Lihong V. Wang

Laser optoacoustic imaging of turbid media: determination of optical properties by comparison with diffusion theory and Monte Carlo simulation

Laser optoacoustic imaging based on time-resolved detection of laser-induced thermoelastic pressure waves can be potentially used in medicine as a diagnostic tool (tomography) and as means to measure tissue optical properties in vivo. Information on tissue optical properties in vivo is important for laser dosimetry and tissue characterization. Analysis of the profile and amplitude of laser-induced transient stress can provide direct information about absorbed energy distribution in irradiated volume. Pressure wave profiles exactly correspond to temperature distributions generated in tissues under irradiation conditions of temporal stress confinement. In this study we experimentally measured pressure wave profile and amplitude upon irradiation of highly scattering gel phantoms and aqueous solutions colored with potassium chromate and made turbid with polystyrene spheres. A wide-band lithium niobate acoustic transducer was used to detect laser-induced pressure waves. The experimentally measured laser-induced stress profiles and the results of a Monte Carlo simulation were in excellent agreement. Computer code was developed to calculate separately absorption and scattering coefficients from transient stress profiles. Our study has demonstrated feasibility of time-resolved detection of laser-induced acoustic transients as a method for tissue optical properties measurements in vivo.

Oblique-incidence reflectometry: one relative profile measurement of diffuse reflectance yields two optical parameters

A new, simple and quick approach, oblique-incidence reflectometry, was used to measure the absorption and reduced scattering coefficients of a semi-infinite turbid medium. An obliquely incident light beam causes the center of the far diffuse reflectance to shift from the point of incidence, where the far diffuse reflectance refers to the diffuse reflectance that is several transport mean free paths away from the incident point. The amount of shift yields the diffusion constant by a simple formula, and the slope of the diffuse reflectance yields the attenuation coefficient. Only the relative profile of the diffuse reflectance is needed to deduce both optical parameters, which makes this method attractive in clinical settings because it does not require a stringent calibration for absolute quantity measurements. This method was tested theoretically by Monte Carlo simulations and experimentally by a reflectometer. Because this method can be used to measure optical properties of biological tissues quickly and requires only inexpensive equipment, it has potential clinical application to the diagnosis of disease or monitoring of treatments.

Noninvasive detection of skin cancers by measuring optical properties of tissues

Skin cancer is the most frequently occurring cancer of all cancers. Each yea rover 500,000 new cases of skin cancer will be detected. A high percentage of skin cancers are diseases in which fatalities can be all but eliminated and morbidity reduced if detected early and treated properly. These skin lesions are distinguished generally by subjective visual inspection and their definitive diagnosis requires time-consuming expensive histopathological evaluation of excisional or incisional biopsies. In vivo experimental evidence published in the literature has shown that cancerous skin lesions have different total diffuse reflectance spectra than non- cancerous lesions or normal skin. Therefore, cancerous skin lesions may be differentiated from non-cancerous skin lesions by comparing the optical properties of the skin lesions with those of the surrounding normal skin sites, where the optical properties of the normal skin sites are used to account for different types of skin or different areas of skin. We have demonstrated that the effect of melanin concentration on the diffuse reflectance may be removed by extrapolating the reflectance at different wavelengths to an apparent pivot point. Because the concentration of melanin does not indicate malignancy, the removal of its effect is important to avoid false detection. The total diffuse reflectance depends on the albedo and anisotropy of tissues. Therefore, the total diffuse reflectance will remain the same as long as the anisotropy and the ratio between the absorption coefficient and the reduced scattering coefficient remain the same. Separating the absorption and scattering effects should enhance the detection sensitivity of skin cancers.

Animated simulation of light transport in tissues

Time-resolved light transport in composite tissues is simulated using the Monte Carlo technique. Snapshots of spatial distributions of physical quantities, including light absorption rate, light fluence rate, and diffuse reflectance rate, are presented. Such multiple snapshots with a given time interval can be shown sequentially to achieve an animation effect. This animated simulation is a tool that aids in the general understanding of light transport in tissues. For example, the simulation of time-resolved spatial distribution of light fluence rate inside a tissue illustrates how fast light is dispersed inside tissues. The simulation of diffuse reflectance rate as a function of time of a short-pulsed laser incident upon a piece of tissue containing a buried object shows that early reflected light does not carry imaging information of the object. The imaging quality of the object can thus be improved by rejecting the early-arriving reflected light.

Computation of the optical properties of tissues from light reflectance using a neural network

We have established a neural network to quickly deduce optical properties of tissue slabs from the diffuse reflectance distribution. Diffusion theory based on multiple image sources mirrored about the two extrapolated boundaries is used to prepare the training and testing sets for the neural network. The neural network is trained using backpropagation with the conjugate gradient method. Once the neural network is trained, it is able to deduce optical properties of tissues within on the order of a millisecond. The range of the tissue optical properties that is covered by our neural network is 0.01 - 2 cm-1 for absorption coefficient, 5 - 25 cm-1 for reduced scattering coefficient, and 0.001 - 1 cm for tissue thickness. A separate network is also trained for thick tissue slabs. A simple experimental setup applying the trained neural network is designed to measure tissue optical properties quickly.

Near-infrared spectroscopy of a heterogeneous turbid system containing distributed absorbers

In most biological tissues, absorbers such as blood in the blood vessels are localized within a low-absorbing background medium. To study the effect of distributed absorbers on the near infrared reflectance, we developed a Monte Carlo code and performed time-domain measurements on heterogeneous tissue-vessel models. The models were made of low absorbing polyester resin mixed with TiO2 as scatters. A series of tubes with diameters of 3.2 or 6.4 mm were made in the resin sample. The volume ratio of the tubes to the total sample is about 20%. During the measurement, these tubes were filled with turbid fluids with different absorption coefficients to simulate blood in various oxygenation states. We found that the apparent absorption coefficient of the resin/tube system, determined by using the diffusion equation fit, can be approximated by a volume-weighted sum of the absorption coefficients of the different absorbing components. This approximation has to be replaced by a more complex expression if the difference in absorption between the absorbers and background is very large (approximately 20 times). The results of the tissue phantom study are supported by the Monte Carlo simulation. Possible explanations for the photon migration in this kind of heterogeneous system is also presented.

Determination of blood oxygenation in the brain by time-resolved reflectance spectroscopy: influence of the skin, skull, and meninges

Near infrared light has been used for the determination of blood oxygenation in the brain but little attention has been paid to the fact that the states of blood oxygenation in arteries, veins, and capillaries differ substantially. In this study, Monte Carlo simulations for a heterogeneous system were conducted, and near infrared time-resolved reflectance measurements were performed on a heterogeneous tissue phantom model. The model was made of a solid polyester resin, which simulates the tissue background. A network of tubes was distributed uniformly through the resin to simulate the blood vessels. The time-resolved reflectance spectra were taken with different absorbing solutions filled in the network. Based on the simulation and experimental results, we investigated the dependence of the absorption coefficient obtained from the heterogeneous system on the absorption of the actual absorbing solution filled in the tubes. We show that light absorption by the brain should result from the combination of blood and blood-free tissue background.

Ultrasound-modulated optical tomography for thick tissue imaging

Continuous-wave ultrasonic modulation of scattered laser light has been used to image objects in tissue-simulating turbid media for the first time. We hypothesize that the ultrasound wave focused into the turbid media modulates the laser light passing through the ultrasonic focal spot. The modulated laser light collected by a photomultiplier tube reflects the local mechanical and optical properties in the focal zone. Buried objects in 5-cm thick tissue phantoms are located with millimeter resolution by scanning and detecting alterations of the ultrasound-modulated optical signal. Ultrasound-modulated optical tomography separates the conflict between signal and resolution in purely optical imaging of tissue and does not rely on ballistic or quasi-ballistic photons but on the abundant diffuse photons. The imaging resolution is determined by the focused ultrasonic wave. This technique has the potential to provide a noninvasive, nonionizing, inexpensive diagnostic tool for diseases such as breast cancer.

Analysis of diffusion theory and similarity relations for light reflectance by turbid media

Both diffusion theory and similarity relations for light reflectance by semi-infinite turbid media have been analyzed by comparing their computational results with Monte Carlo simulation results. Since a large number of photon packets are traced, the variance of the Monte Carlo simulation results is small enough to reveal the detailed defects of diffusion theories and similarity relations. We have demonstrated that both diffusion theory and similarity relations provide very accurate results when the photon sources are isotropic and one transport mean free path below the turbid medium surface or deeper. This analysis has led to a hybrid model of Monte Carlo simulation and diffusion theory, which combines the accuracy advantage of Monte Carlo simulation and the speed advantage of diffusion theory. The similarity relations are used for the transition from the Monte Carlo simulation to the diffusion theory.

Laser Action in dye-infused biological tissue

The narrowing of the spectral linewidth and the increasing of the peak intensity characteristic of laser action was observed in emission spectra of dye-infused biological tissues. The fresh tissue was infused with a solution of Rhodamine 640 perchlorate in ethanol and then excited with frequency-doubled Q-switched Nd:YAG laser pulses. The sharp spectral peaks of laser action in tissues may find applications in detection of superficial disease.