Xin-a Hu

Photosensitizers in clinical PDT

Photosensitizers in photodynamic therapy allow for the transfer and translation of light energy into a type II chemical reaction. In clinical practice, photosensitizers arise from three families-porphyrins, chlorophylls, and dyes. All clinically successful photosensitizers have the ability to a greater or lesser degree, to target specific tissues or their vasculature to achieve ablation. Each photosensitizer needs to reliably activate at a high enough light wavelength useful for therapy. Their ability to fluoresce and visualize the lesion is a bonus. Photosensitizers developed from each family have unique properties that have so far been minimally clinically exploited. This review looks at the potential benefits and consequences of each major photosensitizer that has been tried in a clinical setting.

Determination of complex refractive index of polystyrene microspheres from 370 to 1610 nm

We introduce an inverse method for determining simultaneously the real and imaginary refractive indices of microspheres based on integrating sphere measurements of diffuse reflectance and transmittance, and Monte Carlo modelling in conjunction with the Mie theory. The results for polystyrene microspheres suspended in water are presented.

Refractive indices of human skin tissues at eight wavelengths and estimated dispersion relations between 300 and 1600 nm

The refractive index of human skin tissues is an important parameter in characterizing the optical response of the skin. We extended a previously developed method of coherent reflectance curve measurement to determine the in vitro values of the complex refractive indices of epidermal and dermal tissues from fresh human skin samples at eight wavelengths between 325 and 1557 nm. Based on these results, dispersion relations of the real refractive index have been obtained and compared in the same spectral region.

Optical properties of porcine skin dermis between 900 nm and 1500 nm

The weak absorption of shortwave infrared light by skin tissues between 700 and 1500 nm offers an important window for diagnosis by optical means. The strong scattering of shortwave infrared light by the skin, however, presents a challenge to the modelling of light propagation through the skin and the understanding of skin optics. We have measured the collimated and diffuse transmittance and diffuse reflectance of porcine skin dermis samples within 30 h post-mortem. Monte Carlo simulations have been performed to inversely determine the absorption coefficient, scattering coefficient and anisotropy factor of the dermis samples in the spectral range from 900 to 1500 nm. We further analyse the sensitivity of the values of the parameters to the experimental errors and inverse calculation procedures. The state of the cellular integrity of the skin samples following optical measurements was verified using transmission electron microscopy. These results were correlated to study post-mortem effects on the in vitro optical properties of porcine dermis. We concluded that for samples stored within crushed ice for up to 30 h post-mortem the wavelength dependence of optical properties of the dermis remains unchanged while the values of the parameters vary moderately due to modification of the water content of the tissue.

Simulations of light scattering from a biconcave red blood cell using the finite-difference time-domain method

Numerical simulations of light scattering by a biconcave shaped human red blood cell (RBC) are carried out using the finite-difference time-domain (FDTD) method. A previously developed FDTD code for the study of light scattering by ice crystals is modified for the current purpose and it is validated against Mie theory using a spherically shaped RBC. Numerical results for the angular distributions of the Mueller scattering matrix elements of an RBC and their dependence on shape, orientation, and wavelength are presented. Also calculated are the scattering and absorption efficiencies. The implication of these results on the possibility of probing RBC shape changes is discussed.

Determination of refractive indices of porcine skin tissues and Intralipid at eight wavelengths between 325 and 1557 nm

We constructed an automated reflectometry system for accurate measurement of coherent reflectance curves of turbid samples and analyzed the presence of coherent and diffuse reflection near the specular reflection angle. An existing method has been validated to determine the complex refractive indices of turbid samples on the basis of nonlinear regression of the coherent reflectance curves by Fresnels equations. The complex refractive indices of fresh porcine skin epidermis and dermis tissues and Intralipid solutions were determined at eight wavelengths: 325, 442, 532, 633, 850, 1064, 1310, and 1557 nm.

A primary method for determination of optical parameters of turbid samples and application to intralipid between 550 and 1630nm

The lack of a primary method for determination of optical parameters remains a significant barrier in optical study of turbid media. We present a complete system of experimental setups and Monte Carlo modeling tools for fast and accurate solution of the inverse problem from the measured signals of homogeneous turbid samples. The calibration of the instrument and validation of the Monte Carlo modeling have been carried out to ensure the accuracy of the inverse solution. We applied this method to determine the optical parameters of turbid media of 10% intralipid between 550 and 940 nm and 20% intralipid between 550 and 1630 nm.

Development of a diffraction imaging flow cytometer

Diffraction images record angle-resolved distribution of scattered light from a particle excited by coherent light and can correlate highly with the 3D morphology of a particle. We present a jet-in-fluid design of flow chamber for acquisition of clear diffraction images in a laminar flow. Diffraction images of polystyrene spheres of different diameters were acquired and found to correlate highly with the calculated ones based on the Mie theory. Fast Fourier transform analysis indicated that the measured images can be used to extract sphere diameter values. These results demonstrate the significant potentials of high-throughput diffraction imaging flow cytometry for extracting 3D morphological features of cells.

Modeling of the rough-interface effect on a converging light beam propagating in a skin tissue phantom

Light distribution in a strong turbid medium such as skin tissue depends on both the bulk optical properties and the profiles of the interfaces where mismatch in the refractive index occurs. We present recent results of a numerical investigation on the light distribution inside a human skin tissue phantom for a converging laser beam with a wavelength near 1 mum and its dependence on the roughness of the interfaces and index mismatch. The skin tissue is modeled by a two-layer structure, and within each layer the tissue is considered macroscopically homogeneous. The two interfaces that separate the epidermis from the ambient medium and the dermis are considered randomly rough. With a recently developed method of Monte Carlo simulation capable of treating inhomogeneous boundary conditions, light distributions in various cases of interface roughness and index mismatch are obtained, and their relevance to the measurements of optical parameters of the skin tissue and laser surgery under the skin surface are discussed.

Evaluation of a parallel FDTD code and application to modeling of light scattering by deformed red blood cells

A parallel Finite-Difference-Time-Domain (FDTD) code has been developed to numerically model the elastic light scattering by biological cells. Extensive validation and evaluation on various computing clusters demonstrated the high performance of the parallel code and its significant potential of reducing the computational cost of the FDTD method with low cost computer clusters. The parallel FDTD code has been used to study the problem of light scattering by a human red blood cell (RBC) of a deformed shape in terms of the angular distributions of the Mueller matrix elements. The dependence of the Mueller matrix elements on the shape and orientation of the deformed RBC has been investigated. Analysis of these data provides valuable insight on determination of the RBC shapes using the method of elastic light scattering measurements.