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![Multiple hyperintense
lesions in the spinal cord
Rovaris et al., Brain 2001
Spinal cord / T2 lesions
MRI & Progressive MS
Number of cord lesions Number of damaged
cord segments
0.0
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Rovarisetal.,Brain2001
PPMSSPMSControls](https://image.slidesharecdn.com/mrimarkerstounderstandprogression-140320114636-phpapp01/85/MRI-markers-to-understand-progression-6-320.jpg)
![Average MD
[x10-3mm2s-1] (SD)
Mean FA
(SD)
Controls
1.203
(0.09)
0.42
(0.04)
PPMS
1.280
(0.10)
0.38
(0.05)
p
0.024
0.007
Agosta et al., Neurology 2005
MRI & Progressive MS
Spinal cord / Diffuse damage
Composite MR model vs EDSS:
Cord area + cord MTR peak height
(r=0.21, p=0.04)
Rovaris et al., Brain 2001
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PPMS](https://image.slidesharecdn.com/mrimarkerstounderstandprogression-140320114636-phpapp01/85/MRI-markers-to-understand-progression-21-320.jpg)
![Tactile stimulation of the palm of the R hand
Progressive MS vs controls: p=0.003
SPMS vs PPMS: p=0.05
Cordaveragesignalchange(%)
Controls
SPMS
PPMS
Valsasina et al., Hum Brain Mapp 2011
MRI & Progressive MS
CNS reorganization / Spinal cord
Valsasina et al., JNNP 2010
Controls RRMS SPMS
3.9 %
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Rocca et al., Mult Scler 2012](https://image.slidesharecdn.com/mrimarkerstounderstandprogression-140320114636-phpapp01/85/MRI-markers-to-understand-progression-28-320.jpg)
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MRI markers to understand progression
The document discusses neuroimaging research focusing on MRI markers to understand mechanisms of disease progression in multiple sclerosis (MS). It details findings related to white matter (WM) lesions, brain atrophy, gray matter (GM) damage, and spinal cord issues, along with their implications for clinical outcomes. Studies presented cover various forms of MS, including relapsing forms and primary progressive MS, highlighting correlations between imaging results and clinical disability over time.
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MRI markers to understand progression
- 1. Neuroimaging Research Unit,Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy. MRI MARKERS TO UNDERSTAND PROGRESSION MECHANISMS Maria A. Rocca
- 2. • WM lesions:brain, spinal cord • Atrophy • WM damage: extent, topography • GM damage: cortical lesions, diffuse and regional damage • Spinal cord damage • CNS reorganization (brain, spinal cord) • Conclusions • WM lesions: brain, spinal cord • Atrophy • WM damage: extent, topography • GM damage: cortical lesions, diffuse and regional damage • Spinal cord damage • CNS reorganization (brain, spinal cord) • Conclusions MRI & Progressive MS Outline of presentation
- 3. SPMS 60 SPMS withmonthly brain MRI for 4 months 32 (53%) had enhancing lesions at baseline 42 (70%) displayed one or more new enhancing lesions at follow-up 14 (23%) showed no enhancing lesions either at baseline or follow-up Tubridyetal.,Neurology1998 Khaleelietal.,MultScler2010 PPMS 45 PPMS with brain and spinal cord MRI for 5 years 15 (33%) had enhancing lesion at baseline 12 (26%) had enhancing lesion at 5 year 26 (58%) had ≥1 enhancing lesion during the study 19 (42%) had no enhancing lesion during the study MRI & Progressive MS Brain WM lesions / Enhancement
- 4. Khaleeli et al.,Ann Neurol 2008 101 PPMS followed up for 10 yrs MRI & Progressive MS Brain WM lesions / Prognosis Mesarosetal.,JNeurol2008 RRMS Sormani et al., Neurology 2009 • Similar slope of the relationship between baseline T2LV and EDSS in RRMS and SPMS • Median yearly T2LV change: 0.27 mL in RRMS, and 0.30 mL in SPMS (p=0.59) T2 lesions
- 5. MRI & ProgressiveMS Brain WM lesions / Distribution Ceccarellietal.,NeuroImage2008 CIS RR SP PP T2 lesion maps Bodinietal.,JNNP2011 T2 lesion location vs disability worsening T1 lesion maps PPMS PP vs RR: 29 vs 19% peak probability DiPerrietal.,ArchNeurol2008 • Higher T1 lesion occurrence in the CC, CST and other tracts adjacent to the lateral ventricles in SPMS vs RRMS Filli et al., MSJ 2012
- 6. Multiple hyperintense lesions inthe spinal cord Rovaris et al., Brain 2001 Spinal cord / T2 lesions MRI & Progressive MS Number of cord lesions Number of damaged cord segments 0.0 1.0 2.0 3.0 4.0 5.0 0.0 1.0 2.0 3.0 4.0 5.0 6.0 p = 0.03 0.0 30.0 60.0 90.0 Cord area [mm2] Rovarisetal.,Brain2001 PPMSSPMSControls
- 7. • WM lesions:brain, spinal cord • Atrophy • WM damage: extent, topography • GM damage: cortical lesions, diffuse and regional damage • Spinal cord damage • CNS reorganization (brain, spinal cord) • Conclusions MRI & Progressive MS Outline of presentation
- 8. Atrophy MRI & ProgressiveMS 1 y FU: 963 untreated MS patients De Stefano et al., Neurology 2010 p = 0.003 Dalton et al., Neurology 2006 CIS MS (<1 year) RRMS SPMS n.s. p=0.003 p=0.001 p=0.001 Ventricularvolumechange 21 CIS, 30 early relapse-onset, 41 RRMS, 23 SPMS
- 9. Atrophy Fisher et al.,Ann Neurol 2008 GM atrophy rates: CIS→RRMS and RRMS stable > HC (p=0.05) RRMS→SPMS and SPMS > HC (p= 0.005) WM atrophy rates similar in all disease groups MRI & Progressive MS NGMV NWMV ** p<0.001 * p<0.01 GM atrophy explains physical disability and cognitive impairment better than WM volume Roosendaal et al., MSJ 2011 ** p<0.001 * p<0.01
- 10. MRI & ProgressiveMS Outline of presentation • WM lesions: brain, spinal cord • Atrophy • WM damage: extent, topography • GM damage: cortical lesions, diffuse and regional damage • Spinal cord damage • CNS reorganization (brain, spinal cord) • Conclusions
- 11. Pulizzi et al.,Arch Neurol 2007 CIS vs HC PPMS vs HC 1 2 3 4 5 t value 2 4 6 8 t value MDFA RRMS vs BMS t value t value SPMS vs RRMS SPMS vs PPMS Preziosa et al., Radiology 2011 MRI & Progressive MS NAWM damage p=0.003 p=0.01 - p=0.004 RRMS BMS SPMS PPMS Tortorella et al., Neurology 2000
- 12. MRI & ProgressiveMS Outline of presentation • WM lesions: brain, spinal cord • Atrophy • WM damage: extent, topography • GM damage: cortical lesions, diffuse and regional damage • Spinal cord damage • CNS reorganization (brain, spinal cord) • Conclusions
- 13. Kutzelnigg et al.,Brain 2005 Focal demyelinated plaques in WM Cortical demyelination Demyelinated plaques in deep GM MRI & Progressive MS GM damage / Cortical lesions Extensive subpial demyelination of the cerebellum in a PPMS case
- 14. Baseline CL volume:B: -0.525, p <0.001 Baseline T2-WM-LV: B: -0.448, p <0.001 48 PPMS patients followed up for 2 years Calabrese et al., Neurology 2009 DIR and disease evolution MRI & PROGRESSIVE MS GM damage / Cortical lesionsMulti-slab 3D DIR Geurtsetal., Radiology2005 vs. SE = +538%; vs. FLAIR = +152% RRMS PPMS Calabreseetal.,Neurology2010 Cohen-Adad et al., NeuroImage 2011 T2*-w / 7 T
- 15. Power to discriminateSPMS from BMS Filippietal.,MSJ2012 MDFA Age: OR 1.2, p =0.001 Baseline CL volume: OR 1.7, p <0.001 Baseline cerebellar cortical volume: OR 0.2, p <0.001 334 relapse-onset MS patients, 5 years FU Calabrese et al., Ann Neurol 2013 MRI & Progressive MS GM damage / Cortical lesions Baseline CL volume: entire group: B=0.511; p<0.001 RRMS: B=0.512; p<0.001 SPMS: B=0.495; p<0.001 107 relapse-onset MS patients, 3-year FU Calabrese et al., Ann Neurol 2010
- 16. Baseline GMF: OR0.79, p=0.01 C index: 69% 73 relapse-onset MS patients followed up for 13 years MRI & Progressive MS Evolution to SPMS at 13 year FU: Baseline T2 LV (OR=1.13, p=0.005) Baseline GMF (OR=0.71, p=0.04) C-index: 84% Cognitive deterioration at 13 year FU: Baseline average GM MTR (OR=0.87, p=0.03) Baseline disease duration (OR=1.50, p=0.08) C-index: 97% Baseline GMF: OR 0.79 (CI 0.7–0.9) Baseline EDSS: OR 2.88 (CI 1.9–4.36) 241 relapse-onset MS patients followed up for 9 years Lavorgna et al., MSJ 2013 “Diffuse” GM damage Filippi et al., Neurology 2013
- 17. MRI & ProgressiveMS “Regional” GM damage SPMS vs RRMS SPMS vs PPMS Ceccarelli et al., NeuroImage 2008 Selective GM loss
- 18. MRI & ProgressiveMS Outline of presentation • WM lesions: brain, spinal cord • Atrophy • WM damage: extent, topography • GM damage: cortical lesions, diffuse and regional damage • Spinal cord damage • CNS reorganization (brain, spinal cord) • Conclusions
- 19. C MRI & ProgressiveMS Spinal cord / Atrophy CSAn vs EDSS: r=-0.49, p<0.0001 EDSS CSAn Differential effect among disease clinical phenotypes (p<0.001): no association in CIS and BMS patients association in RRMS (r=-0.30), SPMS (r=-0.34) and PPMS patients (r=-0.27) Roccaetal.,Neurology2011
- 20. Roccaetal.,JNNP2013 BMS vs RRMSSPMS vs RRMS SPMS vs BMS SPMS vs PPMSPPMS vs HC P A L R P A L R P A L R P A L R P A L R T2 lesion probability RRMS BMS PPMS SPMSCIS MRI & Progressive MS Spinal cord damage
- 21. Average MD [x10-3mm2s-1] (SD) MeanFA (SD) Controls 1.203 (0.09) 0.42 (0.04) PPMS 1.280 (0.10) 0.38 (0.05) p 0.024 0.007 Agosta et al., Neurology 2005 MRI & Progressive MS Spinal cord / Diffuse damage Composite MR model vs EDSS: Cord area + cord MTR peak height (r=0.21, p=0.04) Rovaris et al., Brain 2001 0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70 80 Controls MTR [%] Normalizedpixelcount SPMS PPMS
- 22. MRI & ProgressiveMS Spinal cord damage Baseline cross-sectional area and FA vs EDSS at follow-up: r = -0.40; p = 0.01 Agosta et al., Brain 2007 -10% -5% 0 +5% +10% +15% +20% FA MD Cross- sectional area RRMS SPMS PPMS Overall UCCA, T1LV, diffuse abnormalities and number of involved segments were significant explanatory factors for clinical disability (R2 = 0.564) Lukas et al., Radiology 2013
- 23. MRI & ProgressiveMS Outline of presentation • WM lesions: brain, spinal cord • Atrophy • WM damage: extent, topography • GM damage: cortical lesions, diffuse and regional damage • Spinal cord damage • CNS reorganization (brain, spinal cord) • Conclusions
- 24. CIS vs non-disabled RRMS SMC Non-disabledvs mildly disabled RRMS SMC, SMA Mildly disabled RRMS vs SPMS Thalamus SII SPMS vs mildly disabled RRMS Precuneus, IPL, MFG MFG, IPL Precuneus, CMA, MFG Rocca et al., Lancet Neurol 2005 MRI & Progressive MS CNS reorganization / Brain
- 25. SPMS (reduced activations) LSMA L putamen R cerebellum Rocca et al., Neurology 2010 BMS L SMC vs T2 lesion volume: r = 0.63, p < 0.001 Rocca et al., Neurology 2010 MRI & Progressive MS CNS reorganization / Brain STG MFG Insula PPMS Filippi et al., NeuroImage 2002
- 26. Correlations between DMN fluctuations and: PASAT (r=0.42, p<0.001) CC FA and JD (r ranging from 0.54 to 0.87, p<0.001) Cingulum FA (r=0.83, p<0.001) Roccaetal.,Neurology2010 DMN fluctuations in progressive MS patients HC PPMS SPMS MRI & Progressive MS CNS reorganization / Brain
- 27. HC R ACC MCC OFC MTG ITG Cereb (cr I) Cereb (crII) L ACC SFG PrecunMCC ITG MTG Cereb (cr I) Cereb (cr II) Thal Put CP ACC MCC OFC ITG MTG Cereb (cr I) Cereb (VIII) Thal Pall ACC MCC OFC MTG ITGSup TP Cereb (cr I) Cereb (cr II) ThalCaud CI ACC MCC OFC ITG MTG Cereb (cr I) Put MCC ITG MTG Ling Cereb (cr II) Cereb (cr I) Cereb (IV-V) Sup TP ACC PrecunMCC MTG SFG Put ITG Thal Cer-crus-II Cer-crus-I MTG MCC ITG ACC OFC Cer-crus-II Cer-crus-I MTG MCC ACC ITGSupTP Cer-crus-I Cer-crus-II BMS ITG MTG MCC SupTP Thal Cer- crus-II Cer-crus-I Cer-lobule-VIII Cer-lobule-IV-V ITG MTG LingSupTP PHG Thal Cer-crus-II Cer-crus-I Cer-lobule-IV-V HCs SPMS RRMS BMS ACC MCC MTG ITG Pall OFC Put Cer-crus-I ACC Pall Put Thal ITG PHG LingMTG OFC Cer- lobule-VI Cer- crus-I MCC ACC OFC ITG MTG Ling Pall Thal Cer-crus-I Cer-crus-II Cer-lobule-VIII RLMRI & Progressive MS CNS reorganization / Brain
- 28. Tactile stimulation ofthe palm of the R hand Progressive MS vs controls: p=0.003 SPMS vs PPMS: p=0.05 Cordaveragesignalchange(%) Controls SPMS PPMS Valsasina et al., Hum Brain Mapp 2011 MRI & Progressive MS CNS reorganization / Spinal cord Valsasina et al., JNNP 2010 Controls RRMS SPMS 3.9 % 1.3 %3. 3 % 1.1 % 2.7 % 0.7 % Task-relatedaveragesignalchange[%] 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 p=0.05 vs controls p=0.02 vs controls Cord fMRI vs fatigue Rocca et al., Mult Scler 2012
- 29. MRI & ProgressiveMS Outline of presentation • T2 lesions: brain, spinal cord • Atrophy • WM damage: extent, topography • GM damage: cortical lesions, diffuse and regional damage • Spinal cord damage • CNS reorganization (brain, spinal cord) • Conclusions
- 30. MRI & ProgressiveMS Conclusions Modality Gd+ lesions Focal lesions Whole-brain atrophy NAWM damage GM damage Spinal cord damage Functional changes Potential clinical value - + ++ ++ +++ +++ ++ Feasibility +++ +++ +++ ++ ++ ++ +
- 31. RIS RRMS SPMS/PPMSCISTime Severity T2 lesions Atrophy Functional changes NAWM damage Cord damage GM damage Gd+ lesions MRI in SPMS Theoretical background
- 32. Neuroimaging Research Unit& WM diseases group Director: M. Filippi DIVISION OF NEUROSCIENCE INSTITUTE OF EXPERIMENTAL NEUROLOGY Scientific coordinator: M.A. Rocca Department of Neurology G. Comi, B. Colombo, M. Comola, F. Esposito, V. Martinelli, F. Martinelli Boneschi, L. Moiola, G. Pavan, M. Rodegher Department of Neuroradiology A. Falini MAGNIMS Physicians: M. Absinta A. Bisecco G. Boffa S. Cirillo E. De Meo G. Longoni F. Mele R. Messina M.E. Morelli L. Parisi P. Preziosa G. Riccitelli Physicists: M. Copetti E. Pagani P. Valsasina Technicians: L. Dall’Occhio A. Meani P. Misci M. Petrolini S. Sala M. Sibilia R. Vuotto University of Belgrade V.S. Kostic, J. Drulovic, S. Mesaros Gallarate Hospital, MS Centre A. Ghezzi