Maxime Chamberland

The challenge of mapping the human connectome based on diffusion tractography

Tractography based on non-invasive diffusion imaging is central to the study of human brain connectivity. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain data set with ground truth tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. Here, we report the encouraging finding that most state-of-the-art algorithms produce tractograms containing 90% of the ground truth bundles (to at least some extent). However, the same tractograms contain many more invalid than valid bundles, and half of these invalid bundles occur systematically across research groups. Taken together, our results demonstrate and confirm fundamental ambiguities inherent in tract reconstruction based on orientation information alone, which need to be considered when interpreting tractography and connectivity results. Our approach provides a novel framework for estimating reliability of tractography and encourages innovation to address its current limitations.Though tractography is widely used, it has not been systematically validated. Here, authors report results from 20 groups showing that many tractography algorithms produce both valid and invalid bundles.

Collaborative patch-based super-resolution for diffusion-weighted images.

In this paper, a new single image acquisition super-resolution method is proposed to increase image resolution of diffusion weighted (DW) images. Based on a nonlocal patch-based strategy, the proposed method uses a non-diffusion image (b0) to constrain the reconstruction of DW images. An extensive validation is presented with a gold standard built on averaging 10 high-resolution DW acquisitions. A comparison with classical interpolation methods such as trilinear and B-spline demonstrates the competitive results of our proposed approach in terms of improvements on image reconstruction, fractional anisotropy (FA) estimation, generalized FA and angular reconstruction for tensor and high angular resolution diffusion imaging (HARDI) models. Besides, first results of reconstructed ultra high resolution DW images are presented at 0.6×0.6×0.6 mm3 and 0.4×0.4×0.4 mm3 using our gold standard based on the average of 10 acquisitions, and on a single acquisition. Finally, fiber tracking results show the potential of the proposed super-resolution approach to accurately analyze white matter brain architecture.

Real-time multi-peak tractography for instantaneous connectivity display

The computerized process of reconstructing white matter tracts from diffusion MRI (dMRI) data is often referred to as tractography. Tractography is nowadays central in structural connectivity since it is the only non-invasive technique to obtain information about brain wiring. Most publicly available tractography techniques and most studies are based on a fixed set of tractography parameters. However, the scale and curvature of fiber bundles can vary from region to region in the brain. Therefore, depending on the area of interest or subject (e.g., healthy control vs. tumor patient), optimal tracking parameters can be dramatically different. As a result, a slight change in tracking parameters may return different connectivity profiles and complicate the interpretation of the results. Having access to tractography parameters can thus be advantageous, as it will help in better isolating those which are sensitive to certain streamline features and potentially converge on optimal settings which are area-specific. In this work, we propose a real-time fiber tracking (RTT) tool which can instantaneously compute and display streamlines. To achieve such real-time performance, we propose a novel evolution equation based on the upsampled principal directions, also called peaks, extracted at each voxel of the dMRI dataset. The technique runs on a single Computer Processing Unit (CPU) without the need for Graphical Unit Processing (GPU) programming. We qualitatively illustrate and quantitatively evaluate our novel multi-peak RTT technique on phantom and human datasets in comparison with the state of the art offline tractography from MRtrix, which is robust to fiber crossings. Finally, we show how our RTT tool facilitates neurosurgical planning and allows one to find fibers that infiltrate tumor areas, otherwise missing when using the standard default tracking parameters.

Tractography-based connectomes are dominated by false-positive connections

Fiber tractography based on non-invasive diffusion imaging is at the heart of connectivity studies of the human brain. To date, the approach has not been systematically validated in ground truth studies. Based on a simulated human brain dataset with ground truth white matter tracts, we organized an open international tractography challenge, which resulted in 96 distinct submissions from 20 research groups. While most state-of-the-art algorithms reconstructed 90% of ground truth bundles to at least some extent, on average they produced four times more invalid than valid bundles. About half of the invalid bundles occurred systematically in the majority of submissions. Our results demonstrate fundamental ambiguities inherent to tract reconstruction methods based on diffusion orientation information, with critical consequences for the approach of diffusion tractography in particular and human connectivity studies in general.

3D interactive tractography-informed resting-state fMRI connectivity.

In the past decade, the fusion between diffusion magnetic resonance imaging (dMRI) and functional magnetic resonance imaging (fMRI) has opened the way for exploring structure-function relationships in vivo. As it stands, the common approach usually consists of analysing fMRI and dMRI datasets separately or using one to inform the other, such as using fMRI activation sites to reconstruct dMRI streamlines that interconnect them. Moreover, given the large inter-individual variability of the healthy human brain, it is possible that valuable information is lost when a fixed set of dMRI/fMRI analysis parameters such as threshold values are assumed constant across subjects. By allowing one to modify such parameters while viewing the results in real-time, one can begin to fully explore the sensitivity of structure-function relations and how they differ across brain areas and individuals. This is especially important when interpreting how structure-function relationships are altered in patients with neurological disorders, such as the presence of a tumor. In this study, we present and validate a novel approach to achieve this: First, we present an interactive method to generate and visualize tractography-driven resting-state functional connectivity, which reduces the bias introduced by seed size, shape and position. Next, we demonstrate that structural and functional reconstruction parameters explain a significant portion of intra- and inter-subject variability. Finally, we demonstrate how our proposed approach can be used in a neurosurgical planning context. We believe this approach will promote the exploration of structure-function relationships in a subject-specific aspect and will open new opportunities for connectomics.

Using fMRI non-local means denoising to uncover activation in sub-cortical structures at 1.5 T for guided HARDI tractography

In recent years, there has been ever-increasing interest in combining functional magnetic resonance imaging (fMRI) and diffusion magnetic resonance imaging (dMRI) for better understanding the link between cortical activity and connectivity, respectively. However, it is challenging to detect and validate fMRI activity in key sub-cortical areas such as the thalamus, given that they are prone to susceptibility artifacts due to the partial volume effects (PVE) of surrounding tissues (GM/WM interface). This is especially true on relatively low-field clinical MR systems (e.g., 1.5 T). We propose to overcome this limitation by using a spatial denoising technique used in structural MRI and more recently in diffusion MRI called non-local means (NLM) denoising, which uses a patch-based approach to suppress the noise locally. To test this, we measured fMRI in 20 healthy subjects performing three block-based tasks : eyes-open closed (EOC) and left/right finger tapping (FTL, FTR). Overall, we found that NLM yielded more thalamic activity compared to traditional denoising methods. In order to validate our pipeline, we also investigated known structural connectivity going through the thalamus using HARDI tractography: the optic radiations, related to the EOC task, and the cortico-spinal tract (CST) for FTL and FTR. To do so, we reconstructed the tracts using functionally based thalamic and cortical ROIs to initiates seeds of tractography in a two-level coarse-to-fine fashion. We applied this method at the single subject level, which allowed us to see the structural connections underlying fMRI thalamic activity. In summary, we propose a new fMRI processing pipeline which uses a recent spatial denoising technique (NLM) to successfully detect sub-cortical activity which was validated using an advanced dMRI seeding strategy in single subjects at 1.5 T.

Active delineation of Meyer's loop using oriented priors through MAGNEtic tractography (MAGNET).

Streamline tractography algorithms infer connectivity from diffusion MRI (dMRI) by following diffusion directions which are similarly aligned between neighboring voxels. However, not all white matter (WM) fascicles are organized in this manner. For example, Meyers loop is a highly curved portion of the optic radiation (OR) that exhibits a narrow turn, kissing and crossing pathways, and changes in fascicle dispersion. From a neurosurgical perspective, damage to Meyers loop carries a potential risk of inducing vision deficits to the patient, especially during temporal lobe resection surgery. To prevent such impairment, achieving an accurate delineation of Meyers loop with tractography is thus of utmost importance. However, current algorithms tend to under‐estimate the full extent of Meyers loop, mainly attributed to the aforementioned rule for connectivity which requires a direction to be chosen across a field of orientations. In this article, it was demonstrated that MAGNEtic Tractography (MAGNET) can benefit Meyers loop delineation by incorporating anatomical knowledge of the expected fiber orientation to overcome local ambiguities. A new ROI‐mechanism was proposed which supplies additional information to streamline reconstruction algorithms by the means of oriented priors. Their results showed that MAGNET can accurately generate Meyers loop in all of our 15 child subjects (8 males; mean age 10.2 years ± 3.1). It effectively improved streamline coverage when compared with deterministic tractography, and significantly reduced the distance between the anterior‐most portion of Meyers loop and the temporal pole by 16.7 mm on average, a crucial landmark used for preoperative planning of temporal lobe surgery. Hum Brain Mapp 38:509–527, 2017.

Seeing More by Showing Less: Orientation-Dependent Transparency Rendering for Fiber Tractography Visualization

Fiber tractography plays an important role in exploring the architectural organization of fiber trajectories, both in fundamental neuroscience and in clinical applications. With the advent of diffusion MRI (dMRI) approaches that can also model “crossing fibers”, the complexity of the fiber network as reconstructed with tractography has increased tremendously. Many pathways interdigitate and overlap, which hampers an unequivocal 3D visualization of the network and impedes an efficient study of its organization. We propose a novel fiber tractography visualization approach that interactively and selectively adapts the transparency rendering of fiber trajectories as a function of their orientation to enhance the visibility of the spatial context. More specifically, pathways that are oriented (locally or globally) along a user-specified opacity axis can be made more transparent or opaque. This substantially improves the 3D visualization of the fiber network and the exploration of tissue configurations that would otherwise be largely covered by other pathways. We present examples of fiber bundle extraction and neurosurgical planning cases where the added benefit of our new visualization scheme is demonstrated over conventional fiber visualization approaches.

On the Origin of Individual Functional Connectivity Variability: The Role of White Matter Architecture

Fingerprint patterns derived from functional connectivity (FC) can be used to identify subjects across groups and sessions, indicating that the topology of the brain substantially differs between individuals. However, the source of FC variability inferred from resting-state functional magnetic resonance imaging remains unclear. One possibility is that these variations are related to individual differences in white matter structural connectivity (SC). However, directly comparing FC with SC is challenging given the many potential biases associated with quantifying their respective strengths. In an attempt to circumvent this, we employed a recently proposed test-retest approach that better quantifies inter-subject variability by first correcting for intra-subject nuisance variability (i.e., head motion, physiological differences in brain state, etc.) that can artificially influence FC and SC measures. Therefore, rather than directly comparing the strength of FC with SC, we asked whether brain regions with, for example, low inter-subject FC variability also exhibited low SC variability. From this, we report two main findings: First, at the whole-brain level, SC variability was significantly lower than FC variability, indicating that an individuals structural connectome is far more similar to another relative to their functional counterpart even after correcting for noise. Second, although FC and SC variability were mutually low in some brain areas (e.g., primary somatosensory cortex) and high in others (e.g., memory and language areas), the two were not significantly correlated across all cortical and sub-cortical regions. Taken together, these results indicate that even after correcting for factors that may differently affect FC and SC, the two, nonetheless, remain largely independent of one another. Further work is needed to understand the role that direct anatomical pathways play in supporting vascular-based measures of FC and to what extent these measures are dictated by anatomical connectivity.

Visualization of Diffusion Propagator and Multiple Parameter Diffusion Signal

New advances in MRI technology allow the acquisition of high resolution diffusion-weighted datasets for multiple parameters such as multiple q-values, multiple b-values, multiple orientations and multiple diffusion times. These new and demanding acquisitions go beyond classical diffusion tensor imaging (DTI) and single b-value high angular resolution diffusion imaging (HARDI) acquisitions. Recent studies show that such multiple parameter diffusion can be used to infer axonal diameter distribution and other biophysical features of the white matter, otherwise not possible. Hence, this calls for novel visualization techniques to interact with such complex high-dimensional and high-resolution datasets. To date, there are no existing visualization techniques to visualize full brain images or fields of diffusion signal profiles and diffusion propagators reconstructed from them. It is important to be able to scroll in these images beyond single voxels, just as one would navigate in a whole brain map of fractional anisotropy extracted from DTI. In this chapter, we give a review of the existing visualization techniques for the local diffusion phenomenon and propose alternative visualization techniques for fields of high-dimensional 3D diffusion profiles. We introduce: (i) a volume rendering approach and (ii) a diffusion propagator silhouette glyph as a complement to existing DTI and HARDI visualization techniques. We show that these visualization techniques allow the real-time exploration of high-dimensional multi-b-value and multi-direction data such as diffusion spectrum imaging (DSI). Our visualization technique therefore opens new perspectives for 3D diffusion MRI visualization and interaction.