Cerebral blood flow (CBF) and cerebral autoregulation (CA) are critically important to maintain proper brain perfusion and supply the brain with the necessary oxygen and energy substrates. Adequate brain perfusion is required to support normal brain function, to achieve successful aging, and to navigate acute and chronic medical conditions. We review the general principles of CBF measurements and the current techniques to measure CBF based on direct intravascular measurements, nuclear medicine, X-ray imaging, magnetic resonance imaging, ultrasound techniques, thermal diffusion, and optical methods. We also review techniques for arterial blood pressure measurements as well as theoretical and experimental methods for the assessment of CA, including recent approaches based on optical techniques. The assessment of cerebral perfusion in the clinical practice is also presented. The comprehensive description of principles, methods, and clinical requirements of CBF and CA measurements highlights the potentially important role that noninvasive optical methods can play in the assessment of neurovascular health. In fact, optical techniques have the ability to provide a noninvasive, quantitative, and continuous monitor of CBF and autoregulation.

This article reviews the basic principles of frequency-domain near-infrared spectroscopy (FD-NIRS), which relies on intensity-modulated light sources and phase-sensitive optical detection, and its non-invasive applications to the brain. The simpler instrumentation and more straightforward data analysis of continuous-wave NIRS (CW-NIRS) accounts for the fact that almost all the current commercial instruments for cerebral NIRS have embraced the CW technique. However, FD-NIRS provides data with richer information content, which complements or exceeds the capabilities of CW-NIRS. One example is the ability of FD-NIRS to measure the absolute optical properties (absorption and reduced scattering coefficients) of tissue, and thus the absolute concentrations of oxyhemoglobin and deoxyhemoglobin in brain tissue. This article reviews the measured values of such optical properties and hemoglobin concentrations reported in the literature for animal models and for the human brain in newborns, infants, children, and adults. We also review the application of FD-NIRS to functional brain studies that focused on slower hemodynamic responses to brain activity (time scale of seconds) and faster optical signals that have been linked to neuronal activation (time scale of 100 ms). Another example of the power of FD-NIRS data is related to the different regions of sensitivity featured by intensity and phase data. We report recent developments that take advantage of this feature to maximize the sensitivity of non-invasive optical signals to brain tissue relative to more superficial extracerebral tissue (scalp, skull, etc.). We contend that this latter capability is a highly appealing quality of FD-NIRS, which complements absolute optical measurements and may result in significant advances in the field of non-invasive optical sensing of the brain.

We have previously reported a comparison between edge-corrected near-infrared optical mammograms and those that have undergone a further image-processing step based on a spatial second derivative. In this work, we go a step further by combining the second-derivative images from four wavelengths (690, 750, 788, and 856 nm) to obtain oxygenation-index images. While the spatial second derivative improves contrast and allows for visibility of fine structures in the images, thereby improving the sensitivity to tumor detection, additional information is needed to avoid false-positive results. The oxygenation-index images are introduced to address this issue. Oxygenation information may help discriminate benign from malignant breast lesions, thereby effectively complementing single-wavelength optical mammograms that display optically dense regions within the breast with high sensitivity. © 2004 Society of Photo-Optical Instrumentation Engineers.

Fluorescence spectroscopy provides potential contrast enhancement for near-infrared tissue imaging and physiologically correlated spectroscopy. We present a fluorescence photon migration model and test its quantitative predictive capabilities with a frequency-domain measurement that involves a homogeneous multiple-scattering tissue phantom (with optical properties similar to those of tissue in the near infrared) that contains a fluorophore (rhodamine B). After demonstrating the validity of the model, we explore its ability to recover the fluorophore's spectral properties from within the multiple-scattering medium. The absolute quantum yield and the lifetime of the fluorophore are measured to within a few percent of the values measured independently in the absence of scattering. Both measurements are accomplished without the use of reference fluorophores. In addition, the model accurately predicts the fluorescence emission spectrum in the scattering medium. Implications of these absolute measurements of lifetime, quantum yield, concentration, and emission spectrum from within multiple-scattering media are discussed.