Imaging with near-infrared diffuse optical imaging (DOI) in the neurosciences has seen increased interest over the past 15 years.1–4
In the commonly used continuous-wave (CW) version,5,6
DOI can only measure relative changes in oxy-(HbO2
) and deoxyhemoglobin (HbR) concentrations. On the contrary, frequency domain (FD)7–10
and time domain (TD)11–19
technologies enable absolute measurements of the medium’s optical properties.20–22
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 (CMRO2
). In addition, the blood-oxygen level dependant (BOLD) signal depends both on cerebral blood flow (CBF) and CMRO2
. 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 CMRO2
. To estimate CMRO2
, one must measure the BOLD signal at two different CBF values but without altering the CMRO2
. This must be done during hypercapnic periods using two different levels of CO2
However, TD measurements could provide an alternative to this procedure.
Brain optical properties have been measured previously in vitro
but physiological factors make those measurements distinct from the in vivo
situation. Among those distinctions is the swelling of the mitochondria, which results in structural changes, and the small fluctuations of the brain temperature, which change the hemoglobin solubility in the blood. Moreover, previous studies performing in vivo
measurements reported noticable intersubject variability.8,26
These results preclude the generalization of single-subject measured values to other subjects and confirm the importance of obtaining these values individually for quantitative imaging.
In previous work, baseline optical measurements with a TD system using multidistances and a homogeneous model has been used to fit the data and estimate the optical parameters.26,27
A major drawback is that this homogeneous model does not distinguish between hemoglobin concentrations in the scalp and those of the cerebral tissues, because it does not account for the layered structure of the head. The superficial layer, the skin and skull, limit the accuracy of DOI, since light is also absorbed and scattered in these regions, which are not part of the cerebral cortex. Moreover, the skin layer is subject to a physiology that may cause interference in the process of recovering cerebral activity. Several methods based on multi-distance measurements have been developed to overcome this problem.28–31
In a multimodal study combining position emission tomography and TD optical imaging, it was shown that the contributions from these superficial layers are reduced significantly, even using a homogeneous model, when source-detector distances are increased beyond 4 cm.32
Such measurements require a large signal-to-noise ratio, which was not available with the system used in our experiment.
Separately, analytical models have been developed by solving the diffusion equation and its boundary conditions for a two-layered medium.22,33–35
These models, validated with Monte Carlo simulations, showed adequate efficiencies at recovering the parameters if the thickness of the first layer of the model was known a priori
. In vivo
measurements with a two-layered model also have been reported using a FD system,8
and as expected, clear distinctions between scalp and cerebral tissues properties were made. The goal here is to provide further confirmation of the above FD results (Choi et al.) with an independent TD technique.
In this work, we report intra- and extracerebral hemoglobin concentrations recovered on individual subjects with a time-resolved system using a two-layered analytical model for the first time. The measurements were taken with four wavelengths (690, 750, 800, and 850 nm) at four distances: 10, 15, 25, and 30 mm. All wavelengths were fit simultaneously with a two-layered analytical model for the absorption and reduced scattering coefficient of both layers. Concentrations were then computed with the recovered absorption coefficients. We observed a large variability between subjects. Results were compared to the literature, and differences between time and frequency measurements for the oxygen saturation in the skin and skull layer were observed.