Gastounioti, Aimilia

Radiomic parenchymal phenotypes on mammograms were used to predict breast cancer risk among both Black and White women, notably for false-negative findings and symptomatic interval cancer.

PURPOSE Breast density is a widely established independent breast cancer risk factor. With the increasing utilization of digital breast tomosynthesis (DBT) in breast cancer screening, there is an opportunity to estimate volumetric breast density (VBD) routinely. However, current available methods extrapolate VBD from two-dimensional (2D) images acquired using DBT and/or depend on the existence of raw DBT data, which is rarely archived by clinical centers because of storage constraints. METHODS We retrospectively analyzed 1,080 nonactionable three-dimensional (3D) reconstructed DBT screening examinations acquired between 2011 and 2016. Reference tissue segmentations were generated using previously validated software that uses 3D reconstructed slices and raw 2D DBT data. We developed a deep learning (DL) model that segments dense and fatty breast tissue from background. We then applied this model to estimate %VBD and absolute dense volume (ADV) in cm 3 in a separate case-control sample (180 cases and 654 controls). We created two conditional logistic regression models, relating each model-derived density measurement to likelihood of contralateral breast cancer diagnosis, adjusted for age, BMI, family history, and menopausal status. RESULTS The DL model achieved unweighted and weighted Dice scores of 0.88 (standard deviation [SD] = 0.08) and 0.76 (SD = 0.15), respectively, on the held-out test set, demonstrating good agreement between the model and 3D reference segmentations. There was a significant association between the odds of breast cancer diagnosis and model-derived VBD (odds ratio [OR], 1.41 [95 % CI, 1.13 to 1.77]; P = .002), with an AUC of 0.65 (95% CI, 0.60 to 0.69). ADV was also significantly associated with breast cancer diagnosis (OR, 1.45 [95% CI, 1.22 to 1.73]; P < .001) with an AUC of 0.67 (95% CI, 0.62 to 0.71). CONCLUSION DL-derived density measures derived from 3D reconstructed DBT images are associated with breast cancer diagnosis.

Abstract Breast parenchymal patterns on radiologic images are associated with breast cancer risk. Radiomic features have been proposed as quantitative measures of parenchymal patterns. We defined intrinsic imaging phenotypes of breast parenchymal patterns based on radiomic features extracted from full field digital mammography (FFDM) in breast screening populations and assessed whether these phenotypes are associated with breast cancer risk and masking. We selected 30,000 women with 4-view FFDM exams from Hologic machines from three institutions (Hospital of the University of Pennsylvania, Mayo Clinic, and San Francisco Mammography Registry), randomly split into a training (20,000 women) and test set (10,000 women). In total, 390 radiomic features were automatically extracted from each image using a validated software pipeline, standardized, and adjusted for site differences using ComBat. We used two methods, hierarchical clustering and Principal Components (PCs) analysis, to classify significant variation among the features in the training set and replicate among the test set. Next, we applied the replicated clusters and PCs to an independent nested case-control set [1082 invasive breast cancer (BC) cases (of which 151 were Black and 893 White women, 38 other race) matched to 2837 controls (411 Black and 2345 White women, 81 other race) on age, race, timing of images, and site]. We examined associations of the clusters and PCs with invasive breast cancer risk, as well as masking [defined as a false-negative (FN) screen (124 cases and 319 matched controls) and additionally the subset with symptomatic interval cancer (IC) within 12 months of negative screen (88 cases and 223 matched controls)] using conditional logistic regression. We evaluated their association with breast cancer alone, and with adjustment for age, body mass index (BMI) and breast density assessed by Breast Imaging Reporting and Data System (BI-RADS) using likelihood ratio tests. We estimated discrimination using area under the curve (AUC) and compared AUCs for models that included the radiomic clusters and PCs with the model that included only age, BMI and density. We also stratified analyses by race (Black/White). From hierarchical clustering, we defined six statistically significant phenotype clusters (each of at least 1000 women) in the training set which were replicated in the test set. For PC Analysis, we identified six PCs in the training set, explaining 85% of the variation in texture features and reproduced these in the test set. The six radiomic phenotype clusters (P&lt; 0.001) and six PCs (P&lt; 0.001) were both associated with invasive BC, including after adjusting for age, BMI, and density (cluster P=0.004; PCs P&lt; 0.001). Improvements in discrimination of invasive BC with inclusion of PCs or clusters were more pronounced among Black women (Table). Further, the PCs (P&lt; 0.001) and clusters (P&lt; 0.001) were significantly associated with FN overall and for symptomatic IC (PCs P&lt; 0.001; clusters P=0.001), but only PCs remained significant after adjusting for age, BMI and density (PCs P=0.004 for FN; PCs P=0.007 for symptomatic IC). Discrimination of masking also improved with inclusion of both clusters and PCs (Table). We identified reproducible radiomic phenotypes that are associated with invasive BC risk, above and beyond breast density with the strongest associations for invasive BC among Black women and symptomatic interval cancers. Citation Format: Stacey Winham, Anne Marie McCarthy, Aimilia Gastounioti, Christopher Scott, Aaron Norman, Walter C. Mankowski, Lauren Pantalone, Matthew Jensen, Eric A. Cohen, Hannah Horng, Kathleen Brandt, Emily F. Conant, Karla Kerlikowske, Despina Kontos, Celine Vachon. Radiomic phenotypes of breast texture and association with breast cancer risk and masking [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-06.

Abstract Background: It has been widely established that breast density is an independent breast cancer risk factor. With the increasing utilization of digital breast tomosynthesis (DBT) in breast cancer screening, there is an opportunity to estimate volumetric breast density (VBD) routinely. However, current available methods extrapolate VBD from 2D images acquired with DBT and/or depend on the existence of raw DBT data which is rarely archived by clinical centers due to cost and storage constraints. This study aims to harness deep learning to develop a computational tool for VBD assessment based solely on 3D reconstructed, “for presentation” DBT images. Methods: We retrospectively analyzed 1,080 negative DBT screening exams (09/20/2011 - 11/25/2016) from the Hospital of the University of Pennsylvania (mean age ± SD, 57 ± 11 years; mean BMI ± SD, 28.7 ± 7.1 kg/m2; racial makeup, 41.2% White, 54.2% Black, 4.6% Other), for which both 3D reconstructed and 2D raw DBT images (Selenia Dimensions, Hologic Inc) were available. All available standard views (left and right mediolateral-oblique and cranio-caudal views) were included for each exam, leading to 7,850 DBT views. Corresponding 3D reference-standard tissue segmentations were generated from a previously validated software that uses both 3D reconstructed slices and raw 2D DBT data to provide VBD metrics, shown to be strongly correlated with VBD measures from MRI image volumes. We based our deep learning algorithm on the U-Net architecture within the open-source Generally Nuanced Deep Learning Framework (GaNDLF) and created a 3-label image segmentation task (background, dense tissue, and fatty tissue). Our dataset was randomly split into training (70%), validation (15%) and test (15%) sets, while ensuring that all views of the same DBT exam were assigned to the same set. The performance of our deep learning algorithm against the corresponding reference-standard segmentations was measured in terms of Dice scores (DSC), with 0 signifying no overlap and 1 signifying perfect overlap, overall, as well as separately for each label. Results: After training was complete, our deep learning algorithm achieved a DSC of 0.78 on the validation, as well as on the test set. Our method accurately segmented background from breast tissue (DSC = 0.94) and demonstrated moderate to high performance in segmenting dense and fatty tissue, respectively (DSC = 0.49 and 0.89). Conclusion: Our preliminary analysis suggests that deep learning shows promise in the estimation of VBD using 3D DBT reconstructed, “for presentation” images. Future work involving transfer learning based on ground truth masks by clinical radiologists could further enhance this method’s performance. In view of rapid clinical conversion to DBT screening, such a tool has the potential to enable large retrospective epidemiologic and personalized risk assessment studies of breast density with DBT. Citation Format: Vinayak S. Ahluwalia, Walter Mankowski, Sarthak Pati, Spyridon Bakas, Ari Brooks, Celine M. Vachon, Emily F. Conant, Aimilia Gastounioti, Despina Kontos. Deep-learning-enabled volumetric breast density estimation with digital breast tomosynthesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1929.

e13538 Background: Breast density is considered a well-established breast cancer risk factor. As quasi-3D, digital breast tomosynthesis (DBT) becomes increasingly utilized for screening, there is an opportunity to routinely estimate volumetric breast density (VBD). However, current methods extrapolate VBD from 2D images acquired with DBT and/or depend on the existence of raw DBT data, which is rarely archived due to cost and storage constraints. Using a racially diverse screening cohort, this study evaluates the potential of deep learning for VBD assessment based solely on 3D reconstructed, “for presentation” DBT images. Methods: We retrospectively analyzed 1,080 negative DBT screening exams obtained between 2011 and 2016 from the Hospital of the University of Pennsylvania (racial makeup, 41.2% White, 54.2% Black, 4.6% Other; mean age ± SD, 57 ± 11 years; mean BMI ± SD, 28.7 ± 7.1 kg/m2), for which both 2D raw and 3D reconstructed DBT images (Selenia Dimensions, Hologic Inc) were available. Corresponding 3D reference-standard tissue segmentations were generated from previously validated software that uses both 3D reconstructed slices and raw 2D DBT data to provide VBD metrics, shown to be strongly correlated with VBD measures from MRI image volumes. We based our deep learning algorithm on the U-Net architecture within the open-source Generally Nuanced Deep Learning Framework (GaNDLF) and created a 3-label image segmentation task (background, dense tissue, and fatty tissue). Our dataset was randomly split into training (70%), validation (15%) and test (15%) sets. We report on the performance of our deep learning algorithm against corresponding reference-standard segmentations for a cranio-caudal (CC) view-only subset. We also stratify our results by the two main racial groups (White and Black). Our evaluation measure was the weighted Dice score (DSC), with 0 signifying no overlap and 1 signifying perfect overlap, overall and separately for each label. Results: Our deep learning algorithm achieved an overall DSC of 0.682 (STD = 0.136). It accurately segmented the three labels of background, fatty tissue, and dense tissue, with DSC scores of 0.995, 0.884, and 0.617, respectively. DSC for White and Black women were 0.688 (STD = 0.127) and 0.680 (STD = 0.146), respectively. Conclusions: Our preliminary analysis suggests that deep learning shows promise in the estimation of VBD using 3D DBT reconstructed, “for presentation” CC view images and does not demonstrate bias among racial groups. Future work involving optimization of performance in other breast views as well as transfer learning based on ground truth masks by clinical radiologists could further enhance this method. In view of rapid clinical conversion to DBT screening, such a tool has the potential to enable large retrospective epidemiological and personalized risk assessment studies of breast density with DBT.

Digital mammography has seen an explosion in the number of radiomic features used for risk-assessment modeling. However, having more features is not necessarily beneficial, as some features may be overly sensitive to imaging physics (contrast, noise, and image sharpness). To measure the effects of imaging physics, we analyzed the feature variation across imaging acquisition settings (kV, mAs) using an anthropomorphic phantom. We also analyzed the intra-woman variation (IWV), a measure of how much a feature varies between breasts with similar parenchymal patterns—a woman’s left and right breasts. From 341 features, we identified “robust” features that minimized the effects of imaging physics and IWV. We also investigated whether robust features offered better case-control classification in an independent data set of 575 images, all with an overall BI-RADS® assessment of 1 (negative) or 2 (benign); 115 images (cases) were of women who developed cancer at least one year after that screening image, matched to 460 controls. We modeled cancer occurrence via logistic regression, using cross-validated area under the receiver-operating-characteristic curve (AUC) to measure model performance. Models using features from the most-robust quartile of features yielded an AUC = 0.59, versus 0.54 for the least-robust, with p < 0.005 for the difference among the quartiles.

Abstract Accurate estimation of mammographic breast density could aid in augmenting breast cancer risk assessment for women undergoing breast screening with full-field digital mammography (FFDM). Breast density can be estimated from FFDM and is most commonly assessed in the clinic by visual grading into one of the four categories defined by the American College of Radiology BI-RADS. However, BI-RADS density assessment is highly subjective and does not provide a quantitative, continuous measure of percent density (PD), which would allow for more refined risk stratification and assessment of density changes. Here, we introduce Deep-LIBRA, an artificial intelligence (AI) tool for fully-automated assessment of breast PD from FFDM images. Two key modules form the core of Deep-LIBRA: 1) an implementation of a modified U-Net architecture for breast segmentation and 2) a radiomic machine learning module that performs PD estimation within the segmented breast region. To develop and validate Deep-LIBRA, raw (i.e., "For Processing") FFDM images (Selenia Dimensions, Hologic Inc.) acquired at two breast cancer screening practices were retrospectively analyzed. For the breast segmentation module, we used a total of 12,100 FFDM studies from 2,200 individual women and a 90%-10% split-sample training-validation approach, using the Dice coefficient to evaluate the accuracy of Deep-LIBRA versus ground-truth manual breast segmentation. For the PD estimation module we used a total of 3,304 FFDM images from 1,652 individual women; manual PD scores obtained with the widely used Cumulus software were used as the "gold standard" in a three-fold cross-validation setting to assess the accuracy of Deep-LIBRA in PD estimation. PD estimates from Deep-LIBRA were also compared with breast density estimates from the commercially available Volpara software. Breast segmentation had a Dice coefficient of 95.31% when compared to ground-truth manual breast segmentation in the validation set. Deep-LIBRA average differences from ground-truth PD scores in the three cross-validation folds were 4.91%, 4.65%, and 4.22%, while Volpara had corresponding average differences of 6.20%, 6.01%, and 5.94%. Deep-LIBRA PD scores were also significantly different from Volpara PD (t-test p-value &lt; 0.001 in all three folds). Preliminary evaluation results show that Deep-LIBRA is a promising AI approach for accurately assessing PD from FFDM images. Citation Format: Omid Haji Maghsoudi, Scott Christopher, Aimilia Gastounioti, Lauren Pantalone, Fang-Fang Wu, Eric A. Cohen, Winham Stacey, Emily F. Conant, Celine Vachon, Despina Kontos. Deep-LIBRA: An artificial intelligence approach for fully-automated assessment of breast density in digital mammography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2600.