Contributions
Abstract: 244
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: The objective of this study was to investigate the presence of an in-vivo gradient of activated microglia from proximal to distal regions in relation to the ventricular cerebro-spinal fluid (CSF) using positron emission tomography (PET) with 18F-DPA714, and to explore its impact on clinical progression.
Methods: Thirty-five patients with MS, classified in “progressing” and “not-progressing” according to the changes in their clinical disability over the 2 years preceding study entry, and 19 healthy controls (HC), underwent conventional MRI and 18F-DPA714 PET. Individual maps of activated microglia were generated from PET-derived parametric maps. Two-mm thick distance rings from the ventricular CSF surface to the periventricular white matter (PWM) and thalamus (TH) were used to calculate the gradient in activated microglia from the CSF to adjacent tissues. Differences in percent volume of activated microglia and in gradient of microglial activation in PWM and TH between patients and HC were calculated with linear regressions. A one-way ANCOVA and Bonferroni-corrected post-hoc t-tests was used to calculate differences in gradient between HC and “progressing” and “not-progressing” patients in periventricular tissues.
Results: Patients showed a greater percent volume of activated microglia in PWM (p=0.003) and TH (p=0.0002), and a steeper gradient in adjacent tissues (PWM p=0.003; TH p=0.001), compared with HC. There was a significant group effect on the gradient of activated microglia from the CSF to both PWM (p=0.001) and TH (p=0.0006), with the group of progressing patients showing the steepest gradient (PWM=-0.64%mm-1; TH=-1.81%mm-1). Post-hoc analyses showed that “progressing” patients presented a steeper gradient in both PWM (p=0.0004) and TH (p=0.004) compared to HC, and in TH (p=0.04) compared to “not-progressing” patients.
Conclusion: We used 18F-DPA714 PET to demonstrate for the first time in-vivo that in patients with MS the activation of microglia was highest adjacent to the ventricles and progressively decreased with distance from them. This gradient was more pronounced in patients showing clinical deterioration in the 2 years preceding study entry than in patients who remained clinically stable. This increase in the activation of the innate immune system in periventricular areas might be triggered by the presence of cytotoxic solubles mediators in the CSF, and could mediate the subsequent development of neuro-axonal irreversible damage in MS.
Disclosure: E. Poirion : nothing to disclose
B. Bodini received honoraria from Genzyme, Novartis and Roche.
C. Benoit : nothing to disclose
M. Tonietto : nothing to disclose
G. Bera : nothing to disclose
C. Giannesini : nothing to disclose
B. Kuhnast : nothing to disclose
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: 244
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Background: The objective of this study was to investigate the presence of an in-vivo gradient of activated microglia from proximal to distal regions in relation to the ventricular cerebro-spinal fluid (CSF) using positron emission tomography (PET) with 18F-DPA714, and to explore its impact on clinical progression.
Methods: Thirty-five patients with MS, classified in “progressing” and “not-progressing” according to the changes in their clinical disability over the 2 years preceding study entry, and 19 healthy controls (HC), underwent conventional MRI and 18F-DPA714 PET. Individual maps of activated microglia were generated from PET-derived parametric maps. Two-mm thick distance rings from the ventricular CSF surface to the periventricular white matter (PWM) and thalamus (TH) were used to calculate the gradient in activated microglia from the CSF to adjacent tissues. Differences in percent volume of activated microglia and in gradient of microglial activation in PWM and TH between patients and HC were calculated with linear regressions. A one-way ANCOVA and Bonferroni-corrected post-hoc t-tests was used to calculate differences in gradient between HC and “progressing” and “not-progressing” patients in periventricular tissues.
Results: Patients showed a greater percent volume of activated microglia in PWM (p=0.003) and TH (p=0.0002), and a steeper gradient in adjacent tissues (PWM p=0.003; TH p=0.001), compared with HC. There was a significant group effect on the gradient of activated microglia from the CSF to both PWM (p=0.001) and TH (p=0.0006), with the group of progressing patients showing the steepest gradient (PWM=-0.64%mm-1; TH=-1.81%mm-1). Post-hoc analyses showed that “progressing” patients presented a steeper gradient in both PWM (p=0.0004) and TH (p=0.004) compared to HC, and in TH (p=0.04) compared to “not-progressing” patients.
Conclusion: We used 18F-DPA714 PET to demonstrate for the first time in-vivo that in patients with MS the activation of microglia was highest adjacent to the ventricles and progressively decreased with distance from them. This gradient was more pronounced in patients showing clinical deterioration in the 2 years preceding study entry than in patients who remained clinically stable. This increase in the activation of the innate immune system in periventricular areas might be triggered by the presence of cytotoxic solubles mediators in the CSF, and could mediate the subsequent development of neuro-axonal irreversible damage in MS.
Disclosure: E. Poirion : nothing to disclose
B. Bodini received honoraria from Genzyme, Novartis and Roche.
C. Benoit : nothing to disclose
M. Tonietto : nothing to disclose
G. Bera : nothing to disclose
C. Giannesini : nothing to disclose
B. Kuhnast : nothing to disclose
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).