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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Vascular and angiogenic processes provide an important target for novel cancer therapeutics. Dynamic contrast-enhanced magnetic resonance imaging is being used increasingly to noninvasively monitor the action of these therapeutics in early-stage clinical trials. This publication reports the outcome of a workshop that considered the methodology and design of magnetic resonance studies, recommending how this new tool might best be used.

Purpose: To investigate the relationship of myelin content, axonal density, and gliosis with the fraction of macromolecular protons (f B ) and T 2 relaxation of the macromolecular pool (T 2B ) acquired using quantitative magnetization transfer (qMT) MRI in postmortem brains of subjects with multiple sclerosis (MS). Conclusion: f B in MS WM is dependent on myelin content and may be a tool to monitor patients with this condition. Materials and Methods

Magnetic resonance imaging (MRI) is being used to probe the central nervous system (CNS) of patients with multiple sclerosis (MS), a chronic demyelinating disease. Conventional T2-weighted MRI (cMRI) largely fails to predict the degree of patients' disability. This shortcoming may be due to poor specificity of cMRI for clinically relevant pathology. Diffusion tensor imaging (DTI) has shown promise to be more specific for MS pathology. In this study we investigated the association between histological indices of myelin content, axonal count and gliosis, and two measures of DTI (mean diffusivity [MD] and fractional anisotropy [FA]), in unfixed post mortem MS brain using a 1.5-T MR system. Both MD and FA were significantly lower in post mortem MS brain compared to published data acquired in vivo. However, the differences of MD and FA described in vivo between white matter lesions (WMLs) and normal-appearing white matter (NAWM) were retained in this study of post mortem brain: average MD in WMLs was 0.35 × 10− 3 mm2/s (SD, 0.09) versus 0.22 (0.04) in NAWM; FA was 0.22 (0.06) in WMLs versus 0.38 (0.13) in NAWM. Correlations were detected between myelin content (Trmyelin) and (i) FA (r = − 0.79, p < 0.001), (ii) MD (r = 0.68, p < 0.001), and (iii) axonal count (r = − 0.81, p < 0.001). Multiple regression suggested that these correlations largely explain the apparent association of axonal count with (i) FA (r = 0.70, p < 0.001) and (ii) MD (r = − 0.66, p < 0.001). In conclusion, this study suggests that FA and MD are affected by myelin content and – to a lesser degree – axonal count in post mortem MS brain.

Serial proton magnetic resonance spectroscopy (MRS), was carried out at 1-2 monthly intervals on eight patients with multiple sclerosis who presented with evidence of a large acute cerebral white matter lesion. An MRS was obtained from acute lesions (volumes of interest 4-12 ml), which at presentation showed gadolinium-diethylenetriamine penta-acetic acid enhancement, and from similar volumes of normal appearing white matter lateral to the lesion and nearer the scalp. Follow-up ranged from 4 to 9 months (mean 6 months). Short echo spectra from acute enhancing lesions invariably showed the presence of large resonances at 0.9 and 1.3 p.p.m. compared with normal appearing white matter and healthy age matched controls, indicating that these peaks were not the result of voxel contamination from scalp fat. These resonances, which probably represent lipid products of myelin breakdown, were detected in lesions which had been enhancing for < 1 month and remained elevated for a mean of 5 months (range 4-8 months). The results provide evidence that short echo proton MRS can detect myelin breakdown products and that myelin breakdown occurs during the initial inflammatory stage of lesion development. The ratio of N-acetylaspartate (NAA) (a neuronal marker) relative to creatine was reduced in acute lesions and in normal appearing white matter. In six of the lesions studied there was, however, a subsequent rise in the NAA/creatine ratio indicating that axonal loss is not the only mechanism of reduction in the NAA/creatine ratio.

From an extensive serial magnetic resonance imaging (MRI) study in multiple sclerosis (MS) we have identified 4 cases in which disruption of the blood-brain barrier, as detected by gadolinium-DTPA enhancement, preceded other MRI abnormalities and in 1 case clinical evidence of the new lesion. This supports the view that a defect in the blood-brain barrier, and therefore inflammation, is an early and possibly crucial event in the pathogenesis of the new lesion in MS. These cases showed a marked discrepancy between MRI abnormality and symptoms. The mechanisms contributing to this disparity are discussed, and it is concluded that far from being surprising it is to be expected.

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