1. ¹Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Department of Clinical Neurology, University of Oxford, John Radcliffe Hospital, Oxford, UK
2. ²CUBRIC, School of Psychology, Cardiff University, Park Place, Cardiff, UK
3. ³Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, UK
4. ⁴Nuffield Department of Anaesthetics, University of Oxford, John Radcliffe Hospital, Oxford, UK
5. ⁵School of Sport and Exercise Sciences, University of Birmingham, Edgbaston, Birmingham, UK

Correspondence: Dr RG Wise, CUBRIC, School of Psychology, Cardiff University, Park Place, Cardiff, CF10 3AT, UK. E-mail: wiserg@cardiff.ac.uk

Received 3 September 2006; Revised 22 December 2006; Accepted 4 January 2007; Published online 4 April 2007.

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 CO₂. 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_CO2 means.d., from 40.91.8 to 46.41.6 mm Hg). This was compared with a traditional fixed-inspired (FI_CO2=5%) hypercapnic challenge (PET_CO2 means.d., from 38.22.1 to 45.61.4 mm Hg). Dynamic end-tidal forcing achieved the desired target PET_CO2 for each subject while maintaining PET_O2 constant. As a result of CO₂-induced increases in ventilation, the FIC showed a greater cyclic fluctuation in PET_O2. These were associated with spatially widespread fluctuations in BOLD signal that were eliminated largely by the control of PET_O2 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.