Methodological issues in volumetric magnetic resonance imaging of the brain in the Edinburgh High Risk Project

The Edinburgh High Risk Project is a longitudinal study of brain structure (and function) in subjects at high risk of developing schizophrenia in the next 5-10 years for genetic reasons. In this article we describe the method s of volumetric analysis of structural magnetic resonance images used in th e study. We also consider potential sources of error in these methods: the validity of our image analysis techniques; inter- and intra-rater reliabili ty; possible positional variation; and thresholding criteria used in separa ting brain from cerebro-spinal fluid (CSF). Investigation with a phantom te st object (of similar imaging characteristics to the brain) provided eviden ce for the validity of our image acquisition and analysis techniques. Both inter- and intra-rater reliability were found to be good in whole brain mea sures but less so for smaller regions. There were no statistically signific ant differences in positioning across the three study groups (patients with schizophrenia, high risk subjects and normal volunteers). A new technique for thresholding MRI scans longitudinally is described (the 'rescale' metho d) and compared with our established method (thresholding by eye). Few diff erences between the two techniques were seen at 3- and 6-month follow-up. T hese findings demonstrate the validity and reliability of the structural MR I analysis techniques used in the Edinburgh High Risk Project, and highligh t methodological issues of general concern in cross-sectional and longitudi nal studies of brain structure in healthy control subjects and neuropsychia tric populations. (C) 1999 Elsevier Science Ireland Ltd. All rights reserve d.