Development of microsurgical forceps equipped with haptics technology for in situ differentiation of tumor tissue from normal brain during microsurgery by tissue stiffness

Abstract Neurosurgeons perform tumor resection based on their tactile perception. However, many years of experience and training are required to appropriately differentiate tumor tissue from surrounding parenchymal tissue. It was reported that the stiffness of human cancer tissue strongly correlates with pathological tissue and it can be used as a biomarker. Comprehensive analysis also revealed that the molecular expression differs greatly between hard and soft tumors.Haptics technology measures and uses the stimulus that causes the sensation as a physical quantity. Force and tactile sensation is a sensation caused by mechanical contact with an object. Real Haptics is our main research field, which is a general term for technologies that quantify and utilize the force-tactile stimuli generated by contact with objects that exist in the real world and / or the virtual world.We have developed a microsurgical forceps equipped with haptics technology to differentiate tumor tissue from surrounding brain tissue during tumor dissection. We generated and used three glioblastoma cell lines (SF126, U87, U251) expressing proteins of firefly luciferase and mCherry. Each cell line was transplanted into forebrain of 5 nude mice. Tumor progression was regularly monitored with In Vivo Imaging System (IVIS) and mice were euthanized at the appropriate stage. Tumor and normal brain stiffness were measured by using the Master-slave integrated haptic forceps device. Importantly, all of the three glioblastomas were shown to be harder than the normal brain (p=0.047). The median stiffness of each tissue was as follows. Normal brain (n=15): 149.98 N/m, SF126 (n=5): 207.70 N/m, U87 (n=5): 214.40 N/m, U251 (n=5): 188.86 N/mThis pilot study showed that brain tumors could be differentiated by their stiffness from normal brain, and the forceps equipped with haptics technology might help the neurosurgeons to dissect tumor margin along the appropriate plane.