Research Goals
The overarching goal of the Buckley lab is to develop new technologies that aid in the assessment of brain health, brain development, autoregulation, vascular reactivity, and responses to therapeutic intervention. To achieve this goal, the Buckley lab employs diffuse optical spectroscopies to non-invasively study the brain. Specifically, we combine two qualitatively different and complementary diffuse optical imaging modalities: Near-Infrared Spectroscopy (NIRS) for quantification of blood oxygen saturation, blood volume, and water content, and Diffuse Correlation Spectroscopy (DCS) for measurement of blood flow. These tools utilize a unique property of biological tissue that light in the near-infrared spectrum is able to penetrate deeply into tissue before being absorbed (Figure 1).
NIRS/DCS are particularly attractive tools for monitoring the brain because they are non-invasive and easily capable of portable bedside monitoring without the use of sedation or anesthesia. Further, NIRS/DCS can easily be integrated with other brain monitoring techniques, such as magnetic resonance imaging (MRI), transcranial Doppler ultrasound (TCD), electroencephalography (EEG), or positron emission tomography (PET), to provide a more complete picture of brain health. Figure 2 shows the Buckley lab’s hybrid NIRS/DCS instrumentation used for patient measurements.
Near Infrared Spectroscopy (NIRS)
NIRS measurements aim to recover the optical properties of tissue, namely the wavelength-dependent absorption and reduced scattering coefficients (μa(λ) and μs’(λ), respectively) defined as the mean number of absorption and/or scattering events per unit length a photon travels. The Buckley lab utilizes a frequency-domain NIRS (FDNIRS) instrument, in which the light source is amplitude modulated at 110 MHz. We then relate the amplitude attenuation and phase shift of detected light at the tissue surface to the tissue absorption and scattering properties using photon diffusion theory. From these optical properties, we extract clinically-relevant information about the tissue, including the concentration of oxy- and deoxy-hemoglobin, blood volume, and oxygen saturation.
Diffuse Correlation Spectroscopy (DCS)
DCS is a relatively new technology that has been used to monitor regional microvascular cerebral blood flow (CBF) non-invasively and without the use of exogenous tracers. In DCS, dynamic light scattering from moving cells (Figure 3,a) causes the detected near-infrared light intensity on the tissue surface to temporally fluctuate (Figure 3, b), and the time scale of these fluctuations is quantified with an intensity autocorrelation function, g2(t) (Figure 3, c). In practice, correlation diffusion theory is used to fit the measured g2(t) data to simple models to derive an index of CBF (CBFi). The units of this index [mm2/s] are not the traditional units of CBF [ml/min/100g]; however, numerous validation studies in adults, children, and animals have shown that the relative changes in CBFi over time agree well with relative CBF changes measured by other CBF modalities. Additionally, in small animals and neonates, absolute CBFi is strongly correlated with absolute CBF measured by other techniques.
When combined, NIRS and DCS can be used to quantify oxygen metabolism via Fick’s law. Functioning neurons need adenosine triphosphate (ATP), and ATP is produced almost entirely through oxidative metabolism. If the oxygen metabolism is insufficient, either because of lack of supply or impaired delivery, then energy-dependent neuronal processes cease, and irreversible cellular damage ensues. We believe NIRS/DCS provide a versatile tool to assess neuronal health in the brain.