Contributions
Abstract: P517
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: Cerebellar involvement occurs early in multiple sclerosis (MS), frequently associated with neurological impairment. Pathology in the cerebellum includes demyelination, neurodegeneration and inflammation with microglia activation. The role of microglial cells in the pathogenesis of cerebellar pathology is unknown. Activated microglia upregulate expression of the 18kDa translocator protein (TSPO), which is imaged in vivo using the 11C-PBR28 radioligand.
Objective: To investigate, using integrated 3 Tesla (3T) magnetic resonance-positron emission tomography (MR-PET) imaging with 11C-PBR28, TSPO expression in the cerebellum of a MS cohort, and its association with lesions and atrophy.
Methods: Twenty MS subjects (11 SPMS and 9 RRMS; mean age=48±9; median EDSS= 3.75, range=1.5 to 7.5) and 18 healthy controls (HC; mean age=48±12) matched for PBR28 affinity underwent 90-min 11C-PBR28 MR-PET. Anatomical images for brain and cerebellum segmentation with Freesurfer were also acquired. In MS, cerebellar lesions were segmented on 7T T1 images obtained on a separate session. Quantification of 11C-PBR28 uptake in the whole cerebellum and lesions was assessed using 60-90min standardized uptake values normalized by a pseudo-reference region (SUVR) in the normal appearing basal ganglia.
Linear regression models were used to compare cerebellar 11C-PBR28 uptake in MS vs controls, and to assess their relationship with EDSS. Age and/or binding affinity were included as covariates of no interest.
Results: Cerebellar lesions were found in all SPMS and in 6 out of 9 RRMS subjects. Cerebellar volume, normalized by intracranial volume, was reduced in MS vs HC (p=0.02), where it also inversely correlated with cerebellar lesion load (p=0.03). MS subjects showed significantly higher 11C-PBR28 uptake in cerebellar lesions relative to HC cerebellum (p=0.01). No differences in uptake, however, were found between the two groups when assessing the whole cerebellum, nor between SPMS and RRMS. There was a trend for correlation between EDSS and 11C-PBR28 uptake in the whole cerebellum (p=0.09), while no association was found with cerebellar volume.
Discussion: Our data provide in vivo evidence for the presence of microglia activation in the cerebellum in MS. Interestingly, in contrast to findings in the brain, activated microglia were mainly concentrated in lesions. Future studies will assess inflammation in the cerebellar gray matter and test for associations with cognition.
Disclosure:
Barletta V: nothing to disclose;
Herranz E: nothing to disclose;
Treaba CA: nothing to disclose;
Ouellette R: nothing to disclose;
Loggia ML: nothing to disclose;
Klawiter EC: has received research grants from Atlas5D, Biogen, EMD Serono and Roche; and consulting fees from Acorda, Atlas5D, Biogen, EMD Serono, Genentech and Shire.
Sloane JA: nothing to disclose;
Mainero C: no conflicts of interest; unrelated funding support from Merck Serono and Genzyme.
Fundings: National Multiple Sclerosis Society (NMSS). Grant Number: RG 4729A2/1
US Army, Department of Defense. Grant Number: W81XWH-13-1-0112
NMSS fellowship. Grant Number: FG-1507-05459
NIH. Grant Number: R01NS078322-01 A1
Abstract: P517
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - 21 Imaging
Introduction: Cerebellar involvement occurs early in multiple sclerosis (MS), frequently associated with neurological impairment. Pathology in the cerebellum includes demyelination, neurodegeneration and inflammation with microglia activation. The role of microglial cells in the pathogenesis of cerebellar pathology is unknown. Activated microglia upregulate expression of the 18kDa translocator protein (TSPO), which is imaged in vivo using the 11C-PBR28 radioligand.
Objective: To investigate, using integrated 3 Tesla (3T) magnetic resonance-positron emission tomography (MR-PET) imaging with 11C-PBR28, TSPO expression in the cerebellum of a MS cohort, and its association with lesions and atrophy.
Methods: Twenty MS subjects (11 SPMS and 9 RRMS; mean age=48±9; median EDSS= 3.75, range=1.5 to 7.5) and 18 healthy controls (HC; mean age=48±12) matched for PBR28 affinity underwent 90-min 11C-PBR28 MR-PET. Anatomical images for brain and cerebellum segmentation with Freesurfer were also acquired. In MS, cerebellar lesions were segmented on 7T T1 images obtained on a separate session. Quantification of 11C-PBR28 uptake in the whole cerebellum and lesions was assessed using 60-90min standardized uptake values normalized by a pseudo-reference region (SUVR) in the normal appearing basal ganglia.
Linear regression models were used to compare cerebellar 11C-PBR28 uptake in MS vs controls, and to assess their relationship with EDSS. Age and/or binding affinity were included as covariates of no interest.
Results: Cerebellar lesions were found in all SPMS and in 6 out of 9 RRMS subjects. Cerebellar volume, normalized by intracranial volume, was reduced in MS vs HC (p=0.02), where it also inversely correlated with cerebellar lesion load (p=0.03). MS subjects showed significantly higher 11C-PBR28 uptake in cerebellar lesions relative to HC cerebellum (p=0.01). No differences in uptake, however, were found between the two groups when assessing the whole cerebellum, nor between SPMS and RRMS. There was a trend for correlation between EDSS and 11C-PBR28 uptake in the whole cerebellum (p=0.09), while no association was found with cerebellar volume.
Discussion: Our data provide in vivo evidence for the presence of microglia activation in the cerebellum in MS. Interestingly, in contrast to findings in the brain, activated microglia were mainly concentrated in lesions. Future studies will assess inflammation in the cerebellar gray matter and test for associations with cognition.
Disclosure:
Barletta V: nothing to disclose;
Herranz E: nothing to disclose;
Treaba CA: nothing to disclose;
Ouellette R: nothing to disclose;
Loggia ML: nothing to disclose;
Klawiter EC: has received research grants from Atlas5D, Biogen, EMD Serono and Roche; and consulting fees from Acorda, Atlas5D, Biogen, EMD Serono, Genentech and Shire.
Sloane JA: nothing to disclose;
Mainero C: no conflicts of interest; unrelated funding support from Merck Serono and Genzyme.
Fundings: National Multiple Sclerosis Society (NMSS). Grant Number: RG 4729A2/1
US Army, Department of Defense. Grant Number: W81XWH-13-1-0112
NMSS fellowship. Grant Number: FG-1507-05459
NIH. Grant Number: R01NS078322-01 A1