Development of an Intraoperative Probe for Brain Tumour Delineation Combining Multimodal Tissue Characterization and Soft-Robotics

Abstract

Accurate identification of surgical margins in brain tumors is of significant prognostic importance. Despite the availability of 5-ALA and image guidance methods, recognizing tumor boundaries is highly subjective, dependent on identifying subtle changes in tissue characteristics, including texture and color, to aid distinction. Therefore, developing an intraoperative tool for delineating tumors from normal tissues during brain tumor resection has significant prognostic importance. The thesis reports the development of an intraoperative probe for brain tumor delineation using the electromechanical characterization of tissues. The study started with understanding the electrical resistivity of fresh and formalin-fixed healthy human brain samples from different anatomical regions and glial tumor samples. A semi-automated system integrated with MEMS-based microchips and resistance measurement circuits was developed. The results showed that the resistivity of the glial tumor was significantly less than the corresponding normal regions. The subsequent study delved into a detailed simultaneous electromechanical characterization approach to understand how these properties contributed complementary information on tissue pathology. For the study, MEMS-based interdigitated electrodes and piezoresistive microforce sensors were fabricated and integrated with the semi-automated system. It was found that simultaneous electromechanical characterization could be an effective biomarker for tumor delineation, grading, and studying heterogeneity between the brain regions. Based on the above studies, a novel tool for brain biopsy imaging using electrical impedance tomography (BBI-EIT) for intraoperative margin assessment was developed. BBI-EIT performs near real-time and non-destructive imaging of tissue samples that can map tissue heterogeneity based on their distinct electrical properties. As a predecessor to an intraoperative probe that can identify tumor margins in vivo, BBI-EIT was developed as an adjunct to current intraoperative assessment techniques, such as frozen section examination, to see if the tumor margin has been achieved. For the intraoperative probe, it was found that traditional manufacturing approaches to developing a universal continuum soft robotic probe, which can navigate complex pathways to access tumors and adjust for varying tumor depths and locations in patients, were challenging. Hence, a flexible and efficient framework was realized for customizable robot designs using parametric modeling and 3D printing technologies. Further, a handheld robotic probe was developed for soft-tissue mechanical characterization integrating the patient-specific continuum robotic tip. Mechanical characterization of the tissues using the robotic probe demonstrated distinct viscoelastic responses between tumors and normal, between different normal brain regions, and between tumor masses with varying hemorrhage. We envisage that an intraoperative probe integrated with electrical impedance tomography and mechanical characterization can have significant prognostic importance in patient outcomes through accurate tumor margin delineation and risk assessment.