title: Increased cortical grey matter lesion detection in multiple sclerosis with 7 T MRI: a post-mortem verification study.
abstract: The relevance of cortical grey matter pathology in multiple sclerosis has become increasingly recognized over the past decade. Unfortunately, a large part of cortical lesions remain undetected on magnetic resonance imaging using standard field strength. In vivo studies have shown improved detection by using higher magnetic field strengths up to 7 T. So far, a systematic histopathological verification of ultra-high field magnetic resonance imaging pulse sequences has been lacking. The aim of this study was to determine the sensitivity of 7 T versus 3 T magnetic resonance imaging pulse sequences for the detection of cortical multiple sclerosis lesions by directly comparing them to histopathology. We obtained hemispheric coronally cut brain sections of 19 patients with multiple sclerosis and four control subjects after rapid autopsy and formalin fixation, and scanned them using 3 T and 7 T magnetic resonance imaging systems. Pulse sequences included T1-weighted, T2-weighted, fluid attenuated inversion recovery, double inversion recovery and T2*. Cortical lesions (type I-IV) were scored on all sequences by an experienced rater blinded to histopathology and clinical data. Staining was performed with antibodies against proteolipid protein and scored by a second reader blinded to magnetic resonance imaging and clinical data. Subsequently, magnetic resonance imaging images were matched to histopathology and sensitivity of pulse sequences was calculated. Additionally, a second unblinded (retrospective) scoring of magnetic resonance images was performed. Regardless of pulse sequence, 7 T magnetic resonance imaging detected more cortical lesions than 3 T. Fluid attenuated inversion recovery (7 T) detected 225% more cortical lesions than 3 T fluid attenuated inversion recovery (Z = 2.22, P < 0.05) and 7 T T2* detected 200% more cortical lesions than 3 T T2* (Z = 2.05, P < 0.05). Sensitivity of 7 T magnetic resonance imaging was influenced by cortical lesion type: 100% for type I (T2), 11% for type II (FLAIR/T2), 32% for type III (T2*), and 68% for type IV (T2). We conclude that ultra-high field 7 T magnetic resonance imaging more than doubles detection of cortical multiple sclerosis lesions, compared to 3 T magnetic resonance imaging. Unfortunately, (subpial) cortical pathology remains more extensive than 7 T magnetic resonance imaging can reveal.
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, The Netherlands i.kilsdonk@vumc.nl.
authors.forename: Iris D
authors.initials: ID
authors.lastname: Kilsdonk
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Jonkman
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Klaver
authors.affiliation: Department of Neurology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Susanne J
authors.initials: SJ
authors.lastname: van Veluw
authors.affiliation: Department of Radiology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Jaco J M
authors.initials: JJ
authors.lastname: Zwanenburg
authors.affiliation: Department of Physics and Medical Technology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Joost P A
authors.initials: JP
authors.lastname: Kuijer
authors.affiliation: Department of Physics and Medical Technology, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Petra J W
authors.initials: PJ
authors.lastname: Pouwels
authors.affiliation: Department of Epidemiology and Biostatistics, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Jos W R
authors.initials: JW
authors.lastname: Twisk
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Mike P
authors.initials: MP
authors.lastname: Wattjes
authors.affiliation: Department of Neurology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Luijten
authors.affiliation: Department of Radiology and Nuclear Medicine, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.affiliation: Department of Anatomy and Neurosciences, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Jeroen J G
authors.initials: JJ
authors.lastname: Geurts
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000473:pathology; D059906:Neuroimaging / Q000379:methods; D012189:Retrospective Studies
keywords: 7 Tesla MRI; cortical lesions; histopathology; multiple sclerosis; subpial demyelination; ultrahigh field MRI