Pulsed photobiomodulation alters cerebrospinal fluid dynamics
Poster No:
38
Submission Type:
Abstract Submission
Authors:
Ariel Motsenyat1, Xiaole Zhong2, Hannah Van Lankveld3, Joanna Chen3, Jean Chen1
Institutions:
1Rotman Research Institute, Baycrest, Toronto, Ontario, 2Rotman Research Institute, Toronto, Ontario, 3University of Toronto, Toronto, Ontario
First Author:
Co-Author(s):
Introduction:
The glymphatic system is the waste clearance hub of the central nervous system, and utilizes cerebrospinal fluid (CSF) as a carrier for toxic materials. CSF flow has been taken as a surrogate of glymphatic flow (1), and fMRI has been used to measure CSF dynamics by leveraging the inflow effect (2). Photobiomodulation (PBM) refers to the use of low-intensity near-infrared light to stimulate biological processes. PBM-induced production of the vasodilator nitric oxide (NO) is a potential mechanism for the enhanced glymphatic drainage associated with PBM therapy (3,4). Previous studies have demonstrated improved amyloid clearance in Alzheimer's mouse models, which were attributed to improved glymphatic pumping due to the effect of PBM on the astrocyte endfeet (5). There is a growing interest in harnessing PBM for glymphatic regulation, which requires optimizing PBM protocols for best outcomes. PBM wavelength, frequency, and power all play potentially crucial roles. Moreover, skin colour also influences light penetration (6). Our primary research objective was to determine whether PBM can modulate CSF dynamics in-vivo in humans. Secondarily, we want to demonstrate the influence of the above factors on the PBM-CSF association.
Methods:
We aimed to investigate how PBM wavelength (808 nm vs 1064 nm), frequency (10 Hz vs 40 Hz), or fluence (5, 7, 9, mW/cm2 for intranasal PBM and 100, 150, or 200 mW/cm2 for forehead PBM), impact the flow of CSF. Additionally, we explored the influence of skin melanin levels (encoded as 1-3 from low to high). Furthermore, we sought to differentiate between the effects of intracranial (iPBM) and transcranial PBM (tPBM) on CSF dynamics. We acquired BOLD fMRI data at 3 T on 30 healthy young participants (dual-echo pCASL, TR = 4.5s, TE1/TE2 =9.8/30 ms, voxel size = 3.5mm3 isotropic). During the fMRI sessions, we applied near-infrared laser light in a block-design (4 min-off 4 min-on 4 min-off, separately for tPBM and iPBM). PBM was not associated with any heating or sound, so the participants were ignorant of when the light was on or off. Using the BOLD response from the 2nd TE, we assessed CSF flow from the bottom slice, fourth ventricle, aqueduct, and foramen magnum regions of interest (ROIs), which were segmented manually (Fig. 1). These time courses were submitted to a general linear model (GLM) to assess significance, with the significant regression coefficients recorded as the CSF flow response. These were in turn submitted to a stepwise linear mixed-effects model (LME) to determine the main variables of interest.
·Figure 1. fMRI regions of interest definitions in sample subject. Yellow corresponds to the lowest slices, red is the 4th ventricle, green is the aqueduct, and blue is the foramen of magnum.
Results:
Sample BOLD time courses in the foramen magnum are shown in (Fig. 2.) As shown by the LME results, across all ROIs the CSF response is highest for melanin group 2, and higher for longer wavelengths. During tPBM 10 Hz elicited a higher response than 40 Hz at 808 nm (a, c), but the latter elicited a higher response for 1064 nm (b, d). During iPBM, 808 nm elicited a higher response at 10 Hz, whereas 1064 nm elicited a higher response at 40 Hz pulsation. tPBM and iPBM elicited similar levels of response, highest for melanin group 2, and higher for higher fluence and 1064 nm.
·Figure 2. The effect of pulsation frequency, wavelength, fluence and melanin. Group-averaged BOLD time courses are shown in the foramen magnum. The solid lines represent the group means and the dashed
Conclusions:
Our study demonstrates that PBM can modulate CSF dynamics and potentially enhance glymphatic clearance. Both iPBM and tPBM were able to produce increases in CSF flow across multiple CSF regions. Light pulsation frequency, power density and wavelength as well as melanin all influenced the extent of CSF flow. iPBM produced similar CSF flow increases as tPBM, albeit with only 1/20 the power density, showing the advantage of the intranasal delivery. This is consistent with the cribriform plate and the olfactory bulb being on the path of the glymphatic-related CSF outflow (7). The wavelength-frequency interaction is unique to iPBM. This study provides new insights into the effects of PBM on CSF dynamics, suggesting a novel approach for improving glymphatic clearance and thus overall brain health.
Brain Stimulation:
Non-Invasive Stimulation Methods Other 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Anatomy and Functional Systems
Novel Imaging Acquisition Methods:
BOLD fMRI
Physiology, Metabolism and Neurotransmission:
Physiology, Metabolism and Neurotransmission Other 2
Keywords:
Cerebro Spinal Fluid (CSF)
FUNCTIONAL MRI
NORMAL HUMAN
Therapy
1|2Indicates the priority used for review
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Provide references using APA citation style.
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