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Extent of resection after surgery is one of the main prognostic factors for patients diagnosed with glioblastoma. To achieve this, accurate segmentation and classification of residual tumor from post-operative MR images is essential. The current standard method for estimating it is subject to high inter- and intra-rater variability, and an automated method for segmentation of residual tumor in early post-operative MRI could lead to a more accurate estimation of extent of resection. In this study, two state-of-the-art neural network architectures for pre-operative segmentation were trained for the task. The models were extensively validated on a multicenter dataset with nearly 1000 patients, from 12 hospitals in Europe and the United States. The best performance achieved was a 61\% Dice score, and the best classification performance was about 80\% balanced accuracy, with a demonstrated ability to generalize across hospitals. In addition, the segmentation performance of the best models was on par with human expert raters. The predicted segmentations can be used to accurately classify the patients into those with residual tumor, and those with gross total resection., Comment: 13 pages, 4 figures, 4 tables

While shrinkage is essential in high-dimensional settings, its use for low-dimensional regression-based prediction has been debated. It reduces variance, often leading to improved prediction accuracy. However, it also inevitably introduces bias, which may harm two other measures of predictive performance: calibration and coverage of confidence intervals. Much of the criticism stems from the usage of standard shrinkage methods, such as lasso and ridge with a single, cross-validated penalty. Our aim is to show that readily available alternatives can strongly improve predictive performance, in terms of accuracy, calibration or coverage. For linear regression, we use small sample splits of a large, fairly typical epidemiological data set to illustrate this. We show that usage of differential ridge penalties for covariate groups may enhance prediction accuracy, while calibration and coverage benefit from additional shrinkage of the penalties. In the logistic setting, we apply an external simulation to demonstrate that local shrinkage improves calibration with respect to global shrinkage, while providing better prediction accuracy than other solutions, like Firth's correction. The benefits of the alternative shrinkage methods are easily accessible via example implementations using \texttt{mgcv} and \texttt{r-stan}, including the estimation of multiple penalties. A synthetic copy of the large data set is shared for reproducibility., Comment: 35 pages including Supplementary Information

For patients suffering from brain tumor, prognosis estimation and treatment decisions are made by a multidisciplinary team based on a set of preoperative MR scans. Currently, the lack of standardized and automatic methods for tumor detection and generation of clinical reports represents a major hurdle. In this study, we investigate glioblastomas, lower grade gliomas, meningiomas, and metastases, through four cohorts of up to 4000 patients. Tumor segmentation models were trained using the AGU-Net architecture with different preprocessing steps and protocols. Segmentation performances were assessed in-depth using a wide-range of voxel and patient-wise metrics covering volume, distance, and probabilistic aspects. Finally, two software solutions have been developed, enabling an easy use of the trained models and standardized generation of clinical reports: Raidionics and Raidionics-Slicer. Segmentation performances were quite homogeneous across the four different brain tumor types, with an average true positive Dice ranging between 80% and 90%, patient-wise recall between 88% and 98%, and patient-wise precision around 95%. With our Raidionics software, running on a desktop computer with CPU support, tumor segmentation can be performed in 16 to 54 seconds depending on the dimensions of the MRI volume. For the generation of a standardized clinical report, including the tumor segmentation and features computation, 5 to 15 minutes are necessary. All trained models have been made open-access together with the source code for both software solutions and validation metrics computation. In the future, an automatic classification of the brain tumor type would be necessary to replace manual user input. Finally, the inclusion of post-operative segmentation in both software solutions will be key for generating complete post-operative standardized clinical reports., Comment: 20 pages, 5 figures, 10 tables

Model transparency is a prerequisite in many domains and an increasingly popular area in machine learning research. In the medical domain, for instance, unveiling the mechanisms behind a disease often has higher priority than the diagnostic itself since it might dictate or guide potential treatments and research directions. One of the most popular approaches to explain model global predictions is the permutation importance where the performance on permuted data is benchmarked against the baseline. However, this method and other related approaches will undervalue the importance of a feature in the presence of covariates since these cover part of its provided information. To address this issue, we propose Covered Information Disentanglement (CID), a method that considers all feature information overlap to correct the values provided by permutation importance. We further show how to compute CID efficiently when coupled with Markov random fields. We demonstrate its efficacy in adjusting permutation importance first on a controlled toy dataset and discuss its effect on real-world medical data.

One of the most common pitfalls often found in high dimensional biological data sets are correlations between the features. This may lead to statistical and machine learning methodologies overvaluing or undervaluing these correlated predictors, while the truly relevant ones are ignored. In this paper, we will define a new method called \textit{pairwise permutation algorithm} (PPA) with the aim of mitigating the correlation bias in feature importance values. Firstly, we provide a theoretical foundation, which builds upon previous work on permutation importance. PPA is then applied to a toy data set, where we demonstrate its ability to correct the correlation effect. We further test PPA on a microbiome shotgun dataset, to show that the PPA is already able to obtain biological relevant biomarkers., Comment: Submitted and accepted by AIMLAI, ECML PKDD 2021: European Conference on Machine Learning and Principles and Practice of Knowledge Discovery in Databases