Detection of laser-associated heating in the brain during simultaneous fMRI and optogenetic stimulation

Purpose To calculate temperatures from T-2*-weighted images collected during optogenetic fMRI based on proton resonance frequency (PRF) shift thermometry, to monitor confounding heating effects and determine appropriate light parameters for optogenetic stimulation. Methods fMRI is mainly based on long-TE gradient-recalled echo acquisitions that are also suitable for measuring small temperature changes via the PRF shift. A motion- and respiration-robust processing pipeline was developed to calculate temperature changes based on the PRF shift directly from the T-2*-weighted images collected for fMRI with a two-shot 2D gradient-recalled echo-EPI sequence at 9.4T. Optogenetic fMRI protocols which differed in stimulation durations (3, 6 and 9 s) within a total block duration of 30 s were applied in a squirrel monkey to validate the methods with blue and green light (20 Hz, 30 mW) delivery interleaved between periods. General linear modeling was performed on the resulting time series temperature maps to verify if light delivery with each protocol resulted in significant heating in the brain around the optical fiber. Results The temperature SD was 0.05 degrees C with the proposed imaging protocol and processing. Statistical analysis showed that the optogenetic stimulation protocol with a 3 s stimulation duration did not result in significant temperature rises. Significant temperature rises up to 0.13 degrees C (p < 0. 05) were observed with 6 and 9 s stimulation durations for blue and green light. Conclusion The proposed processing pipeline can be useful for the design of optogenetic stimulation protocols and for monitoring confounding heating effects.