Table 1. Longitudinal MRI biomarkers of disability progression.
| MRI metric | Description | Effect size | References |
|---|---|---|---|
| Atrophied lesion volume | Atrophied T2 lesion volume was significantly increased in MS/CIS patients with conversion to disability progression compared to patients without conversion | 93 vs. 59 mm3; d=0.27; P<0.001 | Genovese et al., 2019 (10) |
| Whole brain atrophy | Brain parenchymal fraction change was significantly increased in RRMS patients with confirmed disability progression compared to stable patients | −1.68% vs. −0.90%; P=0.01 | Rudick et al., 2000 (3) |
| Percentage brain volume change was greater in RRMS patients with sustained disability progression compared to stable patients | −4.8% vs. −2.6%; P<0.001 | Zivadinov et al., 2013 (4) | |
| Percentage brain volume change was greater in RRMS patients with confirmed disability progression compared to stable patients | −7.5% vs. −5.2%; d=0.55; P<0.001 | Zivadinov et al., 2016 (5) | |
| The difference between expected normalized brain volume (NBV) vs. observed brain volume (a surrogate for atrophy) was significantly correlated with 2-year probability of 3 month confirmed disability worsening | HR 1.69 (for low NBV vs. high NBV); CI: 1.11, 2.57; P=0.01 | Bovis et al., 2019 (2) | |
| Grey matter atrophy | Baseline grey matter volume predicted progression of EDSS in RRMS patients | OR 0.85; CI 0.77, 0.93 | Lavorgna et al., 2014 (11) |
| Grey matter volume change predicted absolute change in EDSS at 24 months in RRMS patients | R2=0.028; P=0.001 | Horakova et al., 2009 (12) | |
| Percentage grey matter volume change was greater in RRMS patients with confirmed disability progression compared to stable patients | −7.1% vs. −5.8%; d=0.40; P<0.006 | Zivadinov et al., 2016 (5) | |
| Thalamic atrophy | Thalamic atrophy was greater in RRMS patients with sustained disability progression compared to stable patients | −6.2% vs. −4.5%; P=0.01 | Zivadinov et al., 2013 (4) |
| Baseline thalamic fraction predicted worsening disability at 8 years in RRMS | OR 0.62; CI 0.42, 0.91; P=0.01 | Rocca et al., 2010 (13) | |
| Lateral ventricular volume change | Ventricular CSF volume change was greater in RRMS patients with confirmed disability progression compared to stable RRMS patients | 41.1% vs. 25.7%; d=0.51; P<0.001 | Zivadinov et al., 2016 (5) |
| Percent ventricular CSF change from baseline to 120 months separated patients with confirmed disability progression from stable patients | VIENA: 49.7% vs. 32.4%; d=0.5; P=0.003. NeuroSTREAM: 45.7% vs. 31.2%; d=0.46; P=0.007 | Dwyer et al., 2017 (14) | |
| Spinal cord atrophy | Upper cervical spinal cord volume change was correlated with EDSS worsening over time in MS | B=2.1×10−5; P<0.05 | Tsagkas et al., 2018 (15) |
| Grey matter diffusion | Normal appearing cortical grey matter FA change in RRMS over 3 years separated patients with EDSS score worsening vs. EDSS Score stable | 0.170 (±0.011) vs. 0.154 (±0.012); P≤0.05 | Calabrese et al., 2011 (16) |
| White matter lesion MTR | Lesion MTR was significantly lower and increasing in patients with MSFC disability progression compared to stable MS patients | H=4.604; P=0.32 | Zheng et al., 2018 (17) |
| Connectome analysis | Higher Network efficiency (shorter mean shortest path length) at baseline defined by structural cortical networks predicted faster progressors compared to slower progressors in PPMS | 3.14 vs. 3.63; P=0.04 (no significant difference in connectivity change over 5 years between slow and fast progressors) | Tur et al., 2019 (18) |
MRI, magnetic resonance imaging; CIS, clinically isolated syndrome; MS, multiple sclerosis; RRMS, relapsing remitting MS; MTR, magnetization transfer ratio.