Monitoring tumor state from thermal images in animal and human models.

PURPOSE: Thermography is a potentially useful method for tumor progress monitoring since it is noninvasive, nonradiative, low-cost, and rapid. Perfusion and metabolism are dominant factors for determining tumor temperature difference and are also correlated to the tumor's growth rate. Therefore, estimating them from the tumor thermal image can be a very useful tumor monitoring method, since thermal changes occur before physical changes. The goal of this work was to study the effect of tumor state on the thermal image in different tumor types, using simulations and measurements. METHODS: Simulated tumor models, representing flat and extruding tumors, typical to transplantable and natural tumors, respectively, were simulated and the effects of tumor metabolism and perfusion on the temperature difference were analyzed. Data regarding tumor size and measured temperature differences were obtained from the literature, discussing five types of transplantable tumors in mice and rats. The growth rates of all tumors were calculated by fitting tumor size measurements to a tumor growth model and were used as an indicator to tumor aggressiveness. Tumor temperature difference was calculated by taking the effect of its extruding shape into account, according to a previously published method. Tumor state was estimated from the normalized temperature differences using simulations and compared to the calculated aggressiveness rates. Computational models of human breast cancers, both in round and flat breast models, were recreated using a finite-element-method heat transfer simulation. Tumor size and state were simulated according to the results obtained from the animal tumor analysis, representing two different tumor aggressiveness levels. The calculated temperature difference as a function of tumor size was calculated for each test case. RESULTS: Perfusion was shown to be highly dominant in determining the tumor's temperature difference. Since both metabolism and perfusion were shown to have a linear effect on the temperature difference, a conversion value was defined between them. The analysis of the animal experimental results showed correlations between tumor aggressiveness and the following factors: the normalized temperature difference, the estimated tumor state, and the temperature difference change rate. The simulated human breast cancer models analysis showed highly varying temperature differences between the simulated models. Although for each model there is a clear difference between the temperature differences of the test cases simulated, the large differences between the results might make tumor state estimation difficult. However, reviewing the gradient of the tumor temperature change as a function of tumor size showed that the ratio between the gradients of both test cases was similar for all models. Therefore, the effect of model errors and differences in the simulated tissue structure and properties and the environmental conditions between the different models, can be mitigated. This pattern may be used to estimate tumor state in in vivo experiments. CONCLUSIONS: Continuous monitoring of tumor temperature difference produces valuable information on tumor state and aggressiveness that can be used both in the clinic and in the laboratory. Monitoring can be either performed on a single image, or continuous on multiple images, revealing changes in tumor state.

Proposed method for internal electron therapy based on high-intensity laser acceleration.

Radiotherapy is one of the main methods to treat cancer. However, due to the propagation pattern of high-energy photons in tissue and their inability to discriminate between healthy and malignant tissues, healthy tissues may also be damaged, causing undesired side effects. A possible method for internal electron therapy, based on laser acceleration of electrons inside the patient's body, is suggested. In this method, an optical waveguide, optimized for high intensities, is used to transmit the laser radiation and accelerate electrons toward the tumor. The radiation profile can be manipulated in order to create a patient-specific radiation treatment profile by changing the laser characteristics. The propagation pattern of electrons in tissues minimizes the side effects caused to healthy tissues. A simulation was developed to demonstrate the use of this method, calculating the trajectories of the accelerated electron as a function of laser properties. The simulation was validated by comparison to theory, showing a good fit for laser intensities of up to 2 × 10(20) (W/cm2), and was then used to calculate suggested treatment profiles for two tumor test cases (with and without penetration to the tumor). The results show that treatment profiles can be designed to cover tumor area with minimal damage to adjacent tissues.

The effect of geometry on tumor thermal profile and its use in tumor functional state estimation.

Thermal differences between transplanted tumors and tumors in humans prevent the implementation of thermographic methods developed in mice models to human models and vise-versa. Transplantable tumors tend to have an extruding shape, which may affect the thermal patterns. This hypothesis was studied in phantom experiments and simulations. A correlation between tumor dimensions and relative temperature was found and used to estimate tumor functional state from previously published in vivo experiments. A correlation was found between temperature differences and tumor growth rates (tumor aggressiveness) and the effect of tumor treatment was demonstrated, showing the potential for in vivo, non-invasive tumor monitoring.

Thermographic investigation of tumor size, and its correlation to tumor relative temperature, in mice with transplantable solid breast carcinoma.

Treating cancer is one of the major challenges of modern medicine. Since mice models are an important tool in cancer treatment research, it is required to assess murine tumor development. Existing methods for investigating tumor development are either high cost and limited by their availability or suffer from low accuracy and reproducibility. In order to overcome these drawbacks, thermography may be used. DA3 breast cancer carcinoma tumors in 12 Balb/c mice were thermally imaged and monitored for a period of several weeks. Eight mice were treated with diffusing alpha emitters radiation therapy (DaRT) wires, while four were treated with inert wires. For large tumors, the area was estimated by analyzing thermal images and was found to be in correlation with manual caliper measurements. In addition, the correlation between tumor area and relative temperatures was calculated and compared to previous works. Temperature differences were larger for tumors treated with DaRT wires than tumors with inert wires. These correlations can be used to assist in tumor size estimation and reveal information regarding its metabolic state. Overall, thermography was shown to be a promising tool for assessing tumor development with the additional advantages of being nonradiative and potentially providing indication of intratumoral biological processes.

Photothermal bundle measurement of phantoms and blood as a proof of concept for oxygenation saturation measurement.

This study's objective is to validate a method for the measurement of two compound phantoms as a proof of concept for oxygen saturation level measurement via a thermal imaging bundle. The method consists of a thermal imaging system and an algorithm which estimates the compound concentration according to temperature rise. A temperature rise is obtained by illuminating the tissue with a laser with different wavelengths in the NIR range and measured using a thermal camera. A coherent thermal imaging bundle was used for image transmittance for minimal invasive transendoscopic use. The algorithm's estimation ability was evaluated using agar phantoms of varying Methylene Blue and ICG ratios as well as blood samples The Methylene Blue ratio in each phantom was estimated and the calculated average RMS of the error was 9.38%, a satisfying value for this stage, verifying the algorithm's and bundle's suitability for the use in a minimal invasive system.

Thermal imaging method for estimating oxygen saturation.

The objective of this study is to develop a minimal invasive thermal imaging method to determine the oxygenation level of an internal tissue. In this method, the tissue is illuminated using an optical fiber by several wavelengths in the visible and near-IR range. Each wavelength is absorbed by the tissue and thus causes increase in its temperature. The temperature increase is observed by a coherent waveguide bundle in the mid-IR range. The thermal imaging of the tissue is done using a thermal camera through the coherent bundle. Analyzing the temperature rise allows estimating the tissue composition in general, and specifically the oxygenation level. Such a system enables imaging of the temperature within body cavities through a commercial endoscope. As an intermediate stage, the method is applied and tested on exposed skin tissue. A curve-fitting algorithm is used to find the most suitable saturation value affecting the temperature function. The algorithm is tested on a theoretical tissue model with various parameters, implemented for this study, and on agar phantom models. The calculated saturation values are in agreement with the real saturation values.