Before meaningful conclusions can be drawn from clinical measures of cerebral blood perfusion, the precision of the measurement must be determined and set in the context of inter-and intrasubject sources of variability. This work establishes the reproducibility of perfusion measurements using the noninvasive MRI technique of continuous arterial spin labeling (CASL). Perfusion was measured in 34 healthy normal subjects. Intersubject variability was assessed, and age and gender contributions were estimated. Intersubject variation was found to be large, with up to 100% perfusion difference for subjects of the same age and gender. Repeated measurements in one subject showed that perfusion remains remarkably stable in the short term when compared with intersubject variation and the large capacity for perfusion change in the brain. A significant decrease in the ratio of gray-matter to white-matter perfusion was found with increasing age (0.79% per year (P < 0.0005)). This appears to be due mainly to a reduction in gray-matter perfusion, which was found to decrease by 0.45% per year (P ‫؍‬ 0.04). Regional analysis suggested that the gray-matter age-related changes were predominantly localized in the frontal cortex. Whole-brain perfusion was 13% higher (P ‫؍‬ 0. Key words: cerebral perfusion; arterial spin labeling; reproducibility; age; gender Arterial spin labeling (ASL), a magnetic resonance imaging (MRI) technique for the measurement of cerebral perfusion, is increasingly being applied to the study of neurological disease. Its complete noninvasiveness and improved quantification is proving popular in comparison with the more standard technique of gadolinium bolus tracking. Since it is possible to perform repeat scanning with ASL, it can be used for functional imaging (1,2) and to monitor the course of perfusion changes in disease (3,4). The invasive nature of other perfusion techniques, such as PET and gadolinium contrast MRI, precludes the use of frequent repeat scanning in humans.It is important to determine the reproducibility of the ASL technique when interpreting measurements made with this technique, particularly serial measurements. Variability in perfusion estimates may be due to technical factors or physiological effects. In this work, continuous ASL (CASL) was used to measure perfusion in 34 normal healthy subjects, and repeat measurements in 10 subjects were used to establish the reproducibility of the technique. To determine the temporal stability of perfusion, a single subject was scanned repeatedly over the course of a day and a week, and five subjects were rescanned after several months. To our knowledge, this is the first study to explore this issue.The variation in both gray-and white-matter perfusion due to age and gender was also measured. Previous studies using positron emission tomography (PET) and single photon emission-computed tomography (SPECT) (5-12) found that gray-matter perfusion decreases with age. However, whether this is real or an artifactual decrease due to atrophy is unclear. Gende...

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Brain atrophy appears to occur in patients with multiple sclerosis (MS) in excess of that associated with normal ageing, and may be observed early in the clinical course of the disease. The dynamics and tissue specificity of this process remain unclear This preliminary study explored the evolution of brain grey matter (GM) and white matter (WM) volume loss (as fractions of total intracranial volumes) in 13 subjects with relapsing-remitting MS (mean disease duration 1.9 years at first scan), compared with nine normal control (NC) subjects. Subjects were scanned every six months for 18 months. In MS compared with NC subjects, significant differences in WM fractional volumes were observed at baseline (mean - 5.8%, P = 0.008) but no apparent progressive WM tissue loss was detected. In contrast, while no significant differences in GM fractional volumes were observed at baseline, there was significantly greater time-related volume loss in MS compared with NC subjects over the follow-up period (circa - 0.0086 per year in MS subjects, - 0.0021 per year in the NC subjects, difference P = 0.010). These results suggest that while both GM and WM atrophy are seen early in the clinical course of MS, they may not occur concurrently and may evolve at different rates.