Korean J Clin Neurophysiol.  2014 Jun;16(1):1-7. 10.14253/kjcn.2014.16.1.1.

Application of Iron Related Magnetic Resonance Imaging in the Neurological Disorders

• Kim TH
• Lee JH

• KMID: 1708884
• DOI: http://doi.org/10.14253/kjcn.2014.16.1.1

Abstract

Iron is an important element for brain oxygen transport, myelination, DNA synthesis and neurotransmission. However, excessive iron can generate reactive oxygen species and contribute neurotoxicity. Although brain iron deposition is the natural process with normal aging, excessive iron accumulation is also observed in various neurological disorders such as neurodegeneration with brain iron accumulation, Parkinson's disease, Alzheimer's disease, multiple sclerosis, Friedreich ataxia, and others. Magnetic resonance image (MRI) is a useful method for detecting iron deposits in the brain. It can be a powerful tool for diagnosis and monitoring, while furthering our understanding of the role of iron in the pathophysiology of a disease. In this review, we will introduce the mechanism of iron toxicity and the basics of several iron-related MRI techniques. Also, we will summarize the previous results concerning the clinical application of such MR imagings in various neurological disorders.

Keyword

Iron; Neurodegenerative disorders; MRI

MeSH Terms

Aging
Alzheimer Disease
Brain
Diagnosis
DNA
Friedreich Ataxia
Iron*
Magnetic Resonance Imaging*
Multiple Sclerosis
Myelin Sheath
Nervous System Diseases*
Neurodegenerative Diseases
Oxygen
Parkinson Disease
Reactive Oxygen Species
Synaptic Transmission
DNA
Iron
Oxygen
Reactive Oxygen Species

Figure

• 

  Figure 1. Axial T2-wighted image (A) corresponding magnitude (B), phase (C), and susceptibility-weighted image after postprocessing (D). The phase image here is for left hand system.

Reference

1.Crichton RR., Dexter DT., Ward RJ. Brain iron metabolism and its perturbation in neurological diseases. J Neural Transm. 2011. 118:301–314.

2.Benarroch EE. Brain iron homeostasis and neurodegenerative disease. Neurology. 2009. 72:1436–1440.

3.Zecca L., Stroppolo A., Gatti A., Tampellini D., Toscani M., Gallorini M, et al. The role of iron and copper molecules in the neuronal vulnerability of locus coeruleus and substantia nigra during aging. Proc Natl Acad Sci U S A. 2004. 101:9843 -9848.

4.Zecca L., Youdim MB., Riederer P., Connor JR., Crichton RR. Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci. 2004. 5:863–873.

5.Gutteridge JM. Iron and oxygen radicals in brain. Ann Neurol. 1992. 32(Suppl):S16–21.

6.Stankiewicz J., Panter SS., Neema M., Arora A., Batt CE., Bakshi R. Iron in chronic brain disorders: imaging and neurotherapeutic implications. Neurotherapeutics. 2007. 4:371–386.

7.van der Kolk AG., Hendrikse J., Zwanenburg JJ., Visser F., Luijten PR. Clinical applications of 7 T MRI in the brain. Eur J Radiol. 2013. 82:708–718.

8.Sian-Hülsmann J., Mandel S., Youdim MB., Riederer P. The relevance of iron in the pathogenesis of Parkinson's disease. J Neurochem. 2011. 118:939–957.

9.Schenck JF. Magnetic resonance imaging of brain iron. J Neurol Sci. 2003. 207:99–102.

10.Westbrook C., Roth CK., Talbot J. MRI in practice. 4th ed.Chichester: Wiley-Blackwell;2011. p. 21–34.

11.Gelman N., Gorell JM., Barker PB., Savage RM., Spickler EM., Windham JP, et al. MR imaging of human brain at 3.0 T: preliminary report on transverse relaxation rates and relation to estimated iron content. Radiology. 1999. 210:759–767.

12.Aquino D., Bizzi A., Grisoli M., Garavaglia B., Bruzzone MG., Nardocci N, et al. Age-related iron deposition in the basal ganglia: quantitative analysis in healthy subjects. Radiology. 2009. 252:165–72.

13.Langkammer C., Krebs N., Goessler W., Scheurer E., Ebner F., Yen K., Fazekas F., Ropele S. Quantitative MR imaging of brain iron: a postmortem validation study. Radiology. 2010. 257:455–462.

14.Haacke EM., Cheng NY., House MJ, et al. Imaging iron stores in the brain using magnetic resonance imaging. Magn Reson Imaging. 2005. 23:1–25.

15.Bartzokis G., Aravagiri M., Oldendorf WH., Mintz J., Marder SR. Field dependent transverse relaxation rate increase may be a specific measure of tissue iron stores. Magn Reson Med. 1993. 29:459–64.

16.Bartzokis G., Beckson M., Hance DB., Marx P., Foster JA., Marder SR. MR evaluation of age-related increase of brain iron in young adult and older normal males. Magn Reson Imaging. 1997. 15:29–35.

17.Haacke EM., Mittal S., Wu Z., Neelavalli J., Cheng YC. Susceptibility-weighted imaging: technical aspects and clinical applications, part 1. AJNR Am J Neuroradiol. 2009. 30:19–30.

18.Mittal S., Wu Z., Neelavalli J., Haacke EM. Susceptibility-weighted imaging: technical aspects and clinical applications, part 2. AJNR Am J Neuroradiol. 2009. 30:232–252.

19.Yan SQ., Sun JZ., Yan YQ., Wang H., Lou M. Evaluation of brain iron content based on magnetic resonance imaging (MRI): comparison among phase value, R2* and magnitude signal intensity. PLoS One. 2012. 7:e31748.

20.Walsh AJ., Wilman AH. Susceptibility phase imaging with comparison to R2 mapping of iron-rich deep grey matter. Neuroimage. 2011. 57:452–461.

21.Gregory A., Polster BJ., Hayflick SJ. Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J Med Genet. 2009. 46:73–80.

22.Schipper HM. Neurodegeneration with brain iron accumulation-clinical syndromes and neuroimaging. Biochim Biophys Acta. 2012. 1822:350–360.

23.McNeill A., Birchall D., Hayflick SJ., Gregory A., Schenk JF., Zimmerman EA, et al. T2* and FSE MRI distinguishes four subtypes of neurodegeneration with brain iron accumulation. Neurology. 2008. 70:1614–1619.

24.Dusek P., Jankovic J., Le W. Iron dysregulation in movement disorders. Neurobiol Dis. 2012. 46:1–18.

25.Kumar N., Boes CJ., Babovic-Vuksanovic D., Boeve BF. The "eye-of-the-tiger" sign is not pathognomonic of the PANK2 mutation. Arch Neurol. 2006. 63:292–293.

26.Lee JH., Kim DS., Baik SK., Nam SO. Nigropallidal iron accumulation in pantothenate kinase-associated neurodegeneration demonstrated by susceptibility-weighted imaging. J Neurol. 2010. 257:661–662.

27.Baraibar MA., Barbeito AG., Muhoberac BB., Vidal R. Iron-mediated aggregation and a localized structural change characterize ferritin from a mutant light chain polypeptide that causes neurodegeneration. J Biol Chem. 2008. 283:31679–31689.

28.Berg D., Hochstrasser H. Iron metabolism in Parkinsonian syndromes. Mov Disord. 2006. 21:1299–1310.

29.Morawski M., Ch Meinecke., Reinert T., Dorffel AC., Riederer P., Arendt T, et al. Determination of trace elements in the human substantia nigra. Nucl Instrum Methods Phys Res B. 2005. 231:224–228.

30.Bartzokis G., Cummings JL., Markham CH., Marmarelis PZ., Treciokas LJ., Tishler TA, et al. MRI evaluation of brain iron in earlier- and later-onset Parkinson's disease and normal subjects. Magn Reson Imaging. 1999. 17:213–222.

31.Gorell JM., Ordidge RJ., Brown GG., Deniau JC., Buderer NM., Helpern JA. Increased iron-related MRI contrast in the substantia nigra in Parkinson's disease. Neurology. 1995. 45:1138–1143.

32.Graham JM., Paley MN., Grünewald RA., Hoggard N., Griffiths PD. Brain iron deposition in Parkinson's disease imaged using the PRIME magnetic resonance sequence. Brain. 2000. 123(Pt 12):2423–2431.

33.Zhang J., Zhang Y., Wang J., Cai P., Luo C, et al. Characterizing iron deposition in Parkinson's disease using susceptibility-weighted imaging: an in vivo MR study. Brain Res. 2010. 1330:124–130.

34.Jin L., Wang J., Zhao L., Jin H., Fei G., Zhang Y, et al. Decreased serum ceruloplasmin levels characteristically aggravate nigral iron deposition in Parkinson's disease. Brain. 2011. 134(Pt 1):50–58.

35.Han YH., Lee JH., Kang BM., Mun CW., Baik SK, et al. Topographical differences of brain iron deposition between progressive supranuclear palsy and parkinsonian variant multiple system atrophy. J Neurol Sci. 2013. 325:29–35.

36.Lee JH., Han YH., Kang BM., Mun CW., Lee SJ, et al. Quantitative assessment of subcortical atrophy and iron content in progressive supranuclear palsy and parkinsonian variant of multiple system atrophy. J Neurol. 2013. 260:2094–2101.

37.Du G., Lewis MM., Sen S., Wang J., Shaffer ML., Styner M, et al. Imaging nigral pathology and clinical progression in Parkin-son's disease. Mov Disord. 2012. 27:1636–1643.

38.Lee JH., Han YH., Cho JW., Lee JS., Lee SJ, et al. Evaluation of brain iron content in idiopathic REM sleep behavior disorder using quantitative magnetic resonance imaging. Parkinsonism Relat Disord.

39.Honda K., Casadesus G., Petersen RB., Perry G., Smith MA. Oxidative stress and redox-active iron in Alzheimer's disease. Ann N Y Acad Sci. 2004. 1012:179–182.

40.Rottkamp CA., Raina AK., Zhu X., Gaier E., Bush AI., Atwood CS, et al. Redox-active iron mediates amyloid-beta toxicity. Free Radic Biol Med. 2001. 30:447–450.

41.Mantyh PW1. Ghilardi JR., Rogers S., DeMaster E., Allen CJ., Stimson ER, et al. Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide. J Neurochem. 1993. 61:1171–1174.

42.Bartzokis G., Sultzer D., Cummings J., Holt LE., Hance DB., Henderson VW, et al. In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging. Arch Gen Psychiatry. 2000. 57:47–53.

43.Zhu WZ., Zhong WD., Wang W., Zhan CJ., Wang CY., Qi JP, et al. Quantitative MR phase-corrected imaging to investigate increased brain iron deposition of patients with Alzheimer disease. Radiology. 2009. 253:497–504.

44.Raven EP., Lu PH., Tishler TA., Heydari P., Bartzokis G. Increased iron levels and decreased tissue integrity in hippocampus of Alzheimer's disease detected in vivo with magnetic resonance imaging. J Alzheimers Dis. 2013. 37:127–136.

45.House MJ., St Pierre TG., Foster JK., Martins RN., Clarnette R. Quantitative MR imaging R2 relaxometry in elderly participants reporting memory loss. AJNR Am J Neuroradiol. 2006. 27:430–439.

46.House MJ., St Pierre TG., Kowdley KV., Montine T., Connor J., Beard J, et al. Correlation of proton transverse relaxation rates (R2) with iron concentrations in postmortem brain tissue from alzheimer's disease patients. Magn Reson Med. 2007. 57:172–180.

47.LeVine SM. Iron deposits in multiple sclerosis and Alzheimer's disease brains. Brain Res. 1997. 760:298–303.

48.Ropele S., de Graaf W., Khalil M., Wattjes MP., Langkammer C., Rocca MA, et al. MRI assessment of iron deposition in multiple sclerosis. J Magn Reson Imaging. 2011. 34:13–21.

49.Bermel RA., Puli SR., Rudick RA., Weinstock-Guttman B., Fisher E., Munschauer FE 3rd, et al. Prediction of longitudinal brain atrophy in multiple sclerosis by gray matter magnetic resonance imaging T2 hypointensity. Arch Neurol. 2005. 62:1371–1376.

50.Ropele S., Kilsdonk ID., Wattjes MP., Langkammer C., de Graaf WL., Frederiksen JL, et al. Determinants of iron accumulation in deep grey matter of multiple sclerosis patients. Mult Scler 2014 Apr 30. [Epub ahead of print].

51.Waldvogel D., van Gelderen P., Hallett M. Increased iron in the dentate nucleus of patients with Friedrich's ataxia. Ann Neurol. 1999. 46:123–125.

52.Boddaert N., Le Quan Sang KH., Rötig A., Leroy-Willig A., Gallet S., Brunelle F, et al. Selective iron chelation in Friedreich ataxia: biologic and clinical implications. Blood. 2007. 110:401–408.

53.Ignjatović A., Stević Z., Lavrnić S., Daković M., Bačić G. Brain iron MRI: a biomarker for amyotrophic lateral sclerosis. J Magn Reson Imaging. 2013. 38:1472–1479.

54.Vinod Desai S., Bindu PS., Ravishankar S., Jayakumar PN., Pal PK. Relaxation and susceptibility MRI characteristics in Hallervorden-Spatz syndrome. J Magn Reson Imaging. 2007. 25:715–720.