Global Cerebral Oxidative Metabolism during Hypercapnia and Hypocapnia in Humans: Implications for BOLD fMRI

Abstract

The effect of carbon dioxide (CO 2 ) on cerebral metabolism is of tremendous interest to functional imaging. In particular, mild-to-moderate hypercapnia is routinely used in calibrated blood oxygenlevel dependent (BOLD)-functional magnetic resonance imaging (fMRI)-based quantification of cerebral oxidative metabolism changes (DCMRO 2 ), and relies on the assumption of a stable CMRO 2 during CO 2 challenges. However, this assumption has been challenged by certain animal studies, necessitating its verification in humans and under conditions customary to fMRI. We report, for the first time, on global DCMRO 2 measurements made noninvasively in humans during graded hypercapnia and hypocapnia. We used computerized end-tidal CO 2 modulation to minimize undesired concurrent changes in oxygen pressure, and our findings suggest that no significant change in global CMRO 2 is expected at the levels of end-tidal CO 2 changes customary to calibrated BOLD.

The Contribution of Arterial Blood Gases in Cerebral Blood Flow Regulation and Fuel Utilization in Man at High Altitude

“…If CMRO 2 does, in fact, vary inversely with PaCO 2 then it is possible we underestimated and overestimated CBF values during hypocapnia and hypercapnia, respectively; indeed, there is some evidence for small ( o10%) increase and decrease in CMRO 2 with moderate hypo-and hypercapnia, respectively. 16,37 However, our CVR values at SL are highly consistent with previous reports 17 and we do not think that subtle underestimated and overestimated CBF values during hypocapnia and hypercapnia detract from our main conclusions.…”

Comparison of Cerebral Vascular Reactivity Measures Obtained Using Breath-Holding and CO2 Inhalation

“…These findings are consistent with those of previous studies reporting significant differences between CVR to hypocapnic and hypercapnic stimuli. 33,34 In terms of the relative advantages and disadvantages of the different methods, the following conclusions can be summarized:…”

Quantitative mapping of cerebrovascular reactivity using resting-state BOLD fMRI: Validation in healthy adults

“…PETCO 2 changes can be induced through manually adjusted administration of blended gases (Bandettini and Wong, 1997 ;Cohen et al, 2004;Yezhuvath et al, 2009), end-tidal forcing (Poulin et al, 1996) or more recently, computerized PETCO 2 targeting (Conklin et al, 2011;Han et al, 2011;Mandell et al, 2011;Mandell et al, 2008;Mark et al, 2010;Mikulis et al, 1989;Mutch et al, 2012;Prisman et al, 2008;Slessarev et al, 2007;Spano et al, 2013;Vesely et al, 2001). The latter method provides immediate and robust PETCO 2 changes, and we have used it extensively in our own work (Chen and Pike, 2010a;Chen and Pike, 2010b;Halani et al, 2015). More recently, breath-holding (Murphy et al, 2011) and deep breathing (Bright et al, 2009) have been proposed as alternatives to modulate PETCO 2 , although CO 2 manipulation through breathing circuits is still the dominating approach.…”

“…In addition, the various styles of breath-holding can introduce difficulties in comparing CVR values across populations. Moreover, undesirable perturbations in neuronal activity (Jain et al, 2011;Xu et al, 2011) due to the sometimes large PETCO 2 changes (Chen and Pike, 2010a) can compromise the accuracy of conventional CVR measures. More concerning are unwanted side effects of conventional CVR tasks, which may be harmful in certain patient types (Karakaya et al, 2006;Laine et al, 1986).…”