title: Development of an Automated MRI-Based Diagnostic Protocol for Amyotrophic Lateral Sclerosis Using Disease-Specific Pathognomonic Features: A Quantitative Disease-State Classification Study.
abstract: BACKGROUND
  Despite significant advances in quantitative neuroimaging, the diagnosis of ALS remains clinical and MRI-based biomarkers are not currently used to aid the diagnosis. The objective of this study is to develop a robust, disease-specific, multimodal classification protocol and validate its diagnostic accuracy in independent, early-stage and follow-up data sets.
  
  
  METHODS
  147 participants (81 ALS patients and 66 healthy controls) were divided into a training sample and a validation sample. Patients in the validation sample underwent follow-up imaging longitudinally. After removing age-related variability, indices of grey and white matter integrity in ALS-specific pathognomonic brain regions were included in a cross-validated binary logistic regression model to determine the probability of individual scans indicating ALS. The following anatomical regions were assessed for diagnostic classification: average grey matter density of the left and right precentral gyrus, the average fractional anisotropy and radial diffusivity of the left and right superior corona radiata, inferior corona radiata, internal capsule, mesencephalic crus of the cerebral peduncles, pontine segment of the corticospinal tract, and the average diffusivity values of the genu, corpus and splenium of the corpus callosum.
  
  
  RESULTS
  Using a 50% probability cut-off value of suffering from ALS, the model was able to discriminate ALS patients and HC with good sensitivity (80.0%) and moderate accuracy (70.0%) in the training sample and superior sensitivity (85.7%) and accuracy (78.4%) in the independent validation sample.
  
  
  CONCLUSIONS
  This diagnostic classification study endeavours to advance ALS biomarker research towards pragmatic clinical applications by providing an approach of automated individual-data interpretation based on group-level observations.
authors.affiliation: Quantitative Neuroimaging Group, Academic Unit of Neurology, Biomedical Sciences Institute, Trinity College Dublin, Ireland.
authors.forename: Christina
authors.initials: C
authors.lastname: Schuster
authors.affiliation: Quantitative Neuroimaging Group, Academic Unit of Neurology, Biomedical Sciences Institute, Trinity College Dublin, Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Hardiman
authors.affiliation: Quantitative Neuroimaging Group, Academic Unit of Neurology, Biomedical Sciences Institute, Trinity College Dublin, Ireland.
authors.forename: Peter
authors.initials: P
authors.lastname: Bede
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging* / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D016015:Logistic Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D066127:White Matter / Q000473:pathology