Simulate, fabricate, and validate an implantable and portable system that can achieve safe, local intracranial cooling in pigs for the purpose of halting GBM.

Glioblastoma (GBM) requires novel approaches to treatment. We have demonstrated that intra-tumoral, non-freezing, ‘cytostatic’ hypothermia, can safely halt GBM growth and extend rodent survival. This was demonstrated through extensive in vitro and in vivo studies. Rats that received this treatment (through an implant) survived their study period – a remarkable feat that outperformed rat studies of tumor-treating-fields. While the mechanisms underlying this approach easily translate to larger animals and humans, the engineering challenges remain unsolved.

Here we used finite-element-modeling to simulate bioheat transfer. This informed our design of a system consisting of a multiprobe array and an artificial internal circulation system. These components were fabricated and tested in vivo in a pig model.

Modeling demonstrated that multiprobe arrays could homogenously cool a region of brain tissue to the target temperature (25°C). Heat transferred out of the tissue did not raise skin temperature by >3°C from baseline. In vitro testing validated these findings. The system was made fully portable (with battery power and data collection). Subsequent testing in vivo in anesthetized pigs successfully reached the same target temperature goals in the brain and skin. Intraoperative EEG showed minimal changes before and during cooling. We have now received approval to awaken a pig with our implanted system.