Contributions
Abstract: P525
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: In the BECOME study 75 multiple sclerosis (MS) (61 relapsing-remitting and 14 clinically isolated syndromes) received monthly triple dose (3-dose) gadopentetate dimeglumine at a high, off-label, 0.3 mmol/kg dosage for up to 26 consecutive months. The clinical outcomes of the study have been reported. Recently, Kanda et al. (Radiology, 2014) and others have described a phenomenon of long-term Gadolinium (Gd) deposition in the dentate nucleus that manifest as hyperintensity on noncontrast T1 weighted (T1w) images, a poorly understood and possibly concerning phenomenon. To date, studies of Gd deposition had inconsistent dosing.
Purpose: Our purpose was to study the “MRI pharmacokinetics” of Gd deposition in the dentate nucleus in a randomly selected cohort of 15 subjects with MS, each of whom had systematically received 14 consecutive monthly 3-doses of Gd.
Methods: The precontrast T1w images of 15 randomly selected patients with MS scanned monthly before & after monthly 3-dose of Gadopentetate Dimeglumine for 14 consecutive months was analysed. Screening scans were obtained without 3-dose Gd, the Month 13 scans were obtained 1 month after the 13th monthly 3-doses (39 dose equivalents). Pre-contrast T1w images were acquired with consistent voxel size, TR, TE, & angulation. The screening and longitudinal T1w images were corrected for MRI coil induced intensity inhomogeneities. Automatic segmentation of the dentate nuclei was performed by non-rigidly registering a cerebellar atlas to the screening scans. The longitudinal T1 scans were spatially aligned to the screening scans using an affine registration method, and their intensities were also normalised to the screening scan using a histogram normalisation method. The mean T1 intensities within the dentate nuclei were used from each longitudinal scan for the Gd dose-dependent trend and correlation analysis using Spearman"s rank correlation.
Results: The mean intensities in the 30 dentate nuclei showed a progressive increasing trend of hyperintensity on pre-contrast T1w images from screening to the fourteenth month. The dose-dependent relationship between T1 hyperintensity and number of triple-doses showed a positive correlation
(>0.6, p< 0.05).
Conclusion: Monthly administration of triple-dose Gadopentetate Dimeglumine over fourteen months is associated with Gd deposition, which progressively increases with subsequent doses.
Disclosure:
The BECOME study was supported by a grant from Bayer Healthcare Pharmaceuticals, but was initiated by & the intellectual property of the investigators.
Leo Wolansky: nothing to disclose.
Jhimli Mitra: nothing to disclose.
Paul A. DiCamillo: nothing to disclose
Stuart Cook: nothing to disclose
Diego Cadavid: nothing to disclose
Tyler Richards: nothing to disclose
Robert T Naismith: Consulting: Alkermes, Acorda, Bayer, Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, Novartis, Pfizer, Teva.
Speaking: Acorda, Biogen, Genzyme.
Samantha Lancia: nothing to disclose
Pallavi Tiwari: nothing to disclose
Abstract: P525
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: In the BECOME study 75 multiple sclerosis (MS) (61 relapsing-remitting and 14 clinically isolated syndromes) received monthly triple dose (3-dose) gadopentetate dimeglumine at a high, off-label, 0.3 mmol/kg dosage for up to 26 consecutive months. The clinical outcomes of the study have been reported. Recently, Kanda et al. (Radiology, 2014) and others have described a phenomenon of long-term Gadolinium (Gd) deposition in the dentate nucleus that manifest as hyperintensity on noncontrast T1 weighted (T1w) images, a poorly understood and possibly concerning phenomenon. To date, studies of Gd deposition had inconsistent dosing.
Purpose: Our purpose was to study the “MRI pharmacokinetics” of Gd deposition in the dentate nucleus in a randomly selected cohort of 15 subjects with MS, each of whom had systematically received 14 consecutive monthly 3-doses of Gd.
Methods: The precontrast T1w images of 15 randomly selected patients with MS scanned monthly before & after monthly 3-dose of Gadopentetate Dimeglumine for 14 consecutive months was analysed. Screening scans were obtained without 3-dose Gd, the Month 13 scans were obtained 1 month after the 13th monthly 3-doses (39 dose equivalents). Pre-contrast T1w images were acquired with consistent voxel size, TR, TE, & angulation. The screening and longitudinal T1w images were corrected for MRI coil induced intensity inhomogeneities. Automatic segmentation of the dentate nuclei was performed by non-rigidly registering a cerebellar atlas to the screening scans. The longitudinal T1 scans were spatially aligned to the screening scans using an affine registration method, and their intensities were also normalised to the screening scan using a histogram normalisation method. The mean T1 intensities within the dentate nuclei were used from each longitudinal scan for the Gd dose-dependent trend and correlation analysis using Spearman"s rank correlation.
Results: The mean intensities in the 30 dentate nuclei showed a progressive increasing trend of hyperintensity on pre-contrast T1w images from screening to the fourteenth month. The dose-dependent relationship between T1 hyperintensity and number of triple-doses showed a positive correlation
(>0.6, p< 0.05).
Conclusion: Monthly administration of triple-dose Gadopentetate Dimeglumine over fourteen months is associated with Gd deposition, which progressively increases with subsequent doses.
Disclosure:
The BECOME study was supported by a grant from Bayer Healthcare Pharmaceuticals, but was initiated by & the intellectual property of the investigators.
Leo Wolansky: nothing to disclose.
Jhimli Mitra: nothing to disclose.
Paul A. DiCamillo: nothing to disclose
Stuart Cook: nothing to disclose
Diego Cadavid: nothing to disclose
Tyler Richards: nothing to disclose
Robert T Naismith: Consulting: Alkermes, Acorda, Bayer, Biogen, EMD Serono, Genentech, Genzyme, Mallinckrodt, Novartis, Pfizer, Teva.
Speaking: Acorda, Biogen, Genzyme.
Samantha Lancia: nothing to disclose
Pallavi Tiwari: nothing to disclose