PhyberSIM: a tool for the generation of ground truth to evaluate brain fiber clustering algorithms.

Diffusion Magnetic Resonance Imaging tractography is a non-invasive technique that produces a collection of streamlines representing the main white matter bundle trajectories. Methods, such as fiber clustering algorithms, are important in computational neuroscience and have been the basis of several white matter analysis methods and studies. Nevertheless, these clustering methods face the challenge of the absence of ground truth of white matter fibers, making their evaluation difficult. As an alternative solution, we present an innovative brain fiber bundle simulator that uses spline curves for fiber representation. The methodology uses a tubular model for the bundle simulation based on a bundle centroid and five radii along the bundle. The algorithm was tested by simulating 28 Deep White Matter atlas bundles, leading to low inter-bundle distances and high intersection percentages between the original and simulated bundles. To prove the utility of the simulator, we created three whole-brain datasets containing different numbers of fiber bundles to assess the quality performance of QuickBundles and Fast Fiber Clustering algorithms using five clustering metrics. Our results indicate that QuickBundles tends to split less and Fast Fiber Clustering tends to merge less, which is consistent with their expected behavior. The performance of both algorithms decreases when the number of bundles is increased due to higher bundle crossings. Additionally, the two algorithms exhibit robust behavior with input data permutation. To our knowledge, this is the first whole-brain fiber bundle simulator capable of assessing fiber clustering algorithms with realistic data.

Phybers: a package for brain tractography analysis.

We present a Python library (Phybers) for analyzing brain tractography data. Tractography datasets contain streamlines (also called fibers) composed of 3D points representing the main white matter pathways. Several algorithms have been proposed to analyze this data, including clustering, segmentation, and visualization methods. The manipulation of tractography data is not straightforward due to the geometrical complexity of the streamlines, the file format, and the size of the datasets, which may contain millions of fibers. Hence, we collected and structured state-of-the-art methods for the analysis of tractography and packed them into a Python library, to integrate and share tools for tractography analysis. Due to the high computational requirements, the most demanding modules were implemented in C/C++. Available functions include brain Bundle Segmentation (FiberSeg), Hierarchical Fiber Clustering (HClust), Fast Fiber Clustering (FFClust), normalization to a reference coordinate system, fiber sampling, calculation of intersection between sets of brain fibers, tools for cluster filtering, calculation of measures from clusters, and fiber visualization. The library tools were structured into four principal modules: Segmentation, Clustering, Utils, and Visualization (Fibervis). Phybers is freely available on a GitHub repository under the GNU public license for non-commercial use and open-source development, which provides sample data and extensive documentation. In addition, the library can be easily installed on both Windows and Ubuntu operating systems through the pip library.

Superficial white matter bundle atlas based on hierarchical fiber clustering over probabilistic tractography data.

The study of short association fibers is still an incomplete task due to their higher inter-subject variability and the smaller size of this kind of fibers in comparison to known long association bundles. However, their description is essential to understand human brain dysfunction and better characterize the human brain connectome. In this work, we present a multi-subject atlas of short association fibers, which was computed using a superficial white matter bundle identification method based on fiber clustering. To create the atlas, we used probabilistic tractography from one hundred subjects from the HCP database, aligned with non-linear registration. The method starts with an intra-subject clustering of short fibers (30-85 mm). Based on a cortical atlas, the intra-subject cluster centroids from all subjects are segmented to identify the centroids connecting each region of interest (ROI) of the atlas. To reduce computational load, the centroids from each ROI group are randomly separated into ten subgroups. Then, an inter-subject hierarchical clustering is applied to each centroid subgroup, followed by a second level of clustering to select the most-reproducible clusters across subjects for each ROI group. Finally, the clusters are labeled according to the regions that they connect, and clustered to create the final bundle atlas. The resulting atlas is composed of 525 bundles of superficial short association fibers along the whole brain, with 384 bundles connecting pairs of different ROIs and 141 bundles connecting portions of the same ROI. The reproducibility of the bundles was verified using automatic segmentation on three different tractogram databases. Results for deterministic and probabilistic tractography data show high reproducibility, especially for probabilistic tractography in HCP data. In comparison to previous work, our atlas features a higher number of bundles and greater cortical surface coverage.

Fiber Clustering Acceleration With a Modified Kmeans++ Algorithm Using Data Parallelism.

Fiber clustering methods are typically used in brain research to study the organization of white matter bundles from large diffusion MRI tractography datasets. These methods enable exploratory bundle inspection using visualization and other methods that require identifying brain white matter structures in individuals or a population. Some applications, such as real-time visualization and inter-subject clustering, need fast and high-quality intra-subject clustering algorithms. This work proposes a parallel algorithm using a General Purpose Graphics Processing Unit (GPGPU) for fiber clustering based on the FFClust algorithm. The proposed GPGPU implementation exploits data parallelism using both multicore and GPU fine-grained parallelism present in commodity architectures, including current laptops and desktop computers. Our approach implements all FFClust steps in parallel, improving execution times in all of them. In addition, our parallel approach includes a parallel Kmeans++ algorithm implementation and defines a new variant of Kmeans++ to reduce the impact of choosing outliers as initial centroids. The results show that our approach provides clustering quality results very similar to FFClust, and it requires an execution time of 3.5 s for processing about a million fibers, achieving a speedup of 11.5 times compared to FFClust.

ABrainVis: an android brain image visualization tool.

BACKGROUND: The visualization and analysis of brain data such as white matter diffusion tractography and magnetic resonance imaging (MRI) volumes is commonly used by neuro-specialist and researchers to help the understanding of brain structure, functionality and connectivity. As mobile devices are widely used among users and their technology shows a continuous improvement in performance, different types of applications have been designed to help users in different work areas. RESULTS: We present, ABrainVis, an Android mobile tool that allows users to visualize different types of brain images, such as white matter diffusion tractographies, represented as fibers in 3D, segmented fiber bundles, MRI 3D images as rendered volumes and slices, and meshes. The tool enables users to choose and combine different types of brain imaging data to provide visual anatomical context for specific visualization needs. ABrainVis provides high performance over a wide range of Android devices, including tablets and cell phones using medium and large tractography datasets. Interesting visualizations including brain tumors and arteries, along with fiber, are given as examples of case studies using ABrainVis. CONCLUSIONS: The functionality, flexibility and performance of ABrainVis tool introduce an improvement in user experience enabling neurophysicians and neuroscientists fast visualization of large tractography datasets, as well as the ability to incorporate other brain imaging data such as MRI volumes and meshes, adding anatomical contextual information.

From Coarse to Fine-Grained Parcellation of the Cortical Surface Using a Fiber-Bundle Atlas.

In this article, we present a hybrid method to create fine-grained parcellations of the cortical surface, from a coarse-grained parcellation according to an anatomical atlas, based on cortico-cortical connectivity. The connectivity information is obtained from segmented superficial and deep white matter bundles, according to bundle atlases, instead of the whole tractography. Thus, a direct matching between the fiber bundles and the cortical regions is obtained, avoiding the problem of finding the correspondence of the cortical parcels among subjects. Generating parcels from segmented fiber bundles can provide a good representation of the human brain connectome since they are based on bundle atlases that contain the most reproducible short and long connections found on a population of subjects. The method first processes the tractography of each subject and extracts the bundles of the atlas, based on a segmentation algorithm. Next, the intersection between the fiber bundles and the cortical mesh is calculated, to define the initial and final intersection points of each fiber. A fiber filtering is then applied to eliminate misclassified fibers, based on the anatomical definition of each bundle and the labels of Desikan-Killiany anatomical parcellation. A parcellation algorithm is then performed to create a subdivision of the anatomical regions of the cortex, which is reproducible across subjects. This step resolves the overlapping of the fiber bundle extremities over the cortical mesh within each anatomical region. For the analysis, the density of the connections and the degree of overlapping, is considered and represented with a graph. One of our parcellations, an atlas composed of 160 parcels, achieves a reproducibility across subjects of ≈0.74, based on the average Dice's coefficient between subject's connectivity matrices, rather than ≈0.73 obtained for a macro anatomical parcellation of 150 parcels. Moreover, we compared two of our parcellations with state-of-the-art atlases, finding a degree of similarity with dMRI, functional, anatomical, and multi-modal atlases. The higher similarity was found for our parcellation composed of 185 sub-parcels with another parcellation based on dMRI data from the same database, but created with a different approach, leading to 130 parcels in common based on a Dice's coefficient ≥0.5.

FFClust: Fast fiber clustering for large tractography datasets for a detailed study of brain connectivity.

Automated methods that can identify white matter bundles from large tractography datasets have several applications in neuroscience research. In these applications, clustering algorithms have shown to play an important role in the analysis and visualization of white matter structure, generating useful data which can be the basis for further studies. This work proposes FFClust, an efficient fiber clustering method for large tractography datasets containing millions of fibers. Resulting clusters describe the whole set of main white matter fascicles present on an individual brain. The method aims to identify compact and homogeneous clusters, which enables several applications. In individuals, the clusters can be used to study the local connectivity in pathological brains, while at population level, the processing and analysis of reproducible bundles, and other post-processing algorithms can be carried out to study the brain connectivity and create new white matter bundle atlases. The proposed method was evaluated in terms of quality and execution time performance versus the state-of-the-art clustering techniques used in the area. Results show that FFClust is effective in the creation of compact clusters, with a low intra-cluster distance, while keeping a good quality Davies-Bouldin index, which is a metric that quantifies the quality of clustering approaches. Furthermore, it is about 8.6 times faster than the most efficient state-of-the-art method for one million fibers dataset. In addition, we show that FFClust is able to correctly identify atlas bundles connecting different brain regions, as an example of application and the utility of compact clusters.

Automatic group-wise whole-brain short association fiber bundle labeling based on clustering and cortical surface information.

BACKGROUND: Diffusion MRI is the preferred non-invasive in vivo modality for the study of brain white matter connections. Tractography datasets contain 3D streamlines that can be analyzed to study the main brain white matter tracts. Fiber clustering methods have been used to automatically group similar fibers into clusters. However, due to inter-subject variability and artifacts, the resulting clusters are difficult to process for finding common connections across subjects, specially for superficial white matter. METHODS: We present an automatic method for labeling of short association bundles on a group of subjects. The method is based on an intra-subject fiber clustering that generates compact fiber clusters. Posteriorly, the clusters are labeled based on the cortical connectivity of the fibers, taking as reference the Desikan-Killiany atlas, and named according to their relative position along one axis. Finally, two different strategies were applied and compared for the labeling of inter-subject bundles: a matching with the Hungarian algorithm, and a well-known fiber clustering algorithm, called QuickBundles. RESULTS: Individual labeling was executed over four subjects, with an execution time of 3.6 min. An inspection of individual labeling based on a distance measure showed good correspondence among the four tested subjects. Two inter-subject labeling were successfully implemented and applied to 20 subjects and compared using a set of distance thresholds, ranging from a conservative value of 10 mm to a moderate value of 21 mm. Hungarian algorithm led to a high correspondence, but low reproducibility for all the thresholds, with 96 s of execution time. QuickBundles led to better correspondence, reproducibility and short execution time of 9 s. Hence, the whole processing for the inter-subject labeling over 20 subjects takes 1.17 h. CONCLUSION: We implemented a method for the automatic labeling of short bundles in individuals, based on an intra-subject clustering and the connectivity of the clusters with the cortex. The labels provide useful information for the visualization and analysis of individual connections, which is very difficult without any additional information. Furthermore, we provide two fast inter-subject bundle labeling methods. The obtained clusters could be used for performing manual or automatic connectivity analysis in individuals or across subjects.

Clustering of Whole-Brain White Matter Short Association Bundles Using HARDI Data.

Human brain connectivity is extremely complex and variable across subjects. While long association and projection bundles are stable and have been deeply studied, short association bundles present higher intersubject variability, and few studies have been carried out to adequately describe the structure, shape, and reproducibility of these bundles. However, their analysis is crucial to understand brain function and better characterize the human connectome. In this study, we propose an automatic method to identify reproducible short association bundles of the superficial white matter, based on intersubject hierarchical clustering. The method is applied to the whole brain and finds representative clusters of similar fibers belonging to a group of subjects, according to a distance metric between fibers. We experimented with both affine and non-linear registrations and, due to better reproducibility, chose the results obtained from non-linear registration. Once the clusters are calculated, our method performs automatic labeling of the most stable connections based on individual cortical parcellations. We compare results between two independent groups of subjects from a HARDI database to generate reproducible connections for the creation of an atlas. To perform a better validation of the results, we used a bagging strategy that uses pairs of groups of 27 subjects from a database of 74 subjects. The result is an atlas with 44 bundles in the left hemisphere and 49 in the right hemisphere, of which 33 bundles are found in both hemispheres. Finally, we use the atlas to automatically segment 78 new subjects from a different HARDI database and to analyze stability and lateralization results.

Fast Automatic Segmentation of White Matter Streamlines Based on a Multi-Subject Bundle Atlas.

This paper presents an algorithm for fast segmentation of white matter bundles from massive dMRI tractography datasets using a multisubject atlas. We use a distance metric to compare streamlines in a subject dataset to labeled centroids in the atlas, and label them using a per-bundle configurable threshold. In order to reduce segmentation time, the algorithm first preprocesses the data using a simplified distance metric to rapidly discard candidate streamlines in multiple stages, while guaranteeing that no false negatives are produced. The smaller set of remaining streamlines is then segmented using the original metric, thus eliminating any false positives from the preprocessing stage. As a result, a single-thread implementation of the algorithm can segment a dataset of almost 9 million streamlines in less than 6 minutes. Moreover, parallel versions of our algorithm for multicore processors and graphics processing units further reduce the segmentation time to less than 22 seconds and to 5 seconds, respectively. This performance enables the use of the algorithm in truly interactive applications for visualization, analysis, and segmentation of large white matter tractography datasets.

Reproducibility of superficial white matter tracts using diffusion-weighted imaging tractography.

Human brain connection map is far from being complete. In particular the study of the superficial white matter (SWM) is an unachieved task. Its description is essential for the understanding of human brain function and the study of pathogenesis triggered by abnormal connectivity. In this work we automatically created a multi-subject atlas of SWM diffusion-based bundles of the whole brain. For each subject, the complete cortico-cortical tractogram is first split into sub-tractograms connecting pairs of gyri. Then intra-subject shape-based fiber clustering performs compression of each sub-tractogram into a set of bundles. Proceeding further with shape-based clustering provides a match of the bundles across subjects. Bundles found in most of the subjects are instantiated in the atlas. To increase robustness, this procedure was performed with two independent groups of subjects, in order to discard bundles without match across the two independent atlases. Finally, the resulting intersection atlas was projected on a third independent group of subjects in order to filter out bundles without reproducible and reliable projection. The final multi-subject diffusion-based U-fiber atlas is composed of 100 bundles in total, 50 per hemisphere, from which 35 are common to both hemispheres.