Summary: The marked improvements in transrectal ultrasound (TRUS) imaging of the prostate in the last 15 years has allowed broad applications of interventional techniques for both benign and malignant diseases. Techniques developed for prostate biopsy by both transperineal and transrectal routes initiated the methodology for other therapeutic options. For benign disease, balloon dilatation was also performed by TRUS guidance rather than digital guidance or fluoroscopy. Transrectal ultrasound guidance initiated the first use of interstitial laser ablation and led to the development of current laser techniques for transurethral resection. Other benign applications for TRUS monitoring have included microwave for benign prostatic hypertrophy and drainage and injection techniques for perirectal, prostatic, and deep pelvic abscess drainage and treatment. Transrectal ultrasound guidance for treatment of prostate cancer primarily involves guidance of I125 implantation (or brachytherapy) and cryotherapy. Both of these techniques represent significant options for current and future prostate cancer treatments. Thorough TRUS evaluation remains the impetus for the evolution of new interventional techniques and evaluation of their outcomes.
Our laboratory has focused on the development of ultrasound tomography (UST) for breast imaging. To that end we have been developing and testing a clinical prototype in the Karmanos Cancer Institute's (KCI) breast center. The development of our prototype has been guided by clinical feedback from data accumulated from over 300 patients recruited over the last 4 years. Our techniques generate whole breast reflection images as well as images of the acoustic parameters of sound speed and attenuation. The combination of these images reveals major breast anatomy, including fat, parenchyma, fibrous stroma and masses. Fusion imaging, utilizing thresholding, is shown to visualize mass characterization and facilitates separation of cancer from benign masses. These results indicate that operator-independent whole-breast imaging and the detection and characterization of cancerous breast masses are feasible using acoustic tomography techniques. Analyses of the prototype images suggests that we can detect the variety of mass attributes noted by current ultrasound-BIRADS criteria, such as mass shape, acoustic mass properties and architecture of the tumor environment. These attributes help quantify current BIRADS criteria (e.g. "shadowing" or high attenuation) and provide greater possibilities for defining a unique signature of cancer. The potential for UST to detect and characterize breast masses was quantified using UST measurements of 86 masses from the most recent cohort of patients imaged with the latest version of our prototype. Our preliminary results suggest that the development of a formal predictive model, in support of larger future trials, is warranted.
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.
Abstract 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.
Abstract PURPOSE. Increased mammographic percent density (MPD) is a strong independent risk factor for developing breast cancer. Previous studies have shown that tissue sound speed, derived from ultrasound tomography, is a surrogate biomarker of MPD. We examined associations of sound speed and MPD with breast cancer risk in a case-control study. METHOD AND MATERIALS. We evaluated breast cancer risk associated with sound speed and MPD in a case-control study involving 59 participants with recent breast cancer diagnoses (cases, aged 30-70 years) and 150 participants with no history of breast cancer (controls), who were matched to cases on age, race, and menopausal status. The cases and controls were imaged with both ultrasound tomography (UST) and mammography. In cases, breast density was measured pre-treatment in the contralateral breast to avoid potential influences of tumor-related changes on MPD or sound speed. In controls, a randomly selected breast was imaged. The ultrasound tomography images were used to estimate the volume averaged sound speed of the breast, and the Cumulus software package was applied to mammograms to determine MPD. Odds Ratios (ORs) and 95% Confidence Intervals (CIs), adjusted for matching factors, were calculated for the relation of quartiles of MPD and sound speed with breast cancer risk. OR differences were tested using a bootstrap approach. RESULTS. MPD was associated with elevated breast cancer risk compared to controls, consistent with previous studies, although the trend did not reach statistical significance (OR per quartile=1.28, 95%CI: 0.95, 1.73; ptrend=0.10). In contrast, elevated sound speed was significantly associated with increased breast cancer risk in a dose-response fashion (OR per quartile=1.79, 95%CI: 1.30, 2.48; ptrend=0.0004). The OR-trend for sound speed was statistically significantly different from that observed for MPD (p=0.01). DISCUSSION. Our case-control study showed that increasing quartiles of whole breast sound speed were consistently and more strongly associated with increasing breast cancer risk than quartiles of MPD. These results show promise for UST’s role in breast cancer risk stratification. CONCLUSION. Elevated breast density strongly increases breast cancer risk. UST has the potential to provide a more accurate, non-ionizing method for assessing breast density and its associated breast cancer risk. Citation Format: Mark Sak, Neb Duric, Ruth Pfeiffer, Mark Sherman, Peter Littrup, Michael Simon, David Gorski, Teri Albrecht, Haythem Ali, Rachel Brem, Rachel Brem, Sharon Fan, Gretchen Gierach. Tissue sound speed is more strongly associated with breast cancer risk than mammographic percent density: A comparative case-control study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-28.
Background. Different indexes that may enhance the early detection capability of prostate specific antigen (PSA) have been proposed. In addition to the indexes relating to the normal PSA level, there are data suggesting the usefulness of the PSA level relative to prostate gland volume (PSA density), age-referenced PSA level, and PSA change. Little research comparing the sensitivity and specificity of these measures in the same population has been reported. Methods. All subjects were participants in the American Cancer Society National Prostate Cancer Detection Project. Specificity was studied in 2011 men without prostate cancer, and sensitivity was determined for 171 men with prostate cancer. Results. Prostate specific antigen change showed the highest specificity (96.4%), and PSA density the lowest (85.3%). The most sensitive index was PSA density, which was positive for 74.7% of the 171 cases of known cancer. A PSA change of more than 0.75 ng/ml per year was the least sensitive index (54.8%). Sensitivity and specificity varied in a narrow range. Improved performance in specificity was achieved only with the loss of sensitivity. Conclusions. None of the alternative indexes commonly used in general early detection practice demonstrated particular advantage when compared with the normal PSA concentration, defined as no more than 4.0 ng/ml.
It is known that breast cancer risk is greater in women with higher breast densities. Currently, breast density is measured using mammographic percent density, defined as the ratio of fibroglandular to total breast area on a two dimensional mammogram. Alternatively, systems that use ultrasound tomography (UST) create tomographic sound speed images of the patient's breast. These volumetric images can be useful as a diagnostic aid because it is also known that sound speed of tissue is proportional to the density of the tissue. The purpose of this work is to expand on the comparisons of the two imaging modalities by introducing new ultrasound tomography measurements that separate and quantify the fatty and dense tissue distributions within the breast. A total of 249 patients were imaged using both imaging modalities. By using k-means clustering, correlations beyond the volume averaged sound speed of the ultrasound images and the mammographic percent density were investigated. Both the ultrasound and mammographic images were separated into dense and fatty regions. Various associations between the global breast properties as well as separate tissue components were found.
