Ashirbani Saha

Effects of MRI scanner parameters on breast cancer radiomics

Purpose To assess the impact of varying magnetic resonance imaging (MRI) scanner parameters on the extraction of algorithmic features in breast MRI radiomics studies. Methods In this retrospective study, breast imaging data for 272 patients were analyzed with magnetic resonance (MR) images. From the MR images, we assembled and implemented 529 algorithmic features of breast tumors and fibrograndular tissue (FGT). We divided the features into 10 groups based on the type of data used for the feature extraction and the nature of the extracted information. Three scanner parameters were considered: scanner manufacturer, scanner magnetic field strength, and slice thickness. We assessed the impact of each of the scanner parameters on each of the feature by testing whether the feature values are systematically diverse for different values of these scanner parameters. A two-sample t-test has been used to establish whether the impact of a scanner parameter on values of a feature is significant and receiver operating characteristics have been used for to establish the extent of that effect. Results On average, higher proportion (69% FGT versus 20% tumor) of FGT related features were affected by the three scanner parameters. Of all feature groups and scanner parameters, the feature group related to the variation in FGT enhancement was found to be the most sensitive to the scanner manufacturer (AUC = 0.81 ± 0.14). Conclusions Features involving calculations from FGT are particularly sensitive to the scanner parameters.

Radiogenomics of lower-grade glioma: algorithmically-assessed tumor shape is associated with tumor genomic subtypes and patient outcomes in a multi-institutional study with The Cancer Genome Atlas data

Recent studies identified distinct genomic subtypes of lower-grade gliomas that could potentially be used to guide patient treatment. This study aims to determine whether there is an association between genomics of lower-grade glioma tumors and patient outcomes using algorithmic measurements of tumor shape in magnetic resonance imaging (MRI). We analyzed preoperative imaging and genomic subtype data from 110 patients with lower-grade gliomas (WHO grade II and III) from The Cancer Genome Atlas. Computer algorithms were applied to analyze the imaging data and provided five quantitative measurements of tumor shape in two and three dimensions. Genomic data for the analyzed cohort of patients consisted of previously identified genomic clusters based on IDH mutation and 1p/19q co-deletion, DNA methylation, gene expression, DNA copy number, and microRNA expression. Patient outcomes were quantified by overall survival. We found that there is a strong association between angular standard deviation (ASD), which measures irregularity of the tumor boundary, and the IDH-1p/19q subtype (p < 0.0017), RNASeq cluster (p < 0.0002), DNA copy number cluster (p < 0.001), and the cluster of clusters (p < 0.0002). The RNASeq cluster was also associated with bounding ellipsoid volume ratio (p < 0.0005). Tumors in the IDH wild type cluster and R2 RNASeq cluster which are associated with much poorer outcomes generally had higher ASD reflecting more irregular shape. ASD also showed association with patient overall survival (p = 0.006). Shape features in MRI were strongly associated with genomic subtypes and patient outcomes in lower-grade glioma.

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

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).

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.

Deep learning for segmentation of brain tumors: Impact of cross‐institutional training and testing

BACKGROUND AND PURPOSE Convolutional neural networks (CNNs) are commonly used for segmentation of brain tumors. In this work, we assess the effect of cross-institutional training on the performance of CNNs. METHODS We selected 44 glioblastoma (GBM) patients from two institutions in The Cancer Imaging Archive dataset. The images were manually annotated by outlining each tumor component to form ground truth. To automatically segment the tumors in each patient, we trained three CNNs: (a) one using data for patients from the same institution as the test data, (b) one using data for the patients from the other institution and (c) one using data for the patients from both of the institutions. The performance of the trained models was evaluated using Dice similarity coefficients as well as Average Hausdorff Distance between the ground truth and automatic segmentations. The 10-fold cross-validation scheme was used to compare the performance of different approaches. RESULTS Performance of the model significantly decreased (P < 0.0001) when it was trained on data from a different institution (dice coefficients: 0.68 ± 0.19 and 0.59 ± 0.19) as compared to training with data from the same institution (dice coefficients: 0.72 ± 0.17 and 0.76 ± 0.12). This trend persisted for segmentation of the entire tumor as well as its individual components. CONCLUSIONS There is a very strong effect of selecting data for training on performance of CNNs in a multi-institutional setting. Determination of the reasons behind this effect requires additional comprehensive investigation.

Breast cancer molecular subtype classification using deep features: preliminary results.

Radiogenomics is a field of investigation that attempts to examine the relationship between imaging characteris- tics of cancerous lesions and their genomic composition. This could offer a noninvasive alternative to establishing genomic characteristics of tumors and aid cancer treatment planning. While deep learning has shown its supe- riority in many detection and classification tasks, breast cancer radiogenomic data suffers from a very limited number of training examples, which renders the training of the neural network for this problem directly and with no pretraining a very difficult task. In this study, we investigated an alternative deep learning approach referred to as deep features or off-the-shelf network approach to classify breast cancer molecular subtypes using breast dynamic contrast enhanced MRIs. We used the feature maps of different convolution layers and fully connected layers as features and trained support vector machines using these features for prediction. For the feature maps that have multiple layers, max-pooling was performed along each channel. We focused on distinguishing the Luminal A subtype from other subtypes. To evaluate the models, 10 fold cross-validation was performed and the final AUC was obtained by averaging the performance of all the folds. The highest average AUC obtained was 0.64 (0.95 CI: 0.57-0.71), using the feature maps of the last fully connected layer. This indicates the promise of using this approach to predict the breast cancer molecular subtypes. Since the best performance appears in the last fully connected layer, it also implies that breast cancer molecular subtypes may relate to high level image features

Relationship between Background Parenchymal Enhancement on High-risk Screening MRI and Future Breast Cancer Risk

RATIONALE AND OBJECTIVES To determine if background parenchymal enhancement (BPE) on screening breast magnetic resonance imaging (MRI) in high-risk women correlates with future cancer. MATERIALS AND METHODS All screening breast MRIs (n = 1039) in high-risk women at our institution from August 1, 2004, to July 30, 2013, were identified. Sixty-one patients who subsequently developed breast cancer were matched 1:2 by age and high-risk indication with patients who did not develop breast cancer (n = 122). Five fellowship-trained breast radiologists independently recorded the BPE. The median reader BPE for each case was calculated and compared between the cancer and control cohorts. RESULTS Cancer cohort patients were high-risk because of a history of radiation therapy (10%, 6 of 61), high-risk lesion (18%, 11 of 61), or breast cancer (30%, 18 of 61); BRCA mutation (18%, 11 of 61); or family history (25%, 15 of 61). Subsequent malignancies were invasive ductal carcinoma (64%, 39 of 61), ductal carcinoma in situ (30%, 18 of 61) and invasive lobular carcinoma (7%, 4of 61). BPE was significantly higher in the cancer cohort than in the control cohort (P = 0.01). Women with mild, moderate, or marked BPE were 2.5 times more likely to develop breast cancer than women with minimal BPE (odds ratio = 2.5, 95% confidence interval: 1.3-4.8, P = .005). There was fair interreader agreement (κ = 0.39). CONCLUSIONS High-risk women with greater than minimal BPE at screening MRI have increased risk of future breast cancer.

Radiogenomic analysis of lower grade glioma: a pilot multi-institutional study shows an association between quantitative image features and tumor genomics

Recent studies showed that genomic analysis of lower grade gliomas can be very effective for stratification of patients into groups with different prognosis and proposed specific genomic classifications. In this study, we explore the association of one of those genomic classifications with imaging parameters to determine whether imaging could serve a similar role to genomics in cancer patient treatment. Specifically, we analyzed imaging and genomics data for 110 patients from 5 institutions from The Cancer Genome Atlas and The Cancer Imaging Archive datasets. The analyzed imaging data contained preoperative FLAIR sequence for each patient. The images were analyzed using the in-house algorithms which quantify 2D and 3D aspects of the tumor shape. Genomic data consisted of a cluster of clusters classification proposed in a very recent and leading publication in the field of lower grade glioma genomics. Our statistical analysis showed that there is a strong association between the tumor cluster-of-clusters subtype and two imaging features: bounding ellipsoid volume ratio and angular standard deviation. This result shows high promise for the potential use of imaging as a surrogate measure for genomics in the decision process regarding treatment of lower grade glioma patients.

Deep learning for segmentation of brain tumors: can we train with images from different institutions?

Deep learning and convolutional neural networks (CNNs) in particular are increasingly popular tools for segmentation and classification of medical images. CNNs were shown to be successful for segmentation of brain tumors into multiple regions or labels. However, in the environment which fosters data-sharing and collection of multi-institutional datasets, a question arises: does training with data from another institution with potentially different imaging equipment, contrast protocol, and patient population impact the segmentation performance of the CNN? Our study presents preliminary data towards answering this question. Specifically, we used MRI data of glioblastoma (GBM) patients for two institutions present in The Cancer Imaging Archive. We performed a process of training and testing CNN multiple times such that half of the time the CNN was tested on data from the same institution that was used for training and half of the time it was tested on another institution, keeping the training and testing set size constant. We observed a decrease in performance as measured by Dice coefficient when the CNN was trained with data from a different institution as compared to training with data from the same institution. The changes in performance for the entire tumor and for four different labels within the tumor were: 0.72 to 0.65 (p=0.06), 0.61 to 0.58 (p=0.49), 0.54 to 0.51 (p=0.82), 0.31 to 0.24 (p<0.03), and 0.43 to 0.31(p<0.003) respectively. In summary, we found that while data across institutions can be used for development of CNNs, this might be associated with a decrease in performance.

Association of high proliferation marker Ki-67 expression with DCEMR imaging features of breast: a large scale evaluation.

One of the methods widely used to measure the proliferative activity of cells in breast cancer patients is the immunohistochemical (IHC) measurement of the percentage of cells stained for nuclear antigen Ki-67. Use of Ki-67 expression as a prognostic marker is still under investigation. However, numerous clinical studies have reported an association between a high Ki-67 and overall survival (OS) and disease free survival (DFS). On the other hand, to offer non-invasive alternative in determining Ki-67 expression, researchers have made recent attempts to study the association of Ki-67 expression with magnetic resonance (MR) imaging features of breast cancer in small cohorts (<30). Here, we present a large scale evaluation of the relationship between imaging features and Ki-67 score as: (a) we used a set of 450 invasive breast cancer patients, (b) we extracted a set of 529 imaging features of shape and enhancement from breast, tumor and fibroglandular tissue of the patients, (c) used a subset of patients as the training set to select features and trained a multivariate logistic regression model to predict high versus low Ki-67 values, and (d) we validated the performance of the trained model in an independent test set using the area-under the receiver operating characteristics (ROC) curve (AUC) of the values predicted. Our model was able to predict high versus low Ki-67 in the test set with an AUC of 0.67 (95% CI: 0.58-0.75, p<1.1e-04). Thus, a moderate strength of association of Ki-67 values and MRextracted imaging features was demonstrated in our experiments.