Diffusion-weighted magnetic resonance imaging (dMRI) allows non-invasive investigation of whole-brain connectivity, which can potentially help to reveal the brains global network architecture and abnormalities involved in neurological and mental disorders. However, the reliability of connection inferences from dMRI-based fiber tracking is still debated, due to low sensitivity, dominance of false positives, and inaccurate and incomplete reconstruction of long-range connections. Furthermore, parameters of tracking algorithms are typically tuned in a heuristic way, which leaves room for manipulation of an intended result. Here we propose a data-driven framework to optimize and validate parameters of dMRI-based fiber-tracking algorithms using neural tracer data as a reference. Japans Brain/MINDS Project provides invaluable datasets containing both dMRI and neural tracer data from the same primates. We considered four criteria for goodness of fiber tracking: distance-weighted coverage, true/false positive ratio, projection coincidence, and commissural passage, applied using a multi-objective optimization algorithm. We implemented a variant of non-dominated sorting genetic algorithm II (NSGA-II) to optimize five major parameters of a global fiber-tracking algorithm over multiple brain samples in parallel. Using optimized parameters compared to the default parameters, dMRI-based fiber tracking performance was significantly improved, while minimizing false positives and impossible cross-hemisphere connections. Parameters optimized for 10 tracer injection sites showed good generalization capability for other brain samples. These results demonstrate the importance of data-driven adjustment of fiber-tracking algorithms and support the validity of dMRI-based tractography, if appropriate adjustments are employed.
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