Abstract
The blood-brain barrier (BBB) is integral to maintaining a suitable microenvironment for neurons to function properly. Despite its importance, there are no bedside methods of assessing BBB disruption to help guide management of critical-care patients. The aim of this study was to demonstrate that dynamic contrast-enhanced (DCE) near-infrared spectroscopy (NIRS) can quantify the permeability surface-area product (PS) of the BBB. Experiments were conducted in rats in which the BBB was opened by image-guided focused ultrasound. DCE-NIRS data were acquired with two dyes of different molecular weight, indocyanine green (ICG, 67 kDa) and 800CW carboxylate (IRDye, 1166 Da), and PS maps were generated by DCE computer tomography (CT) for comparison. Both dyes showed a strong correlation between measured PS values and sonication power (R2 = 0.95 and 0.92 for ICG and IRDye respectively), and the PS values for IRDye were in good agreement with CT values obtained with a contrast agent of similar molecular weight. These proof-of-principle experiments demonstrate that DCE NIRS can quantify BBB permeability. The next step in translating this method to critical care practice will be to adapt depth sensitive methods to minimize the effects of scalp contamination on NIRS PS values.
Highlights
The blood-brain barrier (BBB), which consists of tight junctions between adjacent endothelial cells, is essential to brain homeostasis as it limits the passage of molecules from blood to brain parenchyma[1, 2]
A similar approach was developed for near-infrared spectroscopy (NIRS) using the clinically approved contrast agent Indocyanine Green (ICG), and it was shown that uptake in the brain was greater following Mannitol-induced disruption[7]
Et al observed significant differences in the clearance rate of ICG from the brains of patients with known BBB disruption compared to healthy controls – a strong indication that Dynamic contrast-enhanced (DCE) NIRS is sensitive to BBB permeability[17]
Summary
The blood-brain barrier (BBB), which consists of tight junctions between adjacent endothelial cells, is essential to brain homeostasis as it limits the passage of molecules from blood to brain parenchyma[1, 2]. A similar approach was developed for near-infrared spectroscopy (NIRS) using the clinically approved contrast agent Indocyanine Green (ICG), and it was shown that uptake in the brain was greater following Mannitol-induced disruption[7]. This is a relatively slow procedure, requiring ICG measurements up to 40 min post injection and it does not provide an estimate of BBB permeability. Other factors can influence the shape of DCE curves, namely the rate of dye delivery and cerebral hemodynamics This qualitative approach provides no means of assessing the degree of BBB permeability, which is related to the risk of vasogenic edema[18]. The PS product was measured independently by DCE CT24
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