On the sensitivity of ASL MRI in detecting regional differences in cerebral blood flow

Arterial-spin-labeling (ASL) magnetic resonance imaging (MRI) provides a noninvasive tool to measure cerebral blood flow (CBF) and is increasingly used as a surrogate for baseline neural activity. However, the power of ASL MRI in detecting CBF differences between patient and control subjects is hampered by inter-subject variations in global CBF, which are associated with non-neural factors and may contribute to the noise in the across-group comparison. Here, we investigated the sensitivity of this technique and proposed a normalization strategy to better detect such a difference. A “model” situation was employed in which two visual stimuli (i.e. cross fixation and flashing checkerboard) were presented to two groups of subjects to mimic “control” and “patient” groups (N=7 for each group), respectively. It was found that absolute CBF (aCBF) in the occipital lobe in the checkerboard group was 26.0% greater compared to the fixation group, but the level of significance was modest (P=.03). In contrast, when normalizing the CBF with whole-brain CBF or CBF in a reference region [termed relative CBF (rCBF)], the statistical significance was improved considerably (P<.003). For voxel-based analysis, the rCBF indices correctly detected CBF differences in the occipital lobe in the across-group comparison, while aCBF failed to detect any significant cluster using the same statistical threshold. We also performed Monte Carlo simulation to confirm the experimental findings and found that the power improvement was most pronounced when signal-to-noise-ratio is moderate and the underlying CBF difference was small. The simulation also showed that, with the proposed normalization, a detection power of 80% can be achieved using a sample size of about 20. In summary, rCBF is a more sensitive index to detect small differences in CBF, rather than the much-sought-after aCBF, since it reduces data noise caused by inter-subject variations in global CBF.     

Effect of high dose isoflurane on cerebral blood flow in macaque monkeys

The effect of high dose isoflurane on cerebral blood flow (CBF) was investigated in adult macaque monkeys receiving 1% to 2% isoflurane with the pseudo continuous arterial-spin-labeling (pCASL) MRI technique. High concentration (2%) of isoflurane resulted in significant increase in the mean CBF of the global, cortical, subcortical regions and the regional CBF in all subcortical structures and most cortical structures (such as motor cortex, anterior cingulate cortex, but not media prefrontal cortex). In addition, the changes of regional CBF in the affected regions correlated linearly with increasing isoflurane concentrations. The study demonstrates region-specific CBF abnormal increase in adult macaque monkeys under high dose (2%) isoflurane and suggests that the brain functionality in the corresponding structures may be affected and need to be taken consideration in either human or non-human primate neuroimaging studies.