title: Interpreting therapeutic effect in multiple sclerosis via MRI contrast enhancing lesions: now you see them, now you don't.
abstract: Gadolinium (Gd) enhancement of multiple sclerosis (MS) lesions on MRI scans is a commonly used outcome measure in therapeutic trials. However, enhancement depends on MRI acquisition parameters that might significantly alter detectability. We investigated how the difference in blood-brain barrier (BBB) permeability threshold between MRI protocols affects lesion detection and apparent enhancement time using dynamic-contrast-enhanced (DCE) MRI. We examined fourty-four relapsing-remitting MS patients with two MRI protocols: 'standard sensitivity' (SS) (1.5 T, single-dose Gd) and 'high sensitivity' (HS) (3 T, triple-dose Gd, delayed acquisition). Eleven patients had at least one enhancing lesion and completed the 1-month follow-up. We acquired DCE-MRI during the HS protocol and calculated BBB permeability. Sixty-five lesions were enhanced with the SS vs. 135 with the HS protocol. The detection threshold of the HS was significantly lower than that of the SS protocol (K trans = 2.64 vs. 4.00E-3 min(-1), p < 0.01). Most lesions (74 %) were in the recovery phase; none were in the onset phase and 26 % were at the peak of enhancement. The estimated duration of detectability with the HS protocol was significantly longer than for the SS protocol (6-12 weeks vs. 3 weeks). Our observations on the protocol-dependent threshold for detection and time-course help explain discrepancies in the observed effects of anti-inflammatory therapies on MS lesions.
authors.affiliation: Montreal Neurological Institute, 3801 University St, WB325, Montreal, QC, H3A 2B4, Canada, ilana.leppert@mcgill.ca.
authors.forename: Ilana R
authors.initials: IR
authors.lastname: Leppert
authors.forename: S
authors.initials: S
authors.lastname: Narayanan
authors.forename: D
authors.initials: D
authors.lastname: Araújo
authors.forename: P S
authors.initials: PS
authors.lastname: Giacomini
authors.forename: Y
authors.initials: Y
authors.lastname: Lapierre
authors.forename: D L
authors.initials: DL
authors.lastname: Arnold
authors.forename: G B
authors.initials: GB
authors.lastname: Pike
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D003287:Contrast Media; D005260:Female; D005682:Gadolinium; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000188:drug therapy*; D059629:Signal-To-Noise Ratio; D055815:Young Adult
chemical_list: D003287:Contrast Media; D005682:Gadolinium