The human brain is a complex and organized network, where the connection between regions is not achieved with single axons crisscrossing each other but rather millions of densely packed and well-ordered axons. Reconstruction from diffusion MRI tractography is only an attempt to capture the full complexity of this network, at the macroscale. This review provides an overview of the misconceptions, biases and pitfalls present in structural white matter bundle and connectome reconstruction using tractography. The goal is not to discourage readers, but rather to inform them of the limitations present in the methods used by researchers in the field in order to focus on what they can do and promote proper interpretations of their results. It also provides a list of open problems that could be solved in future research projects for the next generation of PhD students.

Investigative studies of white matter (WM) brain structures using diffusion MRI (dMRI) tractography frequently require manual WM bundle segmentation, often called “virtual dissection.” Human errors and personal decisions make these manual segmentations hard to reproduce, which have not yet been quantified by the dMRI community. It is our opinion that if the field of dMRI tractography wants to be taken seriously as a widespread clinical tool, it is imperative to harmonize WM bundle segmentations and develop protocols aimed to be used in clinical settings. The EADC‐ADNI Harmonized Hippocampal Protocol achieved such standardization through a series of steps that must be reproduced for every WM bundle. This article is an observation of the problematic. A specific bundle segmentation protocol was used in order to provide a real‐life example, but the contribution of this article is to discuss the need for reproducibility and standardized protocol, as for any measurement tool. This study required the participation of 11 experts and 13 nonexperts in neuroanatomy and “virtual dissection” across various laboratories and hospitals. Intra‐rater agreement (Dice score) was approximately 0.77, while inter‐rater was approximately 0.65. The protocol provided to participants was not necessarily optimal, but its design mimics, in essence, what will be required in future protocols. Reporting tractometry results such as average fractional anisotropy, volume or streamline count of a particular bundle without a sufficient reproducibility score could make the analysis and interpretations more difficult. Coordinated efforts by the diffusion MRI tractography community are needed to quantify and account for reproducibility of WM bundle extraction protocols in this era of open and collaborative science.

Abstract. 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.

Supervised machine learning (ML) algorithms have recentlybeen proposed as an alternative to traditional tractography methods in order to address some of their weaknesses. They can be path-based and local-model-free, and easily incorporate anatomical priors to make contextual and non-local decisions that should help the tracking process. ML-based techniques have thus shown promising reconstructions of larger spatial extent of existing white matter bundles, promising reconstructions of less false positives, and promising robustness to known position and shape biases of current tractography techniques. But as of today, none of these ML-based methods have shown conclusive performances or have been adopted as a de facto solution to tractography. One reason for this might be the lack of well-defined and extensive frameworks to train, evaluate, and compare these methods.In this paper, we describe several datasets and evaluation tools that contain useful features for ML algorithms, along with the various methods proposed in the recent years.We then discuss the strategies that are used to evaluate and compare those methods, as well as their shortcomings. Finally, we describe the particular needs of ML tractography methods and discuss tangible solutions for future works. K E Y W O R D SDiffusion MRI, tractography, machine learning, benchmark 1 arXiv:1902.05568v1 [q-bio.NC]

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.