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.

Short-term changes in ultrasound tomography measures of breast density and treatment-associated endocrine symptoms after tamoxifen therapy.

Although breast density decline with tamoxifen therapy is associated with greater therapeutic benefit, limited data suggest that endocrine symptoms may also be associated with improved breast cancer outcomes. However, it is unknown whether endocrine symptoms are associated with reductions in breast density after tamoxifen initiation. We evaluated treatment-associated endocrine symptoms and breast density change among 74 women prescribed tamoxifen in a 12-month longitudinal study. Treatment-associated endocrine symptoms and sound speed measures of breast density, assessed via novel whole breast ultrasound tomography (m/s), were ascertained before tamoxifen (T0) and at 1-3 (T1), 4-6 (T2), and 12 months (T3) after initiation. CYP2D6 status was genotyped, and tamoxifen metabolites were measured at T3. Using multivariable linear regression, we estimated mean change in breast density by treatment-associated endocrine symptoms adjusting for age, race, menopausal status, body mass index, and baseline density. Significant breast density declines were observed in women with treatment-associated endocrine symptoms (mean change (95% confidence interval) at T1:-0.26 m/s (-2.17,1.65); T2:-2.12 m/s (-4.02,-0.22); T3:-3.73 m/s (-5.82,-1.63); p-trend = 0.004), but not among women without symptoms (p-trend = 0.18) (p-interaction = 0.02). Similar declines were observed with increasing symptom frequency (p-trends for no symptoms = 0.91; low/moderate symptoms = 0.03; high symptoms = 0.004). Density declines remained among women with detectable tamoxifen metabolites or intermediate/efficient CYP2D6 metabolizer status. Emergent/worsening endocrine symptoms are associated with significant, early declines in breast density after tamoxifen initiation. Further studies are needed to assess whether these observations predict clinical outcomes. If confirmed, endocrine symptoms may be a proxy for tamoxifen response and useful for patients and providers to encourage adherence.

Mesenteric fat cryolipolysis attenuates insulin resistance in the Ossabaw swine model of the metabolic syndrome.

BACKGROUND: The rising prevalence of insulin resistance (IR), metabolic syndrome, and type 2 diabetes are associated with increases in abdominal mesenteric fat. Adipocytes are sensitive to low temperatures, making cryolipolysis of mesenteric fat an attractive treatment modality to potentially reduce IR. OBJECTIVES: We aimed to determine whether (1) cryolipolysis is safe in reducing the volume of the mesenteric fat and (2) reduction in mesenteric fat volume reduces indices of IR and glycemic dysfunction. SETTING: Indiana University School of Medicine. METHODS: A novel cooling device and method delivered cryolipolysis in a controlled manner to avoid tissue ablative temperatures. Ossabaw pigs (n = 8) were fed a high-fat diet for 9 months to develop visceral obesity, IR, and metabolic syndrome. Following laparotomy, mesenteric fat cryolipolysis (MFC) was performed in 5 pigs, while 3 served as sham surgery controls. The volume of the mesenteric fat was measured by computed tomography and compared with indices of glucose intolerance before and at 3 and 6 months postprocedure. RESULTS: MFC safely reduced mesenteric fat volume by ∼30% at 3 months, which was maintained at 6 months. Body weight did not change in either the MFC or sham surgery control groups. Measure of glycemic control, insulin sensitivity, and blood pressure significantly improved after MFC compared with sham controls. CONCLUSION: MFC reduces the volume of mesenteric fat and improves glycemic control in obese, IR Ossabaw pigs, without adverse effects.

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 ECLIPSE Study: Efficacy of Cryoablation on Metastatic Lung Tumors With a 5-Year Follow-Up.

INTRODUCTION: The ECLIPSE study aimed to evaluate the feasibility and efficacy of cryoablation (CA) for local tumor control in patients with pulmonary metastatic disease in 5 years of follow-up. METHODS: ECLIPSE was a prospective, multicenter, single-arm study that included patients treated with CA if they had one to five metastatic lung tumors, each with a diameter of less than or equal to 3.5 cm. Patients were followed up in the course of 5 years. The primary end point was local tumor control, both per tumor and per patient; secondary end points included cancer-specific survival, overall survival, and quality of life (QoL). QoL was evaluated using the Karnofsky Performance Score, the Eastern Cooperative Oncology Group performance score, and the Short Form-12 health survey. RESULTS: The study included 40 patients across four sites (three in United States and one in Europe). A total of 60 metastatic pulmonary tumors were treated with 48 CA procedures. Overall local tumor control rates were 87.9% (29 of 33) and 79.2% (19 of 24) per tumor, 83.3% (20 of 24) and 75.0% (15 of 20) per patient, at 3 and 5 years, respectively. A total of five treated patients had local progression throughout the duration of the study. Disease-specific survival rate was 74.8% at 3 years and 55.3% at 5 years, whereas overall survival at 3 and 5 years was 63.2% and 46.7%, respectively. Patient QoL scores did not reach statistical significance. CONCLUSIONS: CA is an effective means of long-term local tumor control in patients with metastatic pulmonary tumors.

Cryoablation for Palliation of Painful Bone Metastases: The MOTION Multicenter Study.

Purpose: To assess the clinical effectiveness of cryoablation for palliation of painful bone metastases. Materials and Methods: MOTION (Multicenter Study of Cryoablation for Palliation of Painful Bone Metastases) (ClinicalTrials.gov NCT02511678) was a multicenter, prospective, single-arm study of adults with metastatic bone disease who were not candidates for or had not benefited from standard therapy, that took place from February 2016 to March 2018. At baseline, participants rated their pain using the Brief Pain Inventory-Short Form (reference range from 0 to 10 points); those with moderate to severe pain, who had at least one metastatic candidate tumor for ablation, were included. The primary effectiveness endpoint was change in pain score from baseline to week 8. Participants were followed for 24 weeks after treatment. Statistical analyses included descriptive statistics and logistic regression to evaluate changes in pain score over the postprocedure follow-up period. Results: A total of 66 participants (mean age, 60.8 years ± 14.3 [standard deviation]; 35 [53.0%] men) were enrolled and received cryoablation; 65 completed follow-up. Mean change in pain score from baseline to week 8 was -2.61 points (95% CI: -3.45, -1.78). Mean pain scores improved by 2 points at week 1 and reached clinically meaningful levels (more than a 2-point decrease) after week 8; scores continued to improve throughout follow-up. Quality of life improved, opioid doses were stabilized, and functional status was maintained over 6 months. Serious adverse events occurred in three participants. Conclusion: Cryoablation of metastatic bone tumors provided rapid and durable pain palliation, improved quality of life, and offered an alternative to opioids for pain control.Keywords: Ablation Techniques, Metastases, Pain Management, Radiation Therapy/OncologySupplemental material is available for this article.© RSNA, 2021.

Cryoablation and Immunotherapy for Breast Cancer: Overview and Rationale for Combined Therapy.

Cryoablation is a well-tolerated outpatient procedure that has been used to treat metastatic sites as well as small breast cancers in patients who are considered poor candidates for surgery. Recent studies suggest that cell disruption caused by cryoablation may increase the expression and immunogenicity of tumor neoantigens, which could enhance the ability of the immune system to recognize and attack cancer cells at both local and distant sites. Such an approach might broaden the role of immunotherapy for the treatment of breast cancer, which has previously demonstrated limited response to these agents, likely owing to the modest immunogenicity of most breast cancer subtypes. If cryoablation can induce a systemic tumor-specific response, it could enhance tumor susceptibility to immunotherapy agents. This review briefly summarizes the necessary components for generating an immune response against tumor cells, reviews the tumor microenvironment of breast cancer, describes the rationale for and limitations of immune checkpoint inhibition, highlights the potential for cryoablation to induce a systemic tumor-specific immune response, and describes the rationale for combining cryoablation and immune checkpoint inhibitors for the treatment of breast cancer. Keywords: Ablation Techniques, Breast, Neoplasms-Primary, Percutaneous, Tumor Microenvironment, Tumor Response, Ultrasonography © RSNA, 2021.

Percutaneous cryoablation of adrenal metastases: technical feasibility and safety.

PURPOSE: To assess the technical feasibility and outcomes of adrenal metastases cryoablation. MATERIALS AND METHODS: This is an IRB approved retrospective review of adrenal metastases cryoablation between April 2003 and October 2018. Forty percutaneous cryoablation procedures were performed on 40 adrenal metastases in 34 patients. Histology, tumor size, ablation zone size, major vessel proximity, local recurrences, complications, and anesthesia-managed hypertension monitoring was collected. Complications were graded according to the Common Terminology of Complications and Adverse Events (CTCAE). RESULTS: Mean tumor and ablation size was 3.2 cm and 5.2 cm, respectively. Local recurrence rate was 10.0% (N = 4/40) for a mean follow-up time of 1.8 years. Recurrences for tumors > 3 cm (21.0%, N = 4/19) was greater than for tumors ≤ 3 cm (0.0%, N = 0/21) (p = 0.027). Proximity of major vasculature (i.e., IVC & aorta) did not statistically effect recurrence rates (p = 0.52), however, those that recurred near vasculature were > 4 cm. Major complication (≥ grade 3) rate was 5.0% (N = 2/40), with one major complication attributable to the procedure. Immediate escalation of blood pressure during the passive stick phase (between freeze cycles) or post procedure thaw phase was greater in patients with residual adrenal tissue (N = 21/38) versus masses replacing the entire adrenal gland (N = 17/38), (p = 0.0020). Lower blood pressure elevation was noted in patients with residual adrenal tissue who were pre-treated with alpha blockade (p = 0.015). CONCLUSIONS: CT-guided percutaneous cryoablation is a safe, effective and low morbidity alternative for patients with adrenal metastases. Transient hypertension is related only to residual viable adrenal tissue but can be safely managed and prophylactically treated.

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.

Whole Breast Sound Speed Measurement from US Tomography Correlates Strongly with Volumetric Breast Density from Mammography.

OBJECTIVE: To assess the feasibility of using tissue sound speed as a quantitative marker of breast density. METHODS: This 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. RESULTS: A 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). CONCLUSION: The 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.

Methylene Blue/Collagen Mixture for CT-Guided Presurgical Lung Nodule Marking: High Efficacy and Safety.

PURPOSE: To assess outcomes of computed tomography (CT)-guided methylene blue/collagen marking of preoperative lung nodules before video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracic surgery (RATS). MATERIALS AND METHODS: A retrospective cohort study assessing 25 methylene blue/collagen solution CT-guided lung nodule localization procedures on 26 nodules in 25 patients was performed. The procedures were performed by a fellowship-trained radiologist 1-2 hours before scheduled surgery under local anesthesia. Approximately 4-6 ml of methylene blue/collagen solution was injected in a perinodular location under CT guidance with a 19-gauge trocar needle and along the track to the visceral pleural surface. Post-procedural CT images confirmed appropriate lung nodule location marking. RESULTS: Perinodular CT-guided trocar needle placement was achieved in all marking procedures (n = 26/26). Increased consolidation near the target nodule was also demonstrated in all patients on the post-procedural localized CT scans. One patient with moderate emphysema developed a small to moderate-sized pneumothorax (∼20%-30%), and an 8-Fr thoracentesis catheter was placed under CT guidance before surgery. There was no bleeding or hemoptysis in any patient. Methylene blue/collagen solution was readily visible by the thoracic surgeon in association with all target nodules. One patient required conversion to open procedure due to the proximal portion of the right lower lobe pulmonary artery segmental branch. Of the 26 identified nodules, pathology specimens confirmed the adequacy of nodule resection in all cases. CONCLUSIONS: Preoperative CT-guided methylene blue/collagen solution injection offers a safe and highly effective technique for marking subpleural lung nodules undergoing VATS or RATS.

Using Whole Breast Ultrasound Tomography to Improve Breast Cancer Risk Assessment: A Novel Risk Factor Based on the Quantitative Tissue Property of Sound Speed.

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.

A Novel Marker, Based on Ultrasound Tomography, for Monitoring Early Response to Neoadjuvant Chemotherapy.

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.

Ultrasound tomography imaging with waveform sound speed: Parenchymal changes in women undergoing tamoxifen therapy.

Ultrasound tomography (UST) is an emerging modality that can offer quantitative measurements of breast density. Recent breakthroughs in UST image reconstruction involve the use of a waveform reconstruction as opposed to a ray-based reconstruction. The sound speed (SS) images that are created using the waveform reconstruction have a much higher image quality. These waveform images offer improved resolution and contrasts between regions of dense and fatty tissues. As part of a study that was designed to assess breast density changes using UST sound speed imaging among women undergoing tamoxifen therapy, UST waveform sound speed images were then reconstructed for a subset of participants. These initial results show that changes to the parenchymal tissue can more clearly be visualized when using the waveform sound speed images. Additional quantitative testing of the waveform images was also started to test the hypothesis that waveform sound speed images are a more robust measure of breast density than ray-based reconstructions. Further analysis is still needed to better understand how tamoxifen affects breast tissue.

Percutaneous Cryoablation of Renal Tumors: Is It Time for a New Paradigm Shift?

PURPOSE: To retrospectively assess long-term outcomes of percutaneous renal cryoablation, including factors affecting complications and local recurrence rates. MATERIALS AND METHODS: A total of 357 computed tomographic (CT) fluoroscopy-guided percutaneous cryoablation procedures were performed for 382 masses in 302 outpatients; 347 were biopsy-proven renal-cell carcinoma (RCC) or Bosniak category > III masses (n = 28). Benign pathologic conditions (n = 18) or metastatic non-RCC disease (n = 17) were included to analyze procedural complication rate, but recurrence rates, tumor staging, and nephrometry score were limited to RCCs. The average tumor diameter was 2.9 cm (range, 1-10.3 cm), and median nephrometry score for RCC was 8 (mean, 7.4). Protection of adjacent vital structures was performed in 34% of procedures (n = 121), and ureteral stent placement was performed for 9.2% (n = 33). All major complications were graded per surgical Clavien-Dindo criteria. RESULTS: The average CT-visible cryoablation zone diameter was 5 cm (range, 2.5-10.5 cm). Grade ≥ 3 complications occurred in 2.8% of procedures (n = 10), and appeared related to only high nephrometry scores (P = .0086) and larger tumors (P = .0034). No significant changes in renal function before and after the procedure were noted (P = .18). At a mean follow-up of 31.8 months, the local tumor recurrence rate was 3.2% (11 of 347) for RCC, and no significant difference was noted between tumors larger or smaller than 3 cm (P = .15). The difference reached significance only among the small number of stage ≥ T2 RCC tumors (P = .0039). CONCLUSIONS: Long-term follow-up of percutaneous renal cryoablation demonstrates low recurrence rates with preserved renal function, even for patients with high nephrometry scores and body mass index, assuming thorough cytotoxic technique and protection measures.

Cryoablation of Abdominal Wall Endometriosis: A Minimally Invasive Treatment.

OBJECTIVE: The objective of this study is to present cryoablation as a minimally invasive definitive treatment for abdominal wall endometriosis. We describe our experience with the outpatient application of cryoablation to treat symptomatic abdominal wall endometriosis in three patients. CONCLUSION: This feasibility study shows that minimally invasive cryoablation treated abdominal wall endometriosis in three patients and provided a prompt clinical response.

Using Speed of Sound Imaging to Characterize Breast Density.

A population of 165 women with negative mammographic screens also received an ultrasound tomography (UST) examination at the Karmanos Cancer Institute 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 body mass index (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.