UC San Diego

Cerebral blood flow (CBF) and blood oxygenation level dependent (BOLD) signal measurements make it possible to estimate steady-state changes in the cerebral metabolic rate of oxygen (CMRO₂) with a calibrated BOLD method. However, extending this approach to measure the dynamics of CMRO₂ requires an additional assumption: that deoxygenated cerebral blood volume (CBV_dHb) follows CBF in a predictable way. A test-case for this assumption is the BOLD post-stimulus undershoot, for which one proposed explanation is a strong uncoupling of flow and blood volume with an elevated level of CBV_dHb during the post-stimulus period compared to baseline due to slow blood volume recovery (Balloon Model). A challenge in testing this model is that CBV_dHb differs from total blood volume, which can be measured with other techniques. In this study, the basic hypothesis of elevated CBV_dHb during the undershoot was tested, based on the idea that the BOLD signal change when a subject switches from breathing a normoxic gas to breathing a hyperoxic gas is proportional to the absolute CBV_dHb. In 19 subjects (8F), dual-echo BOLD responses were measured in primary visual cortex during a flickering radial checkerboard stimulus in normoxia, and the identical experiment was repeated in hyperoxia (50% O₂/balance N₂). The BOLD signal differences between normoxia and hyperoxia for the pre-stimulus baseline, stimulus, and post-stimulus periods were compared using an equivalent BOLD signal calculated from measured R₂* changes to eliminate signal drifts. Relative to the pre-stimulus baseline, the average BOLD signal change from normoxia to hyperoxia was negative during the undershoot period (p = 0.0251), consistent with a reduction of CBV_dHb and contrary to the prediction of the Balloon Model. Based on these results, the BOLD post-stimulus undershoot does not represent a case of strong uncoupling of CBV_dHb and CBF, supporting the extension of current calibrated BOLD methods to estimate the dynamics of CMRO₂.