TZAROUCHI LCTZAROUCHI LC11, , TSIFETAKI NTSIFETAKI N22,, KONITSIOTIS S KONITSIOTIS S 3 3, ASTRAKAS LG, ASTRAKAS LG 44, , ZIKOU AKZIKOU AK11, , ΒΟΒΟTZORIS VTZORIS V 2 2, DROSOS A, DROSOS A 2 2, , ARGYROPOULOU MIARGYROPOULOU MI11

Diffusion Tensor Imaging and TDiffusion Tensor Imaging and T2 2

Relaxometry in primary Sjogren’s Relaxometry in primary Sjogren’s SundromeSundrome

1.1.DEPARTMENT OF RADIOLOGYDEPARTMENT OF RADIOLOGY2.2.DEPERTMENT OF RHEUMATOLOGYDEPERTMENT OF RHEUMATOLOGY

3.3.DEPARTMENT OF NEUROLOGYDEPARTMENT OF NEUROLOGY4.4.DEPARTMENT OF MEDICAL PHYSICSDEPARTMENT OF MEDICAL PHYSICS

MEDICAL SCHOOL, UNIVERSITY OF IOANNINA, GREECEMEDICAL SCHOOL, UNIVERSITY OF IOANNINA, GREECE

INTRODUCTIONINTRODUCTION

Sjogren’s SyndromeSjogren’s Syndrome 2-3 %2-3 % adult populationadult populationAutoimmune disorderAutoimmune disorder

Glandular, extra-glandular manifestationsGlandular, extra-glandular manifestations

Central Nervous System involvement Central Nervous System involvement ?? 1-25%1-25%, neurological or psychiatric symptoms, neurological or psychiatric symptoms

• Primary Primary ( (pSS)pSS)• SecondarySecondary

Ann Rheum Dis. 2004 Jun;63(6):616-20

INTRODUCTION INTRODUCTION • MRI studies T2/FLAIR : white matter hyperintensities (WMHIs)MRI studies T2/FLAIR : white matter hyperintensities (WMHIs)• SPECT studies perfusionSPECT studies perfusion

• Tzarouchi et al (ECR 2009): 52 pSS/35 controls Tzarouchi et al (ECR 2009): 52 pSS/35 controls WMHIs 80.8%/48.6%WMHIs 80.8%/48.6% Voxel-Based Morphometry (VBM)Voxel-Based Morphometry (VBM)

Grey matter Grey matter atrophyatrophy

White matter White matter atrophatrophy

INTRODUCTIONINTRODUCTION

• RelaxometryRelaxometry: measurment of transverse T: measurment of transverse T2 2 relaxation relaxation timetime tissue properties (e.g. water, protein, iron content,tissue properties (e.g. water, protein, iron content, gliosis)gliosis)

• Diffusion Tensor ImagingDiffusion Tensor Imaging: fractional anisotropy index : fractional anisotropy index (FA)(FA) tissue microstructural changes, tracking white matter tissue microstructural changes, tracking white matter fibers fibers

PURPOSEPURPOSE

To assess in pSS:To assess in pSS:

TT2 2 relaxation time (Trelaxation time (T22) Fractional anisotropy index ) Fractional anisotropy index (FA)(FA)

Voxel Based Relaxometry Voxel Based Relaxometry (VBR)(VBR)

Voxel Based Diffusion Voxel Based Diffusion Tensor ImagingTensor Imaging

MATERIALS AND METHODSMATERIALS AND METHODS Ι ΙStudy populationStudy population 3232 patients with pSSpatients with pSS AgedAged: : 64.56±15.6 years64.56±15.6 years Disease DurationDisease Duration: 10.5±5.75: 10.5±5.75 years years 1818 age-matched controlsage-matched controls

Exclusion criteriaExclusion criteria: Head trauma, neuropsychiatric disorder, : Head trauma, neuropsychiatric disorder, uncontrolled hypertension, diabetes mellitus, blood uncontrolled hypertension, diabetes mellitus, blood dyscrasias, metabolic disorders or renal, hepatic or dyscrasias, metabolic disorders or renal, hepatic or respiratory failure, smoking habits, alcohol intake, migrainerespiratory failure, smoking habits, alcohol intake, migraine

MATERIALS AND METHODSMATERIALS AND METHODS ΙΙ ΙΙ1.5 Tesla unit, head coil1.5 Tesla unit, head coil

Multi-slice, spin-echo Multi-slice, spin-echo planar diffusion tensor pulse planar diffusion tensor pulse sequence (TE=131 msec, TR=9807 msec, matrix sequence (TE=131 msec, TR=9807 msec, matrix size=112 x 128, thickness=3 mm, FOV=230 mm, max size=112 x 128, thickness=3 mm, FOV=230 mm, max b-value=700 sec/mm2, 16 non-collinear directions)b-value=700 sec/mm2, 16 non-collinear directions)

Multi-echo , multi-slice T2-weighted (TR=2200 sec, Multi-echo , multi-slice T2-weighted (TR=2200 sec, TE=32-112 sec, thickness=5 mm, gap=0.5, TE=32-112 sec, thickness=5 mm, gap=0.5, acquisition matrix=156, reconstruction matrix=256)acquisition matrix=156, reconstruction matrix=256)

Voxel by voxel Voxel by voxel Student’sStudent’s t-tes t-testt

SmoothingSmoothingNormalisationNormalisation

MNI templateMNI templateP < 0.0P < 0.055

FWE correctionFWE correction

SPM 5.0 softwareSPM 5.0 software

Voxel-Based Relaxometry Voxel-Based Relaxometry data postprocessing data postprocessing

TT2 2 mapsmaps

Voxel-Based DTI – data postprocessingVoxel-Based DTI – data postprocessing

NormalizationNormalization

b0 imageb0 image

SmoothingSmoothingFA mapFA map

NormalizationNormalization

SPM 5.0SPM 5.0 softwaresoftware

Voxel by voxel Voxel by voxel Student’sStudent’s t-tes t-testt

DTI studio DTI studio

P < 0.0P < 0.055FWE correctionFWE correction

VBR RESULTS VBR RESULTS

Voxel-Based DTI Voxel-Based DTI resultsresults

Does brain atrophy affect T2 time

Biological Parametring Mapping (BPM)

Analysis of Covariance (ANCOVA) VBR data: primary modalityVBM data: imaging regressors

??TT2 2 relaxation timerelaxation time

DISCUSSIONDISCUSSION Ι Ι

**Neuroimage Neuroimage (2007); (2007); 3434(1): 137-43(1): 137-43

VBR resultsVBR results ANCOVA resultsANCOVA results

DISCUSSIONDISCUSSION ΙΙ ΙΙ

* * Rheumatol Int 2003; 23:174-177Rheumatol Int 2003; 23:174-177* J Nuclear Med 1998; 39:8* J Nuclear Med 1998; 39:8

fractional anisotropy fractional anisotropy

Early white matter damageEarly white matter damage

• Small vessel vasculitisSmall vessel vasculitisoror• Degenerative process due to grey matter atrophyDegenerative process due to grey matter atrophy

CONCLUSIONCONCLUSION

In primary Sjogren’s Syndrome:In primary Sjogren’s Syndrome:

•Brain atrophy affects TBrain atrophy affects T2 2 relaxation time relaxation time measurmentsmeasurments

•Diffusion tensor imaging detects early white Diffusion tensor imaging detects early white matter lesionsmatter lesions