Opto-acoustic imaging of relative blood oxygen saturation and total hemoglobin for breast cancer diagnosis.

Opto-acoustic imaging involves using light to produce sound waves for visualizing blood in biological tissue. By using multiple optical wavelengths, diagnostic images of blood oxygen saturation and total hemoglobin are generated using endogenous optical contrast, without injection of any external contrast agent and without using any ionizing radiation. The technology has been used in recent clinical studies for diagnosis of breast cancer to help distinguish benign from malignant lesions, potentially reducing the need for biopsy through improved diagnostic imaging accuracy. To enable this application, techniques for mapping oxygen saturation differences within tissue are necessary. Using biologically relevant opto-acoustic phantoms, we analyze the ability of an opto-acoustic imaging system to display colorized parametric maps that are generated using a statistical mapping approach. To mimic breast tissue, a material with closely matching properties for optical absorption, optical scattering, acoustic attenuation, and speed of sound is used. The phantoms include two vessels filled with whole blood at oxygen saturation levels determined using a sensor-based approach. A flow system with gas-mixer and membrane oxygenator adjusts the oxygen saturation of each vessel independently. Datasets are collected with an investigational Imagio® breast imaging system. We examine the ability to distinguish vessels as the oxygen saturation level and imaging depth are varied. At depth of 15 mm and hematocrit of 42%, a sufficient level of contrast to distinguish between two 1.6-mm diameter vessels was measured for an oxygen saturation difference of ∼4.6 % . In addition, an oxygenated vessel was visible at a depth of 48 mm using an optical wavelength of 1064 nm, and a deoxygenated vessel was visible to a depth of 42 mm with 757 nm. The results provide insight toward using color mapped opto-acoustic images for diagnosing breast cancer.

Optoacoustic Imaging and Gray-Scale US Features of Breast Cancers: Correlation with Molecular Subtypes.

Background Optoacoustic imaging can assess tumor hypoxia coregistered with US gray-scale images. The combination of optoacoustic imaging and US may have a role in distinguishing breast cancer molecular subtypes. Purpose To investigate whether optoacoustic US feature scores correlate with breast cancer molecular subtypes. Materials and Methods A total of 1972 women (with a total of 2055 breast masses) underwent prebiopsy optoacoustic US in a prospective multi-institutional study between December 2012 and September 2015. Seven readers blinded to pathologic diagnosis scored gray-scale US and optoacoustic US features of the known cancers. Optoacoustic US features within (internal) and outside of the tumor boundary (external) were scored. Immunohistochemistry findings were obtained from pathology reports. Multinomial logistic regression analysis was used to fit the US scores, adding optoacoustic US features to the model to investigate the incremental benefit of each feature. Kruskal-Wallis tests were used to analyze the relationship between molecular subtypes and feature scores. Results Among 653 invasive cancers identified in 629 women, a total of 532 cancers in 519 women, all of which had molecular markers available, were included in the analysis. Mean age ± standard deviation was 57.9 years ± 12.6. Mean total external optoacoustic US feature scores of luminal (A and B) breast cancers were higher (9.9 vs 8.8; P < .05) and total internal scores were lower (6.8 vs 7.7; P < .001) than those of triple-negative and human epidermal growth factor receptor 2-positive (HER2+) cancers. A multinomial logistic regression model showed that optoacoustic internal vessel (odds ratio [OR], 0.6; 95% confidence interval [CI]: 0.5, 0.8; P = .002), optoacoustic internal blush (OR, 0.7; 95% CI: 0.5, 0.9; P = .02), and optoacoustic internal hemoglobin (OR, 0.6; 95% CI: 0.5, 0.8; P = .001) were associated with classification of luminal versus triple-negative and HER2+ cancer subtypes. Conclusion Combined optoacoustic US imaging and gray-scale US features may help distinguish luminal breast cancers from triple-negative and human epidermal growth factor receptor 2-positive cancers. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Mann in this issue.

Optoacoustic imaging of the breast: correlation with histopathology and histopathologic biomarkers.

AIM: This study was conducted in order to investigate the role of gray-scale ultrasound (US) and optoacoustic imaging combined with gray-scale ultrasound (OA/US) to better differentiate between breast cancer molecular subtypes. MATERIALS AND METHODS: All 67 malignant masses included in the Maestro trial were retrospectively reviewed to compare US and OA/US feature scores and histopathological findings. Kruskal-Wallis tests were used to analyze the relationship between US and OA/US features and molecular subtypes of breast cancer. If a significant relationship was found, additional Wilcoxon-Mann-Whitney tests were used to identify the differences between molecular subtype groups. RESULTS: US sound transmission helped to differentiate between LUMA and LUMB, LUMB and TNBC, and LUMB and all other molecular subtypes combined (p values < 0.05). Regarding OA/US features, the sum of internal features helped to differentiate between TNBC and HER2-enriched subtypes (p = 0.049). Internal vessels (p = 0.025), sum of all internal features (p = 0.019), and sum of internal and external features (p = 0.028) helped to differentiate between LUMA and LUMB. All internal features, the sum of all internal features, the sum of all internal and external features, and the ratio of internal and external features helped to differentiate between LUMA and TNBC. The same features also helped to differentiate between LUMA and TNBC from other molecular subtypes (p values < 0.05). CONCLUSIONS: The use of OA/US might help radiologists to better differentiate between breast cancer molecular subtypes. Further studies need to be carried out in order to validate these results. KEY POINTS: • The combination of functional and morphologic information provided by optoacoustic imaging (OA) combined with gray-scale US helped to differentiate between breast cancer molecular subtypes.

Downgrading of Breast Masses Suspicious for Cancer by Using Optoacoustic Breast Imaging.

Purpose To assess the ability of optoacoustic (OA) ultrasonography (US) to help correctly downgrade benign masses classified as Breast Imaging Reporting and Data System (BI-RADS) 4a and 4b to BI-RADS 3 or 2. Materials and Methods OA/US technology uses laser light to detect relative amounts of oxygenated and deoxygenated hemoglobin in and around suspicious breast masses. In this prospective, multicenter study, results of 209 patients with 215 breast masses classified as BI-RADS 4a or 4b at US are reported. Patients were enrolled between 2015 and 2016. Masses were first evaluated with US with knowledge of previous clinical information and imaging results, and from this information a US imaging-based probability of malignancy (POM) and BI-RADS category were assigned to each mass. The same masses were then re-evaluated at OA/US. During the OA/US evaluation, radiologists scored five OA/US features, and then reassigned an OA/US-based POM and BI-RADS category for each mass. BI-RADS downgrade and upgrade percentages at OA/US were assessed by using a weighted sum of the five OA feature scores. Results At OA/US, 47.9% (57 of 119; 95% CI: 0.39, 0.57) of benign masses classified as BI-RADS 4a and 11.1% (three of 27; 95% CI: 0.03, 0.28) of masses classified as BI-RADS 4b were correctly downgraded to BI-RADS 3 or 2. Two of seven malignant masses classified as BI-RADS 4a at US were incorrectly downgraded, and one of 60 malignant masses classified as BI-RADS 4b at US was incorrectly downgraded for a total of 4.5% (three of 67; 95% CI: 0.01, 0.13) false-negative findings. Conclusion At OA/US, benign masses classified as BI-RADS 4a could be downgraded in BI-RADS category, which would potentially decrease biopsies negative for cancer and short-interval follow-up examinations, with the limitation that a few masses may be inappropriately downgraded.

Erratum to: Dynamic contrast-enhanced breast MRI at 7T and 3T: an intra-individual comparison study.

[This corrects the article DOI: 10.1186/s40064-015-1654-7.].

Dynamic contrast-enhanced breast MRI at 7T and 3T: an intra-individual comparison study.

The aim of this study is to compare the current state of lesion identification, the BI-RADS classification and the contrast-enhancement behavior at 7T and 3T breast MRI in the same patient group. Twenty-seven patients with thirty suspicious lesions were selected for this prospective study and underwent both 7T and 3T MRI. All examinations were rated by two radiologists (R1 and R2) independently on image quality, lesion identification and BI-RADS classification. We assessed sensitivity, specificity, NPV and PPV, observer agreement, lesion sizes, and contrast-enhancement-to-noise ratios (CENRs) of mass lesions. Fifteen of seventeen histopathological proven malignant lesions were detected at both field strengths. Image quality of the dynamic series was good at 7T, and excellent at 3T (P = 0.001 for R1 and P = 0.88 for R2). R1 found higher rates of specificity, NPV and PPV at 7T when compared to 3T, while R2 found the same results for sensitivity, specificity, NPV and PPV for both field strengths. The observers showed excellent agreement for BI-RADS categories at 7T (κ = 0.86) and 3T (κ = 0.93). CENRs were higher at 7T (P = 0.015). Lesion sizes were bigger at 7T according to R2 (P = 0.039). Our comparison study shows that 7T MRI allows BI-RADS conform analysis. Technical improvements, such as acquisition of T2w sequences and adjustment of B1+ field inhomogeneity, are still necessary to allow clinical use of 7T breast MRI.

High Prevalence of MRI-Detected Contralateral and Ipsilateral Malignant Findings in Patients With Invasive Ductolobular Breast Cancer: Impact on Surgical Management.

INTRODUCTION: Invasive breast cancer comprises a spectrum of histologic changes with purely lobular and purely ductal cancer on either side and mixed lesions in between. Our aim was to evaluate to what extent preoperative magnetic resonance imaging (MRI) leads to the finding of additional malignancies and the effect on surgical management in the subcategory of women with invasive ductolobular disease. PATIENTS AND METHODS: From 2007 to 2012, 109 patients diagnosed with breast cancer containing a lobular component underwent preoperative MRI. The MRI findings were compared with the findings from mammography and ultrasonography. Clinically relevant additional MRI findings were verified histologically. The histologic slides were reviewed, and the percentage of the lobular component was determined. In a multidisciplinary setting, the TNM classification and surgical policy were determined using the conventional imaging findings and as a scenario that included preoperative MRI. RESULTS: MRI revealed additional malignant foci in 28 of 109 patients (26%). More extensive disease was seen in 25 patients (23%). The preoperative MRI findings changed the TNM classification in 42% of the patients and altered the surgical policy in 37%. No correlation was found between the lobular component and the probability of detecting additional malignant foci, more extensive disease, or the frequency of a change in TNM classification or surgical policy. According to the final pathology report, the change in surgical policy was justified in 85% of the patients. CONCLUSION: In patients with breast cancer presenting with lobular differentiation at biopsy, preoperative MRI can lead to the detection of additional malignancies and clinically relevant changes in surgical policy in a high percentage of patients, irrespective of the lobular component. The use of MRI as a part of the standard workup of such patients deserves consideration.

Current clinical indications for magnetic resonance imaging of the breast.

MRI is increasingly used in breast cancer patients. MRI has a high sensitivity compared to mammography and ultrasound. The specificity is moderate leading to an increased risk of false positive findings. Currently, a beneficial effect of breast MRI has been established in some patient groups and is debated in the general breast cancer population. The diagnostic ability of MRI and its role in various groups of breast cancer patients are discussed in this review.