title: Sensitivity of contrast enhanced MRI in multiple sclerosis. Effects of gadolinium dose, magnetization transfer contrast and delayed imaging.
abstract: Although clinical end points remain the definitive measure of therapeutic efficacy in multiple sclerosis, more sensitive markers of disease activity are required to screen potential disease-modifying agents. The use of gadolinium contrast-media in MRI studies increases both the reliability and sensitivity of detecting active lesions in multiple sclerosis. We studied three potential methods for further improving sensitivity; the use of 0.3 mmol/kg (triple dose) gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA), magnetization transfer (MT) contrast imaging and the introduction of a delay between contrast-medium injection and imaging. Fifty patients were studied (seven with benign, 14 with relapsing-remitting, 10 with secondary progressive, 16 with primary progressive and three with transitional multiple sclerosis). Imaging was performed on two occasions, 24-72 h apart, with triple- and single-dose Gd-DTPA. Pairs of contrast-enhanced T 1-weighted studies, with and without MT, were obtained at three different times, i.e. within early (0-20 min), short-delay (20-40 min) and long-delay (40-60 min) time-windows. Nineteen patients did not have the full complement of studies. Seven patients suffered minor self-limiting adverse events possibly related to triple-dose Gd-DTPA. Overall, triple-dose Gd-DTPA resulted in a 75% increase in the number of enhancing lesions detected compared with the single dose (P < 0.002). The use of MT or delay alone did not significantly increase the sensitivity of either single- or triple-dose studies. The combination of MT and short delay increased the number of enhancing lesions detected with single-dose Gd-DTPA by 47% (P < 0.05) and with triple-dose Gd-DTPA by 27% (P < 0.01). Detection was not significantly further improved by a long delay. The most sensitive modality was MT imaging with a long delay following triple-dose Gd-DTPA, resulting in the detection of 126% more enhancing lesions than in standard single-dose imaging (P < 0.05). This applies to all subgroups except for primary progressive multiple sclerosis, in which none of these methods alone or in combination improved the sensitivity. We conclude that for relapsing-remitting and secondary progressive multiple sclerosis, the combination of triple-dose Gd-DTPA and delayed MT imaging more than doubles the sensitivity to contrast-enhancing lesions.
authors.affiliation: NMR Research Unit, Institute of Neurology, London, UK.
authors.forename: N C
authors.initials: NC
authors.lastname: Silver
authors.forename: C D
authors.initials: CD
authors.lastname: Good
authors.forename: G J
authors.initials: GJ
authors.lastname: Barker
authors.forename: D G
authors.initials: DG
authors.lastname: MacManus
authors.forename: A J
authors.initials: AJ
authors.lastname: Thompson
authors.forename: I F
authors.initials: IF
authors.lastname: Moseley
authors.forename: W I
authors.initials: WI
authors.lastname: McDonald
authors.forename: D H
authors.initials: DH
authors.lastname: Miller
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D003287:Contrast Media / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005682:Gadolinium / Q000008:administration & dosage*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D003287:Contrast Media; D005682:Gadolinium