Computational modeling of the photon transport, tissue heating, and cytochrome C oxidase absorption during transcranial near-infrared stimulation

Abstract

Transcranial near-infrared stimulation (tNIRS) has been proposed as a tool to modulate 1 cortical excitability. However, the underlying mechanisms are not clear where the heating effects on 2 the brain tissue needs investigation due to increased near-infrared (NIR) absorption by water and fat. 3Moreover, the risk of localized heating of tissues (including the skin) during optical stimulation of 4 the brain tissue is a concern. The challenge in estimating localized tissue heating is due to the light 5 interaction with the tissues' constituents, which is dependent on the combination ratio of the scattering 6 and absorption properties of the constituent. Here, apart from tissue heating that can modulate the 7 cortical excitability ("photothermal effects"); the other mechanism reported in the literature is the 8 stimulation of the mitochondria in the cells which are active in the adenosine triphosphate (ATP) 9 synthesis. In the mitochondrial respiratory chain, the complex IV, also named as the cytochrome c 10 oxidase(CCO), is the unit four with three copper atoms. The absorption peaks of CCO are in the visible 11 (420-450nm and 600-700nm) and the near-infrared (760-980nm) spectral region which have been 12 shown to be promising for low level light therapy (LLLT), also known as "photobiomodulation". While 13 much higher CCO absorption peaks in the visible spectrum can be used for the photobiomodulation 14 of the skin, 810nm has been proposed for the non-invasive brain stimulation (using tNIRS) due to the 15 optical window in the NIR spectral region. In this article, we applied a computational approach to 16 delineate the "photothermal effects" from the "photobiomodulation," i.e., to estimate the amount of 17 light absorbed individually by each chromophore in the brain tissue (with constant scattering) and the 18 related tissue heating. Photon migration simulations were performed for motor cortex tNIRS based 19 on a prior work that used a 500mW cm −2 light source placed on the scalp. We simulated photon 20 migration at 630nm and 700nm (red spectral region) and 810nm (near-infrared spectral region). We 21 found a temperature increase in the scalp below 0.25°C and a minimal temperature increase in the 22 gray matter less than 0.04°C at 810nm. Similar heating was found for 630nm and 700nm used for 23 LLLT, so photothermal effects are postulated to be unlikely in the brain tissue. 24

Tether-free photothermal deep-brain stimulation in freely behaving mice via wide-field illumination in the near-infrared-II window

“…The brain’s absorption coefficient was calculated using the absorption coefficients of water 69 , lipid 69 , oxyhemoglobin and deoxyhemoglobin 70 , and reduced and oxidized cytochrome c oxidase 71 weighted by their compositions or concentrations in the brain tissue 72 .…”

Transcranial photobiomodulation add-on therapy to valproic acid for pentylenetetrazole-induced seizures in peripubertal rats

“…Additionally, the thermal effect was not evaluated in this study. However, the photothermal effects of tPBM are less likely to occur in the brain tissue due to poor heat penetration deep into the brain [ 101 ], and the superficial heat of the skin and scalp did not affect the therapeutic effect of tPBM due to CcO and cerebral hemodynamics [ 100 ]. However, future studies should examine the calibration of thermal effect.…”

Pharmacodynamic Implications of Transcranial Photobiomodulation and Quantum Physics in Clinical Medicine

“…Applications of monochromatic wavelengths across the NIR and IR spectra via tPBM interventions affect complexes within functional mitochondrial pathways differentially [20][21][22]. NIR is considered as light that is emitted at a frequency between 700 nm and 1 mm whereas IR is photic energy emitted at 1 mm or 300 GHz and above [6]. Examination of homeostatic processes that are mediated by CCO, or complex IV within the electron transport chain, suggests that this target of PBM interventions can be stimulated to increase ROS production, oxygen consumption, and ATP synthesis when activated by red light and NIR frequencies between 633 nm and 808 nm [20][21][22].…”

“…Calculations of fluence rate must use multifactorial analyses that account for divergent properties of biological tissues in tPBM applications. As tPBM interventions target subcortical structures and neurophysiological pathways, considerations of the radiation transfer equation (RTE) allow for derivation of photon transport and alterations in the mitochondrial membrane potential [6]. RTE allows for the derivation of fluence rate as a function of photonic distribution, absorption, and scattering effects across tissues such as the dura, skull, cerebrospinal fluid, and white and gray matter [6,33].…”

“…This hypothesis is based upon the ability of cytochrome c oxidase (CCO), an enzyme within the electron transport chain, to alter mitochondrial membrane potential via exposure to photonic energy in the spectra of 360-860 nm [5]. Near infrared light (NIR) is defined as the emission of light within the 700 to 980 nm spectra whereas infrared light (IR) is energy that is emitted at 1000 nm or 300 GHz and above [6].…”