Contributions
Abstract: 57
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: A subset of white matter MS lesions slowly expands with time, a finding that is generally considered as a marker of disease evolution. Pathological studies have suggested that iron laden microglia cells may drive this expansion, but the relationship between microglial activation and lesion enlargement has not yet been investigated in vivo. In this longitudinal study we explored whether microglial activation profiles, assessed by 18F-DPA714 positron emission tomography (PET), could predict lesion expansion after one year.
Methods: Patients with MS (n=22), and healthy controls (HC, n=19) underwent dynamic18F-DPA714 PET and MRI at baseline, and were followed-up at one year with a new MRI scan. Individual maps of microglial activation were derived from voxel-wise differences in the tracer binding between patients and HC and were employed to classify each lesion as active, inactive or smoldering based on the extent and the localization of microglial activation. Subtraction maps obtained from T2-weighted sequences at the 2 time-points were used to identify lesions that enlarged over the follow-up. Pearson's Chi-square test was employed to assess the relationship between the neuropathological classification of lesions at baseline and the increase in lesional volume after 1 year. Post-hoc analysis based on the adjusted standardized residuals was performed to identify which lesional class was most likely associated with volume enlargement over time (significant levels set at z=1.96).
Results: Out of the 737 T2-w lesions identified at study entry, 37.6% were classified as inactive, 19.3% as active, 2.7% as smoldering, and 40.4 as undifferentiated. Only 3 lesions were enhanced by gadolinium. Five % of baseline T2-w lesions increased in volume after 1 year. A significant relationship between the PET-derived neuropathological classification of lesions at baseline and lesional volume increase over time was demonstrated (p=0.016). Post-hoc analysis showed that lesions classified as active at baseline were the most likely to increase in volume after 1 year (z=2.9).
Conclusions: 18F-DPA-714 microglial PET allows to identify active lesions not detected by MRI that are more likely to enlarge over time. The impact of these expanding lesions on neurodegeneration and clinical disability will be investigated through a longer follow-up.
Disclosure:
C. Benoit : nothing to disclose
E. Poirion : nothing to disclose
M. Tonietto : nothing to disclose
G. Bera : nothing to disclose
B. Bodini received honoraria from Genzyme, Novartis and Roche.
Pr B. Stankoff received honoraria from Biogen, Teva, Novartis, Genzyme, Roche and research support from Genzyme, Merck-Serono and Roche.
The study was supported by a ANR MNP-2008-007125 specific grant, the program “Investissements d'avenir” ANR-10-IAIHU-06, MS research foundation ARSEP, INSERM (Institut National de la Santé et de la recherche médicale), ECTRIMS, JNLF (Journées de Neurologie de Langue Française), FRM (Fondation pour la Recherche Médicale), and sponsored by APHP (Assistance Publique des Hôpitaux de Paris).
Abstract: 57
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: A subset of white matter MS lesions slowly expands with time, a finding that is generally considered as a marker of disease evolution. Pathological studies have suggested that iron laden microglia cells may drive this expansion, but the relationship between microglial activation and lesion enlargement has not yet been investigated in vivo. In this longitudinal study we explored whether microglial activation profiles, assessed by 18F-DPA714 positron emission tomography (PET), could predict lesion expansion after one year.
Methods: Patients with MS (n=22), and healthy controls (HC, n=19) underwent dynamic18F-DPA714 PET and MRI at baseline, and were followed-up at one year with a new MRI scan. Individual maps of microglial activation were derived from voxel-wise differences in the tracer binding between patients and HC and were employed to classify each lesion as active, inactive or smoldering based on the extent and the localization of microglial activation. Subtraction maps obtained from T2-weighted sequences at the 2 time-points were used to identify lesions that enlarged over the follow-up. Pearson's Chi-square test was employed to assess the relationship between the neuropathological classification of lesions at baseline and the increase in lesional volume after 1 year. Post-hoc analysis based on the adjusted standardized residuals was performed to identify which lesional class was most likely associated with volume enlargement over time (significant levels set at z=1.96).
Results: Out of the 737 T2-w lesions identified at study entry, 37.6% were classified as inactive, 19.3% as active, 2.7% as smoldering, and 40.4 as undifferentiated. Only 3 lesions were enhanced by gadolinium. Five % of baseline T2-w lesions increased in volume after 1 year. A significant relationship between the PET-derived neuropathological classification of lesions at baseline and lesional volume increase over time was demonstrated (p=0.016). Post-hoc analysis showed that lesions classified as active at baseline were the most likely to increase in volume after 1 year (z=2.9).
Conclusions: 18F-DPA-714 microglial PET allows to identify active lesions not detected by MRI that are more likely to enlarge over time. The impact of these expanding lesions on neurodegeneration and clinical disability will be investigated through a longer follow-up.
Disclosure:
C. Benoit : nothing to disclose
E. Poirion : nothing to disclose
M. Tonietto : nothing to disclose
G. Bera : nothing to disclose
B. Bodini received honoraria from Genzyme, Novartis and Roche.
Pr B. Stankoff received honoraria from Biogen, Teva, Novartis, Genzyme, Roche and research support from Genzyme, Merck-Serono and Roche.
The study was supported by a ANR MNP-2008-007125 specific grant, the program “Investissements d'avenir” ANR-10-IAIHU-06, MS research foundation ARSEP, INSERM (Institut National de la Santé et de la recherche médicale), ECTRIMS, JNLF (Journées de Neurologie de Langue Française), FRM (Fondation pour la Recherche Médicale), and sponsored by APHP (Assistance Publique des Hôpitaux de Paris).