Abstract
Millimeter-depth sensitivity with frequency domain near-infrared spectroscopy has been challenging due to the breakdown of the diffusion equation for source-detection separations < 1cm. To overcome this challenge, we employ a Monte-Carlo lookup table-based inverse algorithm to fit small separation (3-6 mm) frequency-domain near-infrared spectroscopy (FDNIRS) data for absorption and reduced scattering coefficients. We verify this small separation FDNIRS method through a series of in vitro and in vivo studies. In vitro, we observed a root mean squared percent error (RMSE) in estimation of the reduced scattering coefficient and absorption coefficient of 2.8% and 7.6%, respectively, in liquid phantoms consisting of Intralipid and Indian ink, and a RMSE in estimation of oxygen saturation and total hemoglobin concentrations of 7.8 and 11.2%, respectively, in blood-mixed liquid phantoms. Next, we demonstrate one particularly valuable in vivo application of this technique wherein we non-invasively measure the optical properties of the mouse brain (n = 4). We find that the measured resting state cerebral oxygen saturation and hemoglobin concentration are consistent with literature reported values, and we observe expected trends during a hyper-/hypoxia challenge that qualitatively mimic changes in partial pressure of oxygen (pO2) measured simultaneously with an invasive pO2 sensor. Further, through simulations of the mouse head geometry, we demonstrate that the skull and scalp exert minimal influence on the estimate oxygen saturation, while leading to small but systematic underestimation of total hemoglobin concentration. In total, these results demonstrate the robustness of small separation FDNIRS to assess tissue optical properties at millimeter depth resolution.
Highlights
Frequency domain near-infrared spectroscopy (FDNIRS) is a non-invasive optical technique used to estimate the optical properties of human tissue, namely the wavelength-dependent absorption and reduced scattering coefficients
In vitro liquid phantom verification The estimated μs and μa of the liquid Intralipid/ink phantoms using small separation FDNIRS show excellent agreement with the expected μs and μa measured with large-separation FDNIRS (Fig. 3)
Alternative techniques exist to estimate optical properties at millimeter depths, including visible steady-state reflectance spectroscopy, which works for source-detector separations < 3 mm [25], and spatial frequency domain imaging [26], which is sensitive to depths of 2-6 mm [27]
Summary
Frequency domain near-infrared spectroscopy (FDNIRS) is a non-invasive optical technique used to estimate the optical properties of human tissue, namely the wavelength-dependent absorption and reduced scattering coefficients (μa and μs , respectively). Tseng et al [4,5] developed a clever small separation FDNIRS approach wherein a diffusing layer is placed between the source/detector and the sample of interest such that a modified two-layer diffusion model can be employed to recover optical properties of the bottom layer. All of these studies require an FDNIRS device that operates at multiple modulation frequencies to extract optical properties. Small separation FDNIRS at a single modulation frequency has not been demonstrated to date
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