Diffusion MRI anomaly detection in glioma patients.

Diffusion-MRI (dMRI) measures molecular diffusion, which allows to characterize microstructural properties of the human brain. Gliomas strongly alter these microstructural properties. Delineation of brain tumors currently mainly relies on conventional MRI-techniques, which are, however, known to underestimate tumor volumes in diffusely infiltrating glioma. We hypothesized that dMRI is well suited for tumor delineation, and developed two different deep-learning approaches. The first diffusion-anomaly detection architecture is a denoising autoencoder, the second consists of a reconstruction and a discrimination network. Each model was exclusively trained on non-annotated dMRI of healthy subjects, and then applied on glioma patients' data. To validate these models, a state-of-the-art supervised tumor segmentation network was modified to generate groundtruth tumor volumes based on structural MRI. Compared to groundtruth segmentations, a dice score of 0.67 ± 0.2 was obtained. Further inspecting mismatches between diffusion-anomalous regions and groundtruth segmentations revealed, that these colocalized with lesions delineated only later on in structural MRI follow-up data, which were not visible at the initial time of recording. Anomaly-detection methods are suitable for tumor delineation in dMRI acquisitions, and may further enhance brain-imaging analysis by detection of occult tumor infiltration in glioma patients, which could improve prognostication of disease evolution and tumor treatment strategies.

Information content of brain states is explained by structural constraints on state energetics.

Signal propagation along the structural connectome of the brain induces changes in the patterns of activity. These activity patterns define global brain states and contain information in accordance with their expected probability of occurrence. Being the physical substrate upon which information propagates, the structural connectome, in conjunction with the dynamics, determines the set of possible brain states and constrains the transition between accessible states. Yet, precisely how these structural constraints on state transitions relate to their information content remains unexplored. To address this gap in knowledge, we defined the information content as a function of the activation distribution, where statistically rare values of activation correspond to high information content. With this numerical definition in hand, we studied the spatiotemporal distribution of information content in functional magnetic resonance imaging (fMRI) data from the Human Connectome Project during different tasks, and report four key findings. First, information content strongly depends on cognitive context; its absolute level and spatial distribution depend on the cognitive task. Second, while information content shows similarities to other measures of brain activity, it is distinct from both Neurosynth maps and task contrast maps generated by a general linear model applied to the fMRI data. Third, the brain's structural wiring constrains the cost to control its state, where the cost to transition into high information content states is larger than that to transition into low information content states. Finally, all state transitions-especially those to high information content states-are less costly than expected from random network null models, thereby indicating the brains marked efficiency. Taken together, our findings establish an explanatory link between the information contained in a brain state and the energetic cost of attaining that state, thereby laying important groundwork for our understanding of large-scale cognitive computations.

Improving Localization of Brain Tumors through 3D GAN Inpainting.

For survival prediction of brain tumor patients based on MRI scans, radiomic features have been a major research focus in the last years. However, radiomic features do not take the location of the lesion into account, which, in relation to the functional regions of the brain, could be a significant factor in predicting survival. An automatic and exact localization of the tumor in relation to specific functional areas is not straightforward, as typical brain parcellation methods fail in presence of large lesions. Here, we propose a model that replaces the tumorous region in 3D brain MRI scans with healthy tissue in order to improve the registration process towards a brain template. Further, we assemble a set of features for quantitative description of brain tumor location. On an openly available dataset, registration is strongly improved. The extracted location features also have better predictive performance when used after the proposed registration step and reach accuracies in survival prediction comparable to radiomic features.Clinical relevance- This work improves the quantification of the location of brain tumors in the human brain and proposes an extension of radiomic features to include the location, resulting in a refined prediction of patient survival.

Dissociation of structural and functional connectomic coherence in glioma patients.

With diffuse infiltrative glioma being increasingly recognized as a systemic brain disorder, the macroscopically apparent tumor lesion is suggested to impact on cerebral functional and structural integrity beyond the apparent lesion site. We investigated resting-state functional connectivity (FC) and diffusion-MRI-based structural connectivity (SC) (comprising edge-weight (EW) and fractional anisotropy (FA)) in isodehydrogenase mutated (IDHmut) and wildtype (IDHwt) patients and healthy controls. SC and FC were determined for whole-brain and the Default-Mode Network (DMN), mean intra- and interhemispheric SC and FC were compared across groups, and partial correlations were analyzed intra- and intermodally. With interhemispheric EW being reduced in both patient groups, IDHwt patients showed FA decreases in the ipsi- and contralesional hemisphere, whereas IDHmut patients revealed FA increases in the contralesional hemisphere. Healthy controls showed strong intramodal connectivity, each within the structural and functional connectome. Patients however showed a loss in structural and reductions in functional connectomic coherence, which appeared to be more pronounced in IDHwt glioma patients. Findings suggest a relative dissociation of structural and functional connectomic coherence in glioma patients at the time of diagnosis, with more structural connectomic aberrations being encountered in IDHwt glioma patients. Connectomic profiling may aid in phenotyping and monitoring prognostically differing tumor types.

Analyzing the effects of free water modeling by deep learning on diffusion MRI structural connectivity estimates in glioma patients.

Diffusion-weighted MRI makes it possible to quantify subvoxel brain microstructure and to reconstruct white matter fiber trajectories with which structural connectomes can be created. However, at the border between cerebrospinal fluid and white matter, or in the presence of edema, the obtained MRI signal originates from both the cerebrospinal fluid as well as from the white matter partial volume. Diffusion tractography can be strongly influenced by these free water partial volume effects. Thus, including a free water model can improve diffusion tractography in glioma patients. Here, we analyze how including a free water model influences structural connectivity estimates in healthy subjects as well as in brain tumor patients. During a clinical study, we acquired diffusion MRI data of 35 glioma patients and 28 age- and sex-matched controls, on which we applied an open-source deep learning based free water model. We performed deterministic as well as probabilistic tractography before and after free water modeling, and utilized the tractograms to create structural connectomes. Finally, we performed a quantitative analysis of the connectivity matrices. In our experiments, the number of tracked diffusion streamlines increased by 13% for high grade glioma patients, 9.25% for low grade glioma, and 7.65% for healthy controls. Intra-subject similarity of hemispheres increased significantly for the patient as well as for the control group, with larger effects observed in the patient group. Furthermore, inter-subject differences in connectivity between brain tumor patients and healthy subjects were reduced when including free water modeling. Our results indicate that free water modeling increases the similarity of connectivity matrices in brain tumor patients, while the observed effects are less pronounced in healthy subjects. As the similarity between brain tumor patients and healthy controls also increased, connectivity changes in brain tumor patients may have been overestimated in studies that did not perform free water modeling.

Radiomics feature reproducibility under inter-rater variability in segmentations of CT images.

Identifying image features that are robust with respect to segmentation variability is a tough challenge in radiomics. So far, this problem has mainly been tackled in test-retest analyses. In this work we analyse radiomics feature reproducibility in two phases: first with manual segmentations provided by four expert readers and second with probabilistic automated segmentations using a recently developed neural network (PHiseg). We test feature reproducibility on three publicly available datasets of lung, kidney and liver lesions. We find consistent results both over manual and automated segmentations in all three datasets and show that there are subsets of radiomic features which are robust against segmentation variability and other radiomic features which are prone to poor reproducibility under differing segmentations. By providing a detailed analysis of robustness of the most common radiomics features across several datasets, we envision that more reliable and reproducible radiomic models can be built in the future based on this work.

Cross-scanner and cross-protocol multi-shell diffusion MRI data harmonization: Algorithms and results.

Cross-scanner and cross-protocol variability of diffusion magnetic resonance imaging (dMRI) data are known to be major obstacles in multi-site clinical studies since they limit the ability to aggregate dMRI data and derived measures. Computational algorithms that harmonize the data and minimize such variability are critical to reliably combine datasets acquired from different scanners and/or protocols, thus improving the statistical power and sensitivity of multi-site studies. Different computational approaches have been proposed to harmonize diffusion MRI data or remove scanner-specific differences. To date, these methods have mostly been developed for or evaluated on single b-value diffusion MRI data. In this work, we present the evaluation results of 19 algorithms that are developed to harmonize the cross-scanner and cross-protocol variability of multi-shell diffusion MRI using a benchmark database. The proposed algorithms rely on various signal representation approaches and computational tools, such as rotational invariant spherical harmonics, deep neural networks and hybrid biophysical and statistical approaches. The benchmark database consists of data acquired from the same subjects on two scanners with different maximum gradient strength (80 and 300 â€‹mT/m) and with two protocols. We evaluated the performance of these algorithms for mapping multi-shell diffusion MRI data across scanners and across protocols using several state-of-the-art imaging measures. The results show that data harmonization algorithms can reduce the cross-scanner and cross-protocol variabilities to a similar level as scan-rescan variability using the same scanner and protocol. In particular, the LinearRISH algorithm based on adaptive linear mapping of rotational invariant spherical harmonics features yields the lowest variability for our data in predicting the fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK) and the rotationally invariant spherical harmonic (RISH) features. But other algorithms, such as DIAMOND, SHResNet, DIQT, CMResNet show further improvement in harmonizing the return-to-origin probability (RTOP). The performance of different approaches provides useful guidelines on data harmonization in future multi-site studies.

Robustness of Radiomics for Survival Prediction of Brain Tumor Patients Depending on Resection Status.

Prediction of overall survival based on multimodal MRI of brain tumor patients is a difficult problem. Although survival also depends on factors that cannot be assessed via preoperative MRI such as surgical outcome, encouraging results for MRI-based survival analysis have been published for different datasets. We assess if and how established radiomic approaches as well as novel methods can predict overall survival of brain tumor patients on the BraTS challenge dataset. This dataset consists of multimodal preoperative images of 211 glioblastoma patients from several institutions with reported resection status and known survival. In the official challenge setting, only patients with a reported gross total resection (GTR) are taken into account. We therefore evaluated previously published methods as well as different machine learning approaches on the BraTS dataset. For different types of resection status, these approaches are compared to a baseline, a linear regression on patient age only. This naive approach won the 3rd place out of 26 participants in the BraTS survival prediction challenge 2018. Previously published radiomic signatures show significant correlations and predictiveness to patient survival for patients with a reported subtotal resection. However, for patients with reported GTR, none of the evaluated approaches was able to outperform the age-only baseline in a cross-validation setting, explaining the poor performance of approaches based on radiomics in the BraTS challenge 2018.