Solid Stress Estimations via Intraoperative 3D Navigation in Patients with Brain Tumors.

Abstract

Physical forces exerted by expanding brain tumors-specifically the compressive stresses propagated through solid tissue structures-reduce brain perfusion and neurologic function but heretofore have not been directly measured in patients in vivo. Solid stress levels estimated from tumor growth patterns are negatively correlated with neurologic performance in patients. We hypothesize that measurements of solid stress can be used to inform clinical management of brain tumors. We developed an intraoperative technique to quantitatively estimate solid stress and brain replacement by the tumor. In 30 patients, we made topographic measurements of brain deformation through the craniotomy site with a neuronavigation system during surgical workflows immediately preceding tumor resection (<5 minutes in the operating room). Utilizing these measurements in conjunction with finite element modeling, we calculated solid stress within the tumor and brain and estimated the amount of brain tissue replaced, i.e., lost, by tumor growth. Mean solid stresses were in the range of 10 to 600 Pa, and the amount of tissue replacement was up to 10% of the brain. Brain loss in patients delineated glioblastoma from brain metastatic tumors, and in mice, solid stress was a sensitive biomarker of chemotherapy response. We present in this study a quantitative approach to intraoperatively measure solid stress in patients that can be readily adopted into standard clinical workflows. Brain loss due to tumor growth is a novel mechanical-based biomarker that, in addition to solid stress, may inform personalized management in future clinical studies in brain cancer.