Development of diffuse correlation techniques for non-invasive measurement of cerebral blood flow and oxygen metabolism in rats

Abstract

Our group has pioneered the development of diffuse correlation tomography (DCT) for measurement of cerebral blood flow (CBF) through the intact skull in animal models and finally in adult human brain. By combining DCT with simultaneous diffuse optical tomography(DOT) which images changes in oxyhemoglobin (rHbO2), deoxyhemoglobin (rHb) and total hemoglobin (rTHC) concentrations, and blood oxygen saturation (dYt), we can derive an image of the relative cerebral metabolic rate of oxygen (rCMRO2). Previously, we have obtained images in rat brain during hypercapnia 1 and focal transient ischemia 2, and now present data in cortical spreading depression (CSD). The development of this technique enables us to carry out longitudinal studies in small animals relatively noninvasively. After validating the combined DOT/DCT technique using a well characterized system (hypercapnia) 1, we then obtained data in a middle cerebral artery occlusion model in the rat 2. In the penumbra, rCBF decreased to 424%, dYt decreased by 114% and rCMRO2 decreased to 594%. These data are in reasonable agreement with values reported in the literature and were the first images of rCMRO2 obtained by diffuse optical methods. Recently, we have induced cortical spreading depression (CSD) in twenty-six rats by applying KCl through a burr hole over the parietal cortex under hypocapnia, normocapnia, and hypercapnia. Figure 1a shows images of rCBF at selected time points and at different depths. A region of increased CBF progressed from the point where the KCl was applied, spreading throughout the cortex. The observed response was mainly constrained to the upper cortex, illustrating the depth selectivity of the imaging technique (Figure 1b). We observed significant correlations of the peak amplitude of rCBF and frequency of the CSD waves with alterations in pCO2 (Figure 1c). Similar results were obtained in the oxygenation and CMRO2 images. By imaging multiple parameters simultaneously we are able to characterize the CSD physiology more thoroughly than usual DOT. Overall these results have validated and demonstrated the utility of DCT methods in obtaining 3D dimensional, dynamic images of blood flow and hence enabling measurement of CMRO2. We discuss the extension of this technique to measurements in the adult human in an accompanying abstract.