Pharmacokinetically optimized anesthesia enables long-term functional ultrasound imaging in the cat visual cortex

Abstract

Functional ultrasound imaging (fUSI) measures cerebral blood-volume responses, so anesthesia protocols developed for BOLD fMRI may not preserve its signal. We screened three fMRI-derived anesthesia regimens for visually evoked fUSI in the cat visual cortex. Isoflurane-ketamine-medetomidine produced the strongest and most consistent responses, but the standard intramuscular medetomidine bolus suppressed the signal in one sensitive cat. Pharmacokinetic modeling guided replacement of this bolus with controlled intravenous dosing, restoring the visual response while maintaining physiological stability. The same weight-based regimen produced robust responses in the other animals. In a direct within-session test, response strength was equivalent in recordings separated by more than three hours. Across 464 recordings from 51 sessions in three cats, it showed no temporal drift during follow-up extending to 23 months. Visually evoked activation also remained clear relative to a small awake dataset, although equivalence was not established. PK-guided control of medetomidine exposure therefore enables stable, repeated fUSI of the cat visual cortex over hours to years.