Scaling of anesthesia-dependent cerebrospinal fluid dynamics across rat and pig brains

This study presents a novel in vivo neuroimaging approach using dynamic single photon emission computed tomography (SPECT/CT) to investigate cerebrospinal fluid (CSF) dynamics in pigs, a translationally relevant model due to their human-like brain structure. The distribution, brain penetration of [99mTc]-DTPA and subsequent clearance were followed by brain SPECT for three hours after injection into the cisterna magna of anesthetized pigs and rats. To investigate the effects of anesthesia and across-species effects, we examine CSF dynamics under two types of anesthesia, propofol and ketamine/dexmedetomidine (K/D), and compare the outcome in pigs to that of rats, in which we also compared isoflurane. Propofol and K/D produced largely similar tracer distribution patterns across both pigs and rats: In both species, K/D was associated with higher tracer penetration into the dorsal striatum compared to propofol while neither species showed a tracer accumulation difference in the thalamus. K/D also increased intracranial radiotracer retention and reduced urinary tracer clearance in rats, but not in pigs. In rats, propofol and isoflurane showed similar tracer distribution, reflecting their shared GABAergic mechanism of action. The differences observed between pigs and rats may reflect species-specific physiology, differences in anesthesia dosing, or methodological factors. The work demonstrates the feasibility of using SPECT/CT to study CSF transport in the large gyrencephalic pig brain to advance understanding of human brain fluid dynamics.