Double-layer estimation of intra- and extracerebral hemoglobin concentration with a time-resolved system

Abstract

Imaging with near-infrared diffuse optical imaging (DOI) in the neurosciences has seen increased interest over the past $15\text{years}$ .^{1, 2, 3, 4} In the commonly used continuous-wave (CW) version,^{5, 6} DOI can only measure relative changes in oxy- $\left(\mathrm{Hb}{\mathrm{O}}_2\right)$ and deoxyhemoglobin (HbR) concentrations. On the contrary, frequency domain (FD)^{7, 8, 9, 10} and time domain (TD) ^{11, 12, 13, 14, 15, 16, 17, 18, 19} technologies enable absolute measurements of the medium’s optical properties.^{20, 21, 22} This is particularly useful to calibrate brain activation and quantify the underlying hemodynamic processes within the brain. For example, multimodal studies (e.g., optical-MRI fusion²³) need quantitative information to estimate the cerebral metabolic rate of oxygen $\left(\mathrm{CMR}{\mathrm{O}}_2\right)$ . In addition, the blood-oxygen level dependant (BOLD) signal depends both on cerebral blood flow (CBF) and $\mathrm{CMR}{\mathrm{O}}_2$ . However, this relation is not straightforward, and a calibration constant must be estimated. The change in CBF can be measured separately by arterial spin labeling fMRI so the only two unknowns are the calibration constant and $\mathrm{CMR}{\mathrm{O}}_2$ . To estimate $\mathrm{CMR}{\mathrm{O}}_2$ , one must measure the BOLD signal at two different CBF values but without altering the $\mathrm{CMR}{\mathrm{O}}_2$ . This must be done during hypercapnic periods using two different levels of $\mathrm{C}{\mathrm{O}}_2$ pressure.²⁴ However, TD measurements could provide an alternative to this procedure.