Birgit Ertl‐Wagner

Khashayar Namdar, Matthias W. Wagner, Birgit B. Ertl-Wagner et al. · utoronto

Background: As an important branch of machine learning pipelines in medical imaging, radiomics faces two major challenges namely reproducibility and accessibility. In this work, we introduce open-radiomics, a set of radiomics datasets along with a comprehensive radiomics pipeline based on our proposed technical protocol to improve the reproducibility of the results. Methods: We curated large-scale radiomics datasets based on three open-source datasets; BraTS 2020 for high-grade glioma (HGG) versus low-grade glioma (LGG) classification and survival analysis, BraTS 2023 for O6-methylguanine-DNA methyltransferase classification, and non-small cell lung cancer survival analysis from the Cancer Imaging Archive. Using BraTS 2020 Magnetic Resonance Imaging (MRI) dataset, we applied our protocol to 369 brain tumor patients (76 LGG, 293 HGG). Leveraging PyRadiomics for LGG vs. HGG classification, we generated 288 datasets from 4 MRI sequences, 3 binWidths, 6 normalization methods, and 4 tumor subregions. Random Forest classifiers were trained and validated (60%,20%,20%) across 100 different data splits (28,800 test results), evaluating Area Under the Receiver Operating Characteristic Curve (AUROC). Results: Unlike binWidth and image normalization, tumor subregion and imaging sequence significantly affected performance of the models. T1 contrast-enhanced sequence and the union of Necrotic and the non-enhancing tumor core subregions resulted in the highest AUROCs (average test AUROC 0.951, 95% confidence interval of (0.949, 0.952)). Although several settings and data splits (28 out of 28800) yielded test AUROC of 1, they were irreproducible. Conclusion: Our experiments demonstrate the sources of variability in radiomics pipelines (e.g., tumor subregion) can have a significant impact on the results, which may lead to superficial perfect performances that are irreproducible.

Meng Zhou, Matthias W Wagner, Uri Tabori et al.

Medical image analysis has significantly benefited from advancements in deep learning, particularly in the application of Generative Adversarial Networks (GANs) for generating realistic and diverse images that can augment training datasets. However, the effectiveness of such approaches is often limited by the amount of available data in clinical settings. Additionally, the common GAN-based approach is to generate entire image volumes, rather than solely the region of interest (ROI). Research on deep learning-based brain tumor classification using MRI has shown that it is easier to classify the tumor ROIs compared to the entire image volumes. In this work, we present a novel framework that uses vector-quantization GAN and a transformer incorporating masked token modeling to generate high-resolution and diverse 3D brain tumor ROIs that can be directly used as augmented data for the classification of brain tumor ROI. We apply our method to two imbalanced datasets where we augment the minority class: (1) the Multimodal Brain Tumor Segmentation Challenge (BraTS) 2019 dataset to generate new low-grade glioma (LGG) ROIs to balance with high-grade glioma (HGG) class; (2) the internal pediatric LGG (pLGG) dataset tumor ROIs with BRAF V600E Mutation genetic marker to balance with BRAF Fusion genetic marker class. We show that the proposed method outperforms various baseline models in both qualitative and quantitative measurements. The generated data was used to balance the data in the brain tumor types classification task. Using the augmented data, our approach surpasses baseline models by 6.4% in AUC on the BraTS 2019 dataset and 4.3% in AUC on our internal pLGG dataset. The results indicate the generated tumor ROIs can effectively address the imbalanced data problem. Our proposed method has the potential to facilitate an accurate diagnosis of rare brain tumors using MRI scans.

Jay J. Yoo, Khashayar Namdar, Matthias W. Wagner et al. · utoronto

Segmentation of regions of interest (ROIs) for identifying abnormalities is a leading problem in medical imaging. Using machine learning for this problem generally requires manually annotated ground-truth segmentations, demanding extensive time and resources from radiologists. This work presents a weakly supervised approach that utilizes binary image-level labels, which are much simpler to acquire, to effectively segment anomalies in 2D magnetic resonance images without ground truth annotations. We train a generative adversarial network (GAN) that converts cancerous images to healthy variants, which are used along with localization seeds as priors to generate improved weakly supervised segmentations. The non-cancerous variants can also be used to evaluate the segmentations in a weakly supervised fashion, which allows for the most effective segmentations to be identified and then applied to downstream clinical classification tasks. On the Multimodal Brain Tumor Segmentation (BraTS) 2020 dataset, our proposed method generates and identifies segmentations that achieve test Dice coefficients of 83.91%. Using these segmentations for pathology classification results with a test AUC of 93.32% which is comparable to the test AUC of 95.80% achieved when using true segmentations.

Khashayar Namdar, Matthias W. Wagner, Cynthia Hawkins et al.

Pediatric Low-Grade Neuroepithelial Tumors (PLGNT) are the most common pediatric cancer type, accounting for 40% of brain tumors in children, and identifying PLGNT molecular subtype is crucial for treatment planning. However, the gold standard to determine the PLGNT subtype is biopsy, which can be impractical or dangerous for patients. This research improves the performance of Convolutional Neural Networks (CNNs) in classifying PLGNT subtypes through MRI scans by introducing a loss function that specifically improves the model's Area Under the Receiver Operating Characteristic (ROC) Curve (AUROC), offering a non-invasive diagnostic alternative. In this study, a retrospective dataset of 339 children with PLGNT (143 BRAF fusion, 71 with BRAF V600E mutation, and 125 non-BRAF) was curated. We employed a CNN model with Monte Carlo random data splitting. The baseline model was trained using binary cross entropy (BCE), and achieved an AUROC of 86.11% for differentiating BRAF fusion and BRAF V600E mutations, which was improved to 87.71% using our proposed AUROC loss function (p-value 0.045). With multiclass classification, the AUROC improved from 74.42% to 76. 59% (p-value 0.0016).

Partoo Vafaeikia, Matthias W. Wagner, Uri Tabori et al.

Brain tumor segmentation is a critical task for tumor volumetric analyses and AI algorithms. However, it is a time-consuming process and requires neuroradiology expertise. While there has been extensive research focused on optimizing brain tumor segmentation in the adult population, studies on AI guided pediatric tumor segmentation are scarce. Furthermore, MRI signal characteristics of pediatric and adult brain tumors differ, necessitating the development of segmentation algorithms specifically designed for pediatric brain tumors. We developed a segmentation model trained on magnetic resonance imaging (MRI) of pediatric patients with low-grade gliomas (pLGGs) from The Hospital for Sick Children (Toronto, Ontario, Canada). The proposed model utilizes deep Multitask Learning (dMTL) by adding tumor's genetic alteration classifier as an auxiliary task to the main network, ultimately improving the accuracy of the segmentation results.

Martin Dyrba, Moritz Hanzig, Slawek Altenstein et al.

Background: Although convolutional neural networks (CNN) achieve high diagnostic accuracy for detecting Alzheimer's disease (AD) dementia based on magnetic resonance imaging (MRI) scans, they are not yet applied in clinical routine. One important reason for this is a lack of model comprehensibility. Recently developed visualization methods for deriving CNN relevance maps may help to fill this gap. We investigated whether models with higher accuracy also rely more on discriminative brain regions predefined by prior knowledge. Methods: We trained a CNN for the detection of AD in N=663 T1-weighted MRI scans of patients with dementia and amnestic mild cognitive impairment (MCI) and verified the accuracy of the models via cross-validation and in three independent samples including N=1655 cases. We evaluated the association of relevance scores and hippocampus volume to validate the clinical utility of this approach. To improve model comprehensibility, we implemented an interactive visualization of 3D CNN relevance maps. Results: Across three independent datasets, group separation showed high accuracy for AD dementia vs. controls (AUC$\geq$0.92) and moderate accuracy for MCI vs. controls (AUC$\approx$0.75). Relevance maps indicated that hippocampal atrophy was considered as the most informative factor for AD detection, with additional contributions from atrophy in other cortical and subcortical regions. Relevance scores within the hippocampus were highly correlated with hippocampal volumes (Pearson's r$\approx$-0.86, p<0.001). Conclusion: The relevance maps highlighted atrophy in regions that we had hypothesized a priori. This strengthens the comprehensibility of the CNN models, which were trained in a purely data-driven manner based on the scans and diagnosis labels.

Fausto Milletari, Seyed-Ahmad Ahmadi, Christine Kroll et al.

In this work we propose a novel approach to perform segmentation by leveraging the abstraction capabilities of convolutional neural networks (CNNs). Our method is based on Hough voting, a strategy that allows for fully automatic localisation and segmentation of the anatomies of interest. This approach does not only use the CNN classification outcomes, but it also implements voting by exploiting the features produced by the deepest portion of the network. We show that this learning-based segmentation method is robust, multi-region, flexible and can be easily adapted to different modalities. In the attempt to show the capabilities and the behaviour of CNNs when they are applied to medical image analysis, we perform a systematic study of the performances of six different network architectures, conceived according to state-of-the-art criteria, in various situations. We evaluate the impact of both different amount of training data and different data dimensionality (2D, 2.5D and 3D) on the final results. We show results on both MRI and transcranial US volumes depicting respectively 26 regions of the basal ganglia and the midbrain.