Massive Mysteries.

Papillary fibroelastomas are benign masses often originating from the endocardium of the aortic and mitral valves. Rarely, these neoplasms are found in areas of the heart embryonically distinct from the aortic and mitral valves. Diagnosis of a papillary fibroelastoma relies on multimodal imaging as well as histologic assessment. A case series of papillary fibroelastomas in unusual locations is presented, highlighting the role of multimodal imaging techniques in identifying these intra-cardiac masses. Differential diagnoses, imaging characteristics, histopathology, and preferred management strategies for cardiac masses are reviewed. The unique imaging qualities of cardiac masses are discussed.

Preoperative Planning for Structural Heart Disease.

Preoperative assessment with computed tomography (CT) is critical before transcatheter interventions for structural heart disease. CT provides information for device selection, device sizing, and vascular access approach. The interpreting radiologist must have knowledge of appropriate CT protocols, how and where to obtain the important measurements, and know additional imaging characteristics that are important to describe for optimal support of the interventionalist. CT is the modality of choice for pre-operative evaluation in patients undergoing transcatheter aortic valve replacement and left atrial appendage occlusion, and is also useful before transcatheter mitral valve replacement, which is an ongoing area of research.

Deep learning for identifying radiogenomic associations in breast cancer.

RATIONALE AND OBJECTIVES: To determine whether deep learning models can distinguish between breast cancer molecular subtypes based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: In this institutional review board-approved single-center study, we analyzed DCE-MR images of 270 patients at our institution. Lesions of interest were identified by radiologists. The task was to automatically determine whether the tumor is of the Luminal A subtype or of another subtype based on the MR image patches representing the tumor. Three different deep learning approaches were used to classify the tumor according to their molecular subtypes: learning from scratch where only tumor patches were used for training, transfer learning where networks pre-trained on natural images were fine-tuned using tumor patches, and off-the-shelf deep features where the features extracted by neural networks trained on natural images were used for classification with a support vector machine. Network architectures utilized in our experiments were GoogleNet, VGG, and CIFAR. We used 10-fold crossvalidation method for validation and area under the receiver operating characteristic (AUC) as the measure of performance. RESULTS: The best AUC performance for distinguishing molecular subtypes was 0.65 (95% CI:[0.57,0.71]) and was achieved by the off-the-shelf deep features approach. The highest AUC performance for training from scratch was 0.58 (95% CI:[0.51,0.64]) and the best AUC performance for transfer learning was 0.60 (95% CI:[0.52,0.65]) respectively. For the off-the-shelf approach, the features extracted from the fully connected layer performed the best. CONCLUSION: Deep learning may play a role in discovering radiogenomic associations in breast cancer.

Association of distant recurrence-free survival with algorithmically extracted MRI characteristics in breast cancer.

BACKGROUND: While important in diagnosis of breast cancer, the scientific assessment of the role of imaging in prognosis of outcomes and treatment planning is limited. PURPOSE: To evaluate the potential of using quantitative imaging variables for stratifying risk of distant recurrence in breast cancer patients. STUDY TYPE: Retrospective. POPULATION: In all, 892 female invasive breast cancer patients. SEQUENCE: Dynamic contrast-enhanced MRI with field strength 1.5 T and 3 T. ASSESSMENT: Computer vision algorithms were applied to extract a comprehensive set of 529 imaging features quantifying size, shape, enhancement patterns, and heterogeneity of the tumors and the surrounding tissue. Using a development set with 446 cases, we selected 20 imaging features with high prognostic value. STATISTICAL TESTS: We evaluated the imaging features using an independent test set with 446 cases. The principal statistical measure was a concordance index between individual imaging features and patient distant recurrence-free survival (DRFS). RESULTS: The strongest association with DRFS that persisted after controlling for known prognostic clinical and pathology variables was found for signal enhancement ratio (SER) partial tumor volume (concordance index [C] = 0.768, 95% confidence interval [CI]: 0.679-0.856), tumor major axis length (C = 0.742, 95% CI: 0.650-0.834), kurtosis of the SER map within tumor (C = 0.640, 95% CI: 0.521-0.760), tumor cluster shade (C = 0.313, 95% CI: 0.216-0.410), and washin rate information measure of correlation (C = 0.702, 95% CI: 0.601-0.803). DATA CONCLUSION: Quantitative assessment of breast cancer features seen in a routine breast MRI might be able to be used for assessment of risk of distant recurrence. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 6 J. Magn. Reson. Imaging 2019.

Multivariate machine learning models for prediction of pathologic response to neoadjuvant therapy in breast cancer using MRI features: a study using an independent validation set.

PURPOSE: To determine whether a multivariate machine learning-based model using computer-extracted features of pre-treatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can predict pathologic complete response (pCR) to neoadjuvant therapy (NAT) in breast cancer patients. METHODS: Institutional review board approval was obtained for this retrospective study of 288 breast cancer patients at our institution who received NAT and had a pre-treatment breast MRI. A comprehensive set of 529 radiomic features was extracted from each patient's pre-treatment MRI. The patients were divided into equal groups to form a training set and an independent test set. Two multivariate machine learning models (logistic regression and a support vector machine) based on imaging features were trained to predict pCR in (a) all patients with NAT, (b) patients with neoadjuvant chemotherapy (NACT), and (c) triple-negative or human epidermal growth factor receptor 2-positive (TN/HER2+) patients who had NAT. The multivariate models were tested using the independent test set, and the area under the receiver operating characteristics (ROC) curve (AUC) was calculated. RESULTS: Out of the 288 patients, 64 achieved pCR. The AUC values for predicting pCR in TN/HER+ patients who received NAT were significant (0.707, 95% CI 0.582-0.833, p < 0.002). CONCLUSIONS: The multivariate models based on pre-treatment MRI features were able to predict pCR in TN/HER2+ patients.

Intra-tumor molecular heterogeneity in breast cancer: definitions of measures and association with distant recurrence-free survival.

PURPOSE: The purpose of the study was to define quantitative measures of intra-tumor heterogeneity in breast cancer based on histopathology data gathered from multiple samples on individual patients and determine their association with distant recurrence-free survival (DRFS). METHODS: We collected data from 971 invasive breast cancers, from 1st January 2000 to 23rd March 2014, that underwent repeat tumor sampling at our institution. We defined and calculated 31 measures of intra-tumor heterogeneity including ER, PR, and HER2 immunohistochemistry (IHC), proliferation, EGFR IHC, grade, and histology. For each heterogeneity measure, Cox proportional hazards models were used to determine whether patients with heterogeneous disease had different distant recurrence-free survival (DRFS) than those with homogeneous disease. RESULTS: The presence of heterogeneity in ER percentage staining was prognostic of reduced DRFS with a hazard ratio of 4.26 (95% CI 2.22-8.18, p < 0.00002). It remained significant after controlling for the ER status itself (p < 0.00062) and for patients that had chemotherapy (p < 0.00032). Most of the heterogeneity measures did not show any association with DRFS despite the considerable sample size. CONCLUSIONS: Intra-tumor heterogeneity of ER receptor status may be a predictor of patient DRFS. Histopathologic data from multiple tissue samples may offer a view of tumor heterogeneity and assess recurrence risk.

A machine learning approach to radiogenomics of breast cancer: a study of 922 subjects and 529 DCE-MRI features.

BACKGROUND: Recent studies showed preliminary data on associations of MRI-based imaging phenotypes of breast tumours with breast cancer molecular, genomic, and related characteristics. In this study, we present a comprehensive analysis of this relationship. METHODS: We analysed a set of 922 patients with invasive breast cancer and pre-operative MRI. The MRIs were analysed by a computer algorithm to extract 529 features of the tumour and the surrounding tissue. Machine-learning-based models based on the imaging features were trained using a portion of the data (461 patients) to predict the following molecular, genomic, and proliferation characteristics: tumour surrogate molecular subtype, oestrogen receptor, progesterone receptor and human epidermal growth factor status, as well as a tumour proliferation marker (Ki-67). Trained models were evaluated on the set of the remaining 461 patients. RESULTS: Multivariate models were predictive of Luminal A subtype with AUC = 0.697 (95% CI: 0.647-0.746, p < .0001), triple negative breast cancer with AUC = 0.654 (95% CI: 0.589-0.727, p < .0001), ER status with AUC = 0.649 (95% CI: 0.591-0.705, p < .001), and PR status with AUC = 0.622 (95% CI: 0.569-0.674, p < .0001). Associations between individual features and subtypes we also found. CONCLUSIONS: There is a moderate association between tumour molecular biomarkers and algorithmically assessed imaging features.

Breast cancer MRI radiomics: An overview of algorithmic features and impact of inter-reader variability in annotating tumors.

PURPOSE: To review features used in MRI radiomics of breast cancer and study the inter-reader stability of the features. METHODS: We implemented 529 algorithmic features that can be extracted from tumor and fibroglandular tissue (FGT) in breast MRIs. The features were identified based on a review of the existing literature with consideration of their usage, prognostic ability, and uniqueness. The set was then extended so that it comprehensively describes breast cancer imaging characteristics. The features were classified into 10 groups based on the type of data used to extract them and the type of calculation being performed. For the assessment of inter-reader variability, four fellowship-trained readers annotated tumors on preoperative dynamic contrast-enhanced MRIs for 50 breast cancer patients. Based on the annotations, an algorithm automatically segmented the image and extracted all features resulting in one set of features for each reader. For a given feature, the inter-reader stability was defined as the intraclass correlation coefficient (ICC) computed using the feature values obtained through all readers for all cases. RESULTS: The average inter-reader stability for all features was 0.8474 (95% CI: 0.8068-0.8858). The mean inter-reader stability was lower for tumor-based features (0.6348, 95% CI: 0.5391-0.7257) than FGT-based features (0.9984, 95% CI: 0.9970-0.9992). The feature group with the highest inter-reader stability quantifies breast and FGT volume. The feature group with the lowest inter-reader stability quantifies variations in tumor enhancement. CONCLUSIONS: Breast MRI radiomics features widely vary in terms of their stability in the presence of inter-reader variability. Appropriate measures need to be taken for reducing this variability in tumor-based radiomics.

A study of association of Oncotype DX recurrence score with DCE-MRI characteristics using multivariate machine learning models.

PURPOSE: To determine whether multivariate machine learning models of algorithmically assessed magnetic resonance imaging (MRI) features from breast cancer patients are associated with Oncotype DX (ODX) test recurrence scores. METHODS: A set of 261 female patients with invasive breast cancer, pre-operative dynamic contrast enhanced magnetic resonance (DCE-MR) images and available ODX score at our institution was identified. A computer algorithm extracted a comprehensive set of 529 features from the DCE-MR images of these patients. The set of patients was divided into a training set and a test set. Using the training set we developed two machine learning-based models to discriminate (1) high ODX scores from intermediate and low ODX scores, and (2) high and intermediate ODX scores from low ODX scores. The performance of these models was evaluated on the independent test set. RESULTS: High against low and intermediate ODX scores were predicted by the multivariate model with AUC 0.77 (95% CI 0.56-0.98, p < 0.003). Low against intermediate and high ODX score was predicted with AUC 0.51 (95% CI 0.41-0.61, p = 0.75). CONCLUSION: A moderate association between imaging and ODX score was identified. The evaluated models currently do not warrant replacement of ODX with imaging alone.

Can algorithmically assessed MRI features predict which patients with a preoperative diagnosis of ductal carcinoma in situ are upstaged to invasive breast cancer?

PURPOSE: To assess the ability of algorithmically assessed magnetic resonance imaging (MRI) features to predict the likelihood of upstaging to invasive cancer in newly diagnosed ductal carcinoma in situ (DCIS). MATERIALS AND METHODS: We identified 131 patients at our institution from 2000-2014 with a core needle biopsy-confirmed diagnosis of pure DCIS, a 1.5 or 3T preoperative bilateral breast MRI with nonfat-saturated T1 -weighted MRI sequences, no preoperative therapy before breast MRI, and no prior history of breast cancer. A fellowship-trained radiologist identified the lesion on each breast MRI using a bounding box. Twenty-nine imaging features were then computed automatically using computer algorithms based on the radiologist's annotation. RESULTS: The rate of upstaging of DCIS to invasive cancer in our study was 26.7% (35/131). Out of all imaging variables tested, the information measure of correlation 1, which quantifies spatial dependency in neighboring voxels of the tumor, showed the highest predictive value of upstaging with an area under the curve (AUC) = 0.719 (95% confidence interval [CI]: 0.609-0.829). This feature was statistically significant after adjusting for tumor size (P < 0.001). CONCLUSION: Automatically assessed MRI features may have a role in triaging which patients with a preoperative diagnosis of DCIS are at highest risk for occult invasive disease. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1332-1340.

Algorithms for prediction of the Oncotype DX recurrence score using clinicopathologic data: a review and comparison using an independent dataset.

PURPOSE: Given the potential savings in cost and resource utilization, several algorithms have been proposed to predict Oncotype DX recurrence score (ODX RS) using commonly acquired histopathologic variables. Although it is promising, additional independent validation of these surrogate markers is needed prior to guide the patient management. METHODS: In this retrospective study, we analyzed 305 patients with invasive breast cancer at our institution who had ODX RS available. We selected five equations that provide a surrogate measure of ODX as previously published by Klein et al. (Magee equations 1-3), Gage et al., and Tang et al. All equations used estrogen receptor status and progesterone receptor status along with different combinations of grade, proliferation indices (Ki-67, mitotic rate), HER2 status, and tumor size. RESULTS: Of all surrogate scores tested, the Magee equation 2 provided the highest correlation with ODX both with regard to raw score (Pearson's correlation coefficient = 0.66 95% CI 0.59-0.72) and categorical correlation (Cohen's kappa = 0.43, 95% CI 0.33-0.53). Although Magee equation 2 provided a way to reliably identify high-risk disease by assigning 95% of the patients with high ODX RS to either the intermediate- or high-risk group, it was unable to reliably identify the potential for patients to have intermediate- or high-risk disease by ODX (66% of such patients identified). CONCLUSIONS: Although commonly available surrogates for ODX appear to predict high-risk ODX RS, they are unable to reliably rule out the presence of patients with intermediate-risk disease by ODX. Given the potential benefit of adjuvant chemotherapy in women with intermediate-risk disease by ODX, current surrogates are unable to safely substitute for ODX. Characterizing the true recurrence risk in patients with intermediate-risk disease by ODX is critical to the clinical adoption of current surrogate markers and is an area of ongoing clinical trials.