title: Interscanner variation in brain MRI lesion load measurements in MS: implications for clinical trials.
abstract: We evaluated the effect of interscanner variation on brain MRI-measured lesion volumes and measurement reproducibility in MS. Twenty clinically definite MS patients were each scanned on two or three scanners (a total of 14 scanners were used). In addition, a formalin-fixed MS brain was studied on eight scanners from different manufacturers and with different field strengths. For the formalin-fixed MS brain, on each machine we obtained two scans with slice thicknesses of 5 and 3 mm. Only 5-mm-thick slices were obtained from patients. The lesion volume present on each scan was evaluated three times by a single observer in random order, using a local thresholding technique. In two groups of eight patients scanned on machines with different field strengths, the mean lesion volumes present on scans obtained at 1.5 T were significantly higher than those measured on scans obtained with machines operating at 0.5 and 1.0 T (p < 0.01). When a single observer repeatedly evaluated the same scan, a median introbserver agreement of 98.7% (95% CI, 97.9 to 99.1) was achieved. However, when the observer evaluated the scans from different MRI scanners, the agreement (an interscanner agreement) fell to 91.1% (CI, 90.2 to 94.1). When only scanners operating at 1.5 T were considered, the median interscanner agreement was 96.7% (CI, 95 to 97.5). Also, for the formalin-fixed MS brain, the intraobserver agreements obtained with both slice thicknesses were significantly higher than the corresponding interscanner agreements. The interscanner agreement, but not the intraobserver agreement, obtained with a slice thickness of 3 mm was higher than that obtained with a slice thickness of 5 mm. Our results indicate that lesion volume measurements in MS are influenced significantly by the use of different MR scanners and that a patient included in a serial study should be always scanned with the same MR machine using 3-mm thick slices.
authors.affiliation: Department of Neurology, Scientific Institute Ospedale San Raffaele, University of Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Filippi
authors.forename: J H
authors.initials: JH
authors.lastname: van Waesberghe
authors.forename: M A
authors.initials: MA
authors.lastname: Horsfield
authors.forename: S
authors.initials: S
authors.lastname: Bressi
authors.forename: C
authors.initials: C
authors.lastname: Gasperini
authors.forename: T A
authors.initials: TA
authors.lastname: Yousry
authors.forename: M L
authors.initials: ML
authors.lastname: Gawne-Cain
authors.forename: S P
authors.initials: SP
authors.lastname: Morrissey
authors.forename: M A
authors.initials: MA
authors.lastname: Rocca
authors.forename: F
authors.initials: F
authors.lastname: Barkhof
authors.forename: G J
authors.initials: GJ
authors.lastname: Lycklama à Nijeholt
authors.forename: S
authors.initials: S
authors.lastname: Bastianello
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
mesh_terms: D000328:Adult; D016477:Artifacts; D001921:Brain / Q000473:pathology*; D002986:Clinical Trials as Topic; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000295:instrumentation*; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis*; D015588:Observer Variation; D015203:Reproducibility of Results
chemical_list: D005404:Fixatives; D005557:Formaldehyde