Magnetic imaging-based CVR mapping during rapid manipulation of end-tidal PCO2 is an exciting new method for determining the location and extent of abnormal vascular reactivity secondary to proximal large-vessel stenoses in moyamoya disease. Although the study group is small, there seems to be considerable potential for guiding preoperative decisions and monitoring efficacy of surgical revascularization.

Cerebrovascular reactivity can be quantified by correlating blood oxygen level dependent (BOLD) signal intensity with changes in end-tidal partial pressure of carbon dioxide (PCO 2 ). Four 3-min cycles of high and low PCO 2 were induced in three subjects, each cycle containing a steady PCO 2 level lasting at least 60 sec. The BOLD signal closely followed the end-tidal PCO 2 . The mean MRI signal intensity difference between high and low PCO 2 (i.e., cerebrovascular reactivity) was 4.0 ؎ 3.4% for gray matter and 0.0 ؎ 2.0% for white matter. This is the first demonstration of the application of a controlled reproducible physiologic stimulus, i.e., alternating steady state levels of PCO 2 , to the quantification of cerebrovascular reactivity. Cerebral blood flow is generally determined by the metabolic demand of the brain tissue. The capacity for autoregulation can be assessed by measuring hemodynamic responses to a quantifiable stimulus such as a change in partial pressure of carbon dioxide (PCO 2 ). The magnitude of the hemodynamic response relative to the alteration in PCO 2 is termed "cerebrovascular reactivity"; changes in blood oxygen level-dependent (BOLD) signal intensity can be used as an indicator of this reactivity.Our aim was to induce changes in MR signal intensity with changes in end-tidal PCO 2 (PETCO 2 ) by:1. Selecting two easily tolerated levels of PETCO 2 sufficiently different from each other to improve the accuracy in estimating cerebrovascular reactivity by minimizing the effect of noise; 2. Maintaining each PETCO 2 at a steady level long enough to allow stabilization of cerebral blood flow and facilitate correlation of the BOLD signal intensity to a specific PETCO 2 ; and 3. Effecting rapid step changes between steady-state levels of PCO 2 in order to allow multiple measurements of cerebrovascular reactivity within the time available for scanning, thereby minimizing the confounding effect of baseline signal drift typically present in functional imaging data. MATERIALS AND METHODSFollowing institutional ethics approval, we studied one healthy female and two healthy male subjects. The subjects' inspired gas concentrations were supplied via the circuit depicted in schematic form in Fig. 1. Each subject breathed through a mouthpiece (No. 109-P; Vacumed, Ventura, CA) attached to a right angle connector (to enable it to fit inside the MRI head coil). This mouthpiece allows occlusion of the teeth and thus aids in the swallowing of excess saliva while supine. Airway PCO 2 was monitored continuously at the mouth (Capnomac Ultima, Datex Engstrom, Helsinki, Finland) and recorded digitally (Dataq, Akron, OH). Control of PETCO 2Our protocol involved four 3-min cycles of raising and lowering the PETCO 2 . During each cycle the high PETCO 2 level was attained by delivering into the circuit 8% CO 2 in O 2 , at 15 L/min for 10 -15 sec, and maintained at that level by delivering 100% O 2 (the fresh gas flow) at 0.5-2 L/min for the remainder of the 90 sec. The low PETCO 2 was attained by delivering 100% O 2 at ...

Respiratory sinus arrhythmia (RSA) may improve the efficiency of pulmonary gas exchange by matching the pulmonary blood flow to lung volume during each respiratory cycle. If so, an increased demand for pulmonary gas exchange may enhance RSA magnitude. We therefore tested the hypothesis that CO2 directly affects RSA in conscious humans even when changes in tidal volume (V(T)) and breathing frequency (F(B)), which indirectly affect RSA, are prevented. In seven healthy subjects, we adjusted end-tidal PCO2 (PET(CO2)) to 30, 40, or 50 mmHg in random order at constant V(T) and F(B). The mean amplitude of the high-frequency component of R-R interval variation was used as a quantitative assessment of RSA magnitude. RSA magnitude increased progressively with PET(CO2) (P < 0.001). Mean R-R interval did not differ at PET(CO2) of 40 and 50 mmHg but was less at 30 mmHg (P < 0.05). Because V(T) and F(B) were constant, these results support our hypothesis that increased CO2 directly increases RSA magnitude, probably via a direct effect on medullary mechanisms generating RSA.