Poster V17 - Shining a Light on the Brain: The Design and Initial Testing of a Novel Intracranial Photobiomodulation Device

Introduction: Alzheimer’s Disease has a high prevalence, currently affecting nearly 47 million people worldwide. Treatments are currently limited to symptomatic treatment through medical management, such as with cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists (1). Recently, photobiomodulation-based therapies have emerged as a potential treatment option for this condition, with small pilot trials demonstrating improvements in cognition with the use of these devices. However, these technologies have been limited to the transcranial and intranasal approaches, introducing critical issues of penetrance and dependence on patient use for potency and long term efficacy (2). As such, there is a need to improve these current approaches. In this study, we aim to construct an intracranial PBM device for use in the treatment of Alzheimer’s disease.

Materials and

Methods: Utilizing Autodesk Fusion for computer-aided design, a preliminary device version was designed (Figure 1) (Autodesk Fusion, San Francisco, United States). The aim of the initial design process was to maximize device surface area for light emitting diode (LED) placement while balancing the invasive nature of the approach. It was decided that the optimal location of placement was in the cranium in the epidural space, analogous to the location of a burr hole. Two versions of the device were designed and printed utilizing 20 mm diameter spherical polylactic acid molds and LEDs: Prototype A and Prototype B. Prototype A consisted of 4 LEDs at wavelengths of 750 nm and 760 nm and emitting powers of 18mW. Prototype B consisted of 3 LEDs at a wavelength of 850nm and an emitting power of 140 mW (McMaster-Carr, Elmhurst, United States). In addition to empiric benchtop testing, mathematical models were constructed to estimate expected light penetrance (Figure 2). Comparative analysis was performed with predicted and empiric light transmission to data from the literature.

Results, Conclusions, and Discussions: Mathematical modeling of light penetration estimated penetration of 4 µW for Prototype A and 14.7 µW for Prototype B. Empiric data measured 3 µW for Prototype A and 13 µW for Prototype B, respectively, and data is presented on the updated Prototype B (Figure 3). Comparative analysis was then performed utilizing data reported in the literature. Notably, 0.11% light penetration to brain parenchyma was noted for an extracranial approach, with a generated power of 54.8 mW (3). Translated, this represents a power of 60.28 µW that must be generated by the present intracranial approach, approximately 4.5 times the value generated by the higher powered Prototype B. Although there is significant potential for improvement in light transmission, this presents a proof-of-concept of a successful prototype for intracranial photobiomodulation. Future work in the development of this device includes further optimizing light penetrance, through the inclusion of higher-powered LEDs, development of a robust power system, and careful consideration of potential adverse effects, including heat generation. Following this, we aim to conduct large animal trials which will be followed by biochemical characterization of neuronal changes, with an eventual goal of pilot studies in a human cohort.

Acknowledgements (Optional): References
(1) Grossberg, George T., et al. "Present algorithms and future treatments for Alzheimer’s disease." Journal of Alzheimer's disease 67.4 (2019): 1157-1171.
(2) Fernandes, Filipa, et al. "Devices used for photobiomodulation of the brain—a comprehensive and systematic review." Journal of NeuroEngineering and Rehabilitation 21.1 (2024): 53.
(3) Spera, Vincenza, et al. "Pilot study on dose-dependent effects of transcranial photobiomodulation on brain electrical oscillations: a potential therapeutic target in Alzheimer’s disease." Journal of Alzheimer's Disease 83.4 (2021): 1481-1498.

The work presented here is supported by the THRIVE Fellowship, which received funding from a Clinical and Translational Science Award grant from the National Center for Advancing Translational Sciences (UL1TR004419-02).