Assessment of MRI scanner performance for preclinical functional studies
Merrifield, Gavin David
Functional Magnetic Resonance Imaging (fMRI) based studies are rapidly expanding in the field of preclinical research. The majority of these studies use Echo Planar Imaging (EPI) to measure Blood Oxygenation Level Dependent (BOLD) signal contrasts in the brain. In such studies the magnitude and statistical significances of these contrasts are then related to brain function and cognition. It is assumed that any observed signal contrast is ultimately due to differences in biological state and that scanner performance is stable and repeatable between subjects and studies. However, due to confounding issues introduced by in vivo subjects, little work has been undertaken to test this basic assumption. As the BOLD signal contrasts generated in such experiments are often very low, even small changes in scanner performance may dominate the BOLD contrast, distorting any biological conclusions drawn. A series of fMRI phantoms were produced to measure scanner performance independent of biological subjects. These phantoms produce specified signal contrast levels on demand during an fMRI scan by means of current-induced magnetic field gradients. These were used to generate data sets that emulated the BOLD signal contrast of in vivo imaging. Two studies examining scanner performance were then conducted on high-field preclinical MRI scanners. Firstly, in a longitudinal study on a single scanner, measurements were taken over a number of days across a week long period and then every two months over a year long period. Secondly, the behaviour of four preclinical scanners (three at 7T, one at 9.4T) was comparatively assessed. Measurements of several imaging parameters including contrast generated and functional contrast to noise ratio (fCNR) were obtained in both studies. If the scanners involved are truly comparable then they should generate similar measurement values. Across both studies parameter measurements showed significant differences for identical contrast settings on the phantom. Although signal contrast itself proved very comparable across the studies fCNR proved to be highly variable. As well as these measurements of longer tem behaviour proving variable, short and mid-term signal stability displayed a wide range of variability. Variations in the level and quality of both signal and noise were observed. Modelling of signal changes based on fundamental physical principles was also performed for comparison. The impact of these behaviours and variations on in vivo studies could result in skewed biological conclusions at any single site, with some sites exhibiting greater problems than others. The multisite results suggest potential difficulties when comparing biological conclusions between sites, even when using identical imaging parameters. In summary, these results suggest that a cautious approach should be taken with the conclusions of both fMRI and associated resting state connectivity studies that use EPI as their acquisition sequence. Improvements to both the experimental design of studies and regular quality monitoring of scanners should be undertaken to minimise these effects. Clinical MRI scanners should also be assessed for similar aberrations in behaviour.