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Laser Ablation: SElectivity and monitoRing for OPTImal tuMor removAL

Periodic Reporting for period 3 - LASER OPTIMAL (Laser Ablation: SElectivity and monitoRing for OPTImal tuMor removAL)

Reporting period: 2021-05-01 to 2022-10-31

Minimally invasive thermal techniques represent promising therapeutic procedures, relying on the induction of controlled temperature change in tumor. In most cases, the local application of high temperature is provided in order to induce irreversible damage to the target cancer cells and consequently tumor apoptosis and coagulative necrosis. The optimal implementation of these minimally invasive treatments could show many advantages when compared to conventional surgical therapies. Among them, the reduction of the operative trauma would lead to the decrease of pain and the minimization of nonfunctional fibrotic scarring tissue formation, as well as the decrease of adhesions and wound dehiscence. Laser ablation, which refers to the exposure of biological tissues to near infrared laser light, represents an interesting thermal therapy for the potential management of cancer tissue, since it has shown encouraging results in solid tumors treatment, especially when associated with minimally invasive guidance techniques, e.g. the echo-endoscopy, suitable for specific and delicate organs, such as the pancreas. A key problem which has limited this technique in clinical practice could refer to the inaccurate monitoring of the ablation effects causing under-treatment (i.e. some cancerous cells still present) or over-treatment (i.e. excessive damage to adjacent healthy tissue or impairment of organ functionalities). Hence, solutions to optimize the real-time tissue damage control, and to make the treatment more selective, by means of dedicated tools for numerical simulation of the laser-tissue interaction and for improving the light absorbing properties of the target tissue are coveted. The development and optimization of these solutions are the missions of the LASER OPTIMAL project, which aims at establishing the following strategy: the use of biocompatible nanoparticles (BNPs) injected in the tumor, to enhance the selective absorption of laser light; the development of accurate and real-time heat-transfer model to simulate laser-tissue-BNPs interaction, predict and visualize the treatment dynamics; the development of real-time temperature measurement system to monitor laser effects on tissue, account for unpredictable physiological events and tune the settings (closed-loop).
So far, the newly established team in Politecnico di Milano has focused on several aspects. Afterward the establishment of the research laboratory, the main activities have concerned the preliminary investigation of laser-tissue-nanostructures interaction in gold nanorod-assisted photothermal therapy, from both a theoretical and experimental point of view. A large campaign of ex-vivo ablation experiments on phantoms loaded with nanoparticles has been carried out, with simultaneous measurement of laser-induced distributed temperature. Experiments aimed at evaluating the effect of different ablation characteristics on heat distribution properties. The main characteristics for analysis were the power and wavelength of the laser source, type, and concentration of nanoparticles injected into ablated tissue.
We established the feasibility of fiber Bragg grating (FBG) arrays as minimally invasive multipoint temperature measurement sensors during in vivo gold nanorod-mediated photothermal therapy in breast cancer models, for achieving high spatial resolution and multiple sensing points in a sub-centimetric long subcutaneous tumor. We analyzed the thermal response induced by different combinations of gold nanorods (GNRs) and NIR laser wavelengths during GNR-assisted photothermal therapy in breast cancer syngrafts in mice. The assessment of quasi-distributed FBGs and Rayleigh scattering-based distributed sensing for accurate and millimeter resolved thermometry in media undergoing laser ablation (LA) was performed. Results showed the excellent performances of laser femtosecond-inscribed highly-dense FBGs for thermometry during LA applications. Thus, the team developed the first software for real-time tissue temperature profiles reconstruction along FBG arrays. Reconstructed temperature data are used to obtain temperature maps of the ablated tissue in real-time during LA procedures. Another software was devised and designed to perform LA power regulation based on real-time temperature monitoring with FBG arrays.
The team has also worked on the implementation of a first-stage computational model based on FEM analysis to simulate the laser ablation treatment for tumor removal, in presence of biocompatible gold nanorods, for the enhancement of the therapy selectivity. The heat transfer in tissue was computed with the Pennes’ bioheat equation, and the simulation of the laser-tissue-nanorods interaction relied on the Mie Theory. Two first in vivo animal studies have been carried out with the Partners of the Consortium to evaluate the thermal effects of different nanoparticles for enhancing laser therapy, and to assess novel and unconventional imaging modalities for thermal damage monitoring, such as hyperspectral imaging. Here, our new methodology quantifies the temperature-related change of tissue chromophores for monitoring thermal damage during LA treatments.
In the next periods, the project aims at the improvement of the computational model for both therapy planning and real-time adjustment of the laser settings, at the development of an improved temperature-driven control strategy based on the measured tissue temperature and tissue-related parameters, as well as at the design and development of an optimized laser-light delivery tool.