We have come a long way since Jöbsis first demonstrated that noninvasive cerebral monitoring was possible in humans within the near-infrared light window (approximately 700 to 1000 nm) in the late 1970s.¹ What started as a tool to quantify blood oxygenation in the brain has exploded into a whole field of study that aims to exploit this window to reveal a battery of information related to human brain physiology, including brain metabolism, blood flow, autoregulation, perfusion pressure, water concentration, light scattering, exogenous contrast agents, and more. In this text, we use the term “diffuse optics” to broadly describe any technique that employs a near-infrared light source and a photodetector to capture multiply scattered photons in the diffusion limit (i.e., in the limit wherein the absorption coefficient, ${\mu }_a$, is much less than the reduced scattering coefficient, ${\mu }_s^{\prime }$, and the source-detector separation is much greater than the photon mean free path). The term “diffuse” has historical connotations in the field and reflects how near-infrared photons propagate through biological tissue. However, it should be noted that this term is in no way associated with how the field/community is organized or conducts its science. On the contrary, the breadth and depth of the progress made in the field over the past decade could only be accomplished by a cohesive, focused, and tight-knit community of researchers!

Using diffusion theory, we show that a dual-slope method is more effective than single-slope methods or single-distance methods at enhancing sensitivity to deeper tissue. The dual-slope method requires a minimum of two sources and two detectors arranged in specially configured arrays. In particular, we present diffusion theory results for a symmetrical linear array of two sources (separated by 55 mm) that sandwich two detectors (separated by 15 mm), for which dual slopes achieve maximal sensitivity at a depth of about 5 mm for direct current (DC) intensity (as measured in continuous-wave spectroscopy) and 11 mm for phase (as measured in frequency-domain spectroscopy) under typical values of the tissue optical properties (absorption coefficient: $\sim\!0.01\,\,{\rm mm}^{ - 1}$, reduced scattering coefficient: $\sim\!1\,\,{\rm mm}^{ - 1}$). This result is a major advance over single-distance or single-slope data, which feature maximal sensitivity to shallow tissue ($ \lt\!{{2}}\,\,{\rm{mm}}$ for the intensity, $ \lt\!{{5}}\,\,{\rm{mm}}$ for the phase).

We propose a new near-infrared spectroscopy (NIRS) method for quantitative measurements of cerebral blood flow (CBF). Because this method uses concepts of coherent hemodynamics spectroscopy (CHS), we identify this new method with the acronym NIRS-CHS. We tested this method on the prefrontal cortex of six healthy human subjects during mean arterial pressure (MAP) transients induced by the rapid deflation of pneumatic thigh cuffs. A comparison of CBF dynamics measured with NIRS-CHS and with diffuse correlation spectroscopy (DCS) showed a good agreement for characteristic times of the CBF transient. We also report absolute measurements of baseline CBF with NIRS-CHS (69 ± 6 ml/100g/min over the six subjects). NIRS-CHS can provide more accurate measurements of CBF with respect to previously reported NIRS surrogates of CBF.

Functional near-infrared spectroscopy (fNIRS) is a noninvasive optical technique for monitoring regional tissue oxygenation based on diffusion and absorption of near-infrared light photons in human tissue. Continuous-wave (cw) fNIRS provides measurements of concentration changes in oxy-, deoxy-, and total-hemoglobin species (${\mathrm{\Delta }[\mathrm{HbO}}_2]$, $\mathrm{\Delta }[\mathrm{Hb}]$, and $\mathrm{\Delta }[\mathrm{HbT}]$, respectively) in tissue with temporal sampling rate of on the order of 10 Hz.¹ Over the past three decades, fNIRS has been used in several brain imaging applications, including noninvasive imaging of cognitive tasks and brain functional activation,^{1 – 4} and brain computer interface (BCI).⁵

This work presents the design and validation of an instrument for dual-slope broadband diffuse reflectance spectroscopy. This instrument affords calibration-free, continuous-wave measurements of broadband absorbance of optically diffusive media, which may be translated into absolute absorption spectra by adding frequency-domain measurements of scattering at two wavelengths. An experiment on a strongly scattering liquid phantom (milk, water, dyes) confirms the instrument’s ability to correctly identify spectral features and measure absolute absorption. This is done by sequentially adding three dyes, each featuring a distinct spectral absorption, to the milk/water phantom. After each dye addition, the absorption spectrum is measured, and it is found to reproduce the spectral features of the added dye. Additionally, the absorption spectrum is compared to the absorption values measured with a commercial frequency-domain instrument at two wavelengths. The measured absorption of the milk/water phantom quantitatively agrees with the known water absorption spectrum ($R^2=0.98$), and the measured absorption of the milk/water/dyes phantom quantitatively agrees with the absorption measured with the frequency-domain instrument in six of eight cases. Additionally, the measured absorption spectrum correctly recovers the concentration of one dye, black India ink, for which we could accurately determine the extinction spectrum (i.e., the specific absorption per unit concentration). The instrumental methods presented in this work can find applications in quantitative spectroscopy of optically diffusive media, and particularly in near-infrared spectroscopy of biological tissue.