title: Estimating Brain Lesion Volume Change in Multiple Sclerosis by Subtraction of Magnetic Resonance Images.
abstract: Change in lesion volume over time, measured on brain magnetic resonance imaging (MRI) scans, is an important outcome measure for natural history studies and clinical trials in multiple sclerosis (MS).
  
  
  
  To develop and test image analysis methods for quantification of lesion volume change in order to improve reliability.
  
  
  
  The technique is based on registration and subtraction, and was evaluated in a cohort of 20 MS patients with dual-echo images acquired annually over a period of four years. The study protocol was approved by the local ethics review boards of participating centers, and all subjects gave written informed consent. The repeatability was compared to that obtained by the standard method for obtaining lesion volume change by evaluating the total volume at each time point, and then subtracting the volumes to obtain the difference.
  
  
  
  Compared to the standard method, the subtraction method had improved intrarater correlation (0.95 and 0.72 for the subtraction method and the standard method, respectively) and interrater correlation (0.51 and 0.28, respectively). Furthermore, the mean time required to analyze the scans from one patient was 41 minutes for the subtraction method compared to 125 minutes for the standard method.
  
  
  
  Use of the subtraction algorithm leads to improved reliability and lower operator fatigue in clinical trials and studies of the natural history of MS.
authors.affiliation: Xinapse Systems Ltd, Colchester, Essex, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Horsfield
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rocca
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pagani
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Loredana
authors.initials: L
authors.lastname: Storelli
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Preziosa
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Messina
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Fabiano
authors.initials: F
authors.lastname: Camesasca
authors.affiliation: Biostatistics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.affiliation: Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Filippi
mesh_terms: D000328:Adult; D000465:Algorithms; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging* / Q000473:pathology; D015588:Observer Variation; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013382:Subtraction Technique
keywords: Lesion volume; MRI; longitudinal; multiple sclerosis