We combined diffuse optical (DOS) and correlation (DCS) spectroscopies to simultaneously measure the oxyhemoglobin (rHbO2), deoxyhemoglobin (rHb), total hemoglobin (rTHC) concentration and blood flow (rCBF) in adult human brain during a hypercapnic episode and sensorimotor stimulation. These measurements allowed calculation of the relative cerebral metabolic rate of oxygen (rCMRO2) in the human brain for the first time, to our knowledge, by use of all-optical methods. Briefly, ∼3 mW of light from three amplitude modulated lasers at 690, 785, and 830 nm were fiber-coupled to the head. Photons transmitted were detected in reflection mode. Spectroscopic analysis was carried to calculate rHb, rHbO2 and rTHC. A narrowband laser (5 mW at 800 nm), photon-counting, avalanche photo-diodes and a custom-build autocorrelator board was used for blood flow by fitting the obtained autocorrelation functions. The maximum penetration depth was about 2 cm from the top of the scalp and we report averaged values from the probed tissue volume after a partial volume correction 1 . As a first step towards validation in human brain, measurements were made in five subjects at a resting cerebral pCO2 and during 4–6 minute periods of increased pCO2 induced by respiration of a 6% CO2 gas mixture. The end tidal CO2, heart rate, blood pressure and arterial oxygenation were monitored continuously. A typical response is shown in Figure 1 (right panel). Over the five subjects a sustained mean CBF increase of 35.4±9.6% corresponding to 14.7±4.7 mmHg increase in pCO2 was observed. This corresponds to a 2.4±0.4 %/mmHg rise in CBF, well within the values reported in the literature (2–3.6%/mmHg). Seven male volunteers participated in the sensorimotor cortical activation studies. One subject further participated in a 3-T fMRI study in which BOLD and arterial spin-labeled (ASL) perfusion data were obtained sequentially to compare to optical results from the same subject. Figure 1 (left panel) shows group averaged results which indicate mean changes for rCBF rHBO2, rHB, rTHC, rCMRO2 of 39±10%, 12.5±2.8 uM, −3.8±0.8 uM, 8.3±2.3 uM and 10.1±4.4% respectively in agreement with the literature. When the probe was placed away from the activation area, no significant, correlated changes were observed in the optical signals, demonstrating the local nature of the response. The feasibility of noninvasive optical measurement of blood flow and oxygen metabolism through the skull of the adult human is thus feasible, and the clinical potential of this hybrid, all-optical noninvasive, methodology is now being explored in patients suffering from severe head trauma. The optical technique offers a great deal of promise as a portable, non-invasive and relatively cheap modality, capable of doing longitudinal measurements of multiple important parameters.
(left) Placement of fibers; the source (red) is 3cm from DOS detector (blue). DCS detectors (green) are 2 cm (x2), 2.5 cm (x3) and 3 cm (x4) away. (left bottom) Left axis shows the rCBF and rCMRO2 values and right axis shows the changes in HBO2 and Hb concentrations due to motor stimulus. (right bottom) Changes in end-tidal CO2 and rCBF during 6% CO2 mixture breathing.