Yichao Chen

Temperature distribution in selective laser-tissue interaction

Selective photothermal interaction using dye enhancement has proven to be effective in minimizing surrounding tissue damage and delivering energy to target tissue. During laser irradiation, the process of photon absorption and thermal energy diffusion in the target tissue and its surrounding tissue are crucial. Such information allows the selection of proper operating parameters such as dye concentrations, laser power, and exposure time for optimal therapeutic effect. Combining the Monte Carlo method for energy absorption and the finite difference method for heat diffusion, the temperature distributions in target tissue and surrounding tissue in dye enhanced laser photothermal interaction are obtained. Different tissue configurations and dye enhancement are used in the simulation, and different incident beam sizes are also used to determine optimum beam sizes for various tissue configurations. Our results show that the algorithm developed in this study could predict the thermal outcome of laser irradiation. Our simulation indicates that with appropriate absorption enhancement of the target tissue, the temperature in the target tissue and in the surrounding tissue can be effectively controlled. This method can be used for optimization of lesion treatment using laser photothermal interactions. It may also provide guidance for laser immunotherapy in cancer treatment, since the immunological responses are believed to be related to tissue temperature changes.

Magnetic resonance imaging guidance for laser photothermal therapy.

Temperature distribution is a crucial factor in determining the outcome of laser phototherapy in cancer treatment. Magnetic resonance imaging (MRI) is an ideal method for 3-D noninvasive temperature measurement. A 7.1-T MRI was used to determine laser-induced high thermal gradient temperature distribution of target tissue with high spatial resolution. Using a proton density phase shift method, thermal mapping is validated for in vivo thermal measurement with light-absorbing enhancement dye. Tissue-simulating phantom gels, biological tissues, and tumor-bearing animals were used in the experiments. An 805-nm laser was used to irradiate the samples, with laser power in the range of 1 to 3 W. A clear temperature distribution matrix within the target and surrounding tissue was obtained with a specially developed processing algorithm. The temperature mapping showed that the selective laser photothermal effect could result in temperature elevation in a range of 10 to 45 degrees C. The temperature resolution of the measurement was about 0.37 degrees C with 0.4-mm spatial resolution. The results of this study provide in vivo thermal information and future reference for optimizing laser dosage and dye concentration in cancer treatment.

Gel Phantom in selective laser phototherapy

Tissue-simulating gel phantoms have been used in selective laser photothermal interaction. The gelatin phantom provides a uniform tissue-simulating medium for analyzing thermal performance under laser radiation. The gelatin phantom gel is used particularly in measurements of thermal reactions in laser thermology. The gelatin phantom is made from gelatin and Liposyn. A special gel sphere with Indocyanine Green (ICG) laser absorption enhancement dye is embedded in normal gel to simulate the dye-enhanced tumor in normal tissue. The concentration of ICG within the dye sphere is optimized using simulation for selective phototherapy. As a first attempt, the concentration of ICG and laser power density was optimized using a temperature ratio of target tissue versus surrounding tissue. The gel thermal performance is also monitored using MRI thermology imaging technology. The thermal imaging shows in vivo, 3D temperature mapping inside the gel. The study of thermal distribution using gel phantom provides information to guide the future selective laser photothermal thermal therapy.

Tissue temperature distribution measurement and laser immunotherapy for cancer treatment

Temperature distribution in tissue can be a crucial factor in laser treatment for inducing immunization responses. In this study, Magnetic Resonance Imaging (MRI) was used to measure thermal temperature distribution in target tissue in laser treatment of metastatic tumors. It is the only feasible method for in vivo, non-invasive temperature distribution measurement. The measurement was conducted using phantom gel and tumor-bearing rats. The thermal couple measurement of target temperature was also was used to calibrate the relative temperature increase. The phantom system was constructed with a dye-enhanced spherical gel embedded in uniform gel phantom, simulating a tumor within normal tissue. Irradiation by an 805-nm laser increased the system temperature. Using an MRI system and proper algorithm processing for small animal studies, a clear temperature distribution matrix was obtained. The temperature profiles of rat tumors, irradiated by the laser with a power in the range of 2-3.5W and injected with a light-absorbing dye, ICG, and an immunoadjuvant, GC, were obtained. The temperature distribution provided in vivo thermal information and future reference for optimizing dye concentration and irradiation parameters to reach the optimum tumor destruction and immunization effects.

Thermal Damage of Tissue during Near-Infrared Laser Irradiation with Assistance of Light-Absorbing Dye

The selective photothermal-tissue interaction using dye enhancement has been proven to be effective in minimizing the peripheral normal tissue damage during cancer treatment. It is important that the tissue-thermal damage be analyzed and the damage rate process be estimated before the photothermal-immunotherapy for cancer treatment. In this study, we have used the EMT6 mouse tumor model for the laser-tumor treatment with a simultaneous surface temperature measurement using infrared thermography. The images acquired were processed to obtain the temperature profiles. The saturation temperature and corresponding time of irradiation from the temporal profiles were used to calculate the damage parameter using Arrhenius rate process equation. The damage parameters obtained from six mice were compared. Our results of in vivo study show that the damage analyses agree with the previous in vitro study on skins.

The correlation study of temperature distribution with the immunology response under laser radiation

The 3-D, in vivo temperature distributions within tumor-bearing rats were measured using Magnetic Resonance Imaging (MRI) technique. The in vivo thermal distributions of rats were measured using MRI chemical shift of water proton density. DMBA-4 tumor bearing rats are treated using laser photothermal therapy combined with immunoadjuvant under the observation of MRI. The thermal images and the immunological responses were studied and their relationships were investigated. The study of thermal distribution and correlation with the immunological response under laser treatment provided rich information with potential guidance for thermal-immunological therapy.

Histological and morphological studies of immune responses induced by laser immunotherapy

Laser energy can induce acute photothermal tissue damage, but without systemic effect in the treatment of tumors. However, it could serve as a precursor of immune responses if its photothermal actions could be used effectively as a means of producing tumor-specific antigens and other immunological stimulation elements. When used in a combination with immunoadjuvants, laser photothermal energy had been successfully applied in the treatment of metastatic tumors. Pre-clinical and preliminary clinical studies have demonstrated the systemic and immunological effects of the combination of laser irradiation and immunological stimulation through eradication of primary and secondary tumors, and through molecular and cellular anti-tumor immune activities. This study focuses on the histological and morphological aspects of laser immunotherapy induced immune responses, using glycated chitosan as the adjuvant and an 805-nm laser as the source of photothermal energy source. Cellular activities, such as tumor destruction and lymphocyte infiltration after the laser immunotherapy treatment were observed and analyzed. These cellular activities further support the hypothesis that induced immune activities are crucial outcome of laser immunotherapy.

Tissue temperature distribution measurement by MRI and laser immunology for cancer treatment

In cancer treatment and immune response enhancement research, Magnetic Resonance Imaging (MRI) is an ideal method for non-invasive, three-dimensional temperature measurement. We used a 7.1-Tesla magnetic resonance imager for ex vivo tissues and small animal to determine temperature distribution of target tissue during laser irradiation. The feasibility of imaging is approved with high spatial resolution and high signal-noise- ratio. Tissue-simulating gel phantom gel, biological tissues, and tumor-bearing animals were used in the experiments for laser treatment and MR imaging. Thermal couple measurement of temperature in target samples was used for system calibration. An 805-nm laser was used to irradiate the samples with a laser power in the range of 1 to 2.5 watts. Using the MRI system and a specially developed processing algorithm, a clear temperature distribution matrix in the target tissue and surrounding tissue was obtained. The temperature profiles show that the selective laser photothermal effect could result in tissue temperature elevation in a range of 10 to 45 °C. The temperature resolution of the measurement was about 0.37°C including the total system error. The spatial resolution was 0.4 mm (128x128 pixels with field of view of 5.5x5.5 cm). The temperature distribution provided in vivo thermal information and future reference for optimizing dye concentration and irradiation parameters to achieve optimal thermal effects in cancer treatment.

Determination of surface temperature distribution in biological tissues during laser-immunotherapy

An ideal cancer treatment method should not only cause primary tumor suppression but also induce an antitumor immunity, which is essential for control of metastatic tumors. A combination therapy using a laser, a laser-absorbing dye, and an immunoadjuvant guided by temperature measurement probes such as magnetic resonance imaging thermometry (MRT) and infrared thermography (IRT) can be an ideal treatment modality. Temperature distribution inside the target tissue is important in laser treatment. The surface temperature often serves as an indicator of the treatment effect. However, real-time monitoring of surface temperature during laser irradiation poses a great challenge. In this study, we investigated the surface temperature distribution using direct measurement and theoretical simulation. The preliminary results of in vitro and in vivo studies are presented. Gel phantom and chicken breast tissue were irradiated by an 805 nm laser and the surface temperature distribution was obtained using an infrared thermal camera. EMT-6 breast tumors in mice were treated using the 805 nm laser and with different dye and immunoadjuvant combinations, including intratumor injections of indocyanine green (ICG) and glycated chitosan (GC). Monte Carlo simulation for selective photothermal-tissue interaction was also performed for the surface temperature distributions. Our results demonstrated that the tissue temperature can be accurately monitored in real time and can be controlled by appropriate treatment parameters.

MRI 3D tissue temperature distribution measurement

A highly accurate, fast three-dimensional in vivo temperature mapping method is developed using MRI water photon chemical shift. It is important to have the precise temperature distribution information during laser-tissue thermal treatment. Several methods can be used for temperature measurement including thermal couple, optical fiber sensor, and MRI (magnetic resonance imaging) methods. MRI is the only feasible method for 3D in vivo, non-invasive temperature distribution measurement for laser-tissue interaction. The water proton chemical shift method is used in 3D MRI mapping. Varies MRI parameters, such as flip angle, TE, TR, spatial resolution, and temporal repetition, were optimized for the temperature mapping. The laser radiation of 805nm wavelength and a light-absorbing dye, indocyanine green (ICG) was used for temperature elevation. The measurement was conducted using gel phantom, chicken tissue and rats. The phantom system was constructed with a dye-enhanced spherical gel embedded in uniform gel phantom, simulating a tumor within normal tissue. The normal temperature elevation within ex vivo tissue such as chicken breast can reach up to 45-50 degree C with a power density of 1.3W/cm2 (with laser power of 3W and 1.7cm beam size). The temperature resolution is 0.37 degree C with a 0.2-mm spatial resolution and repetition rate of around 40 seconds. The external magnetic field drift effect is also evaluated.