Dynamic Forcing of End-Tidal Carbon Dioxide and Oxygen Applied to Functional Magnetic Resonance Imaging

Abstract

Investigations into the blood oxygenation level-dependent (BOLD) functional MRI signal have used respiratory challenges with the aim of probing cerebrovascular physiology. Such challenges have altered the inspired partial pressures of either carbon dioxide or oxygen, typically to a fixed and constant level (fixed inspired challenge (FIC)). The resulting end-tidal gas partial pressures then depend on the subject's metabolism and ventilatory responses. In contrast, dynamic end-tidal forcing (DEF) rapidly and independently sets end-tidal oxygen and carbon dioxide to desired levels by altering the inspired gas partial pressures on a breath-by-breath basis using computer-controlled feedback. This study implements DEF in the MRI environment to map BOLD signal reactivity to CO(2). We performed BOLD (T2(*)) contrast FMRI in four healthy male volunteers, while using DEF to provide a cyclic normocapnic-hypercapnic challenge, with each cycle lasting 4 mins (PET(CO(2)) mean+/-s.d., from 40.9+/-1.8 to 46.4+/-1.6 mm Hg). This was compared with a traditional fixed-inspired (FI(CO(2))=5%) hypercapnic challenge (PET(CO(2)) mean+/-s.d., from 38.2+/-2.1 to 45.6+/-1.4 mm Hg). Dynamic end-tidal forcing achieved the desired target PET(CO(2)) for each subject while maintaining PET(O(2)) constant. As a result of CO(2)-induced increases in ventilation, the FIC showed a greater cyclic fluctuation in PET(O(2)). These were associated with spatially widespread fluctuations in BOLD signal that were eliminated largely by the control of PET(O(2)) during DEF. The DEF system can provide flexible, convenient, and physiologically well-controlled respiratory challenges in the MRI environment for mapping dynamic responses of the cerebrovasculature.

Opioids Depress Cortical Centers Responsible for the Volitional Control of Respiration

“…The subjects breathed a mixture of oxygen and air, and the end-tidal O 2 partial pressure (P ET O 2 ) was maintained at 225 mmHg by manual control of the gas mixture, by a dedicated experimenter. This achieved similar control over end-tidal gas concentrations as an automated system (Wise et al, 2007).…”

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

“…Early methods [15][16][17] focused on maintenance of constant partial pressures using sequential rebreathing approaches, wherein subjects receive an externally administered gas up to a certain flow rate, beyond which they rebreathe expired gas. Feedback approaches have also been explored, 18 although these require extremely high flow rates (e.g., 70 L/min). Slessarev et al 19 have extended the sequential rebreathing approach to incorporate physiologic modeling of CO 2 fluxes in the body to make predictive, breath-by-breath adjustments of inspired gases to achieve prospective and independent control of end-tidal PCO 2 and PO 2 at lower flow rates.…”

MRI Mapping of Cerebrovascular Reactivity via Gas Inhalation Challenges

“…In our design, we bring the bag before the start of the scan and, following the scan, the bag is emptied, folded, and put away. Finally, compared to several other systems 18,21 , the current gas delivery system is simpler, requires less training time, and its consumables are less expensive.…”

“…While an exhaustive survey of other gas delivery systems used in the literature is beyond the scope of this article, it is useful to compare the current system to a few commonly used ones 17,18 . A major difference is that our system uses a mouthpiece to deliver the intended gas while most other systems have used a mask in design.…”

“…In physiology and anesthesiology literature, it is known that, because CO 2 gas is a potent vasodilator, CVR can be assessed by altering the arterial CO 2 level (e.g., inhalation of a small amount of CO 2 ) while monitoring vascular responses [10][11][12][13] . In the imaging and radiology field, CVR mapping using MRI is rapidly emerging as a new marker of interest for many basic scientists and clinicians 8,[14][15][16][17][18][19] . It is usually estimated by examining how much vascular response is induced by a vasoactive challenge.…”