Abstract
Absolute measurements of cerebral blood flow (CBF) are an important endpoint in studies of cerebral pathophysiology. Currently no accepted method exists for in vivo longitudinal monitoring of CBF with high resolution in rats and mice. Using three-dimensional Doppler Optical Coherence Tomography and cranial window preparations, we present methods and algorithms for regional CBF measurements in the rat cortex. Towards this end, we develop and validate a quantitative statistical model to describe the effect of static tissue on velocity sensitivity. This model is used to design scanning protocols and algorithms for sensitive 3D flow measurements and angiography of the cortex. We also introduce a method of absolute flow calculation that does not require explicit knowledge of vessel angles. We show that OCT estimates of absolute CBF values in rats agree with prior measures by autoradiography, suggesting that Doppler OCT can perform absolute flow measurements in animal models.
Highlights
In the normal brain cerebral blood flow (CBF) is regulated to satisfy metabolic demand determined by brain activity
Quantitative flow measurements were performed in the somatosensory cortex in 4 rats
Because flow measurements are performed by scanning an optical beam over the cortex, the most natural units for the Doppler Optical Coherence Tomography (OCT) flow measurements are volume per unit cortical surface area per unit time
Summary
In the normal brain cerebral blood flow (CBF) is regulated to satisfy metabolic demand determined by brain activity. Quantitative and localized measurements of CBF may significantly advance understanding of major cerebrovascular diseases. A method for in vivo determination of absolute CBF values with high resolution in small animals is currently lacking. The gold standard for determination of regional blood flow is autoradiography. In this technique, a tracer, such as iodo[14C]antipyrine, is typically administered over a short period of time, followed by cardiac arrest and quick freezing. Autoradiographic methods provide three-dimensional spatial information, they contain no information about the temporal evolution of CBF changes [2]. Studies of disease progression or response to treatment using intra-animal comparisons cannot be performed, limiting the utility of this method
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