Author Of 2 Presentations
P0626 - Quantitative Susceptibility Mapping at 7 Tesla detects ongoing active lesions in relapse-free RRMS patients (ID 1540)
Abstract
Background
Microglia are iron-rich cells, found surrounding multiple sclerosis (MS) lesions in areas of active inflammation. Quantitative Susceptibility Mapping (QSM) can detect this increased iron and thus could be a novel MRI biomarker for microglia-associated inflammation in the brain. The proportion of patients with active inflammation is currently unknown, as is the proportion of MS lesions seen on conventional MRI sequences that are active across patients. Ultra-high field MRI (7 Tesla +) provides superior signal to noise and susceptibility contrast making it the optimal method for detecting iron in MS lesions and tracking active inflammation.
Objectives
To compare the number of lesions with positive QSM signal indicating active inflammation with lesion size and number in patients with relapsing-remitting MS (RRMS) using 7T MRI.
Methods
21 people with RRMS (mean ± SD age = 42 ± 11 yrs; sex: 2m/19f; mean ± SD disease duration = 5.5 ± 3.2 yrs; all EDSS < 4; no relapses in previous 12 months) were scanned using MP2RAGE anatomical and multi-echo gradient echo sequences on a Siemens 7T MAGNETOM MRI scanner. MP2RAGE was used to identify lesions and then co-registered to QSM (calculated from gradient echo phase images using an in-house pipeline). The number of lesions with an average QSM value over 0 (QSM+), indicating the presence of iron associated with active inflammation, were compared to the total number and total volume (log10 transformed) of lesions across patients using linear regression.
Results
The number of lesions in patients ranged from 3 to 92 (mean ± SD = 33 ± 25) and volumes ranged from 26 to 14505 mm3 (mean ± SD = 2554 ± 3445 mm3). Across all patients, the average proportion of QSM+ lesions was 0.61 (95% CI = 0.50-0.72, R2=0.87, p<0.0001), and for each log10 cubic millimeter change in the lesion volume, there were an additional 15 QSM+ lesions (95% CI = 7.0-24, R2=0.43, p=0.0012). There were no associations between the proportion of QSM+ lesions and any disease or demographic variables.
Conclusions
Irrespective of disease severity or duration, the proportion of QSM+ lesions was highly consistent. Based on the assumption that QSM+ lesions are undergoing active inflammation, our results indicate that around ~60% of lesions in RRMS patients could be active.
P0636 - Relationship of real-world brain atrophy to MS disability using icobrain: 4 centre pilot study (ID 716)
- A. Nguyen
- D. Horakova
- E. Havrdova
- M. Barnett
- M. Sormani
- E. Lui
- F. Gaillard
- P. Desmond
- H. Prime
- M. Datta
- A. Van Der Walt
- V. Jokubaitis
- B. Weinstock-Guttman
- M. D’hooghe
- G. Nagels
- V. Van Pesch
- G. Laureys
- L. Van Hijfte
- J. Lechner-Scott
- F. Patti
- E. Cristiano
- J. Rojas
- D. Sima
- W. Van Hecke
- T. Kalincik
- H. Butzkueven
Abstract
Background
To date, no studies have explored the relationship between brain atrophy and MS disability using differing MRI protocols and scanners at multiple sites.
Objectives
To assess the association between brain atrophy and MS disability, as measured by EDSS and 6-month confirmed disability progression (CDP).
Methods
In this retrospective study at 4 MS centres, a total of 1300 patients had brain MRI imaging assessed by icobrain. Relapse-onset MS patients were included if they had two clinical MRIs 12 (±3) months apart and ≥2 EDSS scores post MRI-2, the first ≤3 months from MRI-2, with ≥6 months between first and last EDSS. Volumetric data were analysed if the alignment similarity between two images was as good as that of same-scanner scan-rescan images (normalised mutual information ≥0.2). The percentage brain volume change (PBVC), percentage grey matter change (PGMC), FLAIR lesion volume change, whole brain volume, grey matter volume, FLAIR lesion volume and T1 hypointense lesion volume at MRI-2 were calculated. Ordinal mixed effect models were used to determine the association between these volumetric MRI measures and all EDSS scores post MRI-2. Cox proportional hazards models were used for the 6-month CDP outcome, using a subset of patients with ≥3 EDSS. Models were adjusted for proportion of time spent on disease-modifying therapy during MRIs ± whole brain/grey matter volume at baseline MRI.
Results
Of the 260 relapse-onset MS patients included, 204 (78%) MRI pairs were performed in the same scanner and 56 (22%) pairs were from different scanners. During the follow-up period (median 3.8 years, range 1.3-8.9), 29 of 244 (12%) patients experienced 6-month CDP. There was no evidence for association between annualised PBVC or PGMC and CDP or EDSS (p>0.05). Cross-sectional whole brain and grey matter volume (at MRI-2) tended to associate with CDP (HR 0.99, 95% CI 0.98-1.00, p=0.06). Every 1ml of whole brain or grey matter volume lost represented a 1% higher chance of reaching 6-month CDP. Only whole brain volume (at MRI-2) was associated with EDSS score (β -0.03, SE 0.01, p<0.001) and the slope of EDSS change over time (β -0.001, SE 0.0003, p=0.02). On average, every 33ml reduction of brain volume was associated with a 1 step increase in EDSS.
Conclusions
In this real-world clinical setting where a fifth of the brain atrophy analysis were performed on different scanners, we found no association between individual brain atrophy and MS disability. However, there was an association between cross-sectional whole brain volume with EDSS and slope of EDSS change.