title: Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  Reliable biomarkers for amyotrophic lateral sclerosis (ALS) are needed, given the clinical heterogeneity of the disease. Here, we provide proof-of-concept for using multimodal magnetic resonance imaging (MRI) as a diagnostic biomarker for ALS. Specifically, we evaluated the added diagnostic utility of proton magnetic resonance spectroscopy (MRS) to diffusion tensor imaging (DTI).
  
  
  METHODS
  Twenty-nine patients with ALS and 30 age- and gender-matched healthy controls underwent brain MRI which used proton MRS including spectral editing techniques to measure γ-aminobutyric acid (GABA) and DTI to measure fractional anisotropy of the corticospinal tract. Data were analyzed using logistic regression, t-tests, and generalized linear models with leave-one-out analysis to generate and compare the resulting receiver operating characteristic (ROC) curves.
  
  
  RESULTS
  The diagnostic accuracy is significantly improved when the MRS data were combined with the DTI data as compared to the DTI data only (area under the ROC curves (AUC) = 0.93 vs. AUC = 0.81; P = 0.05). The combined MRS and DTI data resulted in sensitivity of 0.93, specificity of 0.85, positive likelihood ratio of 6.20, and negative likelihood ratio of 0.08 whereas the DTI data only resulted in sensitivity of 0.86, specificity of 0.70, positive likelihood ratio of 2.87, and negative likelihood ratio of 0.20.
  
  
  CONCLUSIONS
  Combining multiple advanced neuroimaging modalities significantly improves disease discrimination between ALS patients and healthy controls. These results provide an important step toward advancing a multimodal MRI approach along the diagnostic test development pathway for ALS.
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine Baltimore, Maryland ; Department of Radiology, University of Michigan Ann Arbor, Michigan ; Ann Arbor VA Healthcare System Ann Arbor, Michigan.
authors.forename: Bradley R
authors.initials: BR
authors.lastname: Foerster
authors.affiliation: Department of Radiology, University of Michigan Ann Arbor, Michigan.
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Carlos
authors.affiliation: Department of Radiology, University of Michigan Ann Arbor, Michigan ; Ann Arbor VA Healthcare System Ann Arbor, Michigan.
authors.forename: Ben A
authors.initials: BA
authors.lastname: Dwamena
authors.affiliation: Department of Neurology, University of Michigan Ann Arbor, Michigan.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Callaghan
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine Baltimore, Maryland ; Department of Radiology, University of Michigan Ann Arbor, Michigan.
authors.forename: Myria
authors.initials: M
authors.lastname: Petrou
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine Baltimore, Maryland ; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute Baltimore, Maryland.
authors.forename: Richard A E
authors.initials: RA
authors.lastname: Edden
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine Baltimore, Maryland ; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute Baltimore, Maryland.
authors.forename: Mona A
authors.initials: MA
authors.lastname: Mohamed
authors.affiliation: Department of Radiology, University of Michigan Ann Arbor, Michigan ; Department of Psychiatry, University of Michigan Ann Arbor, Michigan.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Welsh
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine Baltimore, Maryland ; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute Baltimore, Maryland.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Barker
authors.affiliation: Department of Neurology, University of Michigan Ann Arbor, Michigan.
authors.forename: Eva L
authors.initials: EL
authors.lastname: Feldman
authors.affiliation: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine Baltimore, Maryland.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper