Potential Role of Convolutional Neural Network Based Algorithm in Patient Selection for DCIS Observation Trials Using a Mammogram Dataset.

RATIONALE AND OBJECTIVES: We investigated the feasibility of utilizing convolutional neural network (CNN) for predicting patients with pure Ductal Carcinoma In Situ (DCIS) versus DCIS with invasion using mammographic images. MATERIALS AND METHODS: An IRB-approved retrospective study was performed. 246 unique images from 123 patients were used for our CNN algorithm. In total, 164 images in 82 patients diagnosed with DCIS by stereotactic-guided biopsy of calcifications without any upgrade at the time of surgical excision (pure DCIS group). A total of 82 images in 41 patients with mammographic calcifications yielding occult invasive carcinoma as the final upgraded diagnosis on surgery (occult invasive group). Two standard mammographic magnification views (CC and ML/LM) of the calcifications were used for analysis. Calcifications were segmented using an open source software platform 3D Slicer and resized to fit a 128 × 128 pixel bounding box. A 15 hidden layer topology was used to implement the neural network. The network architecture contained five residual layers and dropout of 0.25 after each convolution. Five-fold cross validation was performed using training set (80%) and validation set (20%). Code was implemented in open source software Keras with TensorFlow on a Linux workstation with NVIDIA GTX 1070 Pascal GPU. RESULTS: Our CNN algorithm for predicting patients with pure DCIS achieved an overall diagnostic accuracy of 74.6% (95% CI, ±5) with area under the ROC curve of 0.71 (95% CI, ±0.04), specificity of 91.6% (95% CI, ±5%) and sensitivity of 49.4% (95% CI, ±6%). CONCLUSION: It's feasible to apply CNN to distinguish pure DCIS from DCIS with invasion with high specificity using mammographic images.

Accuracy of Distinguishing Atypical Ductal Hyperplasia From Ductal Carcinoma In Situ With Convolutional Neural Network-Based Machine Learning Approach Using Mammographic Image Data.

OBJECTIVE. The purpose of this study was to test the hypothesis that convolutional neural networks can be used to predict which patients with pure atypical ductal hyperplasia (ADH) may be safely monitored rather than undergo surgery. MATERIALS AND METHODS. A total of 298 unique images from 149 patients were used for our convolutional neural network algorithm. A total of 134 images from 67 patients with ADH that had been diagnosed by stereotactic-guided biopsy of calcifications but had not been upgraded to ductal carcinoma in situ or invasive cancer at the time of surgical excision. A total of 164 images from 82 patients with mammographic calcifications indicated that ductal carcinoma in situ was the final diagnosis. Two standard mammographic magnification views of the calcifications (a craniocaudal view and a mediolateral or lateromedial view) were used for analysis. Calcifications were segmented using an open-source software platform and images were resized to fit a bounding box of 128 × 128 pixels. A topology with 15 hidden layers was used to implement the convolutional neural network. The network architecture contained five residual layers and dropout of 0.25 after each convolution. Patients were randomly separated into a training-and-validation set (80% of patients) and a test set (20% of patients). Code was implemented using open-source software on a workstation with an open-source operating system and a graphics card. RESULTS. The AUC value was 0.86 (95% CI, ± 0.03) for the test set. Aggregate sensitivity and specificity were 84.6% (95% CI, ± 4.0%) and 88.2% (95% CI, ± 3.0%), respectively. Diagnostic accuracy was 86.7% (95% CI, ± 2.9). CONCLUSION. It is feasible to apply convolutional neural networks to distinguish pure atypical ductal hyperplasia from ductal carcinoma in situ with the use of mammographic images. A larger dataset will likely result in further improvement of our prediction model.

Bennett lesions in overhead athletes and associated shoulder abnormalities on MRI.

OBJECTIVE: To determine if a Bennett lesion and its size are associated with additional MRI shoulder abnormalities in an overhead athlete. MATERIALS AND METHODS: An IRB-approved retrospective review of our database from 1 January 2012 to 1 April 2018 identified 35 overhead athletes with a Bennett lesion on MRI. A control group consisting of 35 overhead athletes without a Bennett lesion were matched for age, level of play (professional vs non-professional), and type of study (arthrogram vs non-arthrogram). Each study was assessed independently by two MSK fellowship trained radiologists. The sizes of the Bennett lesions were measured. Each MRI was assessed for the presence of a labral tear, posterior glenoid cartilage abnormality, humeral head notching or cysts, and fraying or tear of the supraspinatus or infraspinatus tendons. Statistical analyses were performed using Student's t test, Fisher's exact test, and Chi-squared test. RESULTS: There was an increased incidence of posterior glenoid cartilage abnormalities in athletes with Bennett lesions vs those without (23% vs 3%, p value = 0.01). There was no difference in any other MRI abnormalities, including labral tears and findings of internal impingement between these two groups (p value range = 0.09-0.46). There was no association between the size of a Bennett lesion and the presence of glenoid cartilage lesions, labral tears, internal impingement, age, professional status, or need for surgery (p value range = 0.08-0.96). CONCLUSION: Symptomatic overhead athletes with Bennett lesions have an increased frequency of posterior glenoid cartilage abnormalities, but not labral tears or findings of internal impingement compared to those without Bennett lesions.

Predicting Breast Cancer Molecular Subtype with MRI Dataset Utilizing Convolutional Neural Network Algorithm.

To develop a convolutional neural network (CNN) algorithm that can predict the molecular subtype of a breast cancer based on MRI features. An IRB-approved study was performed in 216 patients with available pre-treatment MRIs and immunohistochemical staining pathology data. First post-contrast MRI images were used for 3D segmentation using 3D slicer. A CNN architecture was designed with 14 layers. Residual connections were used in the earlier layers to allow stabilization of gradients during backpropagation. Inception style layers were utilized deeper in the network to allow learned segregation of more complex feature mappings. Extensive regularization was utilized including dropout, L2, feature map dropout, and transition layers. The class imbalance was addressed by doubling the input of underrepresented classes and utilizing a class sensitive cost function. Parameters were tuned based on a 20% validation group. A class balanced holdout set of 40 patients was utilized as the testing set. Software code was written in Python using the TensorFlow module on a Linux workstation with one NVidia Titan X GPU. Seventy-four luminal A, 106 luminal B, 13 HER2+, and 23 basal breast tumors were evaluated. Testing set accuracy was measured at 70%. The class normalized macro area under receiver operating curve (ROC) was measured at 0.853. Non-normalized micro-aggregated AUC was measured at 0.871, representing improved discriminatory power for the highly represented Luminal A and Luminal B subtypes. Aggregate sensitivity and specificity was measured at 0.603 and 0.958. MRI analysis of breast cancers utilizing a novel CNN can predict the molecular subtype of breast cancers. Larger data sets will likely improve our model.

Fully Automated Convolutional Neural Network Method for Quantification of Breast MRI Fibroglandular Tissue and Background Parenchymal Enhancement.

The aim of this study is to develop a fully automated convolutional neural network (CNN) method for quantification of breast MRI fibroglandular tissue (FGT) and background parenchymal enhancement (BPE). An institutional review board-approved retrospective study evaluated 1114 breast volumes in 137 patients using T1 precontrast, T1 postcontrast, and T1 subtraction images. First, using our previously published method of quantification, we manually segmented and calculated the amount of FGT and BPE to establish ground truth parameters. Then, a novel 3D CNN modified from the standard 2D U-Net architecture was developed and implemented for voxel-wise prediction whole breast and FGT margins. In the collapsing arm of the network, a series of 3D convolutional filters of size 3 × 3 × 3 are applied for standard CNN hierarchical feature extraction. To reduce feature map dimensionality, a 3 × 3 × 3 convolutional filter with stride 2 in all directions is applied; a total of 4 such operations are used. In the expanding arm of the network, a series of convolutional transpose filters of size 3 × 3 × 3 are used to up-sample each intermediate layer. To synthesize features at multiple resolutions, connections are introduced between the collapsing and expanding arms of the network. L2 regularization was implemented to prevent over-fitting. Cases were separated into training (80%) and test sets (20%). Fivefold cross-validation was performed. Software code was written in Python using the TensorFlow module on a Linux workstation with NVIDIA GTX Titan X GPU. In the test set, the fully automated CNN method for quantifying the amount of FGT yielded accuracy of 0.813 (cross-validation Dice score coefficient) and Pearson correlation of 0.975. For quantifying the amount of BPE, the CNN method yielded accuracy of 0.829 and Pearson correlation of 0.955. Our CNN network was able to quantify FGT and BPE within an average of 0.42 s per MRI case. A fully automated CNN method can be utilized to quantify MRI FGT and BPE. Larger dataset will likely improve our model.

Convolutional Neural Network Using a Breast MRI Tumor Dataset Can Predict Oncotype Dx Recurrence Score.

BACKGROUND: Oncotype Dx is a validated genetic analysis that provides a recurrence score (RS) to quantitatively predict outcomes in patients who meet the criteria of estrogen receptor positive / human epidermal growth factor receptor-2 negative (ER+/HER2-)/node negative invasive breast carcinoma. Although effective, the test is invasive and expensive, which has motivated this investigation to determine the potential role of radiomics. HYPOTHESIS: We hypothesized that convolutional neural network (CNN) can be used to predict Oncotype Dx RS using an MRI dataset. STUDY TYPE: Institutional Review Board (IRB)-approved retrospective study from January 2010 to June 2016. POPULATION: In all, 134 patients with ER+/HER2- invasive ductal carcinoma who underwent both breast MRI and Oncotype Dx RS evaluation. Patients were classified into three groups: low risk (group 1, RS <18), intermediate risk (group 2, RS 18-30), and high risk (group 3, RS >30). FIELD STRENGTH/SEQUENCE: 1.5T and 3.0T. Breast MRI, T1 postcontrast. ASSESSMENT: Each breast tumor underwent 3D segmentation. In all, 1649 volumetric slices in 134 tumors (mean 12.3 slices/tumor) were evaluated. A CNN consisted of four convolutional layers and max-pooling layers. Dropout at 50% was applied to the second to last fully connected layer to prevent overfitting. Three-class prediction (group 1 vs. group 2 vs. group 3) and two-class prediction (group 1 vs. group 2/3) models were performed. STATISTICAL TESTS: A 5-fold crossvalidation test was performed using 80% training and 20% testing. Diagnostic accuracy, sensitivity, specificity, and receiver operating characteristic (ROC) area under the curve (AUC) were evaluated. RESULTS: The CNN achieved an overall accuracy of 81% (95% confidence interval [CI] ± 4%) in three-class prediction with specificity 90% (95% CI ± 5%), sensitivity 60% (95% CI ± 6%), and the area under the ROC curve was 0.92 (SD, 0.01). The CNN achieved an overall accuracy of 84% (95% CI ± 5%) in two-class prediction with specificity 81% (95% CI ± 4%), sensitivity 87% (95% CI ± 5%), and the area under the ROC curve was 0.92 (SD, 0.01). DATA CONCLUSION: It is feasible for current deep CNN architecture to be trained to predict Oncotype DX RS. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:518-524.

Prior to Initiation of Chemotherapy, Can We Predict Breast Tumor Response? Deep Learning Convolutional Neural Networks Approach Using a Breast MRI Tumor Dataset.

We hypothesize that convolutional neural networks (CNN) can be used to predict neoadjuvant chemotherapy (NAC) response using a breast MRI tumor dataset prior to initiation of chemotherapy. An institutional review board-approved retrospective review of our database from January 2009 to June 2016 identified 141 locally advanced breast cancer patients who (1) underwent breast MRI prior to the initiation of NAC, (2) successfully completed adriamycin/taxane-based NAC, and (3) underwent surgical resection with available final surgical pathology data. Patients were classified into three groups based on their NAC response confirmed on final surgical pathology: complete (group 1), partial (group 2), and no response/progression (group 3). A total of 3107 volumetric slices of 141 tumors were evaluated. Breast tumor was identified on first T1 postcontrast dynamic images and underwent 3D segmentation. CNN consisted of ten convolutional layers, four max-pooling layers, and dropout of 50% after a fully connected layer. Dropout, augmentation, and L2 regularization were implemented to prevent overfitting of data. Non-linear functions were modeled by a rectified linear unit (ReLU). Batch normalization was used between the convolutional and ReLU layers to limit drift of layer activations during training. A three-class neoadjuvant prediction model was evaluated (group 1, group 2, or group 3). The CNN achieved an overall accuracy of 88% in three-class prediction of neoadjuvant treatment response. Three-class prediction discriminating one group from the other two was analyzed. Group 1 had a specificity of 95.1% ± 3.1%, sensitivity of 73.9% ± 4.5%, and accuracy of 87.7% ± 0.6%. Group 2 (partial response) had a specificity of 91.6% ± 1.3%, sensitivity of 82.4% ± 2.7%, and accuracy of 87.7% ± 0.6%. Group 3 (no response/progression) had a specificity of 93.4% ± 2.9%, sensitivity of 76.8% ± 5.7%, and accuracy of 87.8% ± 0.6%. It is feasible for current deep CNN architectures to be trained to predict NAC treatment response using a breast MRI dataset obtained prior to initiation of chemotherapy. Larger dataset will likely improve our prediction model.

Convolutional Neural Network Based Breast Cancer Risk Stratification Using a Mammographic Dataset.

RATIONALE AND OBJECTIVES: We propose a novel convolutional neural network derived pixel-wise breast cancer risk model using mammographic dataset. MATERIALS AND METHODS: An institutional review board approved retrospective case-control study of 1474 mammographic images was performed in average risk women. First, 210 patients with new incidence of breast cancer were identified. Mammograms from these patients prior to developing breast cancer were identified and made up the case group [420 bilateral craniocaudal mammograms]. The control group consisted of 527 patients without breast cancer from the same time period. Prior mammograms from these patients made up the control group [1054 bilateral craniocaudal mammograms]. A convolutional neural network (CNN) architecture was designed for pixel-wise breast cancer risk prediction. Briefly, each mammogram was normalized as a map of z-scores and resized to an input image size of 256 × 256. Then a contracting and expanding fully convolutional CNN architecture was composed entirely of 3 × 3 convolutions, a total of four strided convolutions instead of pooling layers, and symmetric residual connections. L2 regularization and augmentation methods were implemented to prevent overfitting. Cases were separated into training (80%) and test sets (20%). A 5-fold cross validation was performed. Software code was written in Python using the TensorFlow module on a Linux workstation with NVIDIA GTX 1070 Pascal GPU. RESULTS: The average age of patients between the case and the control groups was not statistically different [case: 57.4years (SD, 10.4) and control: 58.2years (SD, 10.9), p = 0.33]. Breast Density (BD) was significantly higher in the case group [2.39 (SD, 0.7)] than the control group [1.98 (SD, 0.75), p < 0.0001]. On multivariate logistic regression analysis, both CNN pixel-wise mammographic risk model and BD were significant independent predictors of breast cancer risk (p < 0.0001). The CNN risk model showed greater predictive potential [OR = 4.42 (95% CI, 3.4-5.7] compared to BD [OR = 1.67 (95% CI, 1.4-1.9). The CNN risk model achieved an overall accuracy of 72% (95%CI, 69.8-74.4) in predicting patients in the case group. CONCLUSION: Novel pixel-wise mammographic breast evaluation using a CNN architecture can stratify breast cancer risk, independent of the BD. Larger dataset will likely improve our model.

Predicting Post Neoadjuvant Axillary Response Using a Novel Convolutional Neural Network Algorithm.

OBJECTIVES: In the postneoadjuvant chemotherapy (NAC) setting, conventional radiographic complete response (rCR) is a poor predictor of pathologic complete response (pCR) of the axilla. We developed a convolutional neural network (CNN) algorithm to better predict post-NAC axillary response using a breast MRI dataset. METHODS: An institutional review board-approved retrospective study from January 2009 to June 2016 identified 127 breast cancer patients who: (1) underwent breast MRI before the initiation of NAC; (2) successfully completed Adriamycin/Taxane-based NAC; and (3) underwent surgery, including sentinel lymph node evaluation/axillary lymph node dissection with final surgical pathology data. Patients were classified into pathologic complete response (pCR) of the axilla group and non-pCR group based on surgical pathology. Breast MRI performed before NAC was used. Tumor was identified on first T1 postcontrast images underwent 3D segmentation. A total of 2811 volumetric slices of 127 tumors were evaluated. CNN consisted of 10 convolutional layers, 4 max-pooling layers. Dropout, augmentation and L2 regularization were implemented to prevent overfitting of data. RESULTS: On final surgical pathology, 38.6% (49/127) of the patients achieved pCR of the axilla (group 1), and 61.4% (78/127) of the patients did not with residual metastasis detected (group 2). For predicting axillary pCR, our CNN algorithm achieved an overall accuracy of 83% (95% confidence interval [CI] ± 5) with sensitivity of 93% (95% CI ± 6) and specificity of 77% (95% CI ± 4). Area under the ROC curve (0.93, 95% CI ± 0.04). CONCLUSIONS: It is feasible to use CNN architecture to predict post NAC axillary pCR. Larger data set will likely improve our prediction model.

Axillary Lymph Node Evaluation Utilizing Convolutional Neural Networks Using MRI Dataset.

The aim of this study is to evaluate the role of convolutional neural network (CNN) in predicting axillary lymph node metastasis, using a breast MRI dataset. An institutional review board (IRB)-approved retrospective review of our database from 1/2013 to 6/2016 identified 275 axillary lymph nodes for this study. Biopsy-proven 133 metastatic axillary lymph nodes and 142 negative control lymph nodes were identified based on benign biopsies (100) and from healthy MRI screening patients (42) with at least 3 years of negative follow-up. For each breast MRI, axillary lymph node was identified on first T1 post contrast dynamic images and underwent 3D segmentation using an open source software platform 3D Slicer. A 32 × 32 patch was then extracted from the center slice of the segmented tumor data. A CNN was designed for lymph node prediction based on each of these cropped images. The CNN consisted of seven convolutional layers and max-pooling layers with 50% dropout applied in the linear layer. In addition, data augmentation and L2 regularization were performed to limit overfitting. Training was implemented using the Adam optimizer, an algorithm for first-order gradient-based optimization of stochastic objective functions, based on adaptive estimates of lower-order moments. Code for this study was written in Python using the TensorFlow module (1.0.0). Experiments and CNN training were done on a Linux workstation with NVIDIA GTX 1070 Pascal GPU. Two class axillary lymph node metastasis prediction models were evaluated. For each lymph node, a final softmax score threshold of 0.5 was used for classification. Based on this, CNN achieved a mean five-fold cross-validation accuracy of 84.3%. It is feasible for current deep CNN architectures to be trained to predict likelihood of axillary lymph node metastasis. Larger dataset will likely improve our prediction model and can potentially be a non-invasive alternative to core needle biopsy and even sentinel lymph node evaluation.

Does breast MRI background parenchymal enhancement indicate metabolic activity? Qualitative and 3D quantitative computer imaging analysis.

PURPOSE: To investigate whether the degree of breast magnetic resonance imaging (MRI) background parenchymal enhancement (BPE) is associated with the amount of breast metabolic activity measured by breast parenchymal uptake (BPU) of 18F-FDG on positron emission tomography / computed tomography (PET/CT). MATERIALS AND METHODS: An Institutional Review Board (IRB)-approved retrospective study was performed. Of 327 patients who underwent preoperative breast MRI from 1/1/12 to 12/31/15, 73 patients had 18F-FDG PET/CT evaluation performed within 1 week of breast MRI and no suspicious findings in the contralateral breast. MRI was performed on a 1.5T or 3.0T system. The imaging sequence included a triplane localizing sequence followed by sagittal fat-suppressed T2 -weighted sequence, and a bilateral sagittal T1 -weighted fat-suppressed fast spoiled gradient-echo sequence, which was performed before and three times after a rapid bolus injection (gadobenate dimeglumine, Multihance; Bracco Imaging; 0.1 mmol/kg) delivered through an IV catheter. The unaffected contralateral breast in these 73 patients underwent BPE and BPU assessments. For PET/CT BPU calculation, a 3D region of interest (ROI) was drawn around the glandular breast tissue and the maximum standardized uptake value (SUVmax ) was determined. Qualitative MRI BPE assessments were performed on a 4-point scale, in accordance with BI-RADS categories. Additional 3D quantitative MRI BPE analysis was performed using a previously published in-house technique. Spearman's correlation test and linear regression analysis was performed (SPSS, v. 24). RESULT: The median time interval between breast MRI and 18F-FDG PET/CT evaluation was 3 days (range, 0-6 days). BPU SUVmax mean value was 1.6 (SD, 0.53). Minimum and maximum BPU SUVmax values were 0.71 and 4.0. The BPU SUVmax values significantly correlated with both the qualitative and quantitative measurements of BPE, respectively (r(71) = 0.59, P < 0.001 and r(71) = 0.54, P < 0.001). Qualitatively assessed high BPE group (BI-RADS 3/4) had significantly higher BPU SUVmax of 1.9 (SD = 0.44) compared to low BPE group (BI-RADS 1/2) with an average BPU SUVmax of 1.17 (SD = 0.32) (P < 0.001). On linear regression analysis, BPU SUVmax significantly predicted qualitative and quantitative measurements of BPE (ß = 1.29, t(71) = 3.88, P < 0.001 and ß = 19.52, t(71) = 3.88, P < 0.001). CONCLUSION: There is a significant association between breast BPU and BPE, measured both qualitatively and quantitatively. Increased breast cancer risk in patients with high MRI BPE could be due to elevated basal metabolic activity of the normal breast tissue, which may provide a susceptible environment for tumor growth. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:753-759.