Background: Physical forces exerted by expanding brain tumors - specifically the compressive stresses propagated through solid tissue structures - reduces brain perfusion and neurological function, but heretofore has not been directly measured in patients in vivo . Solid stress levels estimated from tumor growth patterns are negatively correlated with neurological performance in patients. We hypothesize that measurements of solid stress can be used to inform clinical management of brain tumors.
Methods: 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 OR). Utilizing these measurements in conjunction with finite element modeling, we calculated solid stress within the tumor and the brain, and estimated the amount of brain tissue replaced, i.e., lost, by the tumor growth.
Results: 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 tissue loss in patients delineated glioblastoma from brain metastatic tumors, and in mice solid stress was a sensitive biomarker of chemotherapy response.
Conclusions: We present here a quantitative approach to intraoperatively measure solid stress in patients that can be readily adopted into standard clinical workflows. Brain tissue 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.
Key points: Intraoperative and computational technique quantified solid stress and tissue loss in 30 patients Solid stress and tissue loss distinguished tumor types, showing potential as clinical biomarkers.
Importance of the study: This study addresses a critical gap, as solid stress has been implicated in tumor progression and treatment resistance but not directly measured in patients with brain cancers before. Here, we present a novel intraoperative technique to quantitatively measure solid stress and brain tissue replacement in brain tumor patients. By combining intraoperative neuro-navigation with finite element modeling, we estimate solid stress and quantify the loss of brain tissue replaced by tumor growth. Importantly, higher tissue replacement was associated with glioblastoma compared to metastatic tumors. In mice, solid stress is a sensitive biomarker of treatment response. These findings establish solid stress and tissue replacement as potential physical biomarkers to inform personalized management of brain tumors. Quantifying these mechanical forces during surgery could help predict patient outcomes and guide clinical decision-making.