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. 2016 May 2:12:965-969.
doi: 10.1016/j.nicl.2016.04.011. eCollection 2016.

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

M Costagli  1 , G Donatelli  2 , L Biagi  3 , E Caldarazzo Ienco  4 , G Siciliano  4 , M Tosetti  1 , M Cosottini  5
Affiliations

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

M Costagli et al. Neuroimage Clin. .

Abstract

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurological disorder that entails degeneration of both upper and lower motor neurons. The primary motor cortex (M1) in patients with upper motor neuron (UMN) impairment is pronouncedly hypointense in Magnetic Resonance (MR) T2* contrast. In the present study, 3D gradient-recalled multi-echo sequences were used on a 7 Tesla MR system to acquire T2*-weighted images targeting M1 at high spatial resolution. MR raw data were used for Quantitative Susceptibility Mapping (QSM). Measures of magnetic susceptibility correlated with the expected concentration of non-heme iron in different regions of the cerebral cortex in healthy subjects. In ALS patients, significant increases in magnetic susceptibility co-localized with the T2* hypointensity observed in the middle and deep layers of M1. The magnetic susceptibility, hence iron concentration, of the deep cortical layers of patients' M1 subregions corresponding to Penfield's areas of the hand and foot in both hemispheres significantly correlated with the clinical scores of UMN impairment of the corresponding limbs. QSM therefore reflects the presence of iron deposits related to neuroinflammatory reaction and cortical microgliosis, and might prove useful in estimating M1 iron concentration, as a possible radiological sign of severe UMN burden in ALS patients.

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Figures

Image 1
Graphical abstract
Supplementary Fig. 1
Supplementary Fig. 1
Examples of ROIs delineating the deep cortical layers of M1 corresponding to Penfield's areas of the hand (a and b, in one HC and one ALS patient, respectively) and foot (c and d, in one HC and one ALS patient, respectively). One example of ROI delineating the SCC is shown in e.
Supplementary Fig. 2
Supplementary Fig. 2
Example of full-thickness ROIs delineating M1 (a), S1 (b), non-S1 parietal cortex (c) and prefrontal cortex (d).
Supplementary Fig. 3
Supplementary Fig. 3
Values of χ in deep cortical layers (four ROIs for each of the 13 HC: left hand, left foot, right hand, right foot – in total 52 ROIs) do not correlate with age (r = − 0.06, p = 0.66).
Fig. 1
Fig. 1
Appearance of M1 in one healthy control and one ALS patient. T2*-weighted images targeting the M1 of one healthy control subject and one ALS patient are shown in (a) and (b), respectively. The corresponding susceptibility maps are shown in (c) and (d), respectively. Arrows indicate the T2* signal hypointensity and QSM hyperintensity in patients' M1 deep layers.
Fig. 2
Fig. 2
Magnetic susceptibility (χ) correlates with the expected concentration of iron (ρ) in different cortical regions in healthy controls.
Fig. 3
Fig. 3
Difference (Δχ) between ALS patients' χ values in deep cortical layers corresponding to the most impaired limb and average χ in the corresponding ROIs in HC. The solid line represents average Δχ = 13 ppb.
Fig. 4
Fig. 4
Among patients, χ in M1 was significantly (p < 0.033) higher in patients of group B (with particularly thin and hypointense cortical deep layers) than in patients of group A (with normal radiological appearance of M1). A binary classifier with χcutoff = 47 ppb (dashed line) allows to separate the ALS patients into the two groups A and B with 2 classification errors (arrows).
Fig. 5
Fig. 5
In patients, χ in the deep layers of M1 subregions correlated (r = 0.46; p < 0.0002) with the UMN-score.
See this image and copyright information in PMC

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