Subject-Specific Automatic Reconstruction of White Matter Tracts.

MRI-based tractography is still underexploited and unsuited for routine use in brain tumor surgery due to heterogeneity of methods and functional-anatomical definitions and above all, the lack of a turn-key system. Standardization of methods is therefore desirable, whereby an objective and reliable approach is a prerequisite before the results of any automated procedure can subsequently be validated and used in neurosurgical practice. In this work, we evaluated these preliminary but necessary steps in healthy volunteers. Specifically, we evaluated the robustness and reliability (i.e., test-retest reproducibility) of tractography results of six clinically relevant white matter tracts by using healthy volunteer data (N = 136) from the Human Connectome Project consortium. A deep learning convolutional network-based approach was used for individualized segmentation of regions of interest, combined with an evidence-based tractography protocol and appropriate post-tractography filtering. Robustness was evaluated by estimating the consistency of tractography probability maps, i.e., averaged tractograms in normalized space, through the use of a hold-out cross-validation approach. No major outliers were found, indicating a high robustness of the tractography results. Reliability was evaluated at the individual level. First by examining the overlap of tractograms that resulted from repeatedly processed identical MRI scans (N = 10, 10 iterations) to establish an upper limit of reliability of the pipeline. Second, by examining the overlap for subjects that were scanned twice at different time points (N = 40). Both analyses indicated high reliability, with the second analysis showing a reliability near the upper limit. The robust and reliable subject-specific generation of white matter tracts in healthy subjects holds promise for future validation of our pipeline in a clinical population and subsequent implementation in brain tumor surgery.

The frontal aslant tract and its role in executive functions: a quantitative tractography study in glioma patients.

Focal white matter lesions can cause cognitive impairments due to disconnections within or between networks. There is some preliminary evidence that there are specific hubs and fiber pathways that should be spared during surgery to retain cognitive performance. A tract potentially involved in important higher-level cognitive processes is the frontal aslant tract. It roughly connects the posterior parts of the inferior frontal gyrus and the superior frontal gyrus. Functionally, the left frontal aslant tract has been associated with speech and the right tract with executive functions. However, there currently is insufficient knowledge about the right frontal aslant tract's exact functional importance. The aim of this study was to investigate the role of the right frontal aslant tract in executive functions via a lesion-symptom approach. We retrospectively examined 72 patients with frontal glial tumors and correlated measures from tractography (distance between tract and tumor, and structural integrity of the tract) with cognitive test performances. The results indicated involvement of the right frontal aslant tract in shifting attention and letter fluency. This involvement was not found for the left tract. Although this study was exploratory, these converging findings contribute to a better understanding of the functional frontal subcortical anatomy. Shifting attention and letter fluency are important for healthy cognitive functioning, and when impaired they may greatly influence a patient's wellbeing. Further research is needed to assess whether or not damage to the right frontal aslant tract causes permanent cognitive impairments, and consequently identifies this tract as a critical pathway that should be taken into account during neurosurgical procedures.

Modeling of intracerebral interictal epileptic discharges: Evidence for network interactions.

OBJECTIVE: The interictal epileptic discharges (IEDs) occurring in stereotactic EEG (SEEG) recordings are in general abundant compared to ictal discharges, but difficult to interpret due to complex underlying network interactions. A framework is developed to model these network interactions. METHODS: To identify the synchronized neuronal activity underlying the IEDs, the variation in correlation over time of the SEEG signals is related to the occurrence of IEDs using the general linear model. The interdependency is assessed of the brain areas that reflect highly synchronized neural activity by applying independent component analysis, followed by cluster analysis of the spatial distributions of the independent components. The spatiotemporal interactions of the spike clusters reveal the leading or lagging of brain areas. RESULTS: The analysis framework was evaluated for five successfully operated patients, showing that the spike cluster that was related to the MRI-visible brain lesions coincided with the seizure onset zone. The additional value of the framework was demonstrated for two more patients, who were MRI-negative and for whom surgery was not successful. CONCLUSIONS: A network approach is promising in case of complex epilepsies. SIGNIFICANCE: Analysis of IEDs is considered a valuable addition to routine review of SEEG recordings, with the potential to increase the success rate of epilepsy surgery.

Stability metrics for optic radiation tractography: Towards damage prediction after resective surgery.

BACKGROUND: An accurate delineation of the optic radiation (OR) using diffusion MR tractography may reduce the risk of a visual field deficit after temporal lobe resection. However, tractography is prone to generate spurious streamlines, which deviate strongly from neighboring streamlines and hinder a reliable distance measurement between the temporal pole and the Meyer's loop (ML-TP distance). NEW METHOD: Stability metrics are introduced for the automated removal of spurious streamlines near the Meyer's loop. Firstly, fiber-to-bundle coherence (FBC) measures can identify spurious streamlines by estimating their alignment with the surrounding streamline bundle. Secondly, robust threshold selection removes spurious streamlines while preventing an underestimation of the extent of the Meyer's loop. Standardized parameter selection is realized through test-retest evaluation of the variability in ML-TP distance. RESULTS: The variability in ML-TP distance after parameter selection was below 2mm for each of the healthy volunteers studied (N=8). The importance of the stability metrics is illustrated for epilepsy surgery candidates (N=3) for whom the damage to the Meyer's loop was evaluated by comparing the pre- and post-operative OR reconstruction. The difference between predicted and observed damage is in the order of a few millimeters, which is the error in measured ML-TP distance. COMPARISON WITH EXISTING METHOD(S): The stability metrics are a novel method for the robust estimate of the ML-TP distance. CONCLUSIONS: The stability metrics are a promising tool for clinical trial studies, in which the damage to the OR can be related to the visual field deficit that may occur after epilepsy surgery.

Structural Brain Network: What is the Effect of LiFE Optimization of Whole Brain Tractography?

Structural brain networks constructed based on diffusion-weighted MRI (dMRI) have provided a systems perspective to explore the organization of the human brain. Some redundant and nonexistent fibers, however, are inevitably generated in whole brain tractography. We propose to add one critical step while constructing the networks to remove these fibers using the linear fascicle evaluation (LiFE) method, and study the differences between the networks with and without LiFE optimization. For a cohort of nine healthy adults and for 9 out of the 35 subjects from Human Connectome Project, the T 1-weighted images and dMRI data are analyzed. Each brain is parcellated into 90 regions-of-interest, whilst a probabilistic tractography algorithm is applied to generate the original connectome. The elimination of redundant and nonexistent fibers from the original connectome by LiFE creates the optimized connectome, and the random selection of the same number of fibers as the optimized connectome creates the non-optimized connectome. The combination of parcellations and these connectomes leads to the optimized and non-optimized networks, respectively. The optimized networks are constructed with six weighting schemes, and the correlations of different weighting methods are analyzed. The fiber length distributions of the non-optimized and optimized connectomes are compared. The optimized and non-optimized networks are compared with regard to edges, nodes and networks, within a sparsity range of 0.75-0.95. It has been found that relatively more short fibers exist in the optimized connectome. About 24.0% edges of the optimized network are significantly different from those in the non-optimized network at a sparsity of 0.75. About 13.2% of edges are classified as false positives or the possible missing edges. The strength and betweenness centrality of some nodes are significantly different for the non-optimized and optimized networks, but not the node efficiency. The normalized clustering coefficient, the normalized characteristic path length and the small-worldness are higher in the optimized network weighted by the fiber number than in the non-optimized network. These observed differences suggest that LiFE optimization can be a crucial step for the construction of more reasonable and more accurate structural brain networks.

The influence of construction methodology on structural brain network measures: A review.

Structural brain networks based on diffusion MRI and tractography show robust attributes such as small-worldness, hierarchical modularity, and rich-club organization. However, there are large discrepancies in the reports about specific network measures. It is hypothesized that these discrepancies result from the influence of construction methodology. We surveyed the methodological options and their influences on network measures. It is found that most network measures are sensitive to the scale of brain parcellation, MRI gradient schemes and orientation model, and the tractography algorithm, which is in accordance with the theoretical analysis of the small-world network model. Different network weighting schemes represent different attributes of brain networks, which makes these schemes incomparable between studies. Methodology choice depends on the specific study objectives and a clear understanding of the pros and cons of a particular methodology. Because there is no way to eliminate these influences, it seems more practical to quantify them, optimize the methodologies, and construct structural brain networks with multiple spatial resolutions, multiple edge densities, and multiple weighting schemes.