Abstract
Arterial spin labeling (ASL)‐MRI can noninvasively map cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), potential biomarkers of cognitive impairment and dementia. Mouse models of disease are frequently used in translational MRI studies, which are commonly performed under anesthesia. Understanding the influence of the specific anesthesia protocol used on the measured parameters is important for accurate interpretation of hemodynamic studies with mice. Isoflurane is a frequently used anesthetic with vasodilative properties. Here, the influence of three distinct isoflurane protocols was studied with pseudo‐continuous ASL in two different mouse strains. The first protocol was a free‐breathing set‐up with medium concentrations, the second a free‐breathing set‐up with low induction and maintenance concentrations, and the third a set‐up with medium concentrations and mechanical ventilation. A protocol with the vasoconstrictive anesthetic medetomidine was used as a comparison. As expected, medium isoflurane anesthesia resulted in significantly higher CBF and lower CVR values than medetomidine (median whole‐brain CBF of 157.7 vs 84.4 mL/100 g/min and CVR of 0.54 vs 51.7% in C57BL/6 J mice). The other two isoflurane protocols lowered the CBF and increased the CVR values compared with medium isoflurane anesthesia, without obvious differences between them (median whole‐brain CBF of 138.9 vs 131.7 mL/100 g/min and CVR of 10.0 vs 9.6%, in C57BL/6 J mice). Furthermore, CVR was shown to be dependent on baseline CBF, regardless of the anesthesia protocol used.
Highlights
Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) are emerging as potential biomarkers for cognitive impairment and dementia.[1,2] They can be measured in the clinic[3] and in preclinical research[4,5] by means of magnetic resonance imaging (MRI)‐based perfusion imaging
The current increase of studies investigating hemodynamics in the mouse brain requires a better understanding of the physiological influence of the anesthesia protocols used
Our results demonstrate exquisite sensitivity of CBF and CVR to the anesthesia protocol employed, findings that reinforce the need for care in the experimental design and interpretation of studies of murine cerebrovascular function, where anesthesia is often required
Summary
Understanding the influence of the specific anesthesia protocol used on the measured parameters is important for accurate interpretation of hemodynamic studies with mice. The influence of three distinct isoflurane protocols was studied with pseudo‐continuous ASL in two different mouse strains. Medium isoflurane anesthesia resulted in significantly higher CBF and lower CVR values than medetomidine (median whole‐brain CBF of 157.7 vs 84.4 mL/100 g/min and CVR of 0.54 vs 51.7% in C57BL/6 J mice). The other two isoflurane protocols lowered the CBF and increased the CVR values compared with medium isoflurane anesthesia, without obvious differences between them (median whole‐brain CBF of 138.9 vs 131.7 mL/100 g/min and CVR of 10.0 vs 9.6%, in C57BL/6 J mice). KEYWORDS anesthesia, arterial spin labeling (ASL)‐MRI, brain, hemodynamics, isoflurane, mouse.
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