Study of tissue temperature distribution during laser-immunotherapy for cancer treatment

Scope and Method of Study: The ideal cancer treatment modality should not only cause primary tumor suppression but also induce an anti-tumor immunity, which is essential in controlling metastatic tumors. Motivation of this work is to monitor temperature during laser-cancer treatment. A Monte Carlo method for the light transport in tissue and a finite difference method for the solution of heat diffusion equation were performed to estimate the laser dose parameters, and concentration levels of dye and immunoadjuvant. The specimens used were gelatin phantom, rats and mice. Magnetic Resonance Imaging thermometry (MRT) and infrared thermography (IRT) have been used for the measurement of temperature in the biological tissues during treatment of the primary tumors. Thermal imaging is used to estimate the laser-dose in application to cancer treatment. The thermal imaging and dose calculation can increase the level of safety in the treatment by providing information on target tissue and also on surrounding normal tissue.Findings and Conclusions: Magnetic Resonance Imaging (MRI) has been applied to measure the thermal distribution in gel phantom and tumor-bearing rats during laser treatment. Infrared thermography has been applied to measure the surface temperature under the same conditions in tumor-bearing mice. Intratumoral injection of both indocyanine green (ICG) and glycated chitosan (GC) followed by 805-nm laser irradiation has been found efficacious in the cancer treatment. The temperature rise with ICG and laser combination therapy was about 25 °C and with the ICG, GC, and laser combination therapy, the temperature increased by 30 °C. This infers that ICG and GC injection potentiates the laser-immunotherapy. In both the cases, the tumor temperature attains the cancer cell damage temperature range of 60 °C - 70 °C resulting in an increase in the survival time of the treated mice. More importantly, the temperature profiles in this study agree with the Monte Carlo simulation results. In summary, a combination therapy using a laser, a laser-absorbing dye, and an immunoadjuvant guided by temperature measurement probes, such as MRT and IRT, is an effective treatment modality

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

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 1to3W. 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 10to45°C. The temperature resolution of the measurement was about 0.37°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

Skin Transcriptome of Middle-Aged Women Supplemented With Natural Herbo-mineral Shilajit Shows Induction of Microvascular and Extracellular Matrix Mechanisms

Objective: Shilajit is a pale-brown to blackish-brown organic mineral substance available from Himalayan rocks. We demonstrated that in type I obese humans, shilajit supplementation significantly upregulated extracellular matrix (ECM)–related genes in the skeletal muscle. Such an effect was highly synergistic with exercise. The present study (clinicaltrials.gov ) aimed to evaluate the effects of shilajit supplementation on skin gene expression profile and microperfusion in healthy adult females. Methods: The study design comprised six total study visits including a baseline visit (V1) and a final 14-week visit (V6) following oral shilajit supplementation (125 or 250 mg bid). A skin biopsy of the left inner upper arm of each subject was collected at visit 2 and visit 6 for gene expression profiling using Affymetrix Clariom™ D Assay. Skin perfusion was determined by MATLAB processing of dermascopic images. Transcriptome data were normalized and subjected to statistical analysis. The differentially regulated genes were subjected to Ingenuity Pathway Analysis (IPA®). The expression of the differentially regulated genes identified by IPA® were verified using real-time polymerasechain reaction (RT-PCR). Results: Supplementation with shilajit for 14 weeks was not associated with any reported adverse effect within this period. At a higher dose (250 mg bid), shilajit improved skin perfusion when compared to baseline or the placebo. Pathway analysis identified shilajit-inducible genes relevant to endothelial cell migration, growth of blood vessels, and ECM which were validated by quantitative real-time polymerasechain reaction (RT-PCR) analysis. Conclusions: This work provides maiden evidence demonstrating that oral shilajit supplementation in adult healthy women induced genes relevant to endothelial cell migration and growth of blood vessels. Shilajit supplementation improved skin microperfusion

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/cm (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