Comparison of Mammography and Mammography with Supplemental Whole-Breast US Tomography for Cancer Detection in Patients with Dense Breasts.

BACKGROUND: Women with dense breasts benefit from supplemental cancer screening with US, but US has low specificity. PURPOSE: To evaluate the performance of breast US tomography (UST) combined with full-field digital mammography (FFDM) compared with FFDM alone for breast cancer screening in women with dense breasts. MATERIALS AND METHODS: This retrospective multireader multicase study included women with dense breasts who underwent FFDM and UST at 10 centers between August 2017 and October 2019 as part of a prospective case collection registry. All patients in the registry with cancer were included; patients with benign biopsy or negative follow-up imaging findings were randomly selected for inclusion. Thirty-two Mammography Quality Standards Act-qualified radiologists independently evaluated FFDM followed immediately by FFDM plus UST for suspicious findings and assigned a Breast Imaging Reporting and Data System (BI-RADS) category. The superiority of FFDM plus UST versus FFDM alone for cancer detection (assessed with area under the receiver operating characteristic curve [AUC]), BI-RADS 4 sensitivity, and BI-RADS 3 sensitivity and specificity were evaluated using the two-sided significance level of α = .05. Noninferiority of BI-RADS 4 specificity was evaluated at the one-sided significance level of α = .025 with a -10% margin. RESULTS: Among 140 women (mean age, 56 years ±10 [SD]; 36 with cancer, 104 without), FFDM plus UST achieved superior performance compared with FFDM alone (AUC, 0.60 [95% CI: 0.51, 0.69] vs 0.54 [95% CI: 0.45, 0.64]; P = .03). For FFDM plus UST versus FFDM alone, BI-RADS 4 mean sensitivity was superior (37% [428 of 1152] vs 30% [343 of 1152]; P = .03) and BI-RADS 4 mean specificity was noninferior (82% [2741 of 3328] vs 88% [2916 of 3328]; P = .004). For FFDM plus UST versus FFDM, no difference in BI-RADS 3 mean sensitivity was observed (40% [461 of 1152] vs 33% [385 of 1152]; P = .08), but BI-RADS 3 mean specificity was superior (75% [2491 of 3328] vs 69% [2299 of 3328]; P = .04). CONCLUSION: In women with dense breasts, FFDM plus UST improved cancer detection by radiologists versus FFDM alone. Clinical trial registration nos. NCT03257839 and NCT04260620 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Mann in this issue.

Computerized assessment of background parenchymal enhancement on breast dynamic contrast-enhanced-MRI including electronic lesion removal.

Purpose: Current clinical assessment qualitatively describes background parenchymal enhancement (BPE) as minimal, mild, moderate, or marked based on the visually perceived volume and intensity of enhancement in normal fibroglandular breast tissue in dynamic contrast-enhanced (DCE)-MRI. Tumor enhancement may be included within the visual assessment of BPE, thus inflating BPE estimation due to angiogenesis within the tumor. Using a dataset of 426 MRIs, we developed an automated method to segment breasts, electronically remove lesions, and calculate scores to estimate BPE levels. Approach: A U-Net was trained for breast segmentation from DCE-MRI maximum intensity projection (MIP) images. Fuzzy c-means clustering was used to segment lesions; the lesion volume was removed prior to creating projections. U-Net outputs were applied to create projection images of both, affected, and unaffected breasts before and after lesion removal. BPE scores were calculated from various projection images, including MIPs or average intensity projections of first- or second postcontrast subtraction MRIs, to evaluate the effect of varying image parameters on automatic BPE assessment. Receiver operating characteristic analysis was performed to determine the predictive value of computed scores in BPE level classification tasks relative to radiologist ratings. Results: Statistically significant trends were found between radiologist BPE ratings and calculated BPE scores for all breast regions (Kendall correlation, p<0.001). Scores from all breast regions performed significantly better than guessing (p<0.025 from the z-test). Results failed to show a statistically significant difference in performance with and without lesion removal. BPE scores of the affected breast in the second postcontrast subtraction MIP after lesion removal performed statistically greater than random guessing across various viewing projections and DCE time points. Conclusions: Results demonstrate the potential for automatic BPE scoring to serve as a quantitative value for objective BPE level classification from breast DCE-MR without the influence of lesion enhancement.

Impact of continuous learning on diagnostic breast MRI AI: evaluation on an independent clinical dataset.

Purpose: We demonstrate continuous learning and assess its impact on the performance of artificial intelligence of breast dynamic contrast-enhanced magnetic resonance imaging in the task of distinguishing malignant from benign lesions on an independent clinical test dataset. Approach: The study included 1979 patients with 1990 lesions who underwent breast MR imaging during 2015, 2016, and 2017, retrospectively collected under an IRB-approved protocol; there were 1494 malignant and 496 benign lesions based on histopathology. AI was conducted in the task of distinguishing malignant and benign lesions, and independent testing was performed to assess the effect of increasing the numbers of training cases. Five training sets mimicking clinical implementation of continuous AI learning included cases from (1) first quarter of 2015, (2) first half of 2015, (3) all 2015, (4) all 2015 and first half of 2016, and (5) all 2015 and 2016. All classifiers were evaluated on the 2017 independent test set. The area under the ROC curve (AUC) served as the performance metric and was calculated over all lesions in the test set, as well as only mass lesions and only non-mass enhancements. The Mann-Kendall test was used to determine if continuous learning resulted in a positive trend in classification performance. P < 0.05 was considered to be statistically significant. Results: Over the continuous training period, the selected feature subsets tended to become more similar and stable. Performance of the five training conditions on the independent test dataset yielded AUCs of 0.86 (95% CI: [0.83,0.90]), 0.87 (95% CI: [0.83,0.90]), 0.88 (95% CI: [0.84,0.91]), 0.89 (95% CI: [0.85,0.92]), and 0.89 (95% CI: [0.86,0.92]). The Mann-Kendall test indicated a statistically significant positive trend ( P = 0.0167 ) in classification performance with continuous learning. Conclusions: Improved diagnostic performance over time was observed when continuous learning of AI was implemented on an independent clinical test dataset.

Robustness of radiomic features of benign breast lesions and hormone receptor positive/HER2-negative cancers across DCE-MR magnet strengths.

Radiomic features extracted from breast lesion images have shown potential in diagnosis and prognosis of breast cancer. As medical centers transition from 1.5 T to 3.0 T magnetic resonance (MR) imaging, it is beneficial to identify potentially robust radiomic features across field strengths because images acquired at different field strengths could be used in machine learning models. Dynamic contrast-enhanced MR images of benign breast lesions and hormone receptor positive/HER2-negative (HR+/HER2-) breast cancers were acquired retrospectively, yielding 612 unique cases: 150 and 99 benign lesions imaged at 1.5 T and 3.0 T, and 223 and 140 HR+/HER2- cancerous lesions imaged at 1.5 T and 3.0 T, respectively. In addition, an independent set of seven lesions imaged at both field strengths, three benign lesions and four HR+/HER2- cancers, was analyzed separately. Lesions were automatically segmented using a 4D fuzzy c-means method; thirty-eight radiomic features were extracted. Feature value distributions were compared by cancer status and imaging field strength using the Kolmogorov-Smirnov test. Features that did not demonstrate a statistically significant difference were considered to be potentially robust. The area under the receiver operating characteristic curve (AUC), for the task of classifying lesions as benign or HR+/HER2- cancer, was determined for each feature at each field strength. Three features were found to be both potentially robust across field strength and of high classification performance, i.e., AUCs statistically greater than 0.5 in the classification task: one shape feature (irregularity), one texture feature (sum average) and one enhancement variance kinetics features (enhancement variance increasing rate). In the demonstration set of lesions imaged at both field strengths, two of the three potentially robust features showed qualitative agreement across field strength. These findings may contribute to the development of computer-aided diagnosis models that are robust across field strength for this classification task.

Artificial Intelligence Applied to Breast MRI for Improved Diagnosis.

Background Recognition of salient MRI morphologic and kinetic features of various malignant tumor subtypes and benign diseases, either visually or with artificial intelligence (AI), allows radiologists to improve diagnoses that may improve patient treatment. Purpose To evaluate whether the diagnostic performance of radiologists in the differentiation of cancer from noncancer at dynamic contrast material-enhanced (DCE) breast MRI is improved when using an AI system compared with conventionally available software. Materials and Methods In a retrospective clinical reader study, images from breast DCE MRI examinations were interpreted by 19 breast imaging radiologists from eight academic and 11 private practices. Readers interpreted each examination twice. In the "first read," they were provided with conventionally available computer-aided evaluation software, including kinetic maps. In the "second read," they were also provided with AI analytics through computer-aided diagnosis software. Reader diagnostic performance was evaluated with receiver operating characteristic (ROC) analysis, with the area under the ROC curve (AUC) as a figure of merit in the task of distinguishing between malignant and benign lesions. The primary study end point was the difference in AUC between the first-read and the second-read conditions. Results One hundred eleven women (mean age, 52 years ± 13 [standard deviation]) were evaluated with a total of 111 breast DCE MRI examinations (54 malignant and 57 nonmalignant lesions). The average AUC of all readers improved from 0.71 to 0.76 (P = .04) when using the AI system. The average sensitivity improved when Breast Imaging Reporting and Data System (BI-RADS) category 3 was used as the cut point (from 90% to 94%; 95% confidence interval [CI] for the change: 0.8%, 7.4%) but not when using BI-RADS category 4a (from 80% to 85%; 95% CI: -0.9%, 11%). The average specificity showed no difference when using either BI-RADS category 4a or category 3 as the cut point (52% and 52% [95% CI: -7.3%, 6.0%], and from 29% to 28% [95% CI: -6.4%, 4.3%], respectively). Conclusion Use of an artificial intelligence system improves radiologists' performance in the task of differentiating benign and malignant MRI breast lesions. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Krupinski in this issue.

Intraoperative vasopressor use during emergency surgery on injured meth users.

BACKGROUND: Methamphetamine is a growing drug of abuse in America. Patients with recent methamphetamine use pose potential complications to general anesthesia due to changes in hemodynamics and arrhythmias. Limited data exists on the incidence of intraoperative complications on methamphetamine-intoxicated patients requiring urgent or emergent trauma surgery. This study aims to describe intraoperative complications observed in methamphetamine and amphetamine-intoxicated patients requiring emergent surgery. METHODS: Using the Trauma Registry at our ACS-verified level I trauma center, we completed a single-center, descriptive, retrospective cohort review between July 1, 2012 and June 30, 2016, of adult patients requiring emergent surgery with a positive urine-drug screen for methamphetamines or amphetamines. The objective was to evaluate vasopressor utilization during surgical operation. RESULTS: A total of 92 patients were identified with a positive UDS for amphetamine and/or methamphetamine who went to the operating room within 24 hours of admission. Thirty-two (34%) patients received one or more (≥1) doses of vasopressor, while 60 patients (66%) received no vasopressor. Changes in mean arterial pressure (MAP) were noted in 64%, while only 3% experienced an EKG change. A binomial logistic regression showed age, base deficit and change in MAP to be predictive of vasopressor use (p<0.002). No intraoperative cardiac events or anesthetic complications were seen. DISCUSSION: Hemodynamic instability in the amphetamine and methamphetamine-intoxicated population may be more directly related to degree of resuscitation required, than the presence of a positive UDS. LEVEL OF EVIDENCE: IV.

Applying Ethical Principles When Discussing Alcohol Use During Pregnancy.

Over the past 2 decades, more women in the United States are engaging in excessive alcohol use, including women of reproductive age. Consuming alcohol in amounts greater than recommended limits is associated with an increased risk for adverse health effects, such as breast cancer, hypertension stroke, spontaneous abortion, and infertility. No safe time, safe amount, or safe type of alcohol to consume during pregnancy has been identified. Contradictory beliefs about alcohol use, fear of stigmatization, and potential legal consequences can provide challenges for health care providers who communicate these risks to clients. Health care providers can help to prevent alcohol-related health issues, including alcohol-exposed pregnancies, by providing their clients with factual information about alcohol and health and client-centered options for reducing their health risks. Clinicians can use alcohol screening and brief intervention as a framework for applying the ethical principles of autonomy, veracity, beneficence, and nonmaleficence when talking with women in ways that are nonstigmatizing and supportive to help reduce their health risks and prevent alcohol-exposed pregnancies.

Breast MRI radiomics for the pretreatment prediction of response to neoadjuvant chemotherapy in node-positive breast cancer patients.

The purpose of this study was to evaluate breast MRI radiomics in predicting, prior to any treatment, the response to neoadjuvant chemotherapy (NAC) in patients with invasive lymph node (LN)-positive breast cancer for two tasks: (1) prediction of pathologic complete response and (2) prediction of post-NAC LN status. Our study included 158 patients, with 19 showing post-NAC complete pathologic response (pathologic TNM stage T0,N0,MX) and 139 showing incomplete response. Forty-two patients were post-NAC LN-negative, and 116 were post-NAC LN-positive. We further analyzed prediction of response by hormone receptor subtype of the primary cancer (77 hormone receptor-positive, 39 HER2-enriched, 38 triple negative, and 4 cancers with unknown receptor status). Only pre-NAC MRIs underwent computer analysis, initialized by an expert breast radiologist indicating index cancers and metastatic axillary sentinel LNs on DCE-MRI images. Forty-nine computer-extracted radiomics features were obtained, both for the primary cancers and for the metastatic sentinel LNs. Since the dataset contained MRIs acquired at 1.5 T and at 3.0 T, we eliminated features affected by magnet strength using the Mann-Whitney U-test with the null-hypothesis that 1.5 T and 3.0 T samples were selected from populations having the same distribution. Bootstrapping and ROC analysis were used to assess performance of individual features in the two classification tasks. Eighteen features appeared unaffected by magnet strength. Pre-NAC tumor features generally appeared uninformative in predicting response to therapy. In contrast, some pre-NAC LN features were able to predict response: two pre-NAC LN features were able to predict pathologic complete response (area under the ROC curve (AUC) up to 0.82 [0.70; 0.88]), and another two were able to predict post-NAC LN-status (AUC up to 0.72 [0.62; 0.77]), respectively. In the analysis by a hormone receptor subtype, several potentially useful features were identified for predicting response to therapy in the hormone receptor-positive and HER2-enriched cancers.

Independent validation of machine learning in diagnosing breast Cancer on magnetic resonance imaging within a single institution.

BACKGROUND: As artificial intelligence methods for the diagnosis of disease advance, we aimed to evaluate machine learning in the predictive task of distinguishing between malignant and benign breast lesions on an independent clinical magnetic resonance imaging (MRI) dataset within a single institution for subsequent use as a computer aid for radiologists. METHODS: Computer analysis was conducted on consecutive dynamic contrast-enhanced MRI (DCE-MRI) studies from 1483 breast cancer and 496 benign patients who underwent MRI examinations between February 2015 and October 2017; with the age ranges of the cancer and benign patients being 19 to 77 and 16 to 76 years old, respectively. Cases were separated into a training dataset (years 2015 & 2016; 1444 cases) and an independent testing dataset (year 2017; 535 cases) based solely on MRI examination date. After radiologist indication of the lesion, the computer automatically segmented and extracted radiomic features, which were subsequently merged with a support-vector machine (SVM) to yield a lesion signature. Area under the receiving operating characteristic (ROC) curve (AUC) with 95% confidence intervals (CI) served as the primary figure of merit in the statistical evaluation for this clinical classification task. RESULTS: In the task of distinguishing malignant and benign breast lesions DCE-MRI, the trained predictive model yielded an AUC value of 0.89 (95% CI: 0.858, 0.922) on the independent image set. AUC values of 0.88 (95% CI: 0.845, 0.926) and 0.90 (95% CI: 0.837, 0.940) were obtained for mass lesions only and non-mass lesions only, respectively. Compared with actual clinical management decisions, the predictive model achieved 99.5% sensitivity with 9.6% fewer recommended biopsies. CONCLUSION: On an independent, consecutive clinical dataset within a single institution, a trained machine learning system yielded promising performance in distinguishing between malignant and benign breast lesions.

Radiogenomics of breast cancer using dynamic contrast enhanced MRI and gene expression profiling.

BACKGROUND: Imaging techniques can provide information about the tumor non-invasively and have been shown to provide information about the underlying genetic makeup. Correlating image-based phenotypes (radiomics) with genomic analyses is an emerging area of research commonly referred to as "radiogenomics" or "imaging-genomics". The purpose of this study was to assess the potential for using an automated, quantitative radiomics platform on magnetic resonance (MR) breast imaging for inferring underlying activity of clinically relevant gene pathways derived from RNA sequencing of invasive breast cancers prior to therapy. METHODS: We performed quantitative radiomic analysis on 47 invasive breast cancers based on dynamic contrast enhanced 3 Tesla MR images acquired before surgery and obtained gene expression data by performing total RNA sequencing on corresponding fresh frozen tissue samples. We used gene set enrichment analysis to identify significant associations between the 186 gene pathways and the 38 image-based features that have previously been validated. RESULTS: All radiomic size features were positively associated with multiple replication and proliferation pathways and were negatively associated with the apoptosis pathway. Gene pathways related to immune system regulation and extracellular signaling had the highest number of significant radiomic feature associations, with an average of 18.9 and 16 features per pathway, respectively. Tumors with upregulation of immune signaling pathways such as T-cell receptor signaling and chemokine signaling as well as extracellular signaling pathways such as cell adhesion molecule and cytokine-cytokine interactions were smaller, more spherical, and had a more heterogeneous texture upon contrast enhancement. Tumors with higher expression levels of JAK/STAT and VEGF pathways had more intratumor heterogeneity in image enhancement texture. Other pathways with robust associations to image-based features include metabolic and catabolic pathways. CONCLUSIONS: We provide further evidence that MR imaging of breast tumors can infer underlying gene expression by using RNA sequencing. Size and shape features were appropriately correlated with proliferative and apoptotic pathways. Given the high number of radiomic feature associations with immune pathways, our results raise the possibility of using MR imaging to distinguish tumors that are more immunologically active, although further studies are necessary to confirm this observation.

Evaluation of pharmacist-led physician-supported inpatient deprescribing model in older patients admitted to an acute general medical unit.

OBJECTIVE: To evaluate the need for and the feasibility of a pharmacist-led physician-supported deprescribing model. METHODS: All patients aged ≥65 years, with polypharmacy, admitted to the acute general medical unit (GMU) of an Australian tertiary hospital over a 6-week period were prospectively evaluated for deprescribing by team pharmacists. Clinical decision-making was supported by physicians. RESULTS: One hundred and twenty-nine patients met inclusion criteria, and 58 (45%) were identified for deprescribing. Ninety-two (7.2%) deprescribing instances were identified of 1277 medications prescribed. Of these, 46 (50%) were successfully deprescribed during inpatient admission in 35 (60%) patients. The most prevalent rationale for deprescribing was "harm outweighing benefits." Outpatient deprescribing was planned in 16 (17%) of instances, and 39 (42%) would require outpatient follow-up to ensure adherence to recommendations and safety. No predictors for deprescribing were identified on univariate analyses. CONCLUSIONS: A pharmacist-led physician-supported deprescribing model is feasible in GMU patients who have polypharmacy.

Additive Benefit of Radiomics Over Size Alone in the Distinction Between Benign Lesions and Luminal A Cancers on a Large Clinical Breast MRI Dataset.

RATIONALE AND OBJECTIVES: The objective of this study was to demonstrate improvement in distinguishing between benign lesions and luminal A breast cancers in a large clinical breast magnetic resonance imaging database by using quantitative radiomics over maximum linear size alone. MATERIALS AND METHODS: In this retrospective study, 264 benign lesions and 390 luminal A breast cancers were automatically segmented from dynamic contrast-enhanced breast magnetic resonance images. Thirty-eight radiomic features were extracted. Tenfold cross validation was performed to assess the ability to distinguish between lesions and cancers using maximum linear size alone and lesion signatures obtained with stepwise feature selection and a linear discriminant analysis classifier including and excluding size features. Area under the receiver operating characteristic curve (AUC) was used as the figure of merit. RESULTS: For maximum linear size alone, AUC and 95% confidence interval was 0.684 (0.642, 0.724) compared to 0.728 (0.687, 0.766) (P = 0.005) and 0.729 (0.689, 0.767) (P = 0.005) for lesion signature feature selection protocols including and excluding size features, respectively. The features of irregularity and entropy were chosen in all folds when size features were included and excluded. AUC for the radiomic signature using feature selection from all features was statistically equivalent to using feature selection from all features excluding size features, within an equivalence margin of 2%. CONCLUSIONS: Inclusion of multiple radiomic features, automatically extracted from magnetic resonance images, in a lesion signature significantly improved the ability to distinguish between benign lesions and luminal A breast cancers, compared to using maximum linear size alone. The radiomic features of irregularity and entropy appear to play an important but not a solitary role within the context of feature selection and computer-aided diagnosis.

Effect of biopsy on the MRI radiomics classification of benign lesions and luminal A cancers.

Radiomic features extracted from magnetic resonance (MR) images have potential for diagnosis and prognosis of breast cancer. However, presentation of lesions on images may be affected by biopsy. Thirty-four nonsize features were extracted from 338 dynamic contrast-enhanced MR images of benign lesions and luminal A cancers (80 benign/34 luminal A prebiopsy; 46 benign/178 luminal A postbiopsy). Feature value distributions were compared by biopsy condition using the Kolmogorov-Smirnov test. Classification performance was assessed by biopsy condition in the task of distinguishing between lesion types using the area under the receiver operating characteristic curve (AUCROC) as performance metric. Superiority and equivalence testing of differences in AUCROC between biopsy conditions were conducted using Bonferroni-Holm-adjusted significance levels. Distributions for most nonsize features for each lesion type failed to show a statistically significant difference between biopsy conditions. Fourteen features outperformed random guessing in classification. Their differences in AUCROC by biopsy condition failed to reach statistical significance, but we were unable to prove equivalence using a margin of Δ AUCROC = ± 0.10 . However, classification performance for lesions imaged either prebiopsy or postbiopsy appears to be similar when taking into account biopsy condition.

Interpretation Time Using a Concurrent-Read Computer-Aided Detection System for Automated Breast Ultrasound in Breast Cancer Screening of Women With Dense Breast Tissue.

OBJECTIVE: The purpose of this study was to compare diagnostic accuracy and interpretation time of screening automated breast ultrasound (ABUS) for women with dense breast tissue without and with use of a recently U.S. Food and Drug Administration-approved computer-aided detection (CAD) system for concurrent read. MATERIALS AND METHODS: In a retrospective observer performance study, 18 radiologists interpreted a cancer-enriched set (i.e., cancer prevalence higher than in the original screening cohort) of 185 screening ABUS studies (52 with and 133 without breast cancer). These studies were from a large cohort of ABUS-screened patients interpreted as BI-RADS density C or D. Each reader interpreted each case twice in a counterbalanced study, once without the CAD system and once with it, separated by 4 weeks. For each case, each reader identified abnormal findings and reported BI-RADS assessment category and level of suspicion for breast cancer. Interpretation time was recorded. Level of suspicion data were compared to evaluate diagnostic accuracy by means of the Dorfman-Berbaum-Metz method of jackknife with ANOVA ROC analysis. Interpretation times were compared by ANOVA. RESULTS: The ROC AUC was 0.848 with the CAD system, compared with 0.828 without it, for a difference of 0.020 (95% CI, -0.011 to 0.051) and was statistically noninferior to the AUC without the CAD system with respect to a margin of -0.05 (p = 0.000086). The mean interpretation time was 3 minutes 33 seconds per case without the CAD system and 2 minutes 24 seconds with it, for a difference of 1 minute 9 seconds saved (95% CI, 44-93 seconds; p = 0.000014), or a reduction in interpretation time to 67% of the time without the CAD system. CONCLUSION: Use of the concurrent-read CAD system for interpretation of screening ABUS studies of women with dense breast tissue who do not have symptoms is expected to make interpretation significantly faster and produce noninferior diagnostic accuracy compared with interpretation without the CAD system.

Most-enhancing tumor volume by MRI radiomics predicts recurrence-free survival "early on" in neoadjuvant treatment of breast cancer.

BACKGROUND: The hypothesis of this study was that MRI-based radiomics has the ability to predict recurrence-free survival "early on" in breast cancer neoadjuvant chemotherapy. METHODS: A subset, based on availability, of the ACRIN 6657 dynamic contrast-enhanced MR images was used in which we analyzed images of all women imaged at pre-treatment baseline (141 women: 40 with a recurrence, 101 without) and all those imaged after completion of the first cycle of chemotherapy, i.e., at early treatment (143 women: 37 with a recurrence vs. 105 without). Our method was completely automated apart from manual localization of the approximate tumor center. The most enhancing tumor volume (METV) was automatically calculated for the pre-treatment and early treatment exams. Performance of METV in the task of predicting a recurrence was evaluated using ROC analysis. The association of recurrence-free survival with METV was assessed using a Cox regression model controlling for patient age, race, and hormone receptor status and evaluated by C-statistics. Kaplan-Meier analysis was used to estimate survival functions. RESULTS: The C-statistics for the association of METV with recurrence-free survival were 0.69 with 95% confidence interval of [0.58; 0.80] at pre-treatment and 0.72 [0.60; 0.84] at early treatment. The hazard ratios calculated from Kaplan-Meier curves were 2.28 [1.08; 4.61], 3.43 [1.83; 6.75], and 4.81 [2.16; 10.72] for the lowest quartile, median quartile, and upper quartile cut-points for METV at early treatment, respectively. CONCLUSION: The performance of the automatically-calculated METV rivaled that of a semi-manual model described for the ACRIN 6657 study (published C-statistic 0.72 [0.60; 0.84]), which involved the same dataset but required semi-manual delineation of the functional tumor volume (FTV) and knowledge of the pre-surgical residual cancer burden.

Automated Breast Ultrasound in Breast Cancer Screening of Women With Dense Breasts: Reader Study of Mammography-Negative and Mammography-Positive Cancers.

OBJECTIVE: The objective of our study was to assess and compare, in a reader study, radiologists' performance in the detection of breast cancer using full-field digital mammography (FFDM) alone and using FFDM with 3D automated breast ultrasound (ABUS). MATERIALS AND METHODS: In this multireader, multicase, sequential-design reader study, 17 Mammography Quality Standards Act-qualified radiologists interpreted a cancer-enriched set of FFDM and ABUS examinations. All imaging studies were of asymptomatic women with BI-RADS C or D breast density. Readers first interpreted FFDM alone and subsequently interpreted FFDM combined with ABUS. The analysis included 185 cases: 133 noncancers and 52 biopsy-proven cancers. Of the 52 cancer cases, the screening FFDM images were interpreted as showing BI-RADS 1 or 2 findings in 31 cases and BI-RADS 0 findings in 21 cases. For the cases interpreted as BI-RADS 0, a forced BI-RADS score was also given. Reader performance was compared in terms of AUC under the ROC curve, sensitivity, and specificity. RESULTS: The AUC was 0.72 for FFDM alone and 0.82 for FFDM combined with ABUS, yielding a statistically significant 14% relative improvement in AUC (i.e., change in AUC = 0.10 [95% CI, 0.07-0.14]; p < 0.001). When a cutpoint of BI-RADS 3 was used, the sensitivity across all readers was 57.5% for FFDM alone and 74.1% for FFDM with ABUS, yielding a statistically significant increase in sensitivity (p < 0.001) (relative increase = 29%). Overall specificity was 78.1% for FFDM alone and 76.1% for FFDM with ABUS (p = 0.496). For only the mammography-negative cancers, the average AUC was 0.60 for FFDM alone and 0.75 for FFDM with ABUS, yielding a statistically significant 25% relative improvement in AUC with the addition of ABUS (p < 0.001). CONCLUSION: Combining mammography with ABUS, compared with mammography alone, significantly improved readers' detection of breast cancers in women with dense breast tissue without substantially affecting specificity.

Level set segmentation of breast masses in contrast-enhanced dedicated breast CT and evaluation of stopping criteria.

Dedicated breast CT (bCT) produces high-resolution 3D tomographic images of the breast, fully resolving fibroglandular tissue structures within the breast and allowing for breast lesion detection and assessment in 3D. In order to enable quantitative analysis, such as volumetrics, automated lesion segmentation on bCT is highly desirable. In addition, accurate output from CAD (computer-aided detection/diagnosis) methods depends on sufficient segmentation of lesions. Thus, in this study, we present a 3D lesion segmentation method for breast masses in contrast-enhanced bCT images. The segmentation algorithm follows a two-step approach. First, 3D radial-gradient index segmentation is used to obtain a crude initial contour, which is then refined by a 3D level set-based active contour algorithm. The data set included contrast-enhanced bCT images from 33 patients containing 38 masses (25 malignant, 13 benign). The mass centers served as input to the algorithm. In this study, three criteria for stopping the contour evolution were compared, based on (1) the change of region volume, (2) the average intensity in the segmented region increase at each iteration, and (3) the rate of change of the average intensity inside and outside the segmented region. Lesion segmentation was evaluated by computing the overlap ratio between computer segmentations and manually drawn lesion outlines. For each lesion, the overlap ratio was averaged across coronal, sagittal, and axial planes. The average overlap ratios for the three stopping criteria ranged from 0.66 to 0.68 (dice coefficient of 0.80 to 0.81), indicating that the proposed segmentation procedure is promising for use in quantitative dedicated bCT analyses.

Impact of lesion segmentation metrics on computer-aided diagnosis/detection in breast computed tomography.

Evaluation of segmentation algorithms usually involves comparisons of segmentations to gold-standard delineations without regard to the ultimate medical decision-making task. We compare two segmentation evaluations methods-a Dice similarity coefficient (DSC) evaluation and a diagnostic classification task-based evaluation method using lesions from breast computed tomography. In our investigation, we use results from two previously developed lesion-segmentation algorithms [a global active contour model (GAC) and a global with local aspects active contour model]. Although similar DSC values were obtained (0.80 versus 0.77), we show that the global + local active contour (GLAC) model, as compared with the GAC model, is able to yield significantly improved classification performance in terms of area under the receivers operating characteristic (ROC) curve in the task of distinguishing malignant from benign lesions. [Area under the [Formula: see text] compared to 0.63, [Formula: see text]]. This is mainly because the GLAC model yields better detailed information required in the calculation of morphological features. Based on our findings, we conclude that the DSC metric alone is not sufficient for evaluating segmentation lesions in computer-aided diagnosis tasks.

Clinically missed cancer: how effectively can radiologists use computer-aided detection?

OBJECTIVE: The purpose of this study was to determine the effectiveness with which radiologists can use computer-aided detection (CADe) to detect cancer missed at screening. MATERIALS AND METHODS: An observer study was performed to measure the ability of radiologists to detect breast cancer on mammograms with and without CADe. The images in the study were from 300 analog mammographic examinations. In 234 cases the mammograms were read clinically as normal and free of cancer for at least 2 subsequent years. In the other 66 cases, cancers were missed clinically. In 256 cases, current and previous mammograms were available. Eight radiologists read the dataset and recorded a BI-RADS assessment, the location of the lesion, and their level of confidence that the patient should be recalled for diagnostic workup for each suspicious lesion. Jackknife alternative free-response receiver operating characteristic analysis was used. RESULTS: The jackknife alternative free-response receiver operating characteristic figure of merit was 0.641 without aid and 0.659 with aid (p = 0.06; 95% CI, -0.001 to 0.036). The sensitivity increased 9.9% (95% CI, 3.4-19%) and the callback rate 12.1% (95% CI, 7.3-20%) with CADe. Both increases were statistically significant (p < 0.001). Radiologists on average ignored 71% of correct computer prompts. CONCLUSION: Use of CADe can increase radiologist sensitivity 10% with a comparable increase in recall rate. There is potential for CADe to have a bigger clinical impact because radiologists failed to recognize a correct computer prompt in 71% of missed cancer cases [corrected].

Relevance vector machine for automatic detection of clustered microcalcifications.

Clustered microcalcifications (MC) in mammograms can be an important early sign of breast cancer in women. Their accurate detection is important in computer-aided detection (CADe). In this paper, we propose the use of a recently developed machine-learning technique--relevance vector machine (RVM)--for detection of MCs in digital mammograms. RVM is based on Bayesian estimation theory, of which a distinctive feature is that it can yield a sparse decision function that is defined by only a very small number of so-called relevance vectors. By exploiting this sparse property of the RVM, we develop computerized detection algorithms that are not only accurate but also computationally efficient for MC detection in mammograms. We formulate MC detection as a supervised-learning problem, and apply RVM as a classifier to determine at each location in the mammogram if an MC object is present or not. To increase the computation speed further, we develop a two-stage classification network, in which a computationally much simpler linear RVM classifier is applied first to quickly eliminate the overwhelming majority, non-MC pixels in a mammogram from any further consideration. The proposed method is evaluated using a database of 141 clinical mammograms (all containing MCs), and compared with a well-tested support vector machine (SVM) classifier. The detection performance is evaluated using free-response receiver operating characteristic (FROC) curves. It is demonstrated in our experiments that the RVM classifier could greatly reduce the computational complexity of the SVM while maintaining its best detection accuracy. In particular, the two-stage RVM approach could reduce the detection time from 250 s for SVM to 7.26 s for a mammogram (nearly 35-fold reduction). Thus, the proposed RVM classifier is more advantageous for real-time processing of MC clusters in mammograms.