TY - JOUR
T1 - Longitudinal spinal cord atrophy in multiple sclerosis using the generalized boundary shift integral
AU - Moccia, Marcello
AU - Prados, Ferran
AU - Filippi, Massimo
AU - Rocca, Maria A.
AU - Valsasina, Paola
AU - Brownlee, Wallace J.
AU - Zecca, Chiara
AU - Gallo, Antonio
AU - Rovira, Alex
AU - Gass, Achim
AU - Palace, Jacqueline
AU - Lukas, Carsten
AU - Vrenken, Hugo
AU - Ourselin, Sebastien
AU - Gandini Wheeler-Kingshott, Claudia A. M.
AU - Ciccarelli, Olga
AU - Barkhof, Frederik
AU - MAGNIMS Study Group
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Objective: Spinal cord atrophy is a clinically relevant feature of multiple sclerosis (MS), but longitudinal assessments on magnetic resonance imaging using segmentation-based methods suffer from measurement variability, especially in multicenter studies. We compared the generalized boundary shift integral (GBSI), a registration-based method, with a standard segmentation-based method. Methods: Baseline and 1-year spinal cord 3-dimensional T1-weighted images (1mm isotropic) were obtained from 282 patients (52 clinically isolated syndrome [CIS], 196 relapsing–remitting MS [RRMS], 34 progressive MS [PMS]), and 82 controls from 8 MAGNIMS (Magnetic Resonance Imaging in Multiple Sclerosis) sites on multimanufacturer and multi–field-strength scans. Spinal Cord Toolbox was used for C2-5 segmentation and cross-sectional area (CSA) calculation. After cord straightening and registration, GBSI measured atrophy based on the probabilistic boundary-shift region of interest. CSA and GBSI percentage annual volume change was calculated. Results: GBSI provided similar rates of atrophy, but reduced measurement variability compared to CSA in all MS subtypes (CIS: −0.95 ± 2.11% vs −1.19 ± 3.67%; RRMS: −1.74 ± 2.57% vs −1.74 ± 4.02%; PMS: −2.29 ± 2.40% vs −1.29 ± 3.20%) and healthy controls (0.02 ± 2.39% vs −0.56 ± 3.77%). GBSI performed better than CSA in differentiating healthy controls from CIS (area under the curve [AUC] = 0.66 vs 0.53; p = 0.03), RRMS (AUC = 0.73 vs 0.59; p < 0.001), PMS (AUC = 0.77 vs 0.53; p < 0.001), and patients with disability progression from patients without progression (AUC = 0.59 vs 0.50; p = 0.04). Sample size to detect 60% treatment effect on spinal cord atrophy over 1 year was lower for GBSI than CSA (CIS: 106 vs 830; RRMS: 95 vs 335; PMS: 44 vs 215; power = 80%; alpha = 5%). Interpretation: The registration-based method (GBSI) allowed better separation between MS patients and healthy controls and improved statistical power, when compared with a conventional segmentation-based method (CSA), although it is still far from perfect. ANN NEUROL 2019.
AB - Objective: Spinal cord atrophy is a clinically relevant feature of multiple sclerosis (MS), but longitudinal assessments on magnetic resonance imaging using segmentation-based methods suffer from measurement variability, especially in multicenter studies. We compared the generalized boundary shift integral (GBSI), a registration-based method, with a standard segmentation-based method. Methods: Baseline and 1-year spinal cord 3-dimensional T1-weighted images (1mm isotropic) were obtained from 282 patients (52 clinically isolated syndrome [CIS], 196 relapsing–remitting MS [RRMS], 34 progressive MS [PMS]), and 82 controls from 8 MAGNIMS (Magnetic Resonance Imaging in Multiple Sclerosis) sites on multimanufacturer and multi–field-strength scans. Spinal Cord Toolbox was used for C2-5 segmentation and cross-sectional area (CSA) calculation. After cord straightening and registration, GBSI measured atrophy based on the probabilistic boundary-shift region of interest. CSA and GBSI percentage annual volume change was calculated. Results: GBSI provided similar rates of atrophy, but reduced measurement variability compared to CSA in all MS subtypes (CIS: −0.95 ± 2.11% vs −1.19 ± 3.67%; RRMS: −1.74 ± 2.57% vs −1.74 ± 4.02%; PMS: −2.29 ± 2.40% vs −1.29 ± 3.20%) and healthy controls (0.02 ± 2.39% vs −0.56 ± 3.77%). GBSI performed better than CSA in differentiating healthy controls from CIS (area under the curve [AUC] = 0.66 vs 0.53; p = 0.03), RRMS (AUC = 0.73 vs 0.59; p < 0.001), PMS (AUC = 0.77 vs 0.53; p < 0.001), and patients with disability progression from patients without progression (AUC = 0.59 vs 0.50; p = 0.04). Sample size to detect 60% treatment effect on spinal cord atrophy over 1 year was lower for GBSI than CSA (CIS: 106 vs 830; RRMS: 95 vs 335; PMS: 44 vs 215; power = 80%; alpha = 5%). Interpretation: The registration-based method (GBSI) allowed better separation between MS patients and healthy controls and improved statistical power, when compared with a conventional segmentation-based method (CSA), although it is still far from perfect. ANN NEUROL 2019.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85070923988&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31385358
U2 - 10.1002/ana.25571
DO - 10.1002/ana.25571
M3 - Article
C2 - 31385358
SN - 0364-5134
VL - 86
SP - 704
EP - 713
JO - Annals of Neurology
JF - Annals of Neurology
IS - 5
ER -