Estimation of water extraction fractions in rat brain using magnetic resonance measurement of perfusion with arterial spin labeling

Abstract

The model used for calculating perfusion by MRI techniques that use endogenous water as a tracer assumes that arterial water is a freely diffusible tracer. Evidence shows that this assumption is not valid in the brain at high blood flow rates, at which movement of water into and out of the microvasculature becomes limited by diffusion across the blood-brain barrier. In this work, the arterial spin-labeling technique is used to show that fraction of arterial water that is dependent on blood flow rate remains in the vasculature and does not exchange with brain tissue water. By using perfusion measurements without and with magnetization transfer (MT) effects, one can distinguish arterial label that exchanges into tissue because blood has much smaller MT than brain tissue. Using this technique, the extraction fraction for water is measured in the rat brain at various cerebral blood flow rates. At high flow rates (approximately 5 ml/g/min), the extraction fraction for water is found to be about 45% in rat brain. Disruption of the blood-brain barrier with D-mannitol caused an increase in the extraction fraction for water. It was possible to form an image related to the extraction fraction for water. The ability to estimate the amount of vascular water exchanging with tissue water by MRI may represent a noninvasive approach to detect the integrity of the blood-brain barrier.

Quantification of rodent cerebral blood flow (CBF) in normal and high flow states using pulsed arterial spin labeling magnetic resonance imaging

“…This was corroborated by the fact that fitting of all ASL data (acquired at TIs from 0.3 to three seconds) with a CBF Ն 100 ml/100 g/minute was only successful if additional variables: 1) extraction fraction (E), and 2) outflow (T out ) time were included. Although there is a wide range of published values for E and T out (16,17,27), and the uncertainty in these estimates is high, it should be noted that in our study E is comparatively low and T out is quite large. Establishing more accurate estimates of these parameters would be an interesting goal for future studies.…”

Single‐coil arterial spin‐tagging for estimating cerebral blood flow as viewed from the capillary: Relative contributions of intra‐ and extravascular signal

“…(An additional sink may be the loss of inverted protons via flow-through to the muscular venules and venous collection vessels.) Previous theoretical treatments (1,12,13,17,22,28) have found that the product of flow and the effective T 1 (T 1eff ) is proportional to the difference in equilibrium magnetization between the label condition (inversion plane in the neck) and the control condition (inversion plane above the head):…”

“…[1] and [13] express essentially the same relationship, to wit: with instantaneous equilibration of microvascular protons and tissue protons, the population of inverted protons in the tissue is proportional to the product of flow and T 1sat .…”

“…A systematic underestimation of CBF becomes sizable and obvious in humans and experimental animals when flow is elevated (8 -10), but is not evident in the steady-state AST technique (1). It is not clear that this apparently linear relationship between single-coil AST contrast and CBF has been explained by theoretical studies (11)(12)(13)(14)(15)(16)(17)(18). Most of these treatments start from the Bloch equations modified for the effect of flow (1) and from there consider the effects of magnetization transfer (17,18).…”

“…Indeed, Silva et al (13) considered the effect of diffusion-limitation of water at the capillary-brain interface but have done so without including the question of the mean transit time of the arterially inverted water through the microvascular bed, which includes both the entry of the signal into the extravascular space as well as its passage through capillaries and pericytic venules. Since the T 1 of capillary blood may be four times greater than that of the tissue under the conditions of the experiment, this omission can have an important consequence.…”