Comparison of cerebral blood flow measurement with [15O]-water positron emission tomography and arterial spin labeling magnetic resonance imaging: A systematic review

Abstract

Noninvasive imaging of cerebral blood flow provides critical information to understand normal brain physiology as well as to identify and manage patients with neurological disorders. To date, the reference standard for cerebral blood flow measurements is considered to be positron emission tomography using injection of the [(15)O]-water radiotracer. Although [(15)O]-water has been used to study brain perfusion under normal and pathological conditions, it is not widely used in clinical settings due to the need for an on-site cyclotron, the invasive nature of arterial blood sampling, and experimental complexity. As an alternative, arterial spin labeling is a promising magnetic resonance imaging technique that magnetically labels arterial blood as it flows into the brain to map cerebral blood flow. As arterial spin labeling becomes more widely adopted in research and clinical settings, efforts have sought to standardize the method and validate its cerebral blood flow values against positron emission tomography-based cerebral blood flow measurements. The purpose of this work is to critically review studies that performed both [(15)O]-water positron emission tomography and arterial spin labeling to measure brain perfusion, with the aim of better understanding the accuracy and reproducibility of arterial spin labeling relative to the positron emission tomography reference standard.

Keywords: Cerebral blood flow; arterial spin labeling; magnetic resonance imaging; perfusion imaging; positron emission tomography.

Figure 1.

Schematic of CBF quantification challenges with ASL MRI. ASL issues related to assumed constants are shown on the left (gray boxes), including the T₁ transition of label from blood to tissue, the labeling efficiency α, and the T₁ relaxation of arterial blood. ASL issues related to imaging parameters selected by the user are shown on the right (white boxes), including the post-label delay, use of crusher gradients, and labeling duration. ASL: arterial spin labeling; MRI: magnetic resonance imaging.

Figure 2.

Mean baseline cerebral blood flow (ml/100 g/min) measured by ASL MRI and [¹⁵O]-water PET in comparative studies across the (a) whole brain and (b) the gray matter. Studies are grouped based on the variant of ASL used for comparison against the PET gold standard. Error bars are estimated 95% confidence intervals that account for the sample size of each study. The solid blue line represents the mean PET CBF values and the dotted gray line represents the mean ASL CBF values across the studies. For each study, the MRI values were also normalized (blue crosses) using the one-compartment model with standardized values for assumed ASL constants in Alsop et al. ASL: arterial spin labeling; MRI: magnetic resonance imaging; PET: positron emission tomography; CBF: cerebral blood flow.

Figure 3.

Mean CBF maps across 16 healthy volunteers measured by (a) [¹⁵O]-water PET, (b) pseudo-continuous ASL (pcASL), and (c) pcASL with MRI crusher gradients. Voxel-wise statistical parametric testing (P < 0.001) reveals areas in which pcASL overestimates (red) or underestimates (blue) quantitative CBF relative to PET (d,e). This analysis revealed systematic overestimation of pcASL CBF in deep cortical tissues and systematic underestimation in the prefrontal area, basal nuclei, and near the sagittal sinus. The difference between rows (d) and (e) reveal that additional crusher gradients in the pcASL MRI sequence reduces the areas of overestimation. Source: reproduced with permission from Elsevier, 2014. ASL: arterial spin labeling; MRI: magnetic resonance imaging; PET: positron emission tomography; CBF: cerebral blood flow.

Figure 4.

Pearson correlation coefficient (R²) between [¹⁵O]-water PET and ASL MRI perfusion measurements reported in comparison studies, plotted against the time elapsed between the PET and MRI scans. Correlations are presented for both absolute and relative CBF metrics, as well as for healthy volunteers (green) and patient populations (gray). Across studies, Spearman rank correlation revealed an inverse relationship between the reported R² values and the elapsed time (ρ = −0.77, P = 0.003). ASL: arterial spin labeling; MRI: magnetic resonance imaging; PET: positron emission tomography; CBF: cerebral blood flow.

Figure 5.

Multi-delay ASL images from a patient with unilateral Moyamoya disease of the right hemisphere. Perfusion images are shown for different PLD times; note that signal decays with increasing PLD, as expected. Arrows indicate areas of low ASL signal on images collected with short PLD times. The multi-delay ASL scans revealed long ATT in these same regions of the occluded hemisphere, suggesting that for PLD = 700 or 1300 ms, not enough time has elapsed for the label to travel through collateral vessels and fully arrive to the imaging volume. If a single-delay ASL technique had been used, inappropriate choice of PLD may have led to CBF underestimation in the symptomatic hemisphere. However, multi-delay ASL imaging indicates that perfusion is preserved in the symptomatic relative to the normal-appearing hemisphere (middle panel). ASL: arterial spin labeling; CBF: cerebral blood flow. PLD: post-label delay; ATT: arterial transit time.

Figure 6.

The COV (%) for (a) scan–rescan reproducibility and (b) and between-subject variations in healthy volunteers across CBF studies. The COV values are shown for studies that performed only ASL, only PET, or both modalities (center). Scan–rescan reproducibility was typically determined from the same imaging session, except in one study in which ASL scans were separated by up to 4 weeks. The solid blue lines represent the mean COV for MRI measurements, whereas the dotted gray lines represent the mean COV for PET measurements across the studies. References for each numbered study are presented in Appendix 1. COV: coefficient of variation; ASL: arterial spin labeling; MRI: magnetic resonance imaging; PET: positron emission tomography; CBF: cerebral blood flow.