Caigang Zhu

Review of Monte Carlo modeling of light transport in tissues

Abstract. A general survey is provided on the capability of Monte Carlo (MC) modeling in tissue optics while paying special attention to the recent progress in the development of methods for speeding up MC simulations. The principles of MC modeling for the simulation of light transport in tissues, which includes the general procedure of tracking an individual photon packet, common light–tissue interactions that can be simulated, frequently used tissue models, common contact/noncontact illumination and detection setups, and the treatment of time-resolved and frequency-domain optical measurements, are briefly described to help interested readers achieve a quick start. Following that, a variety of methods for speeding up MC simulations, which includes scaling methods, perturbation methods, hybrid methods, variance reduction techniques, parallel computation, and special methods for fluorescence simulations, as well as their respective advantages and disadvantages are discussed. Then the applications of MC methods in tissue optics, laser Doppler flowmetry, photodynamic therapy, optical coherence tomography, and diffuse optical tomography are briefly surveyed. Finally, the potential directions for the future development of the MC method in tissue optics are discussed.

Validity of the semi-infinite tumor model in diffuse reflectance spectroscopy for epithelial cancer diagnosis: a Monte Carlo study

The accurate understanding of optical properties of human tissues plays an important role in the optical diagnosis of early epithelial cancer. Many inverse models used to determine the optical properties of a tumor have assumed that the tumor was semi-infinite, which infers infinite width and length but finite thickness. However, this simplified assumption could lead to large errors for small tumor, especially at the early stages. We used a modified Monte Carlo code, which is able to simulate light transport in a layered tissue model with buried tumor-like targets, to investigate the validity of the semi-infinite tumor assumption in two common epithelial tissue models: a squamous cell carcinoma (SCC) tissue model and a basal cell carcinoma (BCC) tissue model. The SCC tissue model consisted of three layers, i.e. the top epithelium, the middle tumor and the bottom stroma. The BCC tissue model also consisted of three layers, i.e. the top epidermis, the middle tumor and the bottom dermis. Diffuse reflectance was simulated for two common fiber-optic probes. In one probe, both source and detector fibers were perpendicular to the tissue surface; while in the other, both fibers were tilted at 45 degrees relative to the normal axis of the tissue surface. It was demonstrated that the validity of the semi-infinite tumor model depends on both the fiber-optic probe configuration and the tumor dimensions. Two look-up tables, which relate the validity of the semi-infinite tumor model to the tumor width in terms of the source-detector separation, were derived to guide the selection of appropriate tumor models and fiber optic probe configuration for the optical diagnosis of early epithelial cancers.

Non-invasive controlled release from gold nanoparticle integrated photo-responsive liposomes through pulse laser induced microbubble cavitation.

Drug-carriers, capable of releasing the drug at the target sites upon external stimuli, are attractive for theranostic applications. In recent years, photo-responsive nanoparticles (NPs) have received considerable attention because of their potentials in providing spatial, temporal, and dosage control over the drug release. However, most of the relevant technologies are still in the process of development and are unprocurable by the clinics. Here, we demonstrated facile fabrication of these photo-responsive NPs by loading hydrophilic gold NPs within thermo-responsive liposomes. Calcein was used as a model drug to evaluate the encapsulation efficiency and the release kinetic profile upon heat/light stimulation. Furthermore, we characterized their size, morphology, phase transition temperature and stability. Finally, we demonstrated that this photo-triggered release might be due to the membrane disruption caused by microbubble cavitation.

Hybrid method for fast Monte Carlo simulation of diffuse reflectance from a multilayered tissue model with tumor-like heterogeneities

We present a hybrid method that combines a multilayered scaling method and a perturbation method to speed up the Monte Carlo simulation of diffuse reflectance from a multilayered tissue model with finite-size tumor-like heterogeneities. The proposed method consists of two steps. In the first step, a set of photon trajectory information generated from a baseline Monte Carlo simulation is utilized to scale the exit weight and exit distance of survival photons for the multilayered tissue model. In the second step, another set of photon trajectory information, including the locations of all collision events from the baseline simulation and the scaling result obtained from the first step, is employed by the perturbation Monte Carlo method to estimate diffuse reflectance from the multilayered tissue model with tumor-like heterogeneities. Our method is demonstrated to shorten simulation time by several orders of magnitude. Moreover, this hybrid method works for a larger range of probe configurations and tumor models than the scaling method or the perturbation method alone.

Numerical investigation of lens based setup for depth sensitive diffuse reflectance measurements in an epithelial cancer model

Lens based setups have been explored for non-contact diffuse reflectance measurements to reduce the uncertainty due to inconsistent probe-sample pressure in the past years. However, there have been no reports describing the details of Monte Carlo modeling of lens based non-contact setup for depth sensitive diffuse reflectance measurements to the best of our knowledge. In this study, we first presented a flexible Monte Carlo method to model non-contact diffuse reflectance measurements in a lens based setup. Then this method was used to simulate diffuse reflectance measurements from a squamous cell carcinoma (SCC) tissue model in the cone shell, cone and hybrid configurations, in which the cone shell configuration has not been previously proposed in optical spectroscopy. Depth sensitive measurements were achieved by adjusting the following two parameters: (1) the depth of focal point of the imaging lens in the SCC model; and (2) the cone radius in the cone configuration or the ring radius in the cone shell configuration. It was demonstrated that the cone shell and the hybrid configurations in general have better depth sensitivity to the tumor and the stroma than the more commonly used cone configuration for diffuse reflectance measurements in the SCC model.

Early Prediction of Skin Viability Using Visible Diffuse Reflectance Spectroscopy and Autofluorescence Spectroscopy

Background: Accurate and early prediction of skin flap viability is vitally important in reconstructive surgery. To the best of the authors’ knowledge, this is the first pilot study to evaluate the simultaneous use of both visible diffuse reflectance and autofluorescence spectroscopy on a reverse MacFarlane rat dorsal skin flap model in the early prediction of skin viability. Methods: A total of 62 flap measurement sites from 11 Sprague-Dawley rats were monitored for 72 hours. Both statistical analysis using measured spectra and quantification of physiologically relevant tissue parameters using empirical methods were performed. Results: The statistical analysis results suggest that either visible diffuse reflectance spectroscopy or autofluorescence spectroscopy alone can predict the skin viability accurately; however, autofluorescence spectroscopy is more sensitive to tissue changes in the first 2 hours after induction of ischemia. The pilot study shows that it is feasible to predict flap failures in the first 2 hours when using autofluorescence spectroscopy alone; moreover, it is possible to predict flap failures even in the first 15 minutes with high accuracy when using diffuse reflectance and autofluorescence spectroscopy simultaneously. Meanwhile, several physiologically relevant parameters including hemoglobin oxygenation, total hemoglobin concentration, and redox ratio indicators estimated from diffuse reflectance and autofluorescence spectra show distinctively different trends over time for nonviable and viable skin. Conclusions: These findings will be helpful to clinicians for making a precise judgment on flap viability. Furthermore, the authors’ results highlight the advantage of using autofluorescence spectroscopy in the early prediction of skin flap viability relative to diffuse reflectance spectroscopy.

Early detection and differentiation of venous and arterial occlusion in skin flaps using visible diffuse reflectance spectroscopy and autofluorescence spectroscopy.

Our previous preclinical study demonstrated that both visible diffuse reflectance and autofluorescence spectroscopy, each of which yields a different set of physiological information, can predict skin flap viability with high accuracy in a MacFarlane rat dorsal skin flap model. In this report, we further evaluated our technique for the early detection and differentiation of venous occlusion and arterial occlusion in a rat groin flap model. We performed both diffuse reflectance and autofluorescence measurements on the skin flap model and statistically differentiated between flaps with and without occlusions as well as between flaps with venous occlusion and those with arterial occlusion based on these non-invasive optical measurements. Our preliminary results suggested that visible diffuse reflectance and autofluorescence spectroscopy can be potentially used clinically to detect both venous and arterial occlusion and differentiate one from the other accurately at an early time point.

Sequential weighted Wiener estimation for extraction of key tissue parameters in color imaging: a phantom study

Abstract. Key tissue parameters, e.g., total hemoglobin concentration and tissue oxygenation, are important biomarkers in clinical diagnosis for various diseases. Although point measurement techniques based on diffuse reflectance spectroscopy can accurately recover these tissue parameters, they are not suitable for the examination of a large tissue region due to slow data acquisition. The previous imaging studies have shown that hemoglobin concentration and oxygenation can be estimated from color measurements with the assumption of known scattering properties, which is impractical in clinical applications. To overcome this limitation and speed-up image processing, we propose a method of sequential weighted Wiener estimation (WE) to quickly extract key tissue parameters, including total hemoglobin concentration (CtHb), hemoglobin oxygenation (StO2), scatterer density (α), and scattering power (β), from wide-band color measurements. This method takes advantage of the fact that each parameter is sensitive to the color measurements in a different way and attempts to maximize the contribution of those color measurements likely to generate correct results in WE. The method was evaluated on skin phantoms with varying CtHb, StO2, and scattering properties. The results demonstrate excellent agreement between the estimated tissue parameters and the corresponding reference values. Compared with traditional WE, the sequential weighted WE shows significant improvement in the estimation accuracy. This method could be used to monitor tissue parameters in an imaging setup in real time.

Multifocal noncontact color imaging for depth-sensitive fluorescence measurements of epithelial cancer

We propose a multifocal noncontact setup to perform depth-sensitive fluorescence imaging on a two-layered epithelial tissue model. The combination of a microlens array and a tunable lens enables the depth of the multifocal plane to be conveniently adjusted without any mechanical movement of the imaging lens or the sample. This advantage is particularly desirable in the clinical setting. Results from the phantom study demonstrate that the setup can achieve depth-sensitive color imaging for fluorescence measurements, which is further confirmed by spectral measurements.

Phantom validation of Monte Carlo modeling for noncontact depth sensitive fluorescence measurements in an epithelial tissue model

Abstract. Experimental investigation and optimization of various optical parameters in the design of depth sensitive optical measurements in layered tissues would require a huge amount of time and resources. A computational method to model light transport in layered tissues using Monte Carlo simulations has been developed for decades to reduce the cost incurred during this process. In this work, we employed the Monte Carlo method to investigate the depth sensitivity achieved by various illumination and detection configurations including both the traditional cone configurations and new cone shell configurations, which are implemented by convex or axicon lenses. Phantom experiments have been carried out to validate the Monte Carlo modeling of fluorescence in a two-layered turbid, epithelial tissue model. The measured fluorescence and depth sensitivity of different illumination–detection configurations were compared with each other. The results indicate excellent agreement between the experimental and simulation results in the trends of fluorescence intensity and depth sensitivity. The findings of this study and the development of the Monte Carlo method for noncontact setups provide useful insight and assistance in the planning and optimization of optical designs for depth sensitive fluorescence measurements.