Contributions
Abstract: 25
Type: Young Scientific Investigators' Session
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: The European medicines agency recently restricted the use of linear gadolinium-based contrast agents (GBCA) in body scans 1. The reason is the novel finding of signal intensity change in unenhanced T1 weighted (T1w) images in the dentate nucleus (DN) and other brain regions after several applications of GBCA. Evidence suggests that such changes relate more to linear chelate GBCA than to macrocyclic GBCA.
Purpose: To assess the association between GBCA chelate type (linear vs. macrocyclic, i.e. gadopentetic vs gadoteric acid) and signal intensity change in the DN in MS patients in a large cohort over several years.
Methods: We analyzed serial T1w images in 881 MS patients with repeated GBCA application (EDSS: 1.61 +/- 1.63; diagnosis: 76% RRMS; 16% CIS, 4% SPMS, 2% PPMS, 1% NNO, 1% RIS. Mean number of applications per person was = 5.4 (+/- 3.9) linear and 0.8 (+/- 0.9) macrocyclic GBCA. Mean interval between first and last GBCA application was 3.6 years, 830 patients received at least one linear and 407 at least one macrocyclic GBCA application (including 51 patients with macrocyclic GBCA application only). T1w images were preprocessed and normalized. DN was defined by a publicly available atlas (SUIT, FSL). After visual exclusion of white matter lesions, control points were defined by MNI coordinates in the pons and smoothed with a 5 mm Gaussian Kernel. For statistical analysis of the unenhanced T1w signal, dentate nucleus -to-pons ratio (DN/P) was calculated. DN/P differences of all pairs of subsequent time points were calculated, averaged over each subject and attributed to either linear or macrocyclic GBCA according to the previous administration. In a two sample t-test, individual DN/P differences were compared between linear and macrocyclic GBCA administrations.
Results: DN/P increase was only observed after administration of linear GBCA with a significant difference in DN/P change compared to macrocyclic GBCA administrations (p < .001).
Conclusion: Our results are in line with previous reports that linear but not macrocyclic GBCA accumulate in the DN.
References
1. Agency EM. PRAC confirms restrictions on the use of linear gadolinium agents.
2017.
Disclosure: This work was funded by the 'German Competence Network Multiple Sclerosis' (German Ministry for Research and Education, grant 01GI1604A).
S. Grahl has nothing to disclose.
M. Bussas has nothing to disclose.
C. Gasperi has nothing to disclose.
V. Pongratz has received research support from Novartis (Oppenheim Förderpreis) and intramural funding from the Technical University of Munich (KKF grant).
M.-M. Hoshi reports a travel grant from Bayer Health Care for participation in the annual Meeting of German Neurologic Society 2016.
A. Berthele reports personal fees from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi Genzyme, and Teva, and compensations for clinical trials from Alexion Pharmaceuticals, Biogen, Novartis, Genzyme, Roche, and Teva - all outside the submitted work.
J. Kirschke has received research funding from the European Research Council and the German Research Foundation, travel support from Kaneka Europe as well as speaker honoraria from Philips Healthcare; all not related to this work.
C. Zimmer has nothing to disclose.
B. Hemmer has served on scientific advisory boards for F. Hoffmann-La Roche Ltd, Novartis, Bayer AG, and Genentech; he has served as DMSC member for AllergyCare and TG Therapeutics; he or his institution have received speaker honoraria from Biogen Idec, Teva Neuroscience, Merck Serono, Medimmune, Novartis, Desitin, and F. Hoffmann-La Roche Ltd; his institution has received research support from Chugai Pharmaceuticals and Hoffmann-La-Roche; holds part of two patents; one for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon β.
M. Mühlau has received research support from Merck Serono and Novartis as well as travel support from Bayer and Merck Serono.
Abstract: 25
Type: Young Scientific Investigators' Session
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Background: The European medicines agency recently restricted the use of linear gadolinium-based contrast agents (GBCA) in body scans 1. The reason is the novel finding of signal intensity change in unenhanced T1 weighted (T1w) images in the dentate nucleus (DN) and other brain regions after several applications of GBCA. Evidence suggests that such changes relate more to linear chelate GBCA than to macrocyclic GBCA.
Purpose: To assess the association between GBCA chelate type (linear vs. macrocyclic, i.e. gadopentetic vs gadoteric acid) and signal intensity change in the DN in MS patients in a large cohort over several years.
Methods: We analyzed serial T1w images in 881 MS patients with repeated GBCA application (EDSS: 1.61 +/- 1.63; diagnosis: 76% RRMS; 16% CIS, 4% SPMS, 2% PPMS, 1% NNO, 1% RIS. Mean number of applications per person was = 5.4 (+/- 3.9) linear and 0.8 (+/- 0.9) macrocyclic GBCA. Mean interval between first and last GBCA application was 3.6 years, 830 patients received at least one linear and 407 at least one macrocyclic GBCA application (including 51 patients with macrocyclic GBCA application only). T1w images were preprocessed and normalized. DN was defined by a publicly available atlas (SUIT, FSL). After visual exclusion of white matter lesions, control points were defined by MNI coordinates in the pons and smoothed with a 5 mm Gaussian Kernel. For statistical analysis of the unenhanced T1w signal, dentate nucleus -to-pons ratio (DN/P) was calculated. DN/P differences of all pairs of subsequent time points were calculated, averaged over each subject and attributed to either linear or macrocyclic GBCA according to the previous administration. In a two sample t-test, individual DN/P differences were compared between linear and macrocyclic GBCA administrations.
Results: DN/P increase was only observed after administration of linear GBCA with a significant difference in DN/P change compared to macrocyclic GBCA administrations (p < .001).
Conclusion: Our results are in line with previous reports that linear but not macrocyclic GBCA accumulate in the DN.
References
1. Agency EM. PRAC confirms restrictions on the use of linear gadolinium agents.
2017.
Disclosure: This work was funded by the 'German Competence Network Multiple Sclerosis' (German Ministry for Research and Education, grant 01GI1604A).
S. Grahl has nothing to disclose.
M. Bussas has nothing to disclose.
C. Gasperi has nothing to disclose.
V. Pongratz has received research support from Novartis (Oppenheim Förderpreis) and intramural funding from the Technical University of Munich (KKF grant).
M.-M. Hoshi reports a travel grant from Bayer Health Care for participation in the annual Meeting of German Neurologic Society 2016.
A. Berthele reports personal fees from Biogen, Merck Serono, Mylan, Novartis, Roche, Sanofi Genzyme, and Teva, and compensations for clinical trials from Alexion Pharmaceuticals, Biogen, Novartis, Genzyme, Roche, and Teva - all outside the submitted work.
J. Kirschke has received research funding from the European Research Council and the German Research Foundation, travel support from Kaneka Europe as well as speaker honoraria from Philips Healthcare; all not related to this work.
C. Zimmer has nothing to disclose.
B. Hemmer has served on scientific advisory boards for F. Hoffmann-La Roche Ltd, Novartis, Bayer AG, and Genentech; he has served as DMSC member for AllergyCare and TG Therapeutics; he or his institution have received speaker honoraria from Biogen Idec, Teva Neuroscience, Merck Serono, Medimmune, Novartis, Desitin, and F. Hoffmann-La Roche Ltd; his institution has received research support from Chugai Pharmaceuticals and Hoffmann-La-Roche; holds part of two patents; one for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon β.
M. Mühlau has received research support from Merck Serono and Novartis as well as travel support from Bayer and Merck Serono.