Cerebral blood volume changes during the BOLD post-stimulus undershoot measured with a combined normoxia/hyperoxia method

Abstract 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 (CMRO 2 ) with a calibrated BOLD method. However, extending this approach to measure the dynamics of CMRO 2 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% O 2 /balance N 2 ). 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 R 2 * 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 CMRO 2 .