Alexandra T Levine1, Benson Li2, Paisley Barnes3, Stephen G Lomber4, Blake E Butler5. 1. Department of Physiology & Pharmacology, University of Western Ontario, London, Ontario, N6A 5C1, Canada; Brain and Mind Institute, University of Western Ontario, London, Ontario, N6A 3K7, Canada. 2. Department of Psychology, University of Western Ontario, London, Ontario, N6A 5C2, Canada. 3. Department of Physiology & Pharmacology, University of Western Ontario, London, Ontario, N6A 5C1, Canada. 4. Department of Psychology, University of Western Ontario, London, Ontario, N6A 5C2, Canada; Department of Physiology & Pharmacology, University of Western Ontario, London, Ontario, N6A 5C1, Canada; Brain and Mind Institute, University of Western Ontario, London, Ontario, N6A 3K7, Canada; National Centre for Audiology, University of Western Ontario, London, Ontario, N6G 1H1, Canada. 5. Department of Psychology, University of Western Ontario, London, Ontario, N6A 5C2, Canada; Brain and Mind Institute, University of Western Ontario, London, Ontario, N6A 3K7, Canada; National Centre for Audiology, University of Western Ontario, London, Ontario, N6G 1H1, Canada. Electronic address: bbutler9@uwo.ca.
Abstract
BACKGROUND: Neuroimaging methods including fMRI provide powerful tools to observe whole-brain functional networks. This is particularly powerful in animal models, allowing these networks to be probed using complementary methods. However, most animals must be anesthetized for neuroimaging, giving rise to complications resulting from anesthetic effects on the animal's physiological and neurological functions. For example, an established protocol for feline neuroimaging involves co-administration of ketamine and isoflurane - the latter of which is known to suppress cortical function. NEW METHOD: Here, we compare this established protocol to alfaxalone, a single-agent anesthetic for functional neuroimaging. We first compare the two in a controlled environment to assess relative safety and to measure physiological stability over an extended time window. We then compare patterns of auditory and visually-evoked activity measured at 7 T to assess mean signal strength and between-subjects signal variability. RESULTS IN COMPARISON WITH EXISTING METHODS: We show that alfaxalone results in more stable respiratory rates over the 120 min testing period, with evidence of smaller between-measurements variability within this time window, when compared to ketamine plus isoflurane. Moreover, we demonstrate that both agents evoke similar mean BOLD signals across animals, but that alfaxalone elicits more consistent BOLD activity in response to sound stimuli across all ROIs observed. CONCLUSIONS: Alfaxalone is observed to be more physiologically stable, evoking a more consistent BOLD signal across animals than the co-administration of ketamine and isoflurane. Thus, an alfaxalone-based protocol may represent a better approach for neuroimaging in animal models requiring anesthesia.
BACKGROUND: Neuroimaging methods including fMRI provide powerful tools to observe whole-brain functional networks. This is particularly powerful in animal models, allowing these networks to be probed using complementary methods. However, most animals must be anesthetized for neuroimaging, giving rise to complications resulting from anesthetic effects on the animal's physiological and neurological functions. For example, an established protocol for feline neuroimaging involves co-administration of ketamine and isoflurane - the latter of which is known to suppress cortical function. NEW METHOD: Here, we compare this established protocol to alfaxalone, a single-agent anesthetic for functional neuroimaging. We first compare the two in a controlled environment to assess relative safety and to measure physiological stability over an extended time window. We then compare patterns of auditory and visually-evoked activity measured at 7 T to assess mean signal strength and between-subjects signal variability. RESULTS IN COMPARISON WITH EXISTING METHODS: We show that alfaxalone results in more stable respiratory rates over the 120 min testing period, with evidence of smaller between-measurements variability within this time window, when compared to ketamine plus isoflurane. Moreover, we demonstrate that both agents evoke similar mean BOLD signals across animals, but that alfaxalone elicits more consistent BOLD activity in response to sound stimuli across all ROIs observed. CONCLUSIONS: Alfaxalone is observed to be more physiologically stable, evoking a more consistent BOLD signal across animals than the co-administration of ketamine and isoflurane. Thus, an alfaxalone-based protocol may represent a better approach for neuroimaging in animal models requiring anesthesia.