New Imaging Techniques: MS Neuroprotection & Repair

Highlights of research from Parallel Session 6: New Techniques to Image Neuroprotection and Repair at ECTRIMS 2016 (Sept 15, 2016) in London, are presented on the following pages.

Imaging Signature of Multiple Sclerosis Phenotypes in Grey Matter

Eshaghi A, et al. UCL Institute of Neurology, London, UK

Can the rate and spatial distribution of cortical and deep gray matter volume loss discriminate among MS phenotypes and indicate degree of disability?

• 820 subjects with longitudinal T1-weighted MRIs from 4 MS centers (London, n=446; Amsterdam, n=212; Siena, n=134; and Rome, n=28) were retrospectively included.

• Researchers used 2377 T1-weighted scans from a total of 155 healthy controls and 655 MS patients.

♦ 96 clinically isolated syndrome (CIS), 388 relapsing remitting MS (RRMS), 102 primary-progressive MS (PPMS), and 79 secondary-progressive MS (SPMS)

• Average follow-up was 4.02 years.

• Results

♦ all patient phenotypes showed lower gray matter volume than controls

♦ at follow-up, progressive patients had fastest total, cortical, and deep gray matter atrophy rate

♦ in all MS phenotypes, atrophy rate was fastest in deep gray matter and slowest in cerebellum and occipital lobe

♦ in all patients, annual changes in deep gray matter were associated with EDSS changes, but not with cortical gray matter

• Conclusion: although the rate is fastest in progressive MS, all phenotypes have a similar regional order of gray matter atrophy over time; progressive gray matter volume loss is a stronger predictor of EDSS changes than cortical gray matter

Physical Exercise-Related Changes in Structural Connectome Architecture in Patients with Relapsing-Remitting Multiple Sclerosis         

Hodecker SC, et al. University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Will changes of connectome properties and architecture be noted after a 24-week exercise intervention?

• 24-week RCT of progressive resistance training

• all patients had relapsing-remitting MS; cranial MRIs were taken at baseline, week 24, and week 48

♦ mean age, 44; median Expanded Disability Status Scale, 3

♦ training group (n=17) & waitlist group (n=12); waitlist group offered training after trial

• researchers investigated changes in different connection classes: within rich-club, between rich-club and non rich-club hubs (feeder connections), peripheral connections

• Results

♦ no significant differences in global graph metrics between pre- and post-exercise connectomes

♦ connectomes had a preserved rich-club architecture

♦ after exercise, amount of rich-club connections did not change significantly

♦ significant increase in relative amount of feeder connections (P<0.05) and decrease in relative amount of peripheral connections (P<0.05)

♦ connectivity loss was inversely pronounced in feeder connections during waiting phase

• Conclusion: exercise may provide neuroprotection

♦ “rich-club” connectivity appeared stable with or without exercise, while feeder connection losses between peripheral and “rich-club” regions were reduced

Lesion Accumulation Rate Is Higher in Cortex than in White Matter and Associated with Cortical Thinning in Multiple Sclerosis: a Longitudinal 7T Study

Granberg T, et al., Karolinska Institutet, Stockholm, Sweden

Can 7T and 3T MRI images show the relative contribution of cortical and white matter lesions and subcortical pathology accumulation on neurodegeneration in MS?

• Longitudinal study using 7T T2-weighted imaging (manual segmentation of white matter lesions, intracortical & leukocortical lesions) and 3T scans (cortical thickness, corpus callosum volume, thalamic volume)

• 18 patients (3 clinically isolated syndrome, 9 relapsing-remitting MS, 6 secondary progressive MS) and 6 controls

♦ MS patients: age, 42±10 years; disease duration, 13±8.0 years; median Expanded Disability Status Scale (EDSS) 2.5, range 1.0-6.5; follow-up, 1.7±0.5 years

♦ controls: age, 39±9.4 years; follow-up, 1.8±0.6 years

• Results in MS patients

♦ at baseline, intracortical & leukocortical lesions found in 17 and 13 patients, respectively

♦ annual lesion accumulation rate higher in cortex 14±18% than in white matter (4.2±22%)

♦ thinner cortices than controls (2.42±0.09 vs. 2.50±0.08 mm)

♦ cortical lesion accumulation associated with more pronounced cortical thinning (0.52, P=0.03)

♦ higher EDSS and lower cognitive index found with

► higher cortical lesion volume (0.71, P=0.001; -0.52, p=0.03)

► white matter lesions (0.72, P=0.001; -0.57, P=0.02)

► lower normalized thalamic volume (-0.63, P=0.003; 0.64, P=0.006)

♦ higher EDSS found with

► lower normalized corpus callosum volume (-0.64, P=0.004) and cortical thickness (-0.52, P=0.03)

• Conclusion: cortical lesions are clinically important and associated with neurodegeneration in MS

♦ Cortical lesion accumulation rate higher than white matter lesion and found with cortical thinning

In vivo Translocator Protein Positron Emission Tomography Imaging Detects a Heterogeneity of Lesion Inflammatory Activity in Multiple Sclerosis Not Evident by MRI

Datta G, et al., Imperial College London, London, UK

In patients with MS, will translocator protein (TSPO) PET show microglial activation in white matter lesions?

• 36 MS patients and 33 age-matched controls underwent PET scan with high affinity TSPO ligand and 3T MRI

♦ MS patients: 24 females, aged 22-66, EDSS 1.0-7.0, 7 secondary-progressive MS, 29 relapsing-remitting MS

♦ controls: 14 females, aged 20-65

• 4 lesion classes of lesions found, based on distribution volume ratio differences of >5% between individual white matter lesions, peri-lesional volume, and normal appearing white matter

♦ active: distribution volume ratio in lesion > normal appearing white matter

♦ inactive: distribution volume ratio in lesion & peri-lesional volume < normal appearing white matter

♦ chronic active: distribution volume ratio in peri-lesional volume > in lesion and normal appearing white matter

♦ undifferentiated: distribution volume ratio about = across three regions

• Results

♦ for both tracers, uptake in normal appearing white matter was increased compared with controls’ white matter

♦ active lesions found in all MS patients

♦ patients with secondary-progressive MS or disease duration >16 years had about 50% more inactive lesions than patients with relapsing-remitting MS or disease duration <8 years

♦ association was found between distribution volume ratio in white matter lesions and EDSS [18F]PBR111 (Spearman’s P=0.69, P=0.027) and [11C]PBR28 group (P=0.37, P=0.073)

• Conclusion: a variety of inflammatory activity was found among lesions, which is consistent with other neuropathologic studies; these active inflammatory lesions were seen across disease stages and treatments