Dose simulation of near-infrared transcranial photobiomodulation therapy for depression
Meaning: Major Depressive Disorder (MDD) affects the lives of over 40 million American adults. Transcranial photobiomodulation (t-PBM) has been proven to be effective in treating MDD, but current treatment doses have not taken into account anatomical changes in the head and brain caused by aging.
Objective: We used state-of-the-art Monte Carlo simulations and age dependent brain maps ranging from 5 to 85 years old to investigate effective t-PBM doses and their changes in different age groups.
Method: The age dependent brain model was derived from 18 MRI brain maps. Simulate two extracranial locations, F3-F4 and Fp1-Fpz-Fp2, in the EEG 10-20 system at five selected wavelengths, and quantify energy deposition in two MDD related cortical regions – the dorsolateral prefrontal cortex (dlPFC) and the ventromedial prefrontal cortex (vmPFC).
Result: As age increases, energy deposition decreases overall. There is a strong negative correlation observed between brain tissue thickness (ECT) and energy deposition, indicating that as age increases, the increase in ECT thickness is the main reason for the decrease in energy transfer. Compared to processing vmPFC through Fp1-Fpz-Fp2 positions, F3-F4 positions seem to reach dlPFC more effectively.
Conclusion: Quantitative simulation reveals age-related light transmission throughout the entire life cycle of the human brain, indicating the need for personalized and age adaptive t-PBM treatment plans.
Keywords: Transcranial photobiomodulation, Monte Carlo method, optical dosimetry, major depression
According to data from the U.S. National Institutes of Health, the estimated lifetime prevalence of major depressive disorder (MDD) in the United States is over 13% of the population. MDD can develop at any age and is considered the leading cause of disability in individuals aged 15 to 44 in the United States. The two most commonly used treatment methods for MDD are antidepressants (87.0%) and psychotherapy (23.2%). These treatment methods face several known challenges: (1) frequent recurrence of cognitive therapy and (2) heavy side effects of antidepressant drugs. In addition, many patients prefer self-management, which leads to low treatment rates. Therefore, new, effective, safe, and easy to manage treatment methods are needed to combat MDD.
Photobiomodulation (PBM) is a therapeutic technique based on near-infrared (NIR) light, which has shown therapeutic effects on various neurological and psychiatric disorders, including MDD. Transcranial PBM (t-PBM) technology provides near-infrared light through the scalp and skull. Due to the penetration depth of near-infrared light in human tissues, clinically effective light doses can be delivered to the brain regions responsible for diseases without damaging superficial tissues. Although the molecular mechanism of PBM is still an actively studied topic, some research reports suggest that the therapeutic effect may stem from the excitation of mitochondrial chromophores (cytochrome c oxidase) on NIR spectra, stimulating the mitochondrial respiratory chain and increasing the production of adenosine triphosphate. The simultaneous production of reactive oxygen species may trigger intracellular cell protection and antioxidant pathways, and their effects may last for several days to weeks. Extensive studies conducted in animal models and humans have shown that PBM produces therapeutic effects without causing or without adverse reactions.
Despite the wide age range of onset of MD
In order to capture the anatomical changes of different age groups, we must first create a brain/whole head model that conforms to anatomy, including the three-dimensional shape and thickness of the skin/skull/brain. Fortunately, recent studies have published comprehensive magnetic resonance imaging (MRI) maps outlining the development of the human brain from infancy to old age. In addition, several of our own groups have developed complex brain segmentation and grid partitioning pipelines, converting neuroanatomical scans into high-quality multi-layer brain models. These resources make it possible to quantitatively study how the development and aging of the human brain affect light penetration at different stages of life.
In addition, advanced photon transport models must be used to accurately explain the complex light tissue interactions in t-PBM programs. In this study, we applied the Monte Carlo (MC) method – a stochastic solver for the radiative transfer equation (RTE) – which is widely regarded as the gold standard for optical modeling in complex tissues. Although alternative models such as diffusion equation (DE) are much faster and applicable to various types of human tissues, for brain tissue, DE is known to produce incorrect solutions due to the presence of low scattering media such as air pockets and cerebrospinal fluid (CSF). The MC method simulates a large number of photons by following a set of known probability models derived from physics, thereby rigorously solving RTE. The only major limitation is the high computational cost of the MC method. In order to improve computational efficiency, we applied the widely spread hardware accelerated MC modeling platform Monte Carlo eXtreme (MCX). Compared to traditional CPU based simulations, this tool can shorten simulation runtime by hundreds of times.