Fixel-based Analysis of Diffusion MRI: Methods, Applications, Challenges and Opportunities

Abstract

Diffusion MRI has provided the neuroimaging community with a powerful tool to acquire in-vivo data sensitive to microstructural features of white matter, up to 3 orders of magnitude smaller than typical voxel sizes. The key to extracting such valuable information lies in complex modelling techniques, which form the link between the rich diffusion MRI data and various metrics related to the microstructural organisation. Over time, increasingly advanced techniques have been developed, up to the point where some diffusion MRI models can now provide access to properties specific to individual fibre populations in each voxel in the presence of multiple "crossing" fibre pathways. While highly valuable, such fibre-specific information poses unique challenges for typical image processing pipelines and statistical analysis. In this work, we review the "fixel-based analysis" (FBA) framework that implements bespoke solutions to this end, and has recently seen a stark increase in adoption for studies of both typical (healthy) populations as well as a wide range of clinical populations. We describe the main concepts related to fixel-based analyses, as well as the methods and specific steps involved in a state-of-the-art FBA pipeline, with a focus on providing researchers with practical advice on how to interpret results. We also include an overview of the scope of current fixel-based analysis studies (until August 2020), categorised across a broad range of neuroscientific domains, listing key design choices and summarising their main results and conclusions. Finally, we critically discuss several aspects and challenges involved with the fixel-based analysis framework, and outline some directions and future opportunities.

The Motor Engram of Functional Connectivity Generated by Acute Whole-Body Dynamic Balance Training

“…Diffusion image processing. We performed FBA using MRtrix3 (http://www.mrtrix.org/), as previously described (18). Standard preprocessing was performed.…”

“…We used slacklining as the whole-body dynamic balance task, as previously reported (6). We also analyzed the gray and white matter microstructure related to each participant's initial balance capability with VBM using T1-weighted images and a newly developed fixel-based analysis (FBA) using diffusion-weighted images (17,18). Furthermore, as previous studies have indicated that 1-2 h of acute motor practice may induce structural changes in the white and gray matter, we investigated whether 30 min of dynamic balance training could induce structural changes (13,19).…”

Detecting Corticospinal Tract Impairment in Tumor Patients With Fiber Density and Tensor-Based Metrics

“…In a recent study we could also demonstrate that the segmental analysis of diffusion tensor imaging (DTI) derived metrics, such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC), correlated with clinical outcomes ( 5 ). Here, we now set out to investigate whether more complex metrics derived from constrained spherical deconvolution (CSD) and probabilistic tractography, which allow for more detailed analysis of the white matter, would prove superior in terms of detecting tumor induced white matter (WM) changes ( 6 ). In this context we analyzed the structural impact of gliomas affecting the corticospinal tract (CST) in 65 patients.…”

Early micro‐ and macrostructure of sensorimotor tracts and development of cerebral palsy in high risk infants

“…An estimated 90% of voxels contain crossing fibers, which make it difficult to accurately interpret DT‐based analyses, as changes at the microstructural level may be undetected or misinterpreted due to a lack of fiber specificity. FB metrics have higher sensitivity than voxel‐wise DT metrics in detecting group‐wide differences in white matter (Dhollander et al, 2020). We also used meticulous tract‐extraction methods based on previously‐published methods (Kaur et al, 2014; Parikh et al, 2019; Teli et al, 2018) and our own systematic, iterative process.…”

“…Studies have shown the improved sensitivity and specificity of CSD‐based tractography for detecting differences in white matter diffusion characteristics, when compared to DT‐tractography (Auriat, Borich, Snow, Wadden, & Boyd, 2015; Jeurissen, Leemans, Jones, Tournier, & Sijbers, 2011; Reijmer et al, 2012). CSD is valuable in group studies; by using a single response function to compute fODs for all subjects, population‐wide differences in diffusivity can be detected (Dhollander et al, 2020; Raffelt et al, 2012).…”