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

Abstract

Background: 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. Methods: 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. Results: 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. Discussion: 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.