**5. Animal models and preclinical studies**

Various canine [32, 64, 65] and murine [48, 66–68] animal models of brain tumors have been used to investigate the efficacy of laser thermal therapy on tumors and surrounding brain

tissue, as well as to evaluate the thermal dose models. First, animal experiments evaluating the impact of laser energy on normal murine brains can be dated back to 1960s. Fine et al. [68] used ruby pulsed laser delivering 100 J of energy to the forehead of mice, which resulted in a mortality rate of 75% within a day of exposure. Later, Earle et al. [67] showed that 20–40 J of energy delivered using ruby laser was not lethal and resulted in sub-arachnoid and intracere‐ bral hemorrhage with minimal neurological effects. Later, Rosomoff et al. [32] reported similar findings using 8 J ruby laser in a rat and dog experiment models. They also reported that the sensitivity to laser could be increased by Cardio-green and Evans blue injections. Kangasnie‐ mi et al. [64] reported the feasibility and utility of MR-guided laser (980 nm diode) ablation of tumors (transmissible venereal tumors) in seven canines. Utility of LITT was studied in Lewis mice implanted with glioma cells [48] and neoplastic lesion was monitored using MRI. In addition, proliferation of implanted tumor cells, gliosis and apoptosis was monitored using immunohistological techniques. LITT caused necrosis of neoplastic cells; however, apoptosis ofresidualtumor cells atthe margin (more vascularized compared to pre-treatment) was noted following LITT [48]. Canine models have also been used to establish various thermal dose models, so as to reliably predict post-LITT tissue damage as well as to monitor tissue abla‐ tion in real time [65]. Localized interstitial thermal therapy using magnetic nanoparticles (dextran- or aminosilane-coated iron-oxide nanoparticles) have been described in a rat model of GBM [69]. Interestingly, rats treated with aminosilane-coated nanoparticles showed improvement in survival (4.5 times prolongation), whereas those treated with dextran-coated particles did not show any difference in survival compared to controls. These animal experi‐ ments paved a way to the development of LITT and future therapeutic options for gliomas.
