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Ther Adv Neurol Disord. 2019 Jan 25;12:1756286418823462. doi: 10.1177/1756286418823462. eCollection 2019.

Comparing longitudinal brain atrophy measurement techniques in a real-world multiple sclerosis clinical practice cohort: towards clinical integration?

Author information

Brain and Mind Centre, The University of Sydney, Sydney, Australia Royal Prince Alfred Hospital, Sydney, Australia.
Brain and Mind Centre, The University of Sydney, Sydney, Australia Sydney Neuroimaging Analysis Centre, Sydney, Australia.
icometrix, Leuven, Belgium.
Royal Prince Alfred Hospital, Sydney, Australia Sydney Neuroimaging Analysis Centre, Sydney, Australia.



Whole brain atrophy (WBA) estimates in multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. We compare Structural Image Evaluation using Normalisation of Atrophy (SIENA) with the icobrain longitudinal pipeline (icobrain long), for assessment of longitudinal WBA in MS patients.


Magnetic resonance imaging (MRI) scan pairs [1.05 (±0.15) year separation] from 102 MS patients were acquired on the same 3T scanner. Three-dimensional (3D) T1-weighted and two-dimensional (2D)/3D fluid-attenuated inversion-recovery sequences were analysed. Percentage brain volume change (PBVC) measurements were calculated using SIENA and icobrain long. Statistical correlation, agreement and consistency between methods was evaluated; MRI brain volumetric and clinical data were compared. The proportion of the cohort with annualized brain volume loss (aBVL) rates ⩾ 0.4%, ⩾0.8% and ⩾0.94% were calculated. No evidence of disease activity (NEDA) 3 and NEDA 4 were also determined.


Mean annualized PBVC was -0.59 (±0.65)% and -0.64 (±0.73)% as measured by icobrain long and SIENA. icobrain long and SIENA-measured annualized PBVC correlated strongly, r = 0.805 (p < 0.001), and the agreement [intraclass correlation coefficient (ICC) 0.800] and consistency (ICC 0.801) were excellent. Weak correlations were found between MRI metrics and Expanded Disability Status Scale scores. Over half the cohort had aBVL ⩾ 0.4%, approximately a third ⩾0.8%, and aBVL was ⩾0.94% in 28.43% and 23.53% using SIENA and icobrain long, respectively. NEDA 3 was achieved in 35.29%, and NEDA 4 in 15.69% and 16.67% of the cohort, using SIENA and icobrain long to derive PBVC, respectively.


icobrain long quantified longitudinal WBA with a strong level of statistical agreement and consistency compared to SIENA in this real-world MS population. Utility of WBA measures in individuals remains challenging, but show promise as biomarkers of neurodegeneration in MS clinical practice. Optimization of MRI analysis algorithms/techniques are needed to allow reliable use in individuals. Increased levels of automation will enable more rapid clinical translation.


MSmetrix; NEDA; SIENA; brain atrophy; brain volume loss; icobrain; magnetic resonance imaging; multiple sclerosis; percentage brain volume change

Conflict of interest statement

Conflict of interest statement: Heidi Beadnall has received compensation for education travel, speaker honoraria and/or consultant fees from Biogen, Novartis, Merck, Sanofi Genzyme and Roche. Chenyu Wang has nothing to disclose. Wim Van Hecke is the CEO and co-founder of icometrix. Annemie Ribbens and Thibo Billiet are employees of icometrix. Michael H Barnett has received institutional support for research, speaking and/or participation in advisory boards (Biogen, Novartis, and Sanofi Genzyme); research consultant (Medical Safety Systems).

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