Quantitative functional magnetic resonance imaging of brain activity using bolus-tracking arterial spin labeling

Abstract

Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) is the most widely used method for mapping neural activity in the brain. The interpretation of altered BOLD signals is problematic when cerebral blood flow (CBF) or cerebral blood volume change because of aging and/or neurodegenerative diseases. In this study, a recently developed quantitative arterial spin labeling (ASL) approach, bolus-tracking ASL (btASL), was applied to an fMRI experiment in the rat brain. The mean transit time (MTT), capillary transit time (CTT), relative cerebral blood volume of labeled water (rCBV(lw)), relative cerebral blood flow (rCBF), and perfusion coefficient in the forelimb region of the somatosensory cortex were quantified during neuronal activation and in the resting state. The average MTT and CTT were 1.939+/-0.175 and 1.606+/-0.106 secs, respectively, in the resting state. Both times decreased significantly to 1.616+/-0.207 and 1.305+/-0.201 secs, respectively, during activation. The rCBV(lw), rCBF, and perfusion coefficient increased on average by a factor of 1.123+/-0.006, 1.353+/-0.078, and 1.479+/-0.148, respectively, during activation. In contrast to BOLD techniques, btASL yields physiologically relevant indices of the functional hyperemia that accompanies neuronal activation.

Figure 1

(A) ASL perfusion map acquired during electrical stimulation of the forepaw of animal 1. The corresponding increase in cerebral perfusion in the right somatosensory cortex can be clearly identified. (B) ASL perfusion map acquired in resting state (control). ASL perfusion maps for animals 2–5 can be found in Supplementary Figure 1.

Figure 2

Least-squares fit of ASL data (yellow and red asterisks for control and activation experiments, respectively) to theoretical model (blue and green solid lines for control and activation experiments, respectively) for the left S1FL of animal 1. LSF results for animals 2–5 can be found in Supplementary Figure 2.

Figure 3

Variation in ASL signal in the activated left S1FL region during 60 secs stimulation of the right forepaw animal 1 to 5.

Figure 4

Pixelwise maps of the MTT, CTT, and rCBV_lw of animal 1 during neuronal activation (A, C, E) and in the resting state (B, D, F). The color bars are in units of time (s) for the MTT and CTT maps and in arbitrary units (a.u.) for the rCBV_lw maps. The decrease in both the MTT and CTT and the increase in rCBV_lw can be clearly identified in the activated S1FL region.

Figure 5

(A) Change in MTT, (B) CTT, and (C) rCBV_lw during neuronal activation. A statistically significant decrease in both transit times and a statistically significant increase in rCBV_lw was measured in the activated S1FL when compared with the same S1FL region in the control experiment (two-tailed paired t-test: P=0.0012 for MTT, P=0.0082 for CTT and, P=0.0026 for rCBV_lw). The error bars represent one standard deviation from the mean.