Marc-Alexandre Côté

Tractometer: Towards validation of tractography pipelines

We have developed the Tractometer: an online evaluation and validation system for tractography processing pipelines. One can now evaluate the results of more than 57,000 fiber tracking outputs using different acquisition settings (b-value, averaging), different local estimation techniques (tensor, q-ball, spherical deconvolution) and different tracking parameters (masking, seeding, maximum curvature, step size). At this stage, the system is solely based on a revised FiberCup analysis, but we hope that the community will get involved and provide us with new phantoms, new algorithms, third party libraries and new geometrical metrics, to name a few. We believe that the new connectivity analysis and tractography characteristics proposed can highlight limits of the algorithms and contribute in solving open questions in fiber tracking: from raw data to connectivity analysis. Overall, we show that (i) averaging improves quality of tractography, (ii) sharp angular ODF profiles helps tractography, (iii) seeding and multi-seeding has a large impact on tractography outputs and must be used with care, and (iv) deterministic tractography produces less invalid tracts which leads to better connectivity results than probabilistic tractography.

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.

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.

Tractometer: online evaluation system for tractography

We have developed a tractometer: an online evaluation system for tractography processing pipelines. One can now evaluate the end effects on fiber tracts of different acquisition parameters (b-value, number of directions, denoising or not, averaging or not), different local estimation techniques (tensor, q-ball, spherical deconvolution, spherical wavelets) and to different tractography parameters (masking, seeding, stopping criteria). At this stage, the system is solely based on a revised FiberCup analysis, but we hope that the community gets involved and provides us with new phantoms, new algorithms, third party libraries and new geometrical metrics, to name a few. We believe that the new connectivity analysis and tractography characteristics proposed can highlight limits of the algorithms and contribute in elucidating the open questions in fiber tracking: from raw data to connectivity analysis.

An infinite restricted boltzmann machine

We present a mathematical construction for the restricted Boltzmann machine (RBM) that does not require specifying the number of hidden units. In fact, the hidden layer size is adaptive and can grow during training. This is obtained by first extending the RBM to be sensitive to the ordering of its hidden units. Then, with a carefully chosen definition of the energy function, we show that the limit of infinitely many hidden units is well defined. As with RBM, approximate maximum likelihood training can be performed, resulting in an algorithm that naturally and adaptively adds trained hidden units during learning. We empirically study the behavior of this infinite RBM, showing that its performance is competitive to that of the RBM, while not requiring the tuning of a hidden layer size.

Recognition of white matter bundles using local and global streamline-based registration and clustering

ABSTRACT Virtual dissection of diffusion MRI tractograms is cumbersome and needs extensive knowledge of white matter anatomy. This virtual dissection often requires several inclusion and exclusion regions‐of‐interest that make it a process that is very hard to reproduce across experts. Having automated tools that can extract white matter bundles for tract‐based studies of large numbers of people is of great interest for neuroscience and neurosurgical planning. The purpose of our proposed method, named RecoBundles, is to segment white matter bundles and make virtual dissection easier to perform. This can help explore large tractograms from multiple persons directly in their native space. RecoBundles leverages latest state‐of‐the‐art streamline‐based registration and clustering to recognize and extract bundles using prior bundle models. RecoBundles uses bundle models as shape priors for detecting similar streamlines and bundles in tractograms. RecoBundles is 100% streamline‐based, is efficient to work with millions of streamlines and, most importantly, is robust and adaptive to incomplete data and bundles with missing components. It is also robust to pathological brains with tumors and deformations. We evaluated our results using multiple bundles and showed that RecoBundles is in good agreement with the neuroanatomical experts and generally produced more dense bundles. Across all the different experiments reported in this paper, RecoBundles was able to identify the core parts of the bundles, independently from tractography type (deterministic or probabilistic) or size. Thus, RecoBundles can be a valuable method for exploring tractograms and facilitating tractometry studies.

A test-retest study on Parkinson's PPMI dataset yields statistically significant white matter fascicles

In this work, we propose a diffusion MRI protocol for mining Parkinsons disease diffusion MRI datasets and recover robust disease-specific biomarkers. Using advanced high angular resolution diffusion imaging (HARDI) crossing fiber modeling and tractography robust to partial volume effects, we automatically dissected 50 white matter (WM) fascicles. These fascicles connect deep nuclei (thalamus, putamen, pallidum) to different cortical functional areas (associative, motor, sensorimotor, limbic), basal forebrain and substantia nigra. Then, among these 50 candidate WM fascicles, only the ones that passed a test-retest reproducibility procedure qualified for further tractometry analysis. Leveraging the unique 2-timepoints test-retest Parkinsons Progression Markers Initiative (PPMI) dataset of over 600 subjects, we found statistically significant differences in tract profiles along the subcortico-cortical pathways between Parkinsons disease patients and healthy controls. In particular, significant increases in FA, apparent fiber density, tract-density and generalized FA were detected in some locations of the nigro-subthalamo-putaminal-thalamo-cortical pathway. This connection is one of the major motor circuits balancing the coordination of motor output. Detailed and quantifiable knowledge on WM fascicles in these areas is thus essential to improve the quality and outcome of Deep Brain Stimulation, and to target new WM locations for investigation.

Fiber tractography using machine learning

We present a fiber tractography approach based on a random forest classification and voting process, guiding each step of the streamline progression by directly processing raw diffusion-weighted signal intensities. For comparison to the state-of-the-art, i.e. tractography pipelines that rely on mathematical modeling, we performed a quantitative and qualitative evaluation with multiple phantom and in vivo experiments, including a comparison to the 96 submissions of the ISMRM tractography challenge 2015. The results demonstrate the vast potential of machine learning for fiber tractography.

Learn to Track: Deep Learning for Tractography

We show that deep learning techniques can be applied successfully to fiber tractography. Specifically, we use feed-forward and recurrent neural networks to learn the generation process of streamlines directly from diffusion-weighted imaging (DWI) data. Furthermore, we empirically study the behavior of the proposed models on a realistic white matter phantom with known ground truth. We show that their performance is competitive to that of commonly used techniques, even when the models are used on DWI data unseen at training time. We also show that our models are able to recover high spatial coverage of the ground truth white matter pathways while better controlling the number of false connections. In fact, our experiments suggest that exploiting past information within a streamline’s trajectory during tracking helps predict the following direction.

A hybrid approach for optimal automatic segmentation of White Matter tracts in HARDI

Whole brain tractography generates a very huge dataset composed by various tracts of different shapes, lengths, positions. Then clustering them into anatomically meaningful bundles is a challenge. Until now, several clustering methods have been proposed such as methods based on similarity measures or methods based on anatomical information, but no optimal clustering criteria were found yet. All methods have deficiencies. The combination of appropriate and distinguishable aspects of both methods is recommended to improve the results. Therefore, the aim of this study was to develop a new combined approach that incorporates various features in order on one hand to overcome the size and the complexity of the tractography datasets and the other for more efficacy and precision of clustering results. We propose a hybrid approach for automatic segmentation of White Matter (WM) tracts in HARDI that combines two complementary levels. The first level of our contribution is based on a similarity measure which aims to reduce the dimensionality of the data. The second level embeds a priori knowledge represented by a subject bundle atlas constructed in this work to improve the result of the clustering. Our method is able to well extract 13 major WM bundles. The results accuracy are measured by a Kappa analysis between the proposed method results and bundle atlas. The average Kappa values is superior to 0.70, it suggests substantial agreement.