Study On Optical Stimulation Methods And Parameters Of Pulsed Near-Infrared Laser Evoked Cochlear Neural Activity

Hearing impairment is one of the multiple diseases in the worldwide scale. For patients with sensorineural deafness, artificial cochlear implant is the most effective treatment for partially restoration of hearing. Improvements in cochlear implant devices during the last decade have been achieved through electronic technology development and novel coding strategies, which provide good speech recognition in quiet listening environment. Despite the good performance in quiet environment, there still exist significant gaps in performance between normal-hearing and cochlear-implant listeners in noise environment and music perception. Research has shown that the electric current spread in the tissue is an impenetrable physical barrier for the cochlear implant, for this reason, the neighboring electrodes cannot be considered independent stimulation sources and simultaneous transfer of information at adjacent electrodes may lead to deleterious interference. The number of implantable electrodes is also limited, which restricts the further development of cochlear implant.To close the performance gap between implant and normal listeners and overcome the current limitations, new ideas and tools are needed to improve the precision and spatial selectivity of auditory neural activation. Recently, Infrared Neural Stimulation (INS) has been proposed as an emerging technology for evoking neural activities. The INS technique can activate neurons directly without the optogenetic modification or other additional interventions. Its features such as contact-free, no stimulus artifact and spatial resolution improvement may bring advantages over the electrical neural stimulation. INS method has also been used in auditory system stimulation which could bring beneficial to cochlear implants. Relative researches have demonstrated that INS with appropriate parameters is an effective tool to trigger hearing response.In previous INS studies, infrared lasers above 1800 nm wavelength have been mainly used due to the relatively high water absorption coefficient. Recently, pulsed short-wavelength near-infrared (SW-NIR) laser was proposed in auditory neural stimulation for its deeper penetration depth in fluids and tissues. Since the cochlea is a hollow chamber of bone filled with lymph fluid, the laser irradiation has to penetrate the fluids before it acts on the target neurons within the modiolus, the SW-NIR laser with deeper penetration depth could pass through the perilymph fluids and activate the auditory nerves effectively. The SW-NIR laser auditory neurons activation research is still in its infancy, the experiment design and technology detail still need further study. In this dissertation, a detailed theoretical and experimental study on auditory neural stimulation with SW-NIR laser was performed.The main research contents and innovations of this dissertation are as follows:1. Through the theoretical analysis of the laser-biotissue interaction and laser induced thermal effect, the derivation process of the biological heat transport equation and typical solutions are given, which provide a theoretical basis for the pulsed laser triggering neural response. Subsequently, mechanisms of optical neural activation are described in detail, including the thermal effect activate the heat sensitive ion channels and change the cell membrane capacitance, the photomechanical pressure waves could also induce the auditory response.2. The model selection and main indicators of the pulsed laser neural stimulation system are listed and their working principles are decribed, including the laser driving circuit with three-state current control, the TEC temperature control circuit, the system control unit, and the man-machine interface and software program design. The protection functions design for laser diodes and the driving current ripple optimization are also introduced.3. The animal experiment methods of laser auditory neurons stimulaton are described, including the selection of animal species, animal anesthetic method and surgery operation process, the necessity analysis of cochlear deafness and deafness methods. Moreover, the electrophysiological indexes and measurement of the cochlear neural response are introduced, including the equipment parameters settings, electrodes placement, test environment and the signal processing method.4. The pulsed 980 nm and 810 nm laser was applied as optical stimuli to irradiate the auditory neurons in the deafened guinea pigs’cochlea and the neural response under the two wavelengths were compared by recording the optically-evoked auditory brainstem responses (OABRs). In addition, the effect of radiant exposure, laser pulse width and threshold with the two laser wavelengths was further investigated and compared. The study results demonstrated that 980 nm and 810 nm laser could both evoke the OABRs effectively in the deafened cochlea and there exist different neural response characteristics between the two wavelengths. The 980 nm laser has advantages in the stimulation efficiency than the 810 nm laser. Concretely, the 980 nm laser could evoke higher OABR amplitude and it has lower threshold radiant exposure than the 810 nm laser. While the 810 nm laser has potential for providing a wider range of optimized pulse duration in the auditory neurons stimulation. In addition, we also analyzed the reason which is in accordance with the absorption coefficient of water at different wavelengths. Experiment results could provide evidence that the photo-thermal effect induced by water absorption of laser radiation is one of the main mechanisms of INS.5. The effect of laser pulse parameters variability on the optically evoked auditory neural response characteristics is studied. Firstly, the 980 nm wavelength laser is used to stimulate the auditory neurons and the effect of laser parameters (pulse energy, pulse durations) on the OABR intensity and latency is investigated. For the laser neural stimulation in cochlea, we considered that it was indispensable to restrict the laser pulse energy in an appropriate range. The laser energy should be sufficient to evoke auditory neural activity, and the level should below the thermal damage threshold. Secondly, the 808 nm pulsed laser with a relatively wide pulse duration range (20-1000 μs) was used to investigate the optical parameters effect on SW-NIR stimulation of auditory neurons, especially under shorter pulse durations. Results show that for the pulse durations between 20 μs and 300 μs, the OABRs are significantly affected by pulse duration variation and OABR amplitude increases along with the pulse duration broadening. However, the pulse duration change in 300-1000 μs range shows non-obvious influence on the OABR intensity. The data indicate that the heat energy net deposit in target might play a more important role in evoking the neural response. Experiment results also demonstrate that the SW-NIR laser with lower water absorption could have a wider available pulse duration range and a larger safety energy interval in the auditory neural stimulation.6. The fiber optic collimation technique is developed and applied in the pulsed SW-NIR laser auditory neural stimulation for the first time. Firstly, the concrete implementation scheme of beam collimation and the collimator design based on C-lens are described. For the animal experiment, the auditory neurons in the cochlea are stimulated with the collimated and uncollimated laser irradiation and the neural responses to the two modes are compared. The results confirm that the beam collimation approach could bring positive effects on auditory neural stimulation such as neural triggering efficiency enhancement, spatial selectivity improvement and the laser energy consumption reduction. The causes of these beneficial effects are also analyzed in this study.