ECTRIMS eLearning

Decreased tract integrity in normal appearing white matter correlates to increased microglial activation and disability in multiple sclerosis in vivo
Author(s): ,
S. Bezukladova
Affiliations:
Åbo Akademi University
,
J. Tuisku
Affiliations:
Turku PET Centre
,
M. Matilainen
Affiliations:
Turku PET Centre
,
A. Vuorimaa
Affiliations:
Turku PET Centre; Division of Clinical Neurosciences, Turku University Hospital and University of Turku
,
M. Nylund
Affiliations:
Turku PET Centre; Division of Clinical Neurosciences, Turku University Hospital and University of Turku
,
S. Smith
Affiliations:
Turku University
,
M. Sucksdorff
Affiliations:
Turku PET Centre; Division of Clinical Neurosciences, Turku University Hospital and University of Turku
,
V. Saunavaara
Affiliations:
Turku PET Centre; Department of Medical physics, Turku University Hospital
,
S. Laaksonen
Affiliations:
Division of Clinical Neurosciences, Turku University Hospital and University of Turku
,
T. Paavilainen
Affiliations:
Medical Imaging Centre of Southwest Finland
,
R. Parkkola
Affiliations:
Department of Radiology, Turku University Hospital and University of Turku, Turku, Finland
,
J. Rokka
Affiliations:
Turku PET Centre
,
J.O. Rinne
Affiliations:
Turku PET Centre; Division of Clinical Neurosciences, Turku University Hospital and University of Turku
,
E. Rissanen
Affiliations:
Turku PET Centre; Division of Clinical Neurosciences, Turku University Hospital and University of Turku
L. Airas
Affiliations:
Division of Clinical Neurosciences, Turku University Hospital and University of Turku
ECTRIMS Learn. Bezukladova S. 10/10/18; 228314; P470
Svetlana Bezukladova
Svetlana Bezukladova
Contributions
Abstract

Abstract: P470

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Background: Neuroinflammation and microglial activation are hallmarks in the pathology of multiple sclerosis (MS). Diffusion tensor imaging (DTI) is a sensitive marker for assessment of pathology related structural alterations in the brain. Quantification of microglial activation with translocator protein (TSPO) binding radioligand [11C]PK11195 positron emission tomography (PET) allows the measurement of neuroinflammation.
Objective: To evaluate structural and molecular brain changes and their correlation to clinical disability using combined in vivo magnetic resonance (MR) and PET imaging in MS patients compared to healthy controls (HC), with correlational analyses of DTI parameters to TSPO radioligand binding.
Methods: A cohort of 55 MS patients (40 RRMS, 15 SPMS, age 28-64 years, EDSS 1-6.5) and 15 HC (age 21-58 years) were imaged with 3T MRI and [11C]PK11195 PET. Mean fractional anisotropy (FA) and mean (MD), axial (AD) and radial (RD) diffusivities were calculated with ExploreDTI within whole normal appearing white matter (NAWM) and segmented NAWM regions (deep WM, cingulate, frontal, temporal, occipital, parietal) derived with Freesurfer. T2 hyperintense lesions were excluded from the WM by segmentation with Lesion Segmentation Tool. Microglial activation was evaluated as the distribution volume ratio (DVR) of [11C]PK11195 from dynamic PET images. Spearman correlations of DTI, PET and clinical data were considered significant at the level of p < 0.05.
Results: Mean FA was significantly decreased in NAWM (p=0.06), occipital (p=0.009) and cingulate WM(p=0.004) of the MS patients compared to HC. MD and RD were significantly increased (p=0.005 and p=0.004, respectively) in cingulate WM of MS patients vs. HC. White matter structural abnormalities (decreased FA and increased MD/AD/RD) correlated with increased TSPO binding in the whole NAWM (p< 0.05 for all correlations), in temporal WM (p< 0.01 for all correlations), and deep WM (p=0.02 for FA). Decreased white matter integrity and increased TSPO binding in NAWM also correlated significantly with higher EDSS disability (with strongest correlation with NAWM FA and RD, p< 0.0001, and with NAWM DVR, p< 0.001).
Conclusion: Microglial activation is strongly linked to widespread disruption of white matter in the NAWM and both associated strongly with clinical disability. Combination of both PET and DTI imaging modalities may enable a better understanding of hidden MS pathology not visible using conventional MRI.
Disclosure: Svetlana Bezukladova, Jouni Tuisku, Markus Matilainen, Anna Vuorimaa, Marjo Nylund, Sarah Smith, Marcus Sucksdorff, Virva Saunavaara, Suvi Laaksonen, Teemu Paavilainen, Riitta Parkkola, Johanna Rokka, Juha O. Rinne have nothing to disclose. Eero Rissanen has received speaker honoraria from Teva, Biogen, and Roche, a consultational fee for Merck and personal research grants from Turku University Hospital and the Finnish MS Foundation. Laura Airas has received honoraria from Biogen, F. Hoffmann-La Roche Ltd, Genzyme, Merck Serono and Teva, and institutional research grant support from Biogen, Genzyme, Merck Serono and Novartis.

Abstract: P470

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - MRI and PET

Background: Neuroinflammation and microglial activation are hallmarks in the pathology of multiple sclerosis (MS). Diffusion tensor imaging (DTI) is a sensitive marker for assessment of pathology related structural alterations in the brain. Quantification of microglial activation with translocator protein (TSPO) binding radioligand [11C]PK11195 positron emission tomography (PET) allows the measurement of neuroinflammation.
Objective: To evaluate structural and molecular brain changes and their correlation to clinical disability using combined in vivo magnetic resonance (MR) and PET imaging in MS patients compared to healthy controls (HC), with correlational analyses of DTI parameters to TSPO radioligand binding.
Methods: A cohort of 55 MS patients (40 RRMS, 15 SPMS, age 28-64 years, EDSS 1-6.5) and 15 HC (age 21-58 years) were imaged with 3T MRI and [11C]PK11195 PET. Mean fractional anisotropy (FA) and mean (MD), axial (AD) and radial (RD) diffusivities were calculated with ExploreDTI within whole normal appearing white matter (NAWM) and segmented NAWM regions (deep WM, cingulate, frontal, temporal, occipital, parietal) derived with Freesurfer. T2 hyperintense lesions were excluded from the WM by segmentation with Lesion Segmentation Tool. Microglial activation was evaluated as the distribution volume ratio (DVR) of [11C]PK11195 from dynamic PET images. Spearman correlations of DTI, PET and clinical data were considered significant at the level of p < 0.05.
Results: Mean FA was significantly decreased in NAWM (p=0.06), occipital (p=0.009) and cingulate WM(p=0.004) of the MS patients compared to HC. MD and RD were significantly increased (p=0.005 and p=0.004, respectively) in cingulate WM of MS patients vs. HC. White matter structural abnormalities (decreased FA and increased MD/AD/RD) correlated with increased TSPO binding in the whole NAWM (p< 0.05 for all correlations), in temporal WM (p< 0.01 for all correlations), and deep WM (p=0.02 for FA). Decreased white matter integrity and increased TSPO binding in NAWM also correlated significantly with higher EDSS disability (with strongest correlation with NAWM FA and RD, p< 0.0001, and with NAWM DVR, p< 0.001).
Conclusion: Microglial activation is strongly linked to widespread disruption of white matter in the NAWM and both associated strongly with clinical disability. Combination of both PET and DTI imaging modalities may enable a better understanding of hidden MS pathology not visible using conventional MRI.
Disclosure: Svetlana Bezukladova, Jouni Tuisku, Markus Matilainen, Anna Vuorimaa, Marjo Nylund, Sarah Smith, Marcus Sucksdorff, Virva Saunavaara, Suvi Laaksonen, Teemu Paavilainen, Riitta Parkkola, Johanna Rokka, Juha O. Rinne have nothing to disclose. Eero Rissanen has received speaker honoraria from Teva, Biogen, and Roche, a consultational fee for Merck and personal research grants from Turku University Hospital and the Finnish MS Foundation. Laura Airas has received honoraria from Biogen, F. Hoffmann-La Roche Ltd, Genzyme, Merck Serono and Teva, and institutional research grant support from Biogen, Genzyme, Merck Serono and Novartis.

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