Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis

Abstract

ObjectiveReliable 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).MethodsTwenty-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.ResultsThe 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.InterpretationCombining 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.

The value of magnetic resonance imaging as a biomarker for amyotrophic lateral sclerosis: a systematic review

“…AD was elevated in the left corona radiata and the internal and external capsulesCorrelation between FA in parts of CC and ALSFRS-R and negative correlation with DD, correlation between RD in parts of CC and DDCiccarelli et al, [45]26/41Low along CSTs, the CC, anterior limb of the internal capsule, external capsule, parts of frontal lobe WM and postcentral gyriCorrelation between DPR and FA in left cerebral peduncle, right PLIC, right corona radiate right WM adjascent to the precentral gyrus and CCDing et al, [74]10/10Elevated in the PLICNot availableEllis et al, [51]22/20Low along CSTsElevated along CSTsCorrelation between mean diffusivity in CST and DD and between FA along CSTs and ALS severity scale and spasticity scales.Filippini et al, [56]24/24Low along CSTs and in the CCElevated RD in WM linked to the primary motor and premotor cortex and the CCInverse correlation between FA and UMN score along CSTs, correlation between FA and ALSFRS-R and DD along CSTsFoerster et al, [55]29/30Low along CSTsCorrelation between FA and ALSFRS-R along CSTsIwata et al, [49]31/31Low along CSTsNegativeIwata et al, [50]18/19Low along CSTs and in the motor part of the CCElevated along CSTsCorrelation between DD and FA along CSTs. Inverse correlation between FA in CSTs and global and localized UMN impairment score and between FA along CST and UMN rapidity index.Kassubek et al, [12, 73]111/74Low along CSTsNot availableKeil et al, [61]24/24Low in parts of CSTs, supplementary motor area, CC, parts of the frontal lobe and the parahippocampal areaElevated in motor areas, parts of CSTs, parts of the frontal and temporal lobe, and the postcentral gyrusCorrelation between FA along CSTs and ALSFRS-R.…”

“…NAA and Cr were correlated in left MCCorrelation between ins in MC and UMN disability, negative correlation between Naa in MC and UMN disability, higher Cho in sever UMN disability groupCervo et al, [90]84/28NAA/(Cho + Cr) was low in the MCNegativeFoerster et al, [95]10/9Low gamma aminobutyric acid in the MC but not in WMNegativeFoerster et al, [55]29/30NAA and gamma aminobutyric acid were low and ins was elevated in the left MCNegative correlation between gamma aminobutyric acid in MC and DD, correlation between Naa peak in MC and ALSFRS-RGovind et al, [92]38/70NAA was low and Cho was elevated in most parts of CST, and Cho/NAA was elevated in all parts of the CSTsNegative correlation between Cho/Naa in the left entire CST and forced vital capacity, negative correlation between Cho/Naa in the left CST and right and left finger tap rate, negative correlation between Cho/Naa in left MC and semiovale centrum and right finger tape or forced vital capacityHan et al, [85]15/15NAA/Cr peak was low in the MC and PLIC, Glu/Cr and Glu + Gln/Cr peaks were low in the MC and PLICNegative correlation between Glu + Gln/Cr with Norris scoreKalra et al, [88, 89]63/18NAA/Cho and NAA/Cr was low in the MC, and Cho/Cr was elevated in the MCRelation between decreased Naa/Cho in the MC and reduced survival.Kalra et al, [88, 89]17/15NAA/Ins, NAA/Cr and NAA/Cho were low in the MC, and Ins/Cr was elevated in the MCNegative (p ≤ 0.05)Liu et al, [87]19/13NAA/Cr was low in the MCNegativeLombardo et al, [79]32/19NAA/Cr was low and ins/Cr and Cho/Cr were elevated in the MC.Abnormalities were correlated with the El Escorial scorePohl et al, [91]70/48NAA, Pcr + Cr, NAA/Cho and NAA/(Pcr + Cr) were low in the MC. At 12 months, NAA/Cho was low and Cho/(Pcr + Cr) was elevatedNot availablePyra et al, [59]14/14NAA/Cho and NAA/Cr were low in the MC and corona radiata, and Cho/Cr was elevated in the MCCorrelation between Naa/Cho peak in MC and DD, negative correlation between Naa/Cho in MC and corona radiata and DPRRooney et al, [86]10/9NAA/(Cho + Cr) was low in the MC and CST but not in other regionsCorrelation between Naa/(Cho + Cr) in the MC and maximum finger tape rateStagg et al, [47]13/14…”

Prospective Validation of 18F-FDG Brain PET Discriminant Analysis Methods in the Diagnosis of Amyotrophic Lateral Sclerosis

“…The best results in single-center studies have been obtained by combined MR imaging approaches (15,16). Combined diffusion tensor imaging and spectroscopy resulted in a sensitivity of 93% and a specificity of 85% (17), whereas diffusion tensor imaging in combination with voxel-based morphometry resulted in a sensitivity of 92% and a specificity of 88% (18). However, no replication of these studies has been performed so far.…”

Diffusion MRI and its Role in Neuropsychology

“…For example, the utility of dMRI data as a tool for diagnostic evaluation in amyotropic lateral sclerosis (ALS) improves when using a multimodal approach that incorporates dMRI and magnetic resonance spectroscopy (MRS) data, so that data from these two modalities allow the best discrimination between patients with ALS and controls (Area under the receiver operating characteristic curve, AUC .93 vs. .81) (Foerster et al 2014). …”