Contributions
Abstract: P488
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Neuropathology shows that cortical demyelination in multiple sclerosis (MS) is often accompanied by microglia activation. The role of microglia activation, however, is still uncertain.
Aim: To assess, using 3T magnetic resonance-positron emission tomography (MR-PET) with 11C-PBR28, a tracer for activated microglia, and quantitative 7T T2*, a marker of myelin and iron content, whether 1) neuroinflammation in MS colocalizes with cortical demyelination, 2) the relation between the two processes.
Methods: Ten cases with secondary-progressive, 9 with relapsing-remitting MS (SPMS, RRMS), and 14 matched controls (HC) underwent 90' 11C-PBR28 MR-PET to obtain 60'-90' normalized standardized uptake value maps (SUVR, 1.25 mm resolution) for sampling SUVR at mid-cortical depth. MS and HC also underwent multi-echo 7T T2* imaging (0.33 mm resolution) for estimating T2* at 25%, 50% and 75% depth from the pial surface, and for cortical lesion (CL) segmentation. Cortical demyelination in MS was defined as CL and clusters with significantly increased T2* at all depths in RRMS and SPMS vs HC at general linear model (GLM, p< 0.05). In these areas mean SUVR were extracted and compared to i) mean SUVR in the normal appearing cortical grey matter (NACGM) within patients (by paired t-test), and ii) mean SUVR in HC cortex (by linear regression). A vertexwise GLM (p< 0.05) was run to assess the relation in MS between laminar T2* and SUVR. Age and binding affinity were included as nuisance factors.
Results: RRMS and SPMS showed, relative to HC, clusters of increased, but not decreased, T2* (myelin/iron loss) at all 3 depths. In RRMS mean SUVR in CL and clusters with increased T2* were higher than mean SUVR in NACGM (p< 0.02) and HC cortex (p< 0.05); there were no differences in patient NACGM SUVR vs HC cortex. In SPMS, mean SUVR in CL and clusters of increased T2* were higher than NACGM SUVR (p< 0.05) and HC cortex (p< 0.003). SUVR in NACGM in SPMS were also higher than HC cortex SUVR (p=0.01). Cortical SUVR and laminar T2* were positively correlated in many cortical areas, and inversely associated in fewer regions.
Conclusions: Cortical microglia activation predominantly affects cortical lesion areas in RRMS, while it extends to the NACGM in SPMS. In most regions, microglia activation seems to contribute detrimentally to cortical demyelination. The inverse relation between SUVR and T2* found in fewer cortical areas could reflect protective effects of microglia.
Disclosure: This study was supported by the Clafin Award; the National Institute of Health (NIH R01NS07832201 A1); the National Multiple Sclerosis Society (NMSS; RG 4729A2/1); the US Army, Department of Defense (DoD; W81XWH1310112). E. Herranz has received research supported by the NMSS fellowship FG150705459. C. Mainero has received research support from EMD Merck Serono and speaker honoraria from Biogen. C.A. Treaba: nothing to disclose. C. Louapre: nothing to disclose. S. T Govindarajan: nothing to disclose. R. Ouellette: nothing to disclose. G. Mangeat: nothing to disclose. M.L. Loggia: nothing to disclose. Jacob A. Sloane: nothing to disclose.
Abstract: P488
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - MRI and PET
Introduction: Neuropathology shows that cortical demyelination in multiple sclerosis (MS) is often accompanied by microglia activation. The role of microglia activation, however, is still uncertain.
Aim: To assess, using 3T magnetic resonance-positron emission tomography (MR-PET) with 11C-PBR28, a tracer for activated microglia, and quantitative 7T T2*, a marker of myelin and iron content, whether 1) neuroinflammation in MS colocalizes with cortical demyelination, 2) the relation between the two processes.
Methods: Ten cases with secondary-progressive, 9 with relapsing-remitting MS (SPMS, RRMS), and 14 matched controls (HC) underwent 90' 11C-PBR28 MR-PET to obtain 60'-90' normalized standardized uptake value maps (SUVR, 1.25 mm resolution) for sampling SUVR at mid-cortical depth. MS and HC also underwent multi-echo 7T T2* imaging (0.33 mm resolution) for estimating T2* at 25%, 50% and 75% depth from the pial surface, and for cortical lesion (CL) segmentation. Cortical demyelination in MS was defined as CL and clusters with significantly increased T2* at all depths in RRMS and SPMS vs HC at general linear model (GLM, p< 0.05). In these areas mean SUVR were extracted and compared to i) mean SUVR in the normal appearing cortical grey matter (NACGM) within patients (by paired t-test), and ii) mean SUVR in HC cortex (by linear regression). A vertexwise GLM (p< 0.05) was run to assess the relation in MS between laminar T2* and SUVR. Age and binding affinity were included as nuisance factors.
Results: RRMS and SPMS showed, relative to HC, clusters of increased, but not decreased, T2* (myelin/iron loss) at all 3 depths. In RRMS mean SUVR in CL and clusters with increased T2* were higher than mean SUVR in NACGM (p< 0.02) and HC cortex (p< 0.05); there were no differences in patient NACGM SUVR vs HC cortex. In SPMS, mean SUVR in CL and clusters of increased T2* were higher than NACGM SUVR (p< 0.05) and HC cortex (p< 0.003). SUVR in NACGM in SPMS were also higher than HC cortex SUVR (p=0.01). Cortical SUVR and laminar T2* were positively correlated in many cortical areas, and inversely associated in fewer regions.
Conclusions: Cortical microglia activation predominantly affects cortical lesion areas in RRMS, while it extends to the NACGM in SPMS. In most regions, microglia activation seems to contribute detrimentally to cortical demyelination. The inverse relation between SUVR and T2* found in fewer cortical areas could reflect protective effects of microglia.
Disclosure: This study was supported by the Clafin Award; the National Institute of Health (NIH R01NS07832201 A1); the National Multiple Sclerosis Society (NMSS; RG 4729A2/1); the US Army, Department of Defense (DoD; W81XWH1310112). E. Herranz has received research supported by the NMSS fellowship FG150705459. C. Mainero has received research support from EMD Merck Serono and speaker honoraria from Biogen. C.A. Treaba: nothing to disclose. C. Louapre: nothing to disclose. S. T Govindarajan: nothing to disclose. R. Ouellette: nothing to disclose. G. Mangeat: nothing to disclose. M.L. Loggia: nothing to disclose. Jacob A. Sloane: nothing to disclose.