Graded Hypercapnia-Calibrated BOLD: Beyond the Iso-metabolic Hypercapnic Assumption

摘要

Calibrated BOLD is a promising technique that overcomes the sensitivity of conventional fMRI to the cerebrovascular state; measuring either the basal level, or the task-induced response of cerebral metabolic rate of oxygen consumption (CMRO_(2)). The calibrated BOLD method is susceptible to errors in the measurement of the calibration parameter M , the theoretical BOLD signal change that would occur if all deoxygenated hemoglobin were removed. The original and most popular method for measuring M uses hypercapnia (an increase in arterial CO_(2)), making the assumption that it does not affect CMRO_(2). This assumption has since been challenged and recent studies have used a corrective term, based on literature values of a reduction in basal CMRO_(2)with hypercapnia. This is not ideal, as this value may vary across subjects and regions of the brain, and will depend on the level of hypercapnia achieved. Here we propose a new approach, using a graded hypercapnia design and the assumption that CMRO_(2)changes linearly with hypercapnia level, such that we can measure M without assuming prior knowledge of the scale of CMRO_(2)change. Through use of a graded hypercapnia gas challenge, we are able to remove the bias caused by a reduction in basal CMRO_(2)during hypercapnia, whilst simultaneously calculating the dose-wise CMRO_(2)change with hypercapnia. When compared with assuming no change in CMRO_(2), this approach resulted in significantly lower M -values in both visual and motor cortices, arising from significant dose-dependent hypercapnia reductions in basal CMRO_(2)of 1.5 ± 0.6%/mmHg (visual) and 1.8 ± 0.7%/mmHg (motor), where mmHg is the unit change in end-tidal CO_(2)level. Variability in the basal CMRO_(2)response to hypercapnia, due to experimental differences and inter-subject variability, is accounted for in this approach, unlike previous correction approaches, which use literature values. By incorporating measurement of, and correction for, the reduction in basal CMRO_(2)during hypercapnia in the measurement of M -values, application of our approach will correct for an overestimation in both CMRO_(2)task-response values and absolute CMRO_(2).