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Gray matter microglial activation in relapsing vs progressive MS: A [F-18]PBR06-PET study.

Abstract

Objective

To determine the value of [F-18]PBR06-PET for assessment of microglial activation in the cerebral gray matter in patients with MS.

Methods

Twelve patients with MS (7 relapsing-remitting and 5 secondary progressive [SP]) and 5 healthy controls (HCs) had standardized uptake value (SUV) PET maps coregistered to 3T MRI and segmented into cortical and subcortical gray matter regions. SUV ratios (SUVRs) were global brain normalized. Voxel-by-voxel analysis was performed using statistical parametric mapping (SPM). Normalized brain parenchymal volumes (BPVs) were determined from MRI using SIENAX.

Results

Cortical SUVRs were higher in the hippocampus, amygdala, midcingulate, posterior cingulate, and rolandic operculum and lower in the medial-superior frontal gyrus and cuneus in the MS vs HC group (all p < 0.05). Subcortical gray matter SUVR was higher in SPMS vs RRMS (+10.8%, p = 0.002) and HC (+11.3%, p = 0.055) groups. In the MS group, subcortical gray matter SUVR correlated with the Expanded Disability Status Scale (EDSS) score (r = 0.75, p = 0.005) and timed 25-foot walk (T25FW) (r = 0.70, p = 0.01). Thalamic SUVRs increased with increasing EDSS scores (r = 0.83, p = 0.0008) and T25FW (r = 0.65, p = 0.02) and with decreasing BPV (r = -0.63, p = 0.03). Putaminal SUVRs increased with increasing EDSS scores (0.71, p = 0.009) and with decreasing BPV (r = -0.67, p = 0.01). On SPM analysis, peak correlations of thalamic voxels with BPV were seen in the pulvinar and with the EDSS score and T25FW in the dorsomedial thalamic nuclei.

Conclusions

This study suggests that [F-18]PBR06-PET detects widespread abnormal microglial activation in the cerebral gray matter in MS. Increased translocator protein binding in subcortical gray matter regions is associated with brain atrophy and may link to progressive MS.

Authors+Show Affiliations

Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.Partners MS Center (T.S., K.O.C., R.C., S.C., S.T., H.L.W., R.B.), Laboratory for Neuroimaging Research, Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School; Division of Nuclear Medicine and Molecular Imaging (S.D., M.K., M.D.), Department of Radiology, Brigham and Women's Hospital, Harvard Medical School; Functional Neuroimaging Laboratory (H.P., D.S., E.S.), Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School; Department of Medicine (S.H.) and Department of Radiology (E.S., R.B.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31355321

Citation

Singhal, Tarun, et al. "Gray Matter Microglial Activation in Relapsing Vs Progressive MS: a [F-18]PBR06-PET Study." Neurology(R) Neuroimmunology & Neuroinflammation, vol. 6, no. 5, 2019, pp. e587.
Singhal T, O'Connor K, Dubey S, et al. Gray matter microglial activation in relapsing vs progressive MS: A [F-18]PBR06-PET study. Neurol Neuroimmunol Neuroinflamm. 2019;6(5):e587.
Singhal, T., O'Connor, K., Dubey, S., Pan, H., Chu, R., Hurwitz, S., ... Bakshi, R. (2019). Gray matter microglial activation in relapsing vs progressive MS: A [F-18]PBR06-PET study. Neurology(R) Neuroimmunology & Neuroinflammation, 6(5), pp. e587. doi:10.1212/NXI.0000000000000587.
Singhal T, et al. Gray Matter Microglial Activation in Relapsing Vs Progressive MS: a [F-18]PBR06-PET Study. Neurol Neuroimmunol Neuroinflamm. 2019;6(5):e587. PubMed PMID: 31355321.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gray matter microglial activation in relapsing vs progressive MS: A [F-18]PBR06-PET study. AU - Singhal,Tarun, AU - O'Connor,Kelsey, AU - Dubey,Shipra, AU - Pan,Hong, AU - Chu,Renxin, AU - Hurwitz,Shelley, AU - Cicero,Steven, AU - Tauhid,Shahamat, AU - Silbersweig,David, AU - Stern,Emily, AU - Kijewski,Marie, AU - DiCarli,Marcelo, AU - Weiner,Howard L, AU - Bakshi,Rohit, Y1 - 2019/07/01/ PY - 2018/11/19/received PY - 2019/05/15/accepted PY - 2019/7/30/entrez PY - 2019/7/30/pubmed PY - 2019/7/30/medline SP - e587 EP - e587 JF - Neurology(R) neuroimmunology & neuroinflammation JO - Neurol Neuroimmunol Neuroinflamm VL - 6 IS - 5 N2 - Objective: To determine the value of [F-18]PBR06-PET for assessment of microglial activation in the cerebral gray matter in patients with MS. Methods: Twelve patients with MS (7 relapsing-remitting and 5 secondary progressive [SP]) and 5 healthy controls (HCs) had standardized uptake value (SUV) PET maps coregistered to 3T MRI and segmented into cortical and subcortical gray matter regions. SUV ratios (SUVRs) were global brain normalized. Voxel-by-voxel analysis was performed using statistical parametric mapping (SPM). Normalized brain parenchymal volumes (BPVs) were determined from MRI using SIENAX. Results: Cortical SUVRs were higher in the hippocampus, amygdala, midcingulate, posterior cingulate, and rolandic operculum and lower in the medial-superior frontal gyrus and cuneus in the MS vs HC group (all p < 0.05). Subcortical gray matter SUVR was higher in SPMS vs RRMS (+10.8%, p = 0.002) and HC (+11.3%, p = 0.055) groups. In the MS group, subcortical gray matter SUVR correlated with the Expanded Disability Status Scale (EDSS) score (r = 0.75, p = 0.005) and timed 25-foot walk (T25FW) (r = 0.70, p = 0.01). Thalamic SUVRs increased with increasing EDSS scores (r = 0.83, p = 0.0008) and T25FW (r = 0.65, p = 0.02) and with decreasing BPV (r = -0.63, p = 0.03). Putaminal SUVRs increased with increasing EDSS scores (0.71, p = 0.009) and with decreasing BPV (r = -0.67, p = 0.01). On SPM analysis, peak correlations of thalamic voxels with BPV were seen in the pulvinar and with the EDSS score and T25FW in the dorsomedial thalamic nuclei. Conclusions: This study suggests that [F-18]PBR06-PET detects widespread abnormal microglial activation in the cerebral gray matter in MS. Increased translocator protein binding in subcortical gray matter regions is associated with brain atrophy and may link to progressive MS. SN - 2332-7812 UR - https://www.unboundmedicine.com/medline/citation/31355321/Gray_matter_microglial_activation_in_relapsing_vs_progressive_MS:_A_[F-18]PBR06-PET_study L2 - http://nn.neurology.org/cgi/pmidlookup?view=long&amp;pmid=31355321 DB - PRIME DP - Unbound Medicine ER -