False negative breast cancers on imaging and associated risk factors: a single institution six-year analysis.

PURPOSE: Mitigating false negative imaging studies remains an important issue given its association with worse morbidity and mortality in patients with breast cancer. We aimed to identify risk factors that predispose to false negative breast imaging exams. METHODS: In an IRB-approved, HIPAA compliant retrospective study, we identified all patients who were diagnosed with breast cancer within 365 days of a negative imaging study assessed as BI-RADS 1-3 between January 1, 2014 and January 31, 2020. A matched cohort based on mammographic breast density was created from randomly selected studies with BI-RADS 4-5 designation that yielded breast cancer at pathology within the same time frame. Patient and cancer characteristics, prior personal history of breast cancer and gene mutation status were collected from patient charts. Pearson chi-squared and Student's t-test on two independent groups with significance at < 0.05 was used for statistical analysis. RESULTS: We identified 155 false negative studies of 129 missed cancers and 128 breast density matched true positive cancers. False negative studies were screening mammograms in 57.42% (89/155), diagnostic mammograms in 29.68% (46/155), ultrasounds in 6.45% (10/155) and MRIs in 6.45% (10/155). Rates of personal (41.09% vs. 18.75%, p < 0.001) and family history of breast cancer (68.22% vs. 49.21%, p = 0.002) were higher in the false negative cohort and remained significant when asymptomatic MRI-detected cancers were removed. CONCLUSION: Our findings suggest that supplemental screening may be useful in breast cancer survivors.

Current status of optoacoustic breast imaging and future trends in clinical application: is it ready for prime time?

Optoacoustic imaging (OAI) is an emerging field with increasing applications in patients and exploratory clinical trials for breast cancer. Optoacoustic imaging (or photoacoustic imaging) employs non-ionizing, laser light to create thermoelastic expansion in tissues and detect the resulting ultrasonic emission. By combining high optical contrast capabilities with the high spatial resolution and anatomic detail of grayscale ultrasound, OAI offers unique opportunities for visualizing biological function of tissues in vivo. Over the past decade, human breast applications of OAI, including benign/malignant mass differentiation, distinguishing cancer molecular subtype, and predicting metastatic potential, have significantly increased. We discuss the current state of optoacoustic breast imaging, as well as future opportunities and clinical application trends. CLINICAL RELEVANCE STATEMENT: Optoacoustic imaging is a novel breast imaging technique that enables the assessment of breast cancer lesions and tumor biology without the risk of ionizing radiation exposure, intravenous contrast, or radionuclide injection. KEY POINTS: • Optoacoustic imaging (OAI) is a safe, non-invasive imaging technique with thriving research and high potential clinical impact. • OAI has been considered a complementary tool to current standard breast imaging techniques. • OAI combines parametric maps of molecules that absorb light and scatter acoustic waves (like hemoglobin, melanin, lipids, and water) with anatomical images, facilitating scalable and real-time molecular evaluation of tissues.

Breast Cancer Disparity and Outcomes in Underserved Women.

Women in the United States who continue to face obstacles accessing health care are frequently termed an underserved population. Safety-net health care systems play a crucial role in mitigating health disparities and reducing burdens of disease, such as breast cancer, for underserved women. Disparities in health care are driven by various factors, including race and ethnicity, as well as socioeconomic factors that affect education, employment, housing, insurance status, and access to health care. Underserved women are more likely to be uninsured or underinsured throughout their lifetimes. Hence they have greater difficulty gaining access to breast cancer screening and are less likely to undergo supplemental imaging when needed. Therefore, underserved women often experience significant delays in the diagnosis and treatment of breast cancer, leading to higher mortality rates. Addressing disparities requires a multifaceted approach, with formal care coordination to help at-risk women navigate through screening, diagnosis, and treatment. Mobile mammography units and community outreach programs can be leveraged to increase community access and engagement, as well as improve health literacy with educational initiatives. Radiology-community partnerships, comprised of imaging practices partnered with local businesses, faith-based organizations, homeless shelters, and public service departments, are essential to establish culturally competent breast imaging care, with the goal of equitable access to early diagnosis and contemporary treatment. Published under a CC BY 4.0 license. Test Your Knowledge questions are available in the Online Learning Center. See the invited commentary by Leung in this issue.

Treatment of multiple adjacent gingival recessions using leucocyte- and platelet-rich fibrin with coronally advanced flap: a 12-month split-mouth controlled randomized clinical trial.

OBJECTIVE: This split-mouth randomized study aimed to assess efficacy of leucocyte-platelet-rich fibrin (L-PRF) versus connective tissue graft (CTG) in achieving root coverage (RC) for multiple adjacent gingival recessions (MAGRs) throughout 12-month period. MATERIALS AND METHODS: The study enrolled 59 teeth from 12 patients with Miller Class I MAGRs ≥ 2 mm on bilateral or contralateral sides. Patients were randomly assigned to receive coronally advanced flap (CAF) with either CTG (control) or L-PRF (test) treatment. Various parameters, including plaque and gingival index, clinical attachment level, recession depth, probing depth, recession width (RW), papilla width (PW), keratinized tissue width (KTW), gingival thickness (GT), percentage of RC, complete root coverage (CRC), and location of the relative gingival margin concerning the cemento-enamel junctions (GMCEJ) after CAF, were recorded at baseline, 3-, 6-, and 12-months post-surgery. On June 29, 2021 the study was registred to ClinicalTrials.gov (NCT04942821). RESULTS: Except KTW and GT gain, all clinical parameters, RC, and CRC were similar between the groups at all follow-up periods (p > 0.05). The higher GT and KTW gains were detected in the control group compared to test group at 12 months (p < 0.05). Both RC and CRC were positively associated with initial PW and GMCEJ, but negatively with initial RW (p < 0.05). CONCLUSIONS: The current study concludes that L-PRF were equally effective as CTG in treating MAGRs in terms of RC and CRC. Additionally, RC and CRC outcomes appeared to be influenced by GMCEJ, PW, and RW. CLINICAL RELEVANCE: L-PRF could represent a feasible substitute for CTG in treating MAGRs.

Surviving the COVID-19 pandemic: navigating the recovery of breast imaging services in a safety-net hospital.

PURPOSE: The purpose of this study was to determine the impact of COVID-19 on county safety-net breast imaging services and describe the steps taken to actively manage and mitigate delays. METHODS: This was an IRB exempt retrospective review of our county safety-net breast imaging practice analyzed for 4 distinct time periods: (1) "Shut-down period": March 17, 2020 to May 17, 2020; (2) "Phased re-opening": May 18, 2020 to June 30, 2020; (3) "Ramp-up": July 1, 2020 to September 30, 2020; and (4) "Current state": October 1, 2020 to September 30, 2021. These time periods were compared to identical time periods 1 year prior. For "Current state," given that the 1-year prior comparison encompassed the first 3 periods of the pandemic, the identical time period 2 years prior was also compared. RESULTS: Our safety-net practice sustained significant volume losses during the first 3 time periods with a 99% reduction in screening mammography in the shut-down period. Cancers diagnosed decreased by 17% in 2020 (n = 229) compared to 2019 (n = 276). By implementing multiple initiatives that targeted improved access to care, including building community-hospital partnerships and engagement through outreach events and a community education roadshow, we were able to recover and significantly exceed our pandemic screening volumes by 48.1% (27,279 vs 18,419) from October 1, 2020 to September 30, 2021 compared to the identical time period 1 year prior, and exceed our pre-pandemic screening volume by 17.4% (27,279 vs 23,234) compared to the identical time period 2 years prior. CONCLUSION: Through specific community outreach programs and optimized navigation, our safety-net breast imaging practice was able to mitigate the impact of COVID-19 on our patient population by increasing patient engagement and breast imaging services.

Optoacoustic Imaging With Decision Support for Differentiation of Benign and Malignant Breast Masses: A 15-Reader Retrospective Study.

BACKGROUND. Overlap in ultrasound features of benign and malignant breast masses yields high rates of false-positive interpretations and benign biopsy results. Optoacoustic imaging is an ultrasound-based functional imaging technique that can increase specificity. OBJECTIVE. The purpose of this study was to compare specificity at fixed sensitivity of ultrasound images alone and of fused ultrasound and optoacoustic images evaluated with machine learning-based decision support tool (DST) assistance. METHODS. This retrospective Reader-02 study included 480 patients (mean age, 49.9 years) with 480 breast masses (180 malignant, 300 benign) that had been classified as BI-RADS category 3-5 on the basis of conventional gray-scale ultrasound findings. The patients were selected by stratified random sampling from the earlier prospective 16-site Pioneer-01 study. For that study, masses were further evaluated by ultrasound alone followed by fused ultrasound and optoacoustic imaging between December 2012 and September 2015. For the current study, 15 readers independently reviewed the previously acquired images after training in optoacoustic imaging interpretation. Readers first assigned probability of malignancy (POM) on the basis of clinical history, mammographic findings, and conventional ultrasound findings. Readers then evaluated fused ultrasound and optoacoustic images, assigned scores for ultrasound and optoacoustic imaging features, and viewed a POM prediction score derived by a machine learning-based DST before issuing final POM. Individual and mean specificities at fixed sensitivity of 98% and partial AUC (pAUC) (95-100% sensitivity) were calculated. RESULTS. Averaged across all readers, specificity at fixed sensitivity of 98% was significantly higher for fused ultrasound and optoacoustic imaging with DST assistance than for ultrasound alone (47.2% vs 38.2%; p = .03). Across all readers, pAUC was higher (p < .001) for fused ultrasound and optoacoustic imaging with DST assistance (0.024 [95% CI, 0.023-0.026]) than for ultrasound alone (0.021 [95% CI, 0.019-0.022]). Better performance using fused ultrasound and optoacoustic imaging with DST assistance than using ultrasound alone was observed for 14 of 15 readers for specificity at fixed sensitivity and for 15 of 15 readers for pAUC. CONCLUSION. Fused ultrasound and optoacoustic imaging with DST assistance had significantly higher specificity at fixed sensitivity than did conventional ultrasound alone. CLINICAL IMPACT. Optoacoustic imaging, integrated with reader training and DST assistance, may help reduce the frequency of biopsy of benign breast masses.

Outcome of Imaging and Biopsy of BI-RADS Category 3 Lesions: Follow-Up Compliance, Biopsy, and Malignancy Rates in a Large Patient Cohort.

OBJECTIVES: To identify biopsy rates and indications for BI-RADS 3 lesions in a large cohort of patients and compare with follow-up compliance and malignancy outcomes. METHODS: We retrospectively reviewed all BI-RADS category-3 lesions seen on mammography and/or ultrasound between 2013 and 2015. Patient age, lesion size, follow-up rates at 6-, 12-, and 24-months were collected. Biopsy timing, indication, and outcomes (malignant vs benign) were recorded using at least 2-year follow-up or biopsy pathology as endpoint. RESULTS: Of 2319 BI-RADS 3 lesions in 2075 women analyzed, biopsy was performed in 173 (7.5%). Most biopsies were performed upfront (99, 57.2%), followed by at 6 (44, 25.4%), 12 (21, 12.1%), and 24-month follow-up (9, 5.2%; P < .001). Palpable (P < .001) and larger (median 1.4 vs 1.0 cm, P < .001) lesions in women <40 years (15.2% vs 4.8%, P < .001) were more likely to undergo biopsy. Most biopsies were prompted by patient/physician desire (64.5%, P < .001). Of 783 lesions with available endpoint, 5 (0.6%) were cancer. All cancers were identified either at presentation (in 0-5 months, n = 1) or 6-month follow-up (in 5-9 months, n = 4) with biopsy prompted by either morphology change (n = 3) or lesion growth (n = 2). Of the 1855 lesions which were expected for follow up, only 310 (16.7%) underwent all follow-ups, while 482 (26.1%) had two, 489 (26.5%) one, and 565 (30.6%) had no follow-up. CONCLUSIONS: In our cohort, BI-RADS category 3 lesions had significantly higher biopsy rates compared with the small malignancy rate, all of which were identified at baseline or first follow-up. Overall patient follow-up compliance low. Imaging follow-up, especially at first 6-month time point, should be encouraged in BI-RADS 3 lesions, instead of upfront biopsies.

Diagnostic Evaluation of Recalled Noncalcified Lesions Using Ultrasound Alone Versus Ultrasound Plus Additional Mammographic Views: A Prospective Study.

BACKGROUND. The diagnostic performance of digital breast tomosynthesis (DBT) has been shown to be equal to that of diagnostic mammography. However, the value of additional mammographic views in diagnostic evaluations remains unclear. OBJECTIVE. The purpose of this study was to compare the performance of diagnostic breast ultrasound (US) alone with that of combined US and diagnostic mammography for specific noncalcified recalled abnormalities detected on screening DBT. METHODS. This was a prospective study with a single-arm management strategy. Women recalled for noncalcified lesions on screening DBT underwent initial diagnostic US as part of the study protocol. Additional diagnostic mammography was performed at the discretion of the radiologist. Imaging assessment decisions determined by BI-RADS assessments and management recommendations, biopsy outcomes, and follow-up were recorded using case report forms completed on the day of the diagnostic evaluation and stored in the electronic medical record. RESULTS. From July 10, 2017, to June 6, 2019, a total of 430 recalled noncalcified lesions in 399 women (mean age, 60 ± 12 [SD] years) were included. US alone was performed for 71.2% (306/430) of lesions, whereas US with diagnostic mammography was performed for 28.8% (124/430). Of the recalled lesions, 93.7% (178/190) of masses, 60.0% (51/85) of focal asymmetries, 46.1% (53/115) of asymmetries, 69.2% (9/13) of developing asymmetries, and 55.6% (15/27) of architectural distortions were evaluated with US alone. Of 93 lesions that underwent needle biopsy, 40.9% (38/93) were cancers, all of which were invasive. Thirty-five of 38 (92.1%) cancers were evaluated by US alone, whereas three (7.9%) were evaluated with US and diagnostic mammography. At a median follow-up of 25 months, six cancers were identified (three with US alone and three with US plus diagnostic mammography) in patients with initially benign workup. US alone had two false-negative cancers (one architectural distortion identified at follow-up and one mass biopsied stereotactically at initial detection). CONCLUSION. US alone is effective in the diagnostic evaluation of noncalcified masses recalled on screening tomosynthesis. For asymmetries, diagnostic mammography may be best without the need for additional US, whereas architectural distortions still warrant diagnostic mammography and US. CLINICAL IMPACT. Radiologists should consider performing US first for DBT-recalled noncalcified masses. Omitting diagnostic mammography when US is negative has a low false-negative rate.

Different scaling and root planing strategies in Turkish patients with aggressive periodontitis: A randomized controlled clinical trial.

OBJECTIVES: The aim of this study was to compare clinical, cytokine and microbiological responses after quadrant-based scaling and root planing (Q-SRP), full-mouth SRP (FM-SRP) and full-mouth disinfection (FMD) in patients with generalized aggressive periodontitis (GAgP), which is currently termed as generalized stage-III and grade-C periodontitis. METHODS: Forty-two patients with GAgP were randomly assigned into groups as Q-SRP, FM-SRP or FMD with chlorhexidine. Clinical parameters were recorded, and gingival crevicular fluid (GCF) and subgingival plaque samples were collected at baseline, 3 and 6 months after treatment. GCF levels of interleukin (IL)-1ß and IL-17 were analysed using ELISA. Quantities of six bacterial species were determined using qPCR. RESULTS: Clinical parameters improved significantly in all groups at 3 and 6 months (p < 0.05). Percentage of sites with probing depth >6 mm was lower in the FMD than Q-SRP group at 3 and 6 months (p < 0.05). FMD showed significantly higher percentage of pocket closure compared with Q-SRP and FM-SRP at both 3 and 6 months after treatment (p < 0.05). The IL-1ß levels decreased only in the FMD group (p < 0.05), whereas no changes were found in IL-17 levels in any group. The levels of five out of six bacterial species decreased at 3 and/or 6 months only in the FMD group (p < 0.05). CONCLUSIONS: The FMD treatment appears to offer superior outcome than Q-SRP and could be the first choice for patients with GAgP.

New horizons in imaging and surgical assessment of breast cancer lymph node metastasis.

Axillary nodal status is one of the most important prognostic factors in breast cancer. While sentinel lymph node biopsy (SLNB) is a safe and validated procedure for clinically node-negative patients, axillary management of clinically node-positive patients has been more controversial. Patients with clinically detected axillary metastases often benefit from neoadjuvant chemotherapy (NAC). Those who convert to node-negative disease following NAC are important to identify, since they can often be spared significant morbidity from axillary dissection. SLNB has shown widely varying false-negative rates (FNR) but with the use of dual mapping and surgical biopsy of 3 or more nodes, it is considered an acceptable method to stage the axilla in clinically node-positive patients who receive NAC. Various methods including targeted axillary dissection (TAD) have been shown to decrease the FNR of SLNB. We will review appropriate methods to identify a metastatic node and subsequent ultrasound-guided biopsy with tissue marking techniques. We underscore key points in monitoring axillary response, techniques to accurately localize the biopsied and clipped known metastatic node for surgical excision and the effect of various methods in reducing the FNR of SLNB, including the emerging concept of TAD on patient care.

Performance of a clinical and imaging-based multivariate model as decision support tool to help save unnecessary surgeries for high-risk breast lesions.

PURPOSE: To investigate the performance of an imaging and biopsy parameters-based multivariate model in decreasing unnecessary surgeries for high-risk breast lesions. METHODS: In an IRB-approved study, we retrospectively reviewed all high-risk lesions (HRL) identified at imaging-guided biopsy in our institution between July 1, 2014-July 1, 2017. Lesions were categorized high-risk-I (HR-I = atypical ductal hyperplasia, atypical lobular hyperplasia, lobular carcinoma in situ and atypical papillary lesion) and II (HR-II = Flat epithelial atypia, radial scar, benign papilloma). Patient risk factors, lesion features, detection and biopsy modality, excision and cancer upgrade rates were collected. Reference standard for upgrade was either excision or at least 2-year imaging follow-up. Multiple logistic regression analysis was performed to develop a multivariate model using HRL type, lesion and biopsy needle size for surgical cancer upgrade with performance assessed using ROC analysis. RESULTS: Of 699 HRL in 652 patients, 525(75%) had reference standard available, and 48/525(9.1%) showed cancer at surgical excision. Excision (84.5% vs 51.1%) and upgrade (17.6%vs1.8%) rates were higher in HR-I compared to HR-II (p < 0.01). In HR-I, small needle size < 12G vs ≥ 12G [32.1% vs 13.2%, p < 0.01] and less cores [< 6 vs ≥ 6, 28.6%vs13.7%, p = 0.01] were significantly associated with higher cancer upgrades. Our multivariate model had an AUC = 0.87, saving 28.1% of benign surgeries with 100% sensitivity, based on HRL subtype, lesion size(mm, continuous), needle size (< 12G vs ≥ 12G) and biopsy modality (US vs MRI vs stereotactic) CONCLUSION: Our multivariate model using lesion size, needle size and patient age had a high diagnostic performance in decreasing unnecessary surgeries and shows promise as a decision support tool.

Mean Apparent Diffusion Coefficient Is a Sufficient Conventional Diffusion-weighted MRI Metric to Improve Breast MRI Diagnostic Performance: Results from the ECOG-ACRIN Cancer Research Group A6702 Diffusion Imaging Trial.

Background The Eastern Cooperative Oncology Group and American College of Radiology Imaging Network Cancer Research Group A6702 multicenter trial helped confirm the potential of diffusion-weighted MRI for improving differential diagnosis of suspicious breast abnormalities and reducing unnecessary biopsies. A prespecified secondary objective was to explore the relative value of different approaches for quantitative assessment of lesions at diffusion-weighted MRI. Purpose To determine whether alternate calculations of apparent diffusion coefficient (ADC) can help further improve diagnostic performance versus mean ADC values alone for analysis of suspicious breast lesions at MRI. Materials and Methods This prospective trial (ClinicalTrials.gov identifier: NCT02022579) enrolled consecutive women (from March 2014 to April 2015) with a Breast Imaging Reporting and Data System category of 3, 4, or 5 at breast MRI. All study participants underwent standardized diffusion-weighted MRI (b = 0, 100, 600, and 800 sec/mm2). Centralized ADC measures were performed, including manually drawn whole-lesion and hotspot regions of interest, histogram metrics, normalized ADC, and variable b-value combinations. Diagnostic performance was estimated by using the area under the receiver operating characteristic curve (AUC). Reduction in biopsy rate (maintaining 100% sensitivity) was estimated according to thresholds for each ADC metric. Results Among 107 enrolled women, 81 lesions with outcomes (28 malignant and 53 benign) in 67 women (median age, 49 years; interquartile range, 41-60 years) were analyzed. Among ADC metrics tested, none improved diagnostic performance versus standard mean ADC (AUC, 0.59-0.79 vs AUC, 0.75; P = .02-.84), and maximum ADC had worse performance (AUC, 0.52; P < .001). The 25th-percentile ADC metric provided the best performance (AUC, 0.79; 95% CI: 0.70, 0.88), and a threshold using median ADC provided the greatest reduction in biopsy rate of 23.9% (95% CI: 14.8, 32.9; 16 of 67 BI-RADS category 4 and 5 lesions). Nonzero minimum b value (100, 600, and 800 sec/mm2) did not improve the AUC (0.74; P = .28), and several combinations of two b values (0 and 600, 100 and 600, 0 and 800, and 100 and 800 sec/mm2; AUC, 0.73-0.76) provided results similar to those seen with calculations of four b values (AUC, 0.75; P = .17-.87). Conclusion Mean apparent diffusion coefficient calculated with a two-b-value acquisition is a simple and sufficient diffusion-weighted MRI metric to augment diagnostic performance of breast MRI compared with more complex approaches to apparent diffusion coefficient measurement. © RSNA, 2020 Online supplemental material is available for this article.

Deep learning in breast radiology: current progress and future directions.

This review provides an overview of current applications of deep learning methods within breast radiology. The diagnostic capabilities of deep learning in breast radiology continue to improve, giving rise to the prospect that these methods may be integrated not only into detection and classification of breast lesions, but also into areas such as risk estimation and prediction of tumor responses to therapy. Remaining challenges include limited availability of high-quality data with expert annotations and ground truth determinations, the need for further validation of initial results, and unresolved medicolegal considerations. KEY POINTS: • Deep learning (DL) continues to push the boundaries of what can be accomplished by artificial intelligence (AI) in breast imaging with distinct advantages over conventional computer-aided detection. • DL-based AI has the potential to augment the capabilities of breast radiologists by improving diagnostic accuracy, increasing efficiency, and supporting clinical decision-making through prediction of prognosis and therapeutic response. • Remaining challenges to DL implementation include a paucity of prospective data on DL utilization and yet unresolved medicolegal questions regarding increasing AI utilization.

ACR BI-RADS Category 3 Lesions in Women Younger Than 30: Follow-up Outcomes and Factors Associated With Biopsy.

OBJECTIVE: Investigate imaging follow-up patterns and assessment of malignancy rate of BI-RADS 3 lesions in women younger than 30 years. METHODS: We retrospectively reviewed consecutive studies between January 1, 2013 and January 1, 2015 with BI-RADS 3 assessment in women <30 years. Lesion size, follow-up rate, and biopsy rate were recorded. Completion of 24-month imaging follow-up or biopsy determined the endpoint. Statistical analysis of follow-up rates and biopsy timing was performed. RESULTS: Of 2525 BI-RADS 3 lesions, 278 were identified in 215 women <30 years. Fifty-two (24%) women underwent a biopsy which was more frequently done at patient request than for lesion growth [33 (63.4%) versus 19 (36.5%), P <.01]. The odds of having biopsy upfront was significantly higher in lesions >2 cm in diameter (OR: 4.4 [95% CI 2.1-9.4], P <.01). The malignancy rate in our cohort was 0% (95% CI 0-1.7%). Of the 188 women expected for follow-up imaging, 58 (30%) were lost to follow-up, while 103 (55%) had 6-month follow-up, 74 (39%) 12-month follow-up, and 56 (30%) 24-month follow-up. CONCLUSIONS: BI-RADS 3 lesions identified in our cohort had high biopsy rates and low compliance with no cancers. Our findings suggest that probable fibroadenomas in young women may only warrant abbreviated short-term follow-up at 6-months.

Salivary and serum markers of angiogenesis in periodontitis in relation to smoking.

OBJECTIVE: Angiogenesis is essential in maintenance of periodontal homeostasis, and it is regulated by growth factors and cytokines, including basic fibroblast growth factor (b-FGF), endoglin, platelet and endothelial cell adhesion molecule (PECAM-1), vascular endothelial growth factor (VEGF), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1). In this study, the salivary and serum concentrations of these angiogenesis-related proteins in relation to smoking and periodontitis were examined. MATERIAL AND METHODS: Full-mouth periodontal status together with unstimulated whole saliva and serum samples was collected from 78 individuals, including 40 periodontitis patients (20 smokers and 20 nonsmokers) and 38 periodontally healthy controls (20 smokers and 18 nonsmokers). The Luminex®-xMAP™ technique was used for protein analyses. RESULTS: Concentrations of all tested proteins in saliva as well as VEGF in serum were significantly higher in periodontitis patients than in healthy controls. In smokers, serum concentrations of endoglin (p = 0.017) and sICAM-1 (p = 0.001) were elevated in comparison to nonsmokers. After adjusting for smoking and gender, periodontitis associated significantly with salivary concentrations of b-FGF, PECAM-1, VEGF, sICAM-1, and sVCAM-1 (p < 0.01). CONCLUSION: Taken together, salivary concentrations of b-FGF, PECAM-1, and VEGF associate with periodontitis. The suppressive effect of smoking on salivary marker levels is limited to periodontitis patients only. CLINICAL RELEVANCE: Smoking-related suppression of salivary marker levels is observed only in periodontitis patients.

Contrast-Enhanced Digital Mammography: Technique, Clinical Applications, and Pitfalls.

OBJECTIVE. Contrast-enhanced digital mammography (CEDM) combines the high spatial resolution of mammography with the improved enhancement provided by contrast medium. In this article, CEDM technique-the current and potential clinical applications and current challenges-will be reviewed. CONCLUSION. CEDM is a promising technique in the supplemental evaluation of patients with mammographically inconclusive findings and potentially in the screening of women with mammographically dense breasts. CEDM is emerging as a cost-effective alternative to dynamic contrast-enhanced MRI to stage newly diagnosed breast cancer and evaluate response to neoadjuvant chemotherapy.

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.

Test-retest repeatability and reproducibility of ADC measures by breast DWI: Results from the ACRIN 6698 trial.

BACKGROUND: Quantitative diffusion-weighted imaging (DWI) MRI is a promising technique for cancer characterization and treatment monitoring. Knowledge of the reproducibility of DWI metrics in breast tumors is necessary to apply DWI as a clinical biomarker. PURPOSE: To evaluate the repeatability and reproducibility of breast tumor apparent diffusion coefficient (ADC) in a multi-institution clinical trial setting, using standardized DWI protocols and quality assurance (QA) procedures. STUDY TYPE: Prospective. SUBJECTS: In all, 89 women from nine institutions undergoing neoadjuvant chemotherapy for invasive breast cancer. FIELD STRENGTH/SEQUENCE: DWI was acquired before and after patient repositioning using a four b-value, single-shot echo-planar sequence at 1.5T or 3.0T. ASSESSMENT: A QA procedure by trained operators assessed artifacts, fat suppression, and signal-to-noise ratio, and determine study analyzability. Mean tumor ADC was measured via manual segmentation of the multislice tumor region referencing DWI and contrast-enhanced images. Twenty cases were evaluated multiple times to assess intra- and interoperator variability. Segmentation similarity was assessed via the Sørenson-Dice similarity coefficient. STATISTICAL TESTS: Repeatability and reproducibility were evaluated using within-subject coefficient of variation (wCV), intraclass correlation coefficient (ICC), agreement index (AI), and repeatability coefficient (RC). Correlations were measured by Pearson's correlation coefficients. RESULTS: In all, 71 cases (80%) passed QA evaluation: 44 at 1.5T, 27 at 3.0T; 60 pretreatment, 11 after 3 weeks of taxane-based treatment. ADC repeatability was excellent: wCV = 4.8% (95% confidence interval [CI] 4.0, 5.7%), ICC = 0.97 (95% CI 0.95, 0.98), AI = 0.83 (95% CI 0.76, 0.87), and RC = 0.16 * 10-3 mm2 /sec (95% CI 0.13, 0.19). The results were similar across field strengths and timepoint subgroups. Reproducibility was excellent: interreader ICC = 0.92 (95% CI 0.80, 0.97) and intrareader ICC = 0.91 (95% CI 0.78, 0.96). DATA CONCLUSION: Breast tumor ADC can be measured with excellent repeatability and reproducibility in a multi-institution setting using a standardized protocol and QA procedure. Improvements to DWI image quality could reduce loss of data in clinical trials. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1617-1628.

Diffusion-weighted MR imaging increases diagnostic accuracy of breast MR imaging for predicting axillary metastases in breast cancer patients.

PURPOSE: To evaluate the incremental value of diffusion-weighted imaging (DWI) to conventional MR imaging (CMRI) to predict ipsilateral metastatic axillary lymphadenopathy in patients with newly diagnosed breast cancer. SUBJECTS AND METHODS: In an IRB approved retrospective single-institution study, newly diagnosed consecutive breast cancer patients with pathological verification of axillary lymph node (LN) status who had undergone breast MR imaging, including DWI as part of their standard MRI between August 1, 2010, and December 31, 2010, were reviewed. Lesion size, tumor grade, and tissue prognostic factors were noted. Ipsilateral axillary LNs were evaluated using morphological criteria on CMRI. Apparent diffusion coefficient (ADC) values of suspicious ipsilateral LNs were obtained and compared with ADC values of contralateral benign axillary LNs. Receiver operating characteristic curves and multivariate logistic regression analyses were used using pathology as the gold standard. RESULTS: Eighty-five eligible patients were identified, with surgical pathology revealing 34 patients (40%) who had malignant and 51 (60%) had benign ipsilateral axillae. The sensitivity of CMRI was 79%, with a specificity of 81%, a positive predictive value (PPV) of 65%, and a negative predictive value (NPV) of 89%. On DWI, the mean ADC value was significantly lower for metastatic LNs (0.89 ± 0.18 × 10-3  mm2 /s) than for benign ipsilateral LNs (1.41 ± 0.21 × 10-3  mm2 /s; P < 0.0001). Using a cutoff ADC value of 0.985 × 10-3  mm2 /s, yielded improved sensitivity, specificity, PPV, and NPV of 83%, 98%, 95%, and 93%, respectively. CONCLUSION: Apparent diffusion coefficient values increase the specificity of CMRI for predicting ipsilateral axillary LN metastases in patients with newly diagnosed breast cancer.

Supplemental ultrasound screening in patients with a history of lobular neoplasia.

To investigate the role of ultrasound (US) screening as an adjunct to annual mammography (M) in breast cancer detection in women with a history of lobular neoplasia (LN) diagnosed following core needle or excisional biopsy. A retrospective review of our database was performed between 11/2006 and 11/2011 to identify patients diagnosed with LN, and underwent annual screening. Patients with a lifetime risk >20% per risk modeling were excluded. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and cancer detection rate (CDR) of each screening test were identified. Cancer type and detection modality were recorded. A total of 100 patients who had M and/or US screening were included. Mean patient age was 54.7 years (range 33-83). All 100 patients underwent a mean of 3.9 rounds of screening M and 93 (93%) received US screening (mean 3.3 rounds). Of 93 patients who received both M and US screening, 12 (13%) were diagnosed with breast cancer. Mammographic CDR was 4%. Incremental US CDR was 6.5%. The sensitivity, specificity, and NPV for M screening alone was 33% (10%, 65%), 77% (67%, 85%), and 89% (80%, 95%), respectively. US and mammography screening had a combined sensitivity: 83% (52%, 98%), Specificity: 72% (62%, 81%), NPV: 97% (89%, 100%). Supplemental US screening resulted in a significant increase in sensitivity, yielding 6.5% incremental CDR in this high-risk patient subgroup that does not fulfill ACS high-risk MRI screening criteria.