Michael Iv

Ujjwal Baid, Satyam Ghodasara, Suyash Mohan et al.

The BraTS 2021 challenge celebrates its 10th anniversary and is jointly organized by the Radiological Society of North America (RSNA), the American Society of Neuroradiology (ASNR), and the Medical Image Computing and Computer Assisted Interventions (MICCAI) society. Since its inception, BraTS has been focusing on being a common benchmarking venue for brain glioma segmentation algorithms, with well-curated multi-institutional multi-parametric magnetic resonance imaging (mpMRI) data. Gliomas are the most common primary malignancies of the central nervous system, with varying degrees of aggressiveness and prognosis. The RSNA-ASNR-MICCAI BraTS 2021 challenge targets the evaluation of computational algorithms assessing the same tumor compartmentalization, as well as the underlying tumor's molecular characterization, in pre-operative baseline mpMRI data from 2,040 patients. Specifically, the two tasks that BraTS 2021 focuses on are: a) the segmentation of the histologically distinct brain tumor sub-regions, and b) the classification of the tumor's O[6]-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. The performance evaluation of all participating algorithms in BraTS 2021 will be conducted through the Sage Bionetworks Synapse platform (Task 1) and Kaggle (Task 2), concluding in distributing to the top ranked participants monetary awards of $60,000 collectively.

Darvin Yi, Endre Grøvik, Michael Iv et al.

We introduce a novel ensembling method, Random Bundle (RB), that improves performance for brain metastases segmentation. We create our ensemble by training each network on our dataset with 50% of our annotated lesions censored out. We also apply a lopsided bootstrap loss to recover performance after inducing an in silico 50% false negative rate and make our networks more sensitive. We improve our network detection of lesions's mAP value by 39% and more than triple the sensitivity at 80% precision. We also show slight improvements in segmentation quality through DICE score. Further, RB ensembling improves performance over baseline by a larger margin than a variety of popular ensembling strategies. Finally, we show that RB ensembling is computationally efficient by comparing its performance to a single network when both systems are constrained to have the same compute.

Darvin Yi, Endre Grøvik, Michael Iv et al.

Deep learning has proven to be an essential tool for medical image analysis. However, the need for accurately labeled input data, often requiring time- and labor-intensive annotation by experts, is a major limitation to the use of deep learning. One solution to this challenge is to allow for use of coarse or noisy labels, which could permit more efficient and scalable labeling of images. In this work, we develop a lopsided loss function based on entropy regularization that assumes the existence of a nontrivial false negative rate in the target annotations. Starting with a carefully annotated brain metastasis lesion dataset, we simulate data with false negatives by (1) randomly censoring the annotated lesions and (2) systematically censoring the smallest lesions. The latter better models true physician error because smaller lesions are harder to notice than the larger ones. Even with a simulated false negative rate as high as 50%, applying our loss function to randomly censored data preserves maximum sensitivity at 97% of the baseline with uncensored training data, compared to just 10% for a standard loss function. For the size-based censorship, performance is restored from 17% with the current standard to 88% with our lopsided bootstrap loss. Our work will enable more efficient scaling of the image labeling process, in parallel with other approaches on creating more efficient user interfaces and tools for annotation.

Endre Grøvik, Darvin Yi, Michael Iv et al.

The purpose was to assess the clinical value of a novel DropOut model for detecting and segmenting brain metastases, in which a neural network is trained on four distinct MRI sequences using an input dropout layer, thus simulating the scenario of missing MRI data by training on the full set and all possible subsets of the input data. This retrospective, multi-center study, evaluated 165 patients with brain metastases. A deep learning based segmentation model for automatic segmentation of brain metastases, named DropOut, was trained on multi-sequence MRI from 100 patients, and validated/tested on 10/55 patients. The segmentation results were compared with the performance of a state-of-the-art DeepLabV3 model. The MR sequences in the training set included pre- and post-gadolinium (Gd) T1-weighted 3D fast spin echo, post-Gd T1-weighted inversion recovery (IR) prepped fast spoiled gradient echo, and 3D fluid attenuated inversion recovery (FLAIR), whereas the test set did not include the IR prepped image-series. The ground truth were established by experienced neuroradiologists. The results were evaluated using precision, recall, Dice score, and receiver operating characteristics (ROC) curve statistics, while the Wilcoxon rank sum test was used to compare the performance of the two neural networks. The area under the ROC curve (AUC), averaged across all test cases, was 0.989+-0.029 for the DropOut model and 0.989+-0.023 for the DeepLabV3 model (p=0.62). The DropOut model showed a significantly higher Dice score compared to the DeepLabV3 model (0.795+-0.105 vs. 0.774+-0.104, p=0.017), and a significantly lower average false positive rate of 3.6/patient vs. 7.0/patient (p<0.001) using a 10mm3 lesion-size limit. The DropOut model may facilitate accurate detection and segmentation of brain metastases on a multi-center basis, even when the test cohort is missing MRI input data.

Darvin Yi, Endre Grøvik, Michael Iv et al.

Magnetic resonance (MR) imaging is an essential diagnostic tool in clinical medicine. Recently, a variety of deep learning methods have been applied to segmentation tasks in medical images, with promising results for computer-aided diagnosis. For MR images, effectively integrating different pulse sequences is important to optimize performance. However, the best way to integrate different pulse sequences remains unclear. In this study, we evaluate multiple architectural features and characterize their effects in the task of metastasis segmentation. Specifically, we consider (1) different pulse sequence integration schemas, (2) different modes of weight sharing for parallel network branches, and (3) a new approach for enabling robustness to missing pulse sequences. We find that levels of integration and modes of weight sharing that favor low variance work best in our regime of small data (n = 100). By adding an input-level dropout layer, we could preserve the overall performance of these networks while allowing for inference on inputs with missing pulse sequence. We illustrate not only the generalizability of the network but also the utility of this robustness when applying the trained model to data from a different center, which does not use the same pulse sequences. Finally, we apply network visualization methods to better understand which input features are most important for network performance. Together, these results provide a framework for building networks with enhanced robustness to missing data while maintaining comparable performance in medical imaging applications.

Endre Grøvik, Darvin Yi, Michael Iv et al.

Detecting and segmenting brain metastases is a tedious and time-consuming task for many radiologists, particularly with the growing use of multi-sequence 3D imaging. This study demonstrates automated detection and segmentation of brain metastases on multi-sequence MRI using a deep learning approach based on a fully convolution neural network (CNN). In this retrospective study, a total of 156 patients with brain metastases from several primary cancers were included. Pre-therapy MR images (1.5T and 3T) included pre- and post-gadolinium T1-weighted 3D fast spin echo, post-gadolinium T1-weighted 3D axial IR-prepped FSPGR, and 3D fluid attenuated inversion recovery. The ground truth was established by manual delineation by two experienced neuroradiologists. CNN training/development was performed using 100 and 5 patients, respectively, with a 2.5D network based on a GoogLeNet architecture. The results were evaluated in 51 patients, equally separated into those with few (1-3), multiple (4-10), and many (>10) lesions. Network performance was evaluated using precision, recall, Dice/F1 score, and ROC-curve statistics. For an optimal probability threshold, detection and segmentation performance was assessed on a per metastasis basis. The area under the ROC-curve (AUC), averaged across all patients, was 0.98. The AUC in the subgroups was 0.99, 0.97, and 0.97 for patients having 1-3, 4-10, and >10 metastases, respectively. Using an average optimal probability threshold determined by the development set, precision, recall, and Dice-score were 0.79, 0.53, and 0.79, respectively. At the same probability threshold, the network showed an average false positive rate of 8.3/patient (no lesion-size limit) and 3.4/patient (10 mm3 lesion size limit). In conclusion, a deep learning approach using multi-sequence MRI can aid in the detection and segmentation of brain metastases.