BACKGROUND: There is a need for a brain volume measure applicable to the clinical routine scans. Nearly every multiple sclerosis (MS) protocol includes low-resolution 2D T2-FLAIR imaging. OBJECTIVES: To develop and validate cross-sectional and longitudinal brain atrophy measures on clinical-quality T2-FLAIR images in MS patients. METHODS: A real-world dataset from 109 MS patients from 62 MRI scanners was used to develop a lateral ventricular volume (LVV) algorithm with a longitudinal Jacobian-based extension, called NeuroSTREAM. Gold-standard LVV was calculated on high-resolution T1 1 mm, while NeuroSTREAM LVV was obtained on low-resolution T2-FLAIR 3 mm thick images. Scan-rescan reliability was assessed in 5 subjects. The variability of LVV measurement at different field strengths was tested in 76 healthy controls and 125 MS patients who obtained both 1.5T and 3T scans in 72 hours. Clinical validation of algorithm was performed in 176 MS patients who obtained serial yearly MRI 1.5T scans for 10 years. RESULTS: Correlation between gold-standard high-resolution T1 LVV and low-resolution T2-FLAIR LVV was r = 0.99, p < 0.001 and the scan-rescan coefficient of variation was 0.84%. Correlation between low-resolution T2-FLAIR LVV on 1.5T and 3T was r = 0.99, p < 0.001 and the scan-rescan coefficient of variation was 2.69% cross-sectionally and 2.08% via Jacobian integration. NeuroSTREAM showed comparable effect size (d = 0.39-0.71) in separating MS patients with and without confirmed disability progression, compared to SIENA and VIENA. CONCLUSIONS: Brain atrophy measurement on clinical quality T2-FLAIR scans is feasible, accurate, reliable, and relates to clinical outcomes.

Buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at Buffalo State University of New York Buffalo NY USA

Buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at Buffalo State University of New York Buffalo NY USA; Magnetic Resonance Laboratory IRCCS Don Gnocchi Foundation Milan Italy

Buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at Buffalo State University of New York Buffalo NY USA; MR Imaging Clinical Translational Research Center Jacobs School of Medicine and Biomedical Sciences University at Buffalo State University of New York Buffalo NY USA

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Radiology 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Novartis Pharma AG Basel Switzerland

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