Limits to anatomical accuracy of diffusion tractography using modern approaches

Abstract

Diffusion MRI fiber tractography is widely used to probe the structural connectivity of the brain, with a range of applications in both clinical and basic neuroscience. Despite widespread use, tractography has well-known pitfalls that limits the anatomical accuracy of this technique. Numerous modern methods have been developed to address these shortcomings through advances in acquisition, modeling, and computation. To test whether these advances improve tractography accuracy, we organized the 3-D Validation of Tractography with Experimental MRI (3D-VoTEM) challenge at the ISBI 2018 conference. We made available three unique independent tractography validation datasets - a physical phantom and two ex vivo brain specimens - resulting in 176 distinct submissions from 9 research groups. By comparing results over a wide range of fiber complexities and algorithmic strategies, this challenge provides a more comprehensive assessment of tractography’s inherent limitations than has been reported previously. The central results were consistent across all sub-challenges in that, despite advances in tractography methods, the anatomical accuracy of tractography has not dramatically improved in recent years. Taken together, our results independently confirm findings from decades of tractography validation studies, demonstrate inherent limitations in reconstructing white matter pathways using diffusion MRI data alone, and highlight the need for alternative or combinatorial strategies to accurately map the fiber pathways of the brain.

Histologically derived fiber response functions for diffusion MRI vary across white matter fibers—An ex vivo validation study in the squirrel monkey brain

“…It is important to point out that we are not suggesting the use of no thresholds for tractography, as it actually causes a distinct loss of specificity, and only use this as an example to show that removing this threshold results in similar tracts for all tested response functions. In fact, no algorithmic parameters have both high specificity and sensitivity, in agreement with tractography validation studies, [49][50][51] and in practice it is important to have some threshold to control the number of false positive bundles. While different choices of tracking parameters can produce large variations, it is important to point out that, with typical usage (ie typical parameters), different response functions also lead to different tractography results.…”

Freewater EstimatoR using iNtErpolated iniTialization (FERNET): Toward Accurate Estimation of Free Water in Peritumoral Region Using Single-Shell Diffusion MRI Data

“…Finally, tractography algorithms with their ability to delineate eloquent fiber tracts has important clinical implications for the surgical treatment of malignant brain tumors [33]. Although no current method solves the inherent limitations of fiber tractography, the techniques available are sufficiently specific and sensitive to make fiber tractography a valuable tool for the neurosurgeon [34,35]. However, the standard tensor fit does not account for any free water compartment, and in the presence of significant partial voluming of extracellular fluid, indices derived from the fitted tensor represent erroneous estimations of the underlying tissue, including low FA.…”

Comparison between diffusion MRI tractography and histological tract-tracing of cortico-cortical structural connectivity in the ferret brain

“…In the case of retrograde tracing, histological tracing also quantifies the number of axons in a projection, since each labeled projection neuron provides one axon. Studies performed in macaque (Azadbakht et al, 2015;Donahue et al, 2016;Schilling, Nath, et al, 2019;Zhang et al, 2018) , squirrel monkey (Gao et al, 2013; , pig (Knösche, Anwander, Liptrot, & Dyrby, 2015) , mouse (Calabrese, Badea, Cofer, Qi, & Johnson, 2015) and rat (Sinke et al, 2018) , have explored the relationship between tract-tracing experiments and tractography. Overall these studies have shown that diffusion MRI tractography provides a good estimate of structural brain connectivity.…”