Johnson, Brendan J., Lipford, Megan E., Barcus, Richard A., Olson, John D., Schaaf, George W., Andrews, Rachel N., Kim, Jeongchul, Dugan, Greg O., Deycmar, Simon, Reed, Colin A., Whitlow, Christopher T., and Cline, J. Mark
• We present a novel, reproducible method for a CO 2 challenge in nonhuman primates. • Pseudo-continuous ASL can be used to evaluate CBF and CVR in NHPs. • Our method induces significant increases in CBF comparable to increases in humans. • CVR measured using our method is comparable to that of humans. Cerebrovascular reactivity (CVR) is a measure of cerebral small vessels' ability to respond to changes in metabolic demand and can be quantified using magnetic resonance imaging (MRI) coupled with a vasoactive stimulus. Reduced CVR occurs with neurodegeneration and is associated with cognitive decline. While commonly measured in humans, few studies have evaluated CVR in animal models. Herein, we describe methods to induce hypercapnia in rhesus macaques (Macaca mulatta) under gas anesthesia to measure cerebral blood flow (CBF) and CVR using pseudo-continuous arterial spin labeling (pCASL). Fifteen (13 M, 2 F) adult rhesus macaques underwent pCASL imaging that included a baseline segment (100% O 2) followed by a hypercapnic challenge (isoflurane anesthesia with 5% CO 2 , 95% O 2 mixed gas). Relative hypercapnia was defined as an end-tidal CO 2 (ETCO 2) ≥5 mmHg above baseline ETCO 2. The mean ETCO 2 during the baseline segment of the pCASL sequence was 34 mmHg (range: 23–48 mmHg). During this segment, mean whole-brain CBF was 51.48 ml/100g/min (range: 21.47–77.23 ml/100g/min). Significant increases (p <0.0001) in ETCO 2 were seen upon inspiration of the mixed gas (5% CO 2 , 95% O 2). The mean increase in ETCO 2 was 8.5 mmHg and corresponded with a mean increase in CBF of 37.1% (p <0.0001). The mean CVR measured was 4.3%/mmHg. No anesthetic complications occurred as a result of the CO 2 challenge. Our methods were effective at inducing a state of relative hypercapnia that corresponds with a detectable increase in whole brain CBF using pCASL MRI. Using these methods, a CO 2 challenge can be performed in conjunction with pCASL imaging to evaluate CBF and CVR in rhesus macaques. The measured CVR in rhesus macaques is comparable to human CVR highlighting the translational utility of rhesus macaques in neuroscience research. These methods present a feasible means to measure CVR in comparative models of neurodegeneration and cerebrovascular dysfunction. [ABSTRACT FROM AUTHOR]