Increased iron level in motor cortex of amyotrophic lateral sclerosis patients: An in vivo MR study

Abstract Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative disorders, but no definite mechanism has been defined on the loss of motor neurons in ALS and currently no therapy can block its progression. Many lines of evidence indicate that there is a disorder of iron homeostasis in ALS, and thus we sought to test the iron level in ALS patients by susceptibility weighted imaging (SWI). Sixteen ALS patients and 16 healthy persons underwent brain scans using SWI with a 3T Siemens MR scanner. The red nucleus, substantia nigra, globus pallidus, putamen, the head of caudate nucleus, and motor cortex were measured in the filtered phase images and analysed for their SWI phase values as relative marker for iron content. We found that phase shift values were significantly higher in the motor cortex of ALS patients by SWI, indicating increased iron level in this area. In contrast, we found that there were no differences of phase shift values between ALS patients and healthy controls in the other nuclei including the red nucleus, substantia nigra, globus pallidus, putamen and the head of the caudate nucleus. Furthermore, we found that there were no relationships between SWI signal and some clinical features of ALS. In conclusion, these results demonstrate that iron level increases in the motor cortex of ALS and that SWI is a reliable method to test iron in the brain.

[1]  K. Okamoto,et al.  Transferrin localizes in Bunina bodies in amyotrophic lateral sclerosis , 2006, Acta Neuropathologica.

[2]  P M Pattany,et al.  MR imaging and localized proton spectroscopy of the precentral gyrus in amyotrophic lateral sclerosis. , 2000, AJNR. American journal of neuroradiology.

[3]  R. Ordidge,et al.  Assessment of relative brain iron concentrations using T2‐weighted and T2*‐weighted MRI at 3 Tesla , 1994, Magnetic resonance in medicine.

[4]  Yu-Chung N. Cheng,et al.  Susceptibility weighted imaging (SWI) , 2004, Zeitschrift fur medizinische Physik.

[5]  Andrew J. Walsh,et al.  Susceptibility phase imaging with comparison to R2* mapping of iron-rich deep grey matter , 2011, NeuroImage.

[6]  M. Gurney,et al.  Disease mechanisms revealed by transcription profiling in SOD1‐G93A transgenic mouse spinal cord , 2001, Annals of neurology.

[7]  M. Valko,et al.  Metals, oxidative stress and neurodegenerative disorders , 2010, Molecular and Cellular Biochemistry.

[8]  W. D. Ehmann,et al.  Aluminum, calcium, and iron in the spinal cord of patients with sporadic amyotrophic lateral sclerosis using laser microprobe mass spectroscopy: a preliminary study , 1995, Journal of the Neurological Sciences.

[9]  K. Fischbeck,et al.  Toxic Proteins in Neurodegenerative Disease , 2002, Science.

[10]  Masataka Kikuchi,et al.  Dysregulation of Iron Metabolism in Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis , 2011, Advances in pharmacological sciences.

[11]  J. Schenck,et al.  High‐field magnetic resonance imaging of brain iron: birth of a biomarker? , 2004, NMR in biomedicine.

[12]  J. Connor,et al.  Plasma biomarkers associated with ALS and their relationship to iron homeostasis , 2010, Muscle & nerve.

[13]  R. Grossman,et al.  Characterizing iron deposition in multiple sclerosis lesions using susceptibility weighted imaging , 2009, Journal of magnetic resonance imaging : JMRI.

[14]  J. Li,et al.  Oxidative Stress and Neurodegenerative Disorders , 2007, International journal of molecular sciences.

[15]  Jeff H. Duyn,et al.  Iron Accumulation in Deep Cortical Layers Accounts for MRI Signal Abnormalities in ALS: Correlating 7 Tesla MRI and Pathology , 2012, PloS one.

[16]  R. A. Knight,et al.  ASSESSMENT OF RELATIVE BRAIN IRON CONCENTRATIONS USING T-2-WEIGHTED AND T-2(ASTERISK)-WEIGHTED MRI AT 3-TESLA , 1994 .

[17]  Jian Wang,et al.  Characterizing iron deposition in Parkinson's disease using susceptibility-weighted imaging: An in vivo MR study , 2010, Brain Research.

[18]  B. Brooks,et al.  El escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis , 1994, Journal of the Neurological Sciences.

[19]  R A Knight,et al.  MR imaging of human brain at 3.0 T: preliminary report on transverse relaxation rates and relation to estimated iron content. , 1999, Radiology.

[20]  S. Petri,et al.  Dysregulation of iron protein expression in the G93A model of amyotrophic lateral sclerosis , 2013, Neuroscience.

[21]  C. Enzinger,et al.  Mapping of iron deposition in conjunction with assessment of nerve fiber tract integrity in amyotrophic lateral sclerosis , 2010, Journal of magnetic resonance imaging : JMRI.

[22]  S. Petri,et al.  Nrf2/ARE Signaling Pathway: Key Mediator in Oxidative Stress and Potential Therapeutic Target in ALS , 2012, Neurology research international.

[23]  Carlo Ciulla,et al.  Establishing a baseline phase behavior in magnetic resonance imaging to determine normal vs. abnormal iron content in the brain , 2007, Journal of magnetic resonance imaging : JMRI.

[24]  C. Fellner,et al.  Cortical T2 signal shortening in amyotrophic lateral sclerosis is not due to iron deposits , 2005, Neuroradiology.

[25]  E Mark Haacke,et al.  Correlation of putative iron content as represented by changes in R2* and phase with age in deep gray matter of healthy adults , 2010, Journal of magnetic resonance imaging : JMRI.

[26]  B. Mohammadi,et al.  ALSFRS-R score and its ratio: A useful predictor for ALS-progression , 2008, Journal of the Neurological Sciences.

[27]  B. Hallgren,et al.  THE EFFECT OF AGE ON THE NON‐HAEMIN IRON IN THE HUMAN BRAIN , 1958, Journal of neurochemistry.

[28]  Iron-Rich Deep Grey Matter , 2015 .

[29]  N. Dokholyan,et al.  The Complex Molecular Biology of Amyotrophic Lateral Sclerosis (als) , 2022 .

[30]  K. Ohtomo,et al.  Amyotrophic lateral sclerosis: T2 shortening in motor cortex at MR imaging. , 1993, Radiology.

[31]  Xiaojun Xu,et al.  Age, gender, and hemispheric differences in iron deposition in the human brain: An in vivo MRI study , 2008, NeuroImage.

[32]  A. Contestabile,et al.  Amyotrophic lateral sclerosis: from research to therapeutic attempts and therapeutic perspectives. , 2011, Current medicinal chemistry.