PID Control of a Novel Cytostatic Hypothermia System for Glioblastoma Multiforme Management

Introduction: Glioblastoma (GBM) is the most common malignant brain tumor with median survival of 15-18 months. Current standard treatment includes surgical resection followed by radiation and chemotherapy. Cytostatic hypothermia is a novel treatment modality that has been shown to slow or halt GBM in rat models ranging from 20 to 25°C. Control of this temperature has thus far been through manual voltage adjustment to a Peltier plate. However, this is not readily feasible or optimal in an implanted device if the subject is to be untethered and in various environments. Here we propose a Proportional, Integral, Derivative (PID) control system that can be used to continuously control multiple parameters in the hypothermia system.

Methods: A hypothermia system consisting of a NeuraTEC and ARC was implanted in anesthetized swine. The NeuraTEC is a neural implant consisting of a Peltier plate pulling heat from an intracranial cooling electrode array. The heat is transferred to a waterblock subcutaneously implanted in the flank via tubing and circulating water (via piezoelectric pumps); these components make up the ARC. Temperature sensors were included within and around the cooling array and on the waterblocks. The system was powered via battery and connected to an Arduino Giga R1 coded with a custom Arduino IDE script. During anesthesia, cooling protocols were conducted and failure modes were evaluated. All data analysis was then completed with custom scripts.

Results: The hypothermia system cooled the desired brain region from 36°C to 25°C rapidly. Once steady state was achieved, the PID control sustained a temperature deviation of 0.05°C or within 0.22% of the target temperature. The waterblock that was taking the heat remained < 1°C well within safety limits of 3°C from baseline.

Conclusion : Our data suggests that PID-based temperature control in an implantable hypothermia device is possible with high precision and accuracy. Accurate control and appropriate responses to failure states are necessary prior to implantation of a hypothermia system to treat patients with GBM both for efficacy and safety.