Laser Thermal Immunomodulation in the Brain

总部位于马尼托巴省的行业合作伙伴蒙特里斯开创了用于人脑选择性组织消融的定向激光热疗技术，并一直是微创精密NeuroBlate®激光技术的市场领先者。新出现的证据表明，激光热疗可以在大脑中诱导出新的免疫调节功能。当组织放置一根细光纤时，从光纤尖端发射的激光热能对组织进行热凝。周围组织对热负荷的吸收会增加纤维尖端的散热。这种激光热组织梯度产生不同的组织学区域，具有不同程度的组织损伤，范围从纤维尖端的坏死区到距离尖端更远的水肿区。激光热组织梯度促进了一系列细胞和分子反应，从而推动了激光治疗大脑中细胞组成和活动的变化。我们将在加拿大建立第一个激光脑瘤小鼠模型，并重点研究激光热疗技术作为细胞免疫活动调节器在应对大脑热应激中的新作用。为了了解激光诱导的细胞免疫调节对脑环境中固有免疫细胞和获得性免疫细胞的影响，我们研究了预先存在低/中/高细胞免疫激活的小鼠大脑模型。我们测试了两种光纤设计在免疫调节方面的能力，并生成了基于组织的时空高分辨率基因表达谱，映射到激光诱导的脑损伤。这些组织图直观地显示了不同大脑环境中沿激光热组织梯度的免疫细胞组成/激活。这项研究启发了用于免疫调节的激光技术的新设计和应用，并支持科学合作伙伴关系和HQP培训，以促进NeuroBlate®激光技术的未来应用。

Manitoba-based industry partner Monteris pioneered targeted laser thermal technology for selective tissue ablation in human brain and remains a market leader in minimally invasive precision NeuroBlate® laser technology. Emerging evidence suggests that laser thermal treatment can elicit novel immunomodulatory functions in the brain. Upon tissue placement of a thin optic fiber, laser thermal energy emitted from the optic fiber tip heat-coagulates tissue. Absorption of thermal load by surrounding tissue causes increasing heat dissipation away from the fiber tip. This laser thermal tissue gradient creates distinct histological regions with different degrees of tissue damage that range from a necrotic zone at the fiber tip to an edema zone farther from the tip. The laser thermal tissue gradient promotes an array of cellular and molecular responses that drive changes in cellular composition and activity in laser-treated brain. We will establish the first laser brain tumor mouse models in Canada and focus on a new role of laser thermal technology as a modulator of cellular immune activity in response to heat stress in brain. To understand the effects of laser-induced cellular immunomodulation on innate and adaptive immune cells in the brain environment, we study mouse brain models with pre-existing low/ moderate/ high cellular immune activation. We test the ability of two optic fiber designs on immunomodulation and generate tissue-based spatiotemporal high-resolution gene expression profiles mapped to laser-induced brain lesions. These tissue maps visualize immune cell composition/ activation along the laser thermal tissue gradient in distinct brain environments. This study inspires new designs and applications of laser technology for immunomodulation and sustains scientific partnership and HQP training for the advancement of future applications of NeuroBlate® laser technology.