Deep learning prediction of axillary lymph node status using ultrasound images.

OBJECTIVE: To investigate the ability of our convolutional neural network (CNN) to predict axillary lymph node metastasis using primary breast cancer ultrasound (US) images. METHODS: In this IRB-approved study, 338 US images (two orthogonal images) from 169 patients from 1/2014-12/2016 were used. Suspicious lymph nodes were seen on US and patients subsequently underwent core-biopsy. 64 patients had metastatic lymph nodes. A custom CNN was utilized on 248 US images from 124 patients in the training dataset and tested on 90 US images from 45 patients. The CNN was implemented entirely of 3 × 3 convolutional kernels and linear layers. The 9 convolutional kernels consisted of 6 residual layers, totaling 12 convolutional layers. Feature maps were down-sampled using strided convolutions. Dropout with a 0.5 keep probability and L2 normalization was utilized. Training was implemented by using the Adam optimizer and a final SoftMax score threshold of 0.5 from the average of raw logits from each pixel was used for two class classification (metastasis or not). RESULTS: Our CNN achieved an AUC of 0.72 (SD ± 0.08) in predicting axillary lymph node metastasis from US images in the testing dataset. The model had an accuracy of 72.6% (SD ± 8.4) with a sensitivity and specificity of 65.5% (SD ± 28.6) and 78.9% (SD ± 15.1) respectively. Our algorithm is available to be shared for research use. (https://github.com/stmutasa/MetUS). CONCLUSION: It's feasible to predict axillary lymph node metastasis from US images using a deep learning technique. This can potentially aid nodal staging in patients with breast cancer.

Weakly Supervised Deep Learning Approach to Breast MRI Assessment.

RATIONALE AND OBJECTIVES: To evaluate a weakly supervised deep learning approach to breast Magnetic Resonance Imaging (MRI) assessment without pixel level segmentation in order to improve the specificity of breast MRI lesion classification. MATERIALS AND METHODS: In this IRB approved study, the dataset consisted of 278,685 image slices from 438 patients. The weakly supervised network was based on the Resnet-101 architecture. Training was implemented using the Adam optimizer and a final SoftMax score threshold of 0.5 was used for two class classification (malignant or benign). 278,685 image slices were combined into 92,895 3-channel images. 79,871 (85%) images were used for training and validation while 13,024 (15%) images were separated for testing. Of the testing dataset, 11,498 (88%) were benign and 1531 (12%) were malignant. Model performance was assessed. RESULTS: The weakly supervised network achieved an AUC of 0.92 (SD ± 0.03) in distinguishing malignant from benign images. The model had an accuracy of 94.2% (SD ± 3.4) with a sensitivity and specificity of 74.4% (SD ± 8.5) and 95.3% (SD ± 3.3) respectively. CONCLUSION: It is feasible to use a weakly supervised deep learning approach to assess breast MRI images without the need for pixel-by-pixel segmentation yielding a high degree of specificity in lesion classification.

Multi-site, multi-platform comparison of MRI T1 measurement using the system phantom.

Recent innovations in quantitative magnetic resonance imaging (MRI) measurement methods have led to improvements in accuracy, repeatability, and acquisition speed, and have prompted renewed interest to reevaluate the medical value of quantitative T1. The purpose of this study was to determine the bias and reproducibility of T1 measurements in a variety of MRI systems with an eye toward assessing the feasibility of applying diagnostic threshold T1 measurement across multiple clinical sites. We used the International Society of Magnetic Resonance in Medicine/National Institute of Standards and Technology (ISMRM/NIST) system phantom to assess variations of T1 measurements, using a slow, reference standard inversion recovery sequence and a rapid, commonly-available variable flip angle sequence, across MRI systems at 1.5 tesla (T) (two vendors, with number of MRI systems n = 9) and 3 T (three vendors, n = 18). We compared the T1 measurements from inversion recovery and variable flip angle scans to ISMRM/NIST phantom reference values using Analysis of Variance (ANOVA) to test for statistical differences between T1 measurements grouped according to MRI scanner manufacturers and/or static field strengths. The inversion recovery method had minor over- and under-estimations compared to the NMR-measured T1 values at both 1.5 T and 3 T. Variable flip angle measurements had substantially greater deviations from the NMR-measured T1 values than the inversion recovery measurements. At 3 T, the measured variable flip angle T1 for one vendor is significantly different than the other two vendors for most of the samples throughout the clinically relevant range of T1. There was no consistent pattern of discrepancy between vendors. We suggest establishing rigorous quality control procedures for validating quantitative MRI methods to promote confidence and stability in associated measurement techniques and to enable translation of diagnostic threshold from the research center to the entire clinical community.

How Many Radiographs Does It Take to Screen for Femoral Cam Morphology?: A Noninferiority Study.

PURPOSE: To compare a 2-view radiograph series (AP of the pelvis and 45° Dunn of the hip) with a 5-view radiograph series for sensitivity in identifying femoral cam morphology. MATERIALS AND METHODS: This is a retrospective review of consecutive patients with a 5-view radiograph series (AP pelvis and AP, 45° Dunn, frog lateral, and false profile of the affected hip) from 2016 to 2017. Three fellowship trained radiologists blindly and independently evaluated 2 views (AP pelvis and Dunn) for a femoral cam lesion, acetabular rim calcification, Tonnis grade, and important incidental findings. Two weeks later, the same assessment was made on all 5 views. A noninferiority test of the 2-view series vs the 5-view series for sensitivity in identifying femoral cam morphology was conducted. Individual reader sensitivity calculations were performed and agreement was determined with the kappa statistic. RESULTS: The 2-view series was noninferior to the 5-view series for cam identification (P value = 0.010). In comparing the 2-view vs 5-view series for individual readers, there was no difference in the sensitivities (84%-100% vs 85%-98%, P = 0.85-1.0) or specificities (11%-56% vs 7%-56%, P = 0.58-1.0) for cam identification. There was fair to excellent 2-view intrareader agreement (k = 0.38-0.93) and similar inter-reader agreement between the 2-view and 5-view (k = 0.33 vs 0.37). CONCLUSIONS: A 2-view radiograph series (AP pelvis and Dunn hip) is noninferior to a 5-view radiograph series for sensitivity in identifying femoral cam morphology.

A novel CNN algorithm for pathological complete response prediction using an I-SPY TRIAL breast MRI database.

PURPOSE: To apply our convolutional neural network (CNN) algorithm to predict neoadjuvant chemotherapy (NAC) response using the I-SPY TRIAL breast MRI dataset. METHODS: From the I-SPY TRIAL breast MRI database, 131 patients from 9 institutions were successfully downloaded for analysis. First post-contrast MRI images were used for 3D segmentation using 3D slicer. Our CNN was implemented entirely of 3 × 3 convolutional kernels and linear layers. The convolutional kernels consisted of 6 residual layers, totaling 12 convolutional layers. Dropout with a 0.5 keep probability and L2 normalization was utilized. Training was implemented by using the Adam optimizer. A 5-fold cross validation was used for performance evaluation. Software code was written in Python using the TensorFlow module on a Linux workstation with one NVidia Titan X GPU. RESULTS: Of 131 patients, 40 patients achieved pCR following NAC (group 1) and 91 patients did not achieve pCR following NAC (group 2). Diagnostic accuracy of our CNN two classification model distinguishing patients with pCR vs non-pCR was 72.5 (SD ± 8.4), with sensitivity 65.5% (SD ± 28.1) and specificity of 78.9% (SD ± 15.2). The area under a ROC Curve (AUC) was 0.72 (SD ± 0.08). CONCLUSION: It is feasible to use our CNN algorithm to predict NAC response in patients using a multi-institution dataset.

Convolutional Neural Network Detection of Axillary Lymph Node Metastasis Using Standard Clinical Breast MRI.

BACKGROUND: Axillary lymph node status is important for breast cancer staging and treatment planning as the majority of breast cancer metastasis spreads through the axillary lymph nodes. There is currently no reliable noninvasive imaging method to detect nodal metastasis associated with breast cancer. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) data were those from the peak contrast dynamic image from 1.5 Tesla MRI scanners at the pre-neoadjuvant chemotherapy stage. Data consisted of 66 abnormal nodes from 38 patients and 193 normal nodes from 61 patients. Abnormal nodes were those determined by expert radiologist based on 18Fluorodeoxyglucose positron emission tomography images. Normal nodes were those with negative diagnosis of breast cancer. The convolutional neural network consisted of 5 convolutional layers with filters from 16 to 128. Receiver operating characteristic analysis was performed to evaluate prediction performance. For comparison, an expert radiologist also scored the same nodes as normal or abnormal. RESULTS: The convolutional neural network model yielded a specificity of 79.3% ± 5.1%, sensitivity of 92.1% ± 2.9%, positive predictive value of 76.9% ± 4.0%, negative predictive value of 93.3% ± 1.9%, accuracy of 84.8% ± 2.4%, and receiver operating characteristic area under the curve of 0.91 ± 0.02 for the validation data set. These results compared favorably with scoring by radiologists (accuracy of 78%). CONCLUSION: The results are encouraging and suggest that this approach may prove useful for classifying lymph node status on MRI in clinical settings in patients with breast cancer, although additional studies are needed before routine clinical use can be realized. This approach has the potential to ultimately be a noninvasive alternative to lymph node biopsy.

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.

Repeatability of Quantitative Diffusion-Weighted Imaging Metrics in Phantoms, Head-and-Neck and Thyroid Cancers: Preliminary Findings.

The aim of this study was to establish the repeatability measures of quantitative Gaussian and non-Gaussian diffusion metrics using diffusion-weighted imaging (DWI) data from phantoms and patients with head-and-neck and papillary thyroid cancers. The Quantitative Imaging Biomarker Alliance (QIBA) DWI phantom and a novel isotropic diffusion kurtosis imaging phantom were scanned at 3 different sites, on 1.5T and 3T magnetic resonance imaging systems, using standardized multiple b-value DWI acquisition protocol. In the clinical component of this study, a total of 60 multiple b-value DWI data sets were analyzed for test-retest, obtained from 14 patients (9 head-and-neck squamous cell carcinoma and 5 papillary thyroid cancers). Repeatability of quantitative DWI measurements was assessed by within-subject coefficient of variation (wCV%) and Bland-Altman analysis. In isotropic diffusion kurtosis imaging phantom vial with 2% ceteryl alcohol and behentrimonium chloride solution, the mean apparent diffusion (Dapp × 10-3 mm2/s) and kurtosis (Kapp, unitless) coefficient values were 1.02 and 1.68 respectively, capturing in vivo tumor cellularity and tissue microstructure. For the same vial, Dapp and Kapp mean wCVs (%) were ≤1.41% and ≤0.43% for 1.5T and 3T across 3 sites. For pretreatment head-and-neck squamous cell carcinoma, apparent diffusion coefficient, D, D*, K, and f mean wCVs (%) were 2.38%, 3.55%, 3.88%, 8.0%, and 9.92%, respectively; wCVs exhibited a higher trend for papillary thyroid cancers. Knowledge of technical precision and bias of quantitative imaging metrics enables investigators to properly design and power clinical trials and better discern between measurement variability versus biological change.

Multicenter Repeatability Study of a Novel Quantitative Diffusion Kurtosis Imaging Phantom.

Quantitative kurtosis phantoms are sought by multicenter clinical trials to establish accuracy and precision of quantitative imaging biomarkers on the basis of diffusion kurtosis imaging (DKI) parameters. We designed and evaluated precision, reproducibility, and long-term stability of a novel isotropic (i)DKI phantom fabricated using four families of chemicals based on vesicular and lamellar mesophases of liquid crystal materials. The constructed iDKI phantoms included negative control monoexponential diffusion materials to independently characterize noise and model-induced bias in quantitative kurtosis parameters. Ten test-retest DKI studies were performed on four scanners at three imaging centers over a six-month period. The tested prototype phantoms exhibited physiologically relevant apparent diffusion, Dapp, and kurtosis, Kapp, parameters ranging between 0.4 and 1.1 (×10-3 mm2/s) and 0.8 and 1.7 (unitless), respectively. Measured kurtosis phantom Kapp exceeded maximum fit model bias (0.1) detected for negative control (zero kurtosis) materials. The material-specific parameter precision [95% CI for Dapp: 0.013-0.022(×10-3 mm2/s) and for Kapp: 0.009-0.076] derived from the test-retest analysis was sufficient to characterize thermal and temporal stability of the prototype DKI phantom through correlation analysis of inter-scan variability. The present study confirms a promising chemical design for stable quantitative DKI phantom based on vesicular mesophase of liquid crystal materials. Improvements to phantom preparation and temperature monitoring procedures have potential to enhance precision and reproducibility for future multicenter iDKI phantom studies.

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 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.

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.

Advanced MR Imaging of the Temporal Bone.

Temporal bone pathologies are challenging to discern because of their small size and subtle contrast. MR imaging is one of the key modalities in evaluating otologic diseases. Current advancement in MR techniques provide multiparametric information for evaluation of these pathologies. The aim of this article is to review state-of-the-art 3-dimensional morphologic and diffusion sequences for otologic MR imaging.

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.

Insulin Hexamer-Caged Gadolinium Ion as MRI Contrast-o-phore.

High-relaxivity protein-complexes of GdIII are being pursued as MRI contrast agents in hope that they can be used at much lower doses that would minimize toxic-side effects of GdIII release from traditional contrast agents. We construct here a new type of protein-based MRI contrast agent, a proteinaceous cage based on a stable insulin hexamer in which GdIII is captured inside a water filled cavity. The macromolecular structure and the large number of "free" GdIII coordination sites available for water binding lead to exceptionally high relaxivities per one GdIII ion. The GdIII slowly diffuses out of this cage, but this diffusion can be prevented by addition of ligands that bind to the hexamer. The ligands that trigger structural changes in the hexamer, SCN- , Cl- and phenols, modulate relaxivities through an outside-in signaling that is allosterically transduced through the protein cage. Contrast-o-phores based on protein-caged metal ions have potential to become clinical contrast agents with environmentally-sensitive properties.

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.

Can diffusion-weighted imaging serve as a biomarker of fibrosis in pancreatic adenocarcinoma?

PURPOSE: To assess the relationship between diffusion-weighted imaging (DWI) and intravoxel incoherent motion (IVIM)-derived quantitative parameters (apparent diffusion coefficient [ADC], perfusion fraction [f], Dslow , diffusion coefficient [D], and Dfast , pseudodiffusion coefficient [D*]) and histopathology in pancreatic adenocarcinoma (PAC). MATERIALS AND METHODS: Subjects with suspected surgically resectable PAC were prospectively enrolled in this Health Insurance Portability and Accountability Act (HIPAA)-compliant, Institutional Review Board-approved study. Imaging was performed at 1.5T with a respiratory-triggered echo planar DWI sequence using 10 b values. Two readers drew regions of interest (ROIs) over the tumor and adjacent nontumoral tissue. Monoexponential and biexponential fits were used to derive ADC2b , ADCall , f, D, and D*, which were compared to quantitative histopathology of fibrosis, mean vascular density, and cellularity. Two biexponential IVIM models were investigated and compared: 1) nonlinear least-square fitting based on the Levenberg-Marquardt algorithm, and 2) linear fit using a fixed D* (20 mm2 /s). Statistical analysis included Student's t-test, Pearson correlation (P < 0.05 was considered significant), intraclass correlation, and coefficients of variance. RESULTS: Twenty subjects with PAC were included in the final cohort. Negative correlation between D and fibrosis (Reader 2: r = -0.57 P = 0.01; pooled P = -0.46, P = 0.04) was observed with a trend toward positive correlation between f and fibrosis (r = 0.44, P = 0.05). ADC2b was significantly lower in PAC with dense fibrosis than with loose fibrosis ADC2b (P = 0.03). Inter- and intrareader agreement was excellent for ADC, D, and f. CONCLUSION: In PAC, D negatively correlates with fibrosis, with a trend toward positive correlation with f suggesting both perfusion and diffusion effects contribute to stromal desmoplasia. ADC2b is significantly lower in tumors with dense fibrosis and may serve as a biomarker of fibrosis architecture. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:393-402.

Evaluation of neonatal brain myelination using the T1- and T2-weighted MRI ratio.

PURPOSE: To validate the T1- and T2-weighted (T1w/T2w) MRI ratio technique in evaluating myelin in the neonatal brain. MATERIALS AND METHODS: T1w and T2w MR images of 10 term neonates with normal-appearing brain parenchyma were obtained from a single 1.5 Tesla MRI and retrospectively analyzed. T1w/T2w ratio images were created with a postprocessing pipeline and qualitatively compared with standard clinical sequences (T1w, T2w, and apparent diffusion coefficient [ADC]). Quantitative assessment was also performed to assess the ratio technique in detecting areas of known myelination (e.g., posterior limb of the internal capsule) and very low myelination (e.g., optic radiations) using linear regression analysis and the Michelson Contrast equation, a measure of luminance contrast intensity. RESULTS: The ratio image provided qualitative improvements in the ability to visualize regional variation in myelin content of neonates. Linear regression analysis demonstrated a significant inverse relationship between the ratio intensity values and ADC values in the posterior limb of the internal capsule and the optic radiations (R2 = 0.96 and P < 0.001). The Michelson Contrast equation showed that contrast differences between these two regions for the ratio images were 1.6 times higher than T1w, 2.6 times higher than T2w, and 1.8 times higher than ADC (all P < 0.001). Finally, the ratio improved visualization of the corticospinal tract, one of the earliest myelinated pathways. CONCLUSION: The T1w/T2w ratio accentuates contrast between myelinated and less myelinated structures and may enhance our diagnostic ability to detect myelination patterns in the neonatal brain. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage2 J. MAGN. RESON. IMAGING 2017;46:690-696.