טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentFarah Nairouz
SubjectPhoto-Thermal Stimulation for Vision Restoration:
In-Vitro Characterization
DepartmentDepartment of Biomedical Engineering
Supervisor Professor Shy Shoham
Full Thesis textFull thesis text - English Version


Abstract

Vision restoration devices based on optical artificial stimulation of neurons are the subject of active development. Optical methods for neural stimulation, when combined with advanced projection systems, offer activation with the spatial and temporal resolutions required for a functional visual prosthetic. Laser pulses in the mid-IR range have recently been introduced as a minimally intrusive optical method for neural stimulation through an underlying photo-thermal mechanism that is not yet fully understood. Our work focused on the development and study of the underlying mechanisms of a new photo-thermal stimulation method - Photo-Absorber Induced Neural Thermal Stimulation (PAINTS). PAINTS is achieved by microscopic thermal transients induced by illumination of photo-absorbers dispersed in the vicinity of the cells. This method has high spatiotemporal resolution and is not restricted to water-absorbed wavelengths, potentially leading to wider applicability.

 PAINTS was investigated in cell cultures and isolated retinas by projecting high intensity light patterns onto particles in close proximity to the cells using a holographic projection system developed in our lab. The activation threshold was investigated for varying pulse durations of 0.1-5 msec. Calcium imaging results indicate the feasibility of reproducible activation of cells in cortical cultures and retinal ganglion cells in artificially blinded retinas. Activation thresholds were found to vary systematically with pulse duration, with shorter pulses having lower energy thresholds. To investigate the underlying mechanism of photothermal stimulation, we used computer simulations of the underlying physics and biophysics to test a quantitative temperature-rate based hypothesis (I ? dT/dt) for describing the effects of photo-thermal stimulation on neural tissue. Simulation results were in good agreement with empirical activation thresholds for a range of photo-thermal stimulation experiments, supporting our model.

Efforts for translating PAINTS to an in vivo model focused on finding an appropriate substance that can create a homogeneously absorbing layer in close proximity to the RGCs, and recording visual evoked potentials resulting from artificial stimulation through PAINTS. Initial results indicate the feasibility of creating a homogenously absorbing layer in close proximity to the RGCs by intravitreal injection of India Ink. Evoked potentials from artificial stimulation of the RGCs reveal an interesting phenomenon, occurring with a relatively long latency after pulse onset, requiring further investigation.

Photo-thermal neuronal stimulation may emerge as a powerful tool for remotely exciting neural circuits, based on a universal biophysical mechanism. Furthermore, PAINTS can be combined with advanced projection systems towards the development of optical visual neuro-prosthetics.