Background: Transcranial Photobiomodulation (tPBM) is the non-invasive application of light to modulate underlying brain activity. There is increasing interest in evaluating tPBM as a therapeutic option. The typical technological questions are extent of light penetration and associated tissue temperature increases. Limited computational efforts to quantify these aspects are restricted to simplified models. Methods: We consider a 3D high-resolution (1 mm) anatomically realistic head model to simulate tPBM at 800 nm wavelength and using power densities spanning three decades (10, 100, and 1,000) mW/cm^2. The intended target was the F3 region. We also tested time-variant application at 100 mW/cm^2 for up to 20 minutes. Finally, tissue temperature rises for the American National Standards Institute (ANSI) safety limit of 330 mW/cm^2 was also investigated at a test case. Results: Our predictions reveal that the induced cortical irradiance is largely focal demarcated by the shape and extent of the source. Around 1% of the injected irradiance reaches the gray matter. Aligned with previous efforts, the scalp accounts for the greatest loss (~65%). The irradiance reduces to a hundredth of the value from gray matter at ~113 mm perpendicular distance from its surface. There is a growing halo-like effect at the level of CSF which is extended down to the underlying cortex. The CSF was found to be mainly responsible for this effect. We observe scalp temperature increases of 0.38 degree C and 3.76 degree C for 100 and 1,000 mW/cm^2 power density, respectively. The corresponding brain temperature increases are predicted to be 0.06 degree C and 0.57 degree C. As expected, irradiance absorption is linear with applied power density. While maximum induced scalp temperature increases linearly with power density, maximum brain temperature increases less slowly with power density. Transient analysis at 100 mW/cm^2 power density demonstrates expected scalp temperature rise with increasing stimulation duration. Temperature rises asymptote in ~ 10 minutes. Conclusions: tPBM presents unique potential to directly impose desired spatial profile using simple alteration of shape and size of the source. Usage of power density of 1,000 mW/cm^2 exceeds scalp and brain temperature safety limits. Contrary to prior reports, light penetration can exceed >10 cm from gray matter surface.

ARG, DQT, and AD are employees of Soterix Medical, Inc. BP and LDT are employees of PThera (NeuroThera) and hold multiple patents and patent applications in tPBM. The remaining author has nothing to disclose.

This work was supported in part by the Department of Defense [W81XWH22C0111] and National Aeronautics and Space Administration [80NSSC22CA071]

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