Purpose: Magnetic resonance current density imaging (MRCDI) combines MR brain imaging with the injection of time-varying weak currents (1-2 mA) to assess the current flow pattern in the brain. However, the utility of MRCDI is still hampered by low measurement sensitivity and poor image quality. Methods: We recently introduced a multi-gradient-echo-based MRCDI approach that has the hitherto best documented efficiency. We now advanced our MRCDI approach in three directions and performed phantom and in-vivo human brain experiments for validation: First, we verified the importance of enhanced spoiling and optimize it for imaging of the human brain. Second, we improved the sensitivity and spatial resolution by using acquisition weighting. Third, we added navigators as a quality control measure for tracking physiological noise. Combining these advancements, we tested our optimized MRCDI method by using 1 mA transcranial electrical stimulation (TES) currents injected via two different electrode montages in five subjects. Results: For a session duration of 4:20 min, the new MRCDI method was able to detect magnetic field changes caused by the TES current flow at a sensitivity level of 84 pT, representing in a twofold increase relative to our original method. Comparing both methods to current flow simulations based on personalized head models demonstrated a consistent increase in the coefficient of determination of {triangleup}R2=0.12 for the current-induced magnetic fields and {triangleup}R2=0.22 for the current flow reconstructions. Interestingly, some of the simulations still clearly deviated from the measurements despite of the strongly improved measurement quality. This suggests that MRCDI can reveal useful information for the improvement of head models used for current flow simulations. Conclusion: The advanced method strongly improves the sensitivity and robustness of MRCDI and is an important step from proof-of-concept studies towards a broader application of MRCDI in clinical and basic neuroscience research.

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