An analysis of the use of hyperoxia for measuring venous cerebral blood volume: comparison of the existing method with a new analysis approach

Abstract

Hyperoxia is known to cause an increase in the blood oxygenation level dependent (BOLD) signal that is primarily localised to the venous vasculature. This contrast mechanism has been proposed as a way to measure venous cerebral blood volume (CBVv) without the need for more invasive contrast media. In the existing method the analysis modelled the data as a dynamic contrast agent experiment, with the assumption that the BOLD signal of tissue was dominated by intravascular signal. The effects on the accuracy of the method due to extravascular BOLD signal changes, as well as signal modulation by intersubject differences in baseline physiology, such as haematocrit and oxygen extraction fraction, have so far been unexplored. In this study the effect of extravascular signal and intersubject physiological variability was investigated by simulating the hyperoxia CBVv experiment using a detailed BOLD signal model. This analysis revealed substantial uncertainty in the measurement of CBVv using the existing analysis based on dynamic contrast agent experiments. Instead, the modelling showed a simple and direct relationship between the BOLD signal change and CBVv, and an alternative analysis method with much reduced uncertainty was proposed based on this finding. Both methods were tested experimentally, with the new method producing results that are consistent with the limited literature in this area.

Figure 1

Simulation of the relationship between the measured signal and true CBVv for the existing (Eq. [10]) and new methods (Eq. [11]). Three different hyperoxia levels were simulated described by the change in arterial PO₂ (ΔPaO₂). The effect of variations in haematocrit (a,d) and OEF (b,e) alone, and in combination (c,f), are considered. A large amount of uncertainty is observed for the existing method suggesting that it cannot accurately account for physiological variability. By plotting the unnormalised tissue BOLD signal response a much tighter and approximately linear response is revealed.

Figure 2

Simulation of the relationship between the measured signal and true CBVv for the new method (Eq. [11]). (a) The effect caused by the distribution of vessel scales was examined by altering the fraction of the total CBV occupied by venous vessels (Ω_v), whilst keeping the combined capillary and venous fraction constant. (b) Hyperoxia has been shown to cause a reduction in CBF (ΔCBF), hence the effect of a 5% flow reduction was examined. (c) It has also been suggested that hyperoxia may alter resting CMRO₂. CMRO₂ changes of ±10% (ΔCMRO₂) were considered.

Figure 3

Maps of CBVv for the existing and new methods, calculated using Eq. [10] and [11] respectively, as a percentage of the total voxel volume. Note the difference in scaling between each of the methods; 0-16% versus 0-4%.