Cochlear implants artificially restore hearing to people with hearing loss through electrical stimulation of the auditory nerve, but hearing outcomes are limited by the broad spread of current throughout the cochlea fluids. Optogenetic stimulation can improve spatial precision within the cochlea, but cannot achieve the high stimulation rates used in contemporary cochlear implants. Hybrid (optogenetic and electrical) stimulation offers a means of achieving both high spatial precision whilst maintaining high stimulation rates. We recorded auditory nerve responses to three modes of stimulation – light/optogenetic, electrical, and hybrid – and compared the activation thresholds and temporal precision across the modalities.

A major constraint in photomedicine is the scattering of photons within tissue, which can limit the penetration of light to reach target structures such as a tumor. Laser-induced shockwaves could offer a potential approach to mitigate this constraint by modifying the optical scattering properties of tissue and re-directing the light to targeted regions. Preliminary results in a skin phantom suggest that laser-induced shockwaves can alter optical characteristics of a turbid medium, and subsequently, induce changes in light propagation.

Photo-mediated Ultrasound Therapy (PUT) is a novel anti-vascular and agree-free technique, which can selectively remove blood vessels by promoting cavitation activity with a significantly lower amount of energy of ultrasound burst and nanosecond laser simultaneity when compared to energy level required by individual laser and ultrasound treatment therapies. We report the development of a high-speed PUT system with 50 kHz pulsed laser, decreasing the treatment time by a factor of 20. In addition, we combined it with optical coherence tomography angiography (OCTA) for real-time monitoring in vivo rabbit experiments. Based on quantitative prescreening and real-time monitoring of treatment response, this combination enables implementation of individualized treatment strategies.

In Spatial Frequency Domain Imaging a sinusoidal intensity pattern is projected onto tissue, and the reflectance is a function of the projected spatial frequency and the tissue optical properties. For low spatial frequencies, the reflectance can be described by diffusion theory and Cuccia et al. developed a model based on the Partial Current Boundary Condition (PCBC) for the Diffusion Approximation. We show that an implicitly used approximation in the derivation by Cuccia et al. introduces errors in the estimated reflectance and tissue optical properties and we derive a new model that reduces these errors by a factor of 2.

In previous Monte Carlo (MC) studies of modeling Fourier-domain optical coherence tomography (FD-OCT), the results obtained at single wavelength are often used to reconstruct the image despite of FD-OCT’s broadband nature. Here, we propose a novel image simulator for full-wavelength MC simulation of FD-OCT based on Mie theory, which combines the inverse discrete Fourier transform (IDFT) with a probability distribution-based signal pre-processing to eliminate the excessive noises in image reconstruction via IDFT caused by missing certain wavelength’s signals in some scattering events. Compared with the conventional method, the proposed simulator is more accurate and could better preserve the wavelength-dependent features.

We present a novel strobe photography system capable of recording a full dynamic sequence in a single camera acquisition, with an effective frame rate of 1 million FPS. This system has been utilized to study pulsed laser ablation from a 1064 nm, 6 ns laser pulse incident on biological tissue. Image sequences enable the extraction of physical parameters, include shock wave and ejecta velocities, and accelerations. Encoding contrast with shadow photography enables the estimation of the mass ejected for a single ablation pulse.

The successful laser ablation of clinically relevant tissue models by means of picosecond laser pulses is presented. This is a potential alternative to overcoming limitations of conventional tumour-surgery tools in terms of precision and thermal damage. The correlation of high-speed imaging of the ablation process, schlieren imaging of the resulting plume dynamics and a histopathological analysis of the post-process tissue morphology enables optimisation of the tissue removal rate whilst avoiding adverse cavitation effects. This facilitates minimal collateral thermal damage. Effective tissue removal is presented for the epithelial laser ablation of colonic tissue; with translation of this process towards infiltrating brain and head and neck cancer surgery further discussed.

In this project, we aim to build an unlabeled, two-photon imaging-based approach to identify cellular biomarkers in the context of traumatic brain injuries with subcellular imaging resolutions. So far, we have identified NAD(P)H, FAD, LipDH, and Lipofuscin, four main contributors from the brain cells. And we built a math model to quantify the fluorophore contributions directly from the two photon images. Therefore, we can calculate cellular redox state, the lipofuscin level, which is associated with oxidative stress, as well as the mitochondrial organization, cell-matrix interactions using established optical biomarkers in the lab in a more robust way.

Light’s helicity refers to the right- or left-handed spin direction of its electric field vector. Light backscattered from incident circularly polarized light upon turbid media typically consists of two sub-populations: photons which have orthogonal (flipped) and parallel (preserved) helicities with respect to the incident state. The flipped and preserved intensities are found to be acutely sensitive to average scatterer size and modestly sensitive to turbidity through an interplay of single and multiple scattering effects. Using a highly sensitive intensified-CCD camera, we perform a novel experimental study on helicity-based images of backscattered light, enabling (1) investigation of photonic pathways and (2) extraction of metrics which provide scatterer size and turbidity information about tissue-like media. An exciting potential application of this work is early cancer detection since malignant tissues have been observed to increase in in scatterer size and turbidity.

In support of previous cell culture work, we wanted to determine if cell density has an effect on the temperature at which cells die. We used the method of microthermography because it provided threshold temperatures. By not using laser dose, we avoided complications from varying absorptivity and diffusivity of samples. Microthermography looks at temperature at the boundary between live and dead cells using a high-speed mid-IR camera and high-magnification optics. The temperature at the boundary of cell death is independent of the irradiance and represents the true biological threshold regardless of the size of damaged area. Using a 2-um laser, we explored whether the boundary of cell death, and thus the damage rate process, is dependent on cell confluency.