Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: Correlating 7 tesla MRI and pathology

Authors

Justin Y. Kwan, National Institutes of Health, Bethesda, MD
Suh Young Jeong, National Institutes of Health, Bethesda, MD
Peter Van Gelderen, National Institutes of Health, Bethesda, MD
Han-Xiang Deng, Northwestern University
Martha M. Quezado, National Institutes of Health, Bethesda, MDFollow
Laura E. Danielian, National Institutes of Health, Bethesda, MD
John Butman, National Institutes of Health, Bethesda, MD
Lingye Chen, National Institutes of Health, Bethesda, MD
Elham Bayat, George Washington UniversityFollow
James Russell, University of Maryland, Baltimore
Teepu Siddique, Northwestern University
Jeff H. Duyn, National Institutes of Health, Bethesda, MD
Tracey A. Rouault, National Institutes of Health, Bethesda, MD
Mary Kay Floeter, National Institutes of Health, Bethesda, MD

Document Type

Journal Article

Publication Date

4-17-2012

Journal

PLoS ONE

Volume

Volume 7, Issue 4

Inclusive Pages

Article number e35241

Keywords

Amyotrophic Lateral Sclerosis--metabolism; Amyotrophic Lateral Sclerosis--pathology; Cerebral Cortex--pathology; Iron--metabolism; Magnetic Resonance Imaging

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by cortical and spinal motor neuron dysfunction. Routine magnetic resonance imaging (MRI) studies have previously shown hypointense signal in the motor cortex on T2-weighted images in some ALS patients, however, the cause of this finding is unknown. To investigate the utility of this MR signal change as a marker of cortical motor neuron degeneration, signal abnormalities on 3T and 7T MR images of the brain were compared, and pathology was obtained in two ALS patients to determine the origin of the motor cortex hypointensity. Nineteen patients with clinically probable or definite ALS by El Escorial criteria and 19 healthy controls underwent 3T MRI. A 7T MRI scan was carried out on five ALS patients who had motor cortex hypointensity on the 3T FLAIR sequence and on three healthy controls. Postmortem 7T MRI of the brain was performed in one ALS patient and histological studies of the brains and spinal cords were obtained post-mortem in two patients. The motor cortex hypointensity on 3T FLAIR images was present in greater frequency in ALS patients. Increased hypointensity correlated with greater severity of upper motor neuron impairment. Analysis of 7T T2*-weighted gradient echo imaging localized the signal alteration to the deeper layers of the motor cortex in both ALS patients. Pathological studies showed increased iron accumulation in microglial cells in areas corresponding to the location of the signal changes on the 3T and 7T MRI of the motor cortex. These findings indicate that the motor cortex hypointensity on 3T MRI FLAIR images in ALS is due to increased iron accumulation by microglia.

Comments

Reproduced with permission of PLoS One

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.

APA Citation

Kwan, J. Y., Jeong, S. Y., van Gelderen, P., Deng, H. -., Quezado, M. M., Danielian, L. E., Butman, J.A., Chen, L., Bayat, E., Russell, J., Siddique, T., Duyn, J.H., Rouault, T.A., Floeter, M. K. (2012). Iron accumulation in deep cortical layers accounts for MRI signal abnormalities in ALS: Correlating 7 tesla MRI and pathology. PLoS ONE, 7(4): e35241.

Peer Reviewed

1

Open Access

1