Abstract
The use of optogenetics or photobiomodulation in non-human primate (NHP) requires the ability to noninvasively stimulate large and deep cortical brain tissues volumes. In this context, the optical and geometrical parameters of optodes are critical. Methods and general guidelines to optimize these parameters have to be defined. Objective. We propose the design of an optode for safe and efficient optical stimulation of a large volume of NHP cortex, down to 3–5 mm depths without inserting fibers into the cortex. Approach. Monte Carlo simulations of optical and thermal transport have been carried out using the Geant4 application for tomographic emission (GATE) platform. Parameters such as the fiber diameter, numerical aperture, number of fibers and their geometrical arrangement have been studied. Optimal hardware parameters are proposed to obtain homogeneous fluence above the fluence threshold for opsin activation without detrimental thermal effects. Main results. The simulations show that a large fiber diameter and a large numerical aperture are preferable since they allow limiting power concentration and hence the resulting thermal increases at the brain surface. To obtain a volume of 200–500 mm3 of brain tissues receiving a fluence above the opsin activation threshold for optogenetics or below a phototocixity threshold for photobiomodulation, a 4 fibers configuration is proposed. The optimal distance between the fibers was found to be 4 mm. A practical implementation of the optode has been performed and the corresponding fluence and thermal maps have been simulated. Significance. The present study defines a method to optimize the design of optode and the choice of stimulation parameters for optogenetics and more generally light delivery to deep and large volumes of tissues in NHP brain with a controlled irradiance dosimetry. The general guidelines are the use of silica fibers with a large numerical aperture and a large diameter. The combination of several fibers is required if large volumes need to be stimulated while avoiding thermal effects.
Highlights
Optogenetics has become ubiquitous in neuroscience research
One is obviously related to the safe and efficient transfection of cells and control of potential immune reaction. We focus on another significant issue, which is the ability to deliver enough fluence to large brain volumes down to several millimeters beneath the brain surface in order to activate the opsins with minimal mechanical invasiveness and thermal increases. Such requirements are essential if noninvasive optical modulation of large cortical volumes connected to deep brain nuclei is to be investigated in non-human primate (NHP) models of central nervous disorders, as recently proposed in a translational perspective [9, 16]
The technique is under active review for use in a vast range of brain diseases including stroke, traumatic brain injury, neurodegenerative diseases, where the non-specific optical stimulation of the cortical tissue was shown in mice models to lead to transient increase of ATP, decrease of inflammatory markers and -in some studies- cognitive improvement
Summary
Optogenetics has become ubiquitous in neuroscience research. It relies on gene transfer in the central nervous system of light sensitive channels, called opsins, so that specific populations of neurons become photosensitive. We focus on another significant issue, which is the ability to deliver enough fluence to large brain volumes down to several millimeters beneath the brain surface in order to activate the opsins with minimal mechanical invasiveness and thermal increases Such requirements are essential if noninvasive optical modulation of large cortical volumes connected to deep brain nuclei is to be investigated in NHP models of central nervous disorders, as recently proposed in a translational perspective [9, 16]. The possibility to simulate a large variety of optode geometries and arrangements in NHP brain tissue volumes with heterogeneous optical and thermal properties would guide the design of such stimulation systems for NHP. NHP large cortical volumes, to be used in future experiments in NHP models for central nervous system disorders
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