Quantification of the cortical contribution to the NIRS signal over the motor cortex using concurrent NIRS-fMRI measurements

Abstract

Near-Infrared Spectroscopy (NIRS) measures the functional hemodynamic response occurring at the surface of the cortex. Large pial veins are located above the surface of the cerebral cortex. Following activation, these veins exhibit oxygenation changes but their volume likely stays constant. The back-reflection geometry of the NIRS measurement renders the signal very sensitive to these superficial pial veins. As such, the measured NIRS signal contains contributions from both the cortical region as well as the pial vasculature. In this work, the cortical contribution to the NIRS signal was investigated using (1) Monte Carlo simulations over a realistic geometry constructed from anatomical and vascular MRI and (2) multimodal NIRS-BOLD recordings during motor stimulation. A good agreement was found between the simulations and the modeling analysis of in vivo measurements. Our results suggest that the cortical contribution to the deoxyhemoglobin signal change (ΔHbR) is equal to 16–22% of the cortical contribution to the total hemoglobin signal change (ΔHbT). Similarly, the cortical contribution of the oxyhemoglobin signal change (ΔHbO) is equal to 73–79% of the cortical contribution to the ΔHbT signal. These results suggest that ΔHbT is far less sensitive to pial vein contamination and therefore, it is likely that the ΔHbT signal provides better spatial specificity and should be used instead of ΔHbO or ΔHbR to map cerebral activity with NIRS. While different stimuli will result in different pial vein contributions, our finger tapping results do reveal the importance of considering the pial contribution.

Introduction

Near-infrared spectroscopy (NIRS) (Hillman, 2007, Hoshi, 2007, Villringer et al., 1993) is a non-invasive technique for monitoring the hemodynamic changes occurring in superficial regions of the cortex. Using non-ionizing light, NIRS measures the fluctuations of the two dominant biological chromophores in the near-infrared spectrum: oxygenated (HbO) and deoxygenated or reduced hemoglobin (HbR).

Over the past 15 years, NIRS has become an attractive alternative to functional Magnetic Resonance Imaging (fMRI), with several clinical advantages (Irani et al., 2010). NIRS is portable and less susceptible to movement artifacts enabling long term monitoring of the hemodynamic activity at the bedside. However, the spatial resolution of NIRS is 1–3 cm (Boas et al., 2004) which is less than the resolution of standard fMRI scanners. Another disadvantage of NIRS is its penetration depth which limits its sensitivity to the upper 1 cm of the cerebral cortex (Boas et al., 2004).

The biophysical origin of the functional NIRS signal is the variation of HbO and HbR concentration resulting from changes in Cerebral Blood Flow (CBF) and Cerebral Metabolic Rate of Oxygen (CMRO₂). For evoked brain activity, the resulting variations in HbO and HbR are described by the Balloon model (Buxton et al., 1998, Buxton et al., 2004, Friston, 2000). According to this model, the arterial dilation driven increase in CBF following brain activation induces a passive volume increase of the capillary and venous vasculature (termed the windkessel compartment) as well as an increase in oxygen saturation. Compartmental microscopic hemodynamic measurements (Drew et al., 2011, Hillman et al., 2007) have revealed that this evoked oxygenation increase propagates through the pial veins located at the surface of the cortex but that this pial compartment exhibits very little volume variation following brain activation. This pial vein signal is generally negligible in fMRI since the high anatomical resolution allows the signal coming from the cortical region to be isolated. Conversely, the NIRS signal is integrated through the different superficial layers of the head. This potentially gives rise to a pial vein contamination of the signal if the pial vessels happen to coincide with the path of the light during its propagation through the tissue.

Preliminary analysis of the impact of pial vasculature in NIRS has been performed by Dehaes et al. (2011). However, very few studies of the effect of pial vein oxygenation changes (termed “the washout effect”) on the NIRS signal have been performed (Firbank et al., 1998, Huppert et al., 2009).

In this paper, the effect of pial vein contamination of the NIRS signal is investigated over the motor cortex where superficial pial veins are present (Gray, 2000). We first quantify cortical and pial vein contributions to the NIRS signal by Monte Carlo simulation performed on a realistic anatomical volume containing pial veins acquired with MRI. We then use a biophysical model of the fMRI signal to analyze concurrent NIRS-fMRI data acquired over the motor cortex of human subjects during a finger tapping task. The cortical contribution to the HbR and HbO signals relative to the cortical contribution of the HbT signal are both estimated by fitting the biophysical model to the multimodal data.