Quantitative Susceptibility Mapping of the Motor Cortex in Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis

Abstract

Objective Diagnosis of amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) is often difficult due to absence of disease biomarkers. Our aim was to investigate quantitative susceptibility mapping (QSM) of the motor cortex as a potential quantitative biomarker for the diagnosis of ALS and PLS. Materials and Methods Utilizing an institutional review board approved retrospective database, QSM images for 16 patients with upper motor neuron disease (12 with ALS and 4 with PLS; mean age 56.3; 56% male) and 23 control patients (mean age 56.6; 57% male) were reviewed. Two neuroradiologists, blinded to diagnosis, qualitatively assessed QSM, T2, T2*, and T2 FLAIR-weighted images. Relative motor cortex susceptibility (RMCS) was quantitatively calculated by subtracting adjacent white matter/CSF signal intensity from mean motor cortex susceptibility on the axial image most representative of the hand lobule, and receiver operating characteristic (ROC) analysis was performed. The Fisher’s exact and Student’s t tests were used to evaluate for statistical differences between the groups. Results Qualitatively, QSM had higher diagnostic accuracy than T2, T2*, or T2 FLAIR for the diagnosis of ALS/PLS. Quantitatively, RMCS was found to be significantly higher in patients with motor neuron disease than in control patients (46.0 and 35.0, respectively; p<0.001). ROC analysis demonstrated an area-under-the-curve of 0.88 (p<0.0001) and an optimal cutoff value of 40.5 ppb for distinguishing between control and ALS/PLS patients (sensitivity, 87.5%; specificity, 87.0%). Conclusions QSM is a sensitive and specific quantitative biomarker of iron deposition in the motor cortex in ALS and PLS.

Magnetic susceptibility in the deep layers of the primary motor cortex in Amyotrophic Lateral Sclerosis

“…The pronounced T2* signal hypointensity in M1 of ALS patients has been reported by recent MRI studies (Ignjatović et al, 2013, Kwan et al, 2012, Schweitzer et al, 2015). However, we observed that M1 appears hypointense also in healthy controls and is not, by itself, an accurate biomarker of ALS.…”

“…One recent study conducted on a 3 T MRI system observed an increase in χ in the M1 of ALS patients (Schweitzer et al, 2015) however the specificity of such increase to the cortical deep layers and its relation with patients' clinical conditions was not reported. In fact, rather than being a candidate direct biomarker of ALS, our results show that χ in M1 correlates with UMN impairment.…”

“…T2*-weighted images of M1 obtained from 3D multi-echo GRE acquisitions were qualitatively evaluated using scores ranging between 0 and 2, similarly to what has been done in the recent literature (Schweitzer et al, 2015): a score of 0 was assigned when M1 did not differ from the neighboring cortices, a score of 1 was assigned when M1 appeared slightly more hypointense than neighboring cortices, and a score of 2 was assigned when M1 appeared much more hypointense than the neighboring cortices.…”

“…Gradient Recalled Echo (GRE) techniques in Magnetic Resonance Imaging (MRI) enable the fine depiction of the most prominent structural changes that involve the cortex and the presence of iron (Adachi et al, 2015, Duyn et al, 2007, Haacke et al, 2009, Ignjatović et al, 2013). M1, which has been described to usually appear slightly more hypointense than neighboring cortices (postcentral gyrus) in the healthy brain in T2* contrast (Kwan et al, 2012, Schweitzer et al, 2015), is pronouncedly hypointense in patients with upper motor neuron impairment (Ignjatović et al, 2013, Schweitzer et al, 2015). In particular, studies that investigated M1 at high spatial resolution with ultra-high field MRI revealed ex vivo (Kwan et al, 2012) and in vivo (Cosottini et al, 2016) that M1 hypointensity in T2* is spatially confined to the deep layers of M1.…”

Susceptibility MRI captures nigral pathology in patients with parkinsonian syndromes

“…Biophysically, susceptibility MRI (R2* and quantitative susceptibility mapping [QSM]) can detect local magnetic susceptibility changes that are sensitive to metals like iron . The apparent transverse relaxation rate (R2*) and QSM have been utilized to detect the distinct pathological patterns in PD, MSA, and PSP .…”