 33% to 25% (P > .28). Survey responses indicated increased confidence in potentially using DBT for screening when 3D-AUS was added (P < .05 for each reader)., Conclusions: In this initial reader study, no significant difference in ROC performance was found with the addition of 3D-AUS to DBT. However, a trend to improved discrimination of malignancy was observed when adding 3D-AUS. Radiologists' confidence also improved with DBT/3DAUS compared to DBT alone.

The purpose of this study was to evaluate the potential for use of image volume based registration (IVBaR) to aid in measurement of changes in the tumor during chemotherapy of breast cancer. Successful IVBaR could aid in the detection of such changes in response to neoadjuvant chemotherapy and potentially be useful for routine breast cancer screening and diagnosis. IVBaR was employed in a new method of automated estimation of tumor volume in studies following the radiologist identification of the tumor region in the prechemotherapy scan. The authors have also introduced a new semiautomated method for validation of registration based on Doppler ultrasound (U.S.) signals that are independent of the grayscale signals used for registration. This Institutional Review Board approved study was conducted on 10 patients undergoing chemotherapy and 14 patients with a suspicious/unknown mass scheduled to undergo biopsy. Reasonably reproducible mammographic positioning and nearly whole breast U.S. imaging were achieved. The image volume was registered offline with a mutual information cost function and global interpolation based on a thin-plate spline using MIAMI FUSE software developed at the University of Michigan. The success and accuracy of registration of the three dimensional (3D) U.S. image volume were measured by means of mean registration error (MRE). IVBaR was successful with MRE of 4.3 +/- 1.7 mm in 9 out of 10 reproducibility automated breast ultrasound (ABU) studies and in 12 out of 17 ABU image pairs collected before, during, or after 115 +/- 14 days of chemotherapy. Semiautomated tumor volume estimation was performed on registered image volumes giving 86 +/- 8% mean accuracy compared to the radiologist hand-segmented tumor volume on seven cases. Doppler studies yielded fractional volume of color pixels in the region surrounding the lesion and its change with changing breast compression. The Doppler study of patients with detectable blood flow included five patients with suspicious masses and three undergoing chemotherapy. Spatial alignment of the 3D blood vessel data from the Doppler studies provided independent measures for the validation of registration. In 15 Doppler image volume pairs scanned with differing breast compression, the mean centerline separation value was 1.5 +/- 0.6 mm, while MRE based on a few identifiable structural points common to the two grayscale image volumes was 1.1 +/- 0.6 mm. Another measure, the overlap ratio of blood vessels, was shown to increase from 0.32 to 0.59 (+84%) with IVBaR for pairs at various compression levels. These results show that successful registration of ABU scans may be accomplished for comparison and integration of information.

Purpose: To assess the diagnostic performance of various Doppler ultrasonographic (US) vascularity measures in conjunction with grayscale (GS) criteria in differentiating benign from malignant breast masses, by using histologic findings as the reference standard., Materials and Methods: Institutional Review Board and HIPAA standards were followed. Seventy-eight women (average age, 49 years; range, 26-70 years) scheduled for breast biopsy were included. Thirty-eight patient scans were partially analyzed and published previously, and 40 additional scans were used as a test set to evaluate previously determined classification indexes. In each patient, a series of color Doppler images was acquired and reconstructed into a volume encompassing a suspicious mass, identified by a radiologist-defined ellipsoid, in which six Doppler vascularity measures were calculated. Radiologist GS ratings and patient age were also recorded. Multivariable discrimination indexes derived from the learning set were applied blindly to the test set. Overall performance was also confirmed by using a fourfold cross-validation scheme on the entire population., Results: By using all cases (46 benign, 32 malignant), the area under the receiver operating characteristic curve (A(z)) values confirmed results of previous analyses: Speed-weighted pixel density (SWPD) performed the best as a diagnostic index, although statistical significance (P = .01) was demonstrated only with respect to the normalized power-weighted pixel density. In both learning and test sets, the three-variable index (SWPD-age-GS) displayed significantly better diagnostic performance (A(z) = 0.97) than did any single index or the one two-variable index (age-GS) that could be obtained without the data from the Doppler scan. Results of the cross validation confirmed the trends in the two data sets., Conclusion: Quantitative Doppler US vascularity measurements considerably contribute to malignant breast tissue identification beyond subjective GS evaluation alone. The SWPD-age-GS index has high performance (A(z) = 0.97), regardless of incidental performance variations in its single variable components., ((c) RSNA, 2008.)

This study evaluated the utility of 3D automated ultrasound in conjunction with 3D digital X-Ray tomosynthesis for breast cancer detection and assessment, to better localize and characterize lesions in the breast. Tomosynthesis image volumes and automated ultrasound image volumes were acquired in the same geometry and in the same view for 27 patients. 3 MQSA certified radiologists independently reviewed the image volumes, visually correlating the images from the two modalities with in-house software. More sophisticated software was used on a smaller set of 10 cases, which enabled the radiologist to draw a 3D box around the suspicious lesion in one image set and isolate an anatomically correlated, similarly boxed region in the other modality image set. In the primary study, correlation was found to be moderately useful to the readers. In the additional study, using improved software, the median usefulness rating increased and confidence in localizing and identifying the suspicious mass increased in more than half the cases. As automated scanning and reading software techniques advance, superior results are expected.

The purpose of this study is to evaluate the accuracy of image volume based registration (IVBaR) of 3D ultrasound (US) image volumes of the whole breast acquired at different times. Successful IVBaR could aid in detection of tumor changes in response to neoadjuvant chemotherapy and potentially be useful for routine breast cancer screening and diagnosis. IVBaR was successful in 9 of 10 reproducibility studies, 11 of 15 image pairs collected before and after approximately 45 days of chemotherapy. Doppler study yielded volume of blood flow to the region surrounding the lesion and its change when reducing breast compression. The color flow vessels provided independent measures for validation of registration of the grayscale portion of those images.

Objective: We prospectively evaluated low-stage breast cancers treated with neoadjuvant chemotherapy using whole-volume sonography and color Doppler imaging., Methods: Thirty-four women with breast cancer (mean maximum size, 2.4 cm) received neoadjuvant chemotherapy with doxorubicin and docetaxel. Targeted whole-volume sonography of tumor sites was performed before and after chemotherapy to assess mass size, color pixel speed-weighted density, and American College of Radiology Breast Imaging Reporting and Data System sonographic characteristics. After chemotherapy, tumor sites were excised by lumpectomy or mastectomy., Results: Three (11.3%) of 34 patients had a complete histologic response. After chemotherapy, correlation was r = 0.716 between final histologic and sonographic sizes. Compared with histologic residual tumors, sonography had 4 false-negative results, 3 false-positive results, and 27 true-positive results (sensitivity, 87%), with no false-negative results among a subgroup of tumors of 7 mm and larger (sensitivity, 100%). The 3 cases with false-positive results were histologic fibrosis or biopsy changes. Mean speed-weighted density was 0.015 before and 0.0082 after chemotherapy (P = .03). After chemotherapy, vascularity was less common within (P = .06) or adjacent to (P = .009) masses or in tumor sites (P = .05). Prechemotherapy variables of gray scale characteristics and vascularity were compared with final histologic size, and all had P > .20., Conclusions: Postchemotherapy sensitivity of sonography was high for residual tumors of 7 mm or larger. Correlation was moderate between histologic and sonographic final tumor sizes. False-positive results were caused by fibrosis or biopsy-related changes. False-negative results occurred with residual tumor size of 6 mm or smaller. After chemotherapy, vascularity usually decreased, and this was not specific for complete response. Before chemotherapy, no vascular or gray scale feature at initial imaging predicted complete responders.

Frequency shift color Doppler imaging was assessed in conjunction with patient age and gray scale (GS) features for discriminating benign from malignant breast masses. Thirty-eight women with sonographically detected masses scheduled for biopsy were evaluated using a 6- to 13-MHz scan head, and the masses were delineated in ultrasonographic image volumes. Vascularity in and around each mass was quantified using speed-weighted pixel density (SWD). Gray scale features were ranked visually on a linear scale. Combinations of indices were compared with histologic findings (18 benign and 20 malignant). Receiver operating characteristic analysis ranked performance in decreasing order from the SWD-Age-GS index, to SWD-GS, SWD-Age, Age-GS, GS criteria, SWD, and Age. At 100% sensitivity, SWD-Age-GS, SWD-GS, and SWD-Age discriminated benign from malignant masses with specificities of 94%, 89%, and 72%, respectively. These results indicate significant improvement in ultrasonographic discrimination of sonographically detected breast masses by combining the vascularity measure SWD with age and GS criteria.

In this article, new measures obtained from color Doppler images are introduced and a pilot study is described, in which these and previously published indices are evaluated for use in future work. Twenty women with breast masses observed on mammography and going to surgical biopsy were studied. Of the masses, 11 proved to be benign and 9 were malignant. Both 3-D mean frequency shift (f-CDI) and power mode Doppler (p-CDI) imaging were performed. To identify the mass and other regions of interest, vessels were displayed as rotatable 3-D color volumes, superimposed on selectable grey-scale/color flow slices. Doppler signals were recorded in each of 6 ellipsoidal regions of interest in and around the mass and 2 in normal tissues. Seven measures were computed in each region, three from power mode, two from mean frequency and two from combinations of both. Radiologists rated the grey-scale appearances of the masses on a scale of 1 to 5 (5=most suspicious) for each of 6 conventional grey-scale criteria. Of the individual vascularity measures in individual ROIs, the log speed-weighted pixel density and log power-weighted pixel density in the lesion internal periphery showed the greatest discrimination of malignancy, although neither was statistically significant nor as good as the peak variables described below. The mean visual grey-scale rating was the best discriminator overall, but two peak vascularity measures each made promising scatterplots in conjunction with the average visual grey-scale rating. These two vascularity measures were the log peak normalized power-weighted pixel density (peak NPD) and log of peak mean Doppler frequency times the peak NPD (vM x NPD(M)). Each of these two values was the maximum in any one of the five chosen ROIs closely associated with the mass. A possible rationale for the relative success of these peak values is the blood signal's normalization and the inhomogeneity of most breast cancers and the expectation that the highest velocities (shunting) and largest collections of blood are not necessarily in the same region in and around the tumor. Peak NPD of cancers varied with age, decreasing by a factor of 45 from 33 to 77 y.

A prospective study was performed in 24 women with breast masses on mammography going on to surgical biopsy. 2D and 3D power mode and frequency shift color flow Doppler scanning and display were compared. Vessels were displayed as rotatable color volumes in 3D, superimposed on gray-scale slices. The latter were stepped sequentially through the imaged volume. Radiologists rated the masses in each display (3D, 2D and videotapes) on a scale of 1 to 5 (5 = most suspicious) for each of six conventional gray-scale and six new vascular criteria. Thirteen masses proved to be benign and 11 were malignant. 3D provided a stronger subjective appreciation of vascular morphology and allowed somewhat better ultrasound discrimination of malignant masses than did the 2D images or videotapes (specificities of 85%, 79% and 71%, respectively, at a sensitivity of 90%). Only in 3D did the vascularity measures display a trend towards significance in this small study.

The relative success of manual palpation in the detection of breast cancer would suggest that a method for remote palpation resulting in a measurement of tissue elasticity could provide a diagnostic tool for detecting cancerous lesions deeper within the breast. This presumption is based in part on the excellent contrast between neoplastic and normal tissue due to the large (orders of magnitude) relative variation in the shear elastic modulus. By comparison, the bulk deformational modulus maintains the same value to within 20% for most soft tissues. A specific method of magnetic-resonance imaging (MRI) which measures tissue displacements has been used in experiments with a phantom containing regions of increased Young's modulus as a demonstration. The spatial modulation of magnetization technique uses the displacement of a spatial grid pattern caused by spin saturation to track regional motion. Mathematical reconstruction of the distribution of elastic moduli is shown for select examples. Any modality, e.g., MRI, ultrasound, etc., which can detect local tissue motion with sufficient spatial resolution can be used and therefore the results presented here should give an indication of the utility of such motion tracking techniques to future measurement of tissue elasticity.

Use of multiple look directions, that is, compound imaging, has been shown previously to increase detection of specular reflectors and averaging of speckle noise in gray-scale images, often at the expense of spatial resolution and other misregistration errors. In color flow imaging, additional view angles can fill in vessels missed due to Doppler angle dropout and increase quantitative and visual Doppler accuracy by triangulation or a simple peak-frequency-shift combination algorithm. Image registration and unwarping throughout multiple three-dimensional (3D) volume sets should correct for many refraction artifacts, motion between and during compounded image sets and even, possibly, positioning errors between image sets, acquired months apart, to display growth of abnormalities. The registration described here does not provide sufficient accuracy for formation of enhanced coherent apertures, but shows promise in some cases to provide superior compound images and possibly comparisons of current and prior studies. In this study, the breast is stabilized by mild compression between a flat plate and a scanning membrane. Registration and unwarping is performed retrospectively on two separate volumetric data sets by defining pairs of corresponding points and, in some cases, line and plane segments. Three-dimensional linear affine transforms are performed using identified points, lines and planes. 3D nonlinear warped transforms are also possible given adequate numbers of identifiable points. More than two data sets are registered by selecting one as the standard, and registering the remainder to match. The most appropriate algorithm, such as averaging or maximum amplitude, may be used to combine the data sets for display. Significant success has been achieved in compound display of a test object and of the breast in vivo, even when there was relative motion or warping between image sets. In pulse-echo imaging, homologous feature registration for compounding appears to have advantages over mechanically registered compounding methods previously employed in the breast and significant increases in lesion and structural conspicuity are noted due to a reduction in speckle noise. The improvements from compounding in 3D, surface-rendered Doppler imaging of vasculature are striking.

Two methods of potentially improving the detection and assessment of breast cancer vasculature by color flow Doppler ultrasonography were studied. Use of continuous wave (CW) Doppler imaging was one method evaluated by a comparison of system sensitivity to small vessel flow by continuous wave and pulsed Doppler methods. The second technique demonstrated color flow image acquisition and three-dimensional (3D) display. Six breast cancer patients were examined with both a color flow pulsed system and a CW Doppler system employing a hand-held transmitter-receiver pair with crossed-beam patterns. The CW unit consistently revealed more regions of tumor flow and multidirectional flow. Good 3D displays were achieved on larger pulsatile vessels, from images obtained during systole and selected for minimal noise.