Dynamic Thermal Mapping of Localized Therapeutic Hypothermia in the Brain

Although whole body cooling is used widely to provide therapeutic hypothermia for the brain, there are undesirable clinical side effects. Selective brain cooling may allow for rapid and controllable neuroprotection while mitigating these undesirable side effects. We evaluated an innovative cerebrospinal fluid (CSF) cooling platform that utilizes chilled saline pumped through surgically implanted intraventricular catheters to induce hypothermia. Magnetic resonance thermal imaging of the healthy sheep brain (n = 4) at 7.0T provided dynamic temperature measurements from the whole brain. Global brain temperature was 38.5 ± 0.8°C at baseline (body temperature of 39.2 ± 0.4°C), and decreased by 3.1 ± 0.3°C over ∼30 min of cooling (p < 0.0001). Significant cooling was achieved in all defined regions across both the ipsilateral and contralateral hemispheres relative to catheter placement. On cooling cessation, global brain temperature increased by 3.1 ± 0.2°C over ∼20 min (p < 0.0001). Rapid and synchronized temperature fall/rise on cooling onset/offset was observed reproducibly with rates ranging from 0.06-0.21°C/min, where rewarming was faster than cooling (p < 0.0001) signifying the importance of thermoregulation in the brain. Although core regions (including the subcortex, midbrain, olfactory tract, temporal lobe, occipital lobe, and parahippocampal cortex) had slightly warmer (∼0.2°C) baseline temperatures, after cooling, temperatures reached the same level as the non-core regions (35.6 ± 0.2°C), indicating the cooling effectiveness of the CSF-based cooling device. In summary, CSF-based intraventricular cooling reliably reduces temperature in all identified brain regions to levels known to be neuroprotective, while maintaining overall systemic normothermia. Dynamic thermal mapping provides high spatiotemporal temperature measurements that can aid in optimizing selective neuroprotective protocols.