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. 2014 Feb;1(2):107-14.
doi: 10.1002/acn3.30. Epub 2014 Jan 13.

Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis

Bradley R Foerster  1 , Ruth C Carlos  2 , Ben A Dwamena  3 , Brian C Callaghan  4 , Myria Petrou  5 , Richard A E Edden  6 , Mona A Mohamed  6 , Robert C Welsh  7 , Peter B Barker  6 , Eva L Feldman  4 , Martin G Pomper  8
Affiliations

Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis

Bradley R Foerster et al. Ann Clin Transl Neurol. 2014 Feb.

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.

Interpretation: 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.

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Figures

Figure 1
Figure 1
Diffusion tractography and voxel placement with resulting magnetic resonance spectra. Images showing diffusion tractography of the corticospinal tract in the sagittal (A) and coronal projections (B). Voxel placement for magnetic resonance spectroscopy of the motor cortex region in the sagittal (C) and axial (D) projections (F). Representative magnetic resonance spectroscopy spectrum from the motor cortex of an ALS subject using PRESS (E) and MEGA-PRESS editing technique (F).
Figure 2
Figure 2
Decreased fractional anisotropy (FA), decreased N-acetylaspartate (NAA), increased myo-inositol (mI), and decreased γ-aminobutyric acid (GABA) levels in amyotrophic lateral sclerosis (ALS) patients. Circles represent respective values of FA in the corticospinal tract (A), NAA in the left motor cortex (B), mI in the left motor cortex (C), and GABA levels in the left motor cortex (D) for individual ALS patients and healthy controls (HC). Horizontal bars indicate the mean. IU, institutional units.
Figure 3
Figure 3
Significant increase in diagnostic accuracy combining magnetic resonance spectroscopy (MRS) and diffusion tensor imaging (DTI) measures. Receiver operating characteristic (ROC) curves comparing DTI diagnostic test accuracy model to combined DTI and MRS model. Solid ROC curve represents the model using DTI fractional anisotropy values. Dashed ROC curve represents the model using DTI fractional anisotropy, MRS N-acetylaspartate, MRS myo-inositol, and MRS γ-aminobutyric acid values combined.
Figure 4
Figure 4
Posttest probabilities using diffusion tensor imaging (DTI) only and diffusion tensor imaging combined with magnetic resonance spectroscopy (MRS). Posttest probabilities for imaging results for each of the two models using hypothetical populations with different pretest disease probabilities. Model 1 used the DTI fractional anisotropy values only. Model 2 uses the DTI fractional anisotropy combined with MRS N-acetylaspartate, MRS myo-inositol and MRS γ-aminobutyric acid values.
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