Abstract
Iron as the most abundant trace element in the human brain is essential to biochemical processes as oxygen transportation, myelin production, and neurotransmitter synthesis. However, it can become toxic when available in excessive amounts. Abnormal high iron concentrations have been linked to neurodegenerative and inflammatory processes occurring in prevalent neurological disorders such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. Therefore investigations of the involvement of iron in the etiology and disease progression rely on its exact measurement. Magnetic Resonance Imaging (MRI) seems a potential candidate for assessing iron concentration in vivo, because of its sensitivity to paramagnetic effects and non-invasiveness.
The potential of MRI relaxation rate mapping, phase imaging, and quantitative susceptibility mapping for assessing iron concentration in the human brain was studied in this work. Because it is unclear which parameters represent valid and sensitive measures for iron, postmortem studies of the human brain chemically validated the theoretical considerations. Iron concentrations were determined for a variety of anatomical brain regions using several MRI techniques and, additionally, using inductively coupled plasma mass spectroscopy. Based on these measurements a model of the biophysical mechanisms underlying MRI contrast generation in the human brain was developed and subsequently applied in clinical studies of multiple sclerosis and amyotrophic lateral sclerosis.
In conclusion, iron concentrations in the human brain can be assessed in vivo by using MRI. While iron is the determinant source of contrast in gray matter, the counteracting diamagnetism of myelin reduces the sensitivity of MRI based iron measurements in white matter. Patients suffering from multiple sclerosis and amyotrophic lateral sclerosis showed regionally increased iron accumulation, which was associated with the clinical severity and type of the disease.
The potential of MRI relaxation rate mapping, phase imaging, and quantitative susceptibility mapping for assessing iron concentration in the human brain was studied in this work. Because it is unclear which parameters represent valid and sensitive measures for iron, postmortem studies of the human brain chemically validated the theoretical considerations. Iron concentrations were determined for a variety of anatomical brain regions using several MRI techniques and, additionally, using inductively coupled plasma mass spectroscopy. Based on these measurements a model of the biophysical mechanisms underlying MRI contrast generation in the human brain was developed and subsequently applied in clinical studies of multiple sclerosis and amyotrophic lateral sclerosis.
In conclusion, iron concentrations in the human brain can be assessed in vivo by using MRI. While iron is the determinant source of contrast in gray matter, the counteracting diamagnetism of myelin reduces the sensitivity of MRI based iron measurements in white matter. Patients suffering from multiple sclerosis and amyotrophic lateral sclerosis showed regionally increased iron accumulation, which was associated with the clinical severity and type of the disease.
| Original language | English |
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| Qualification | Doctor of Technology |
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| Supervisors/Advisors |
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| Publication status | Published - 27 Mar 2012 |
Keywords
- quantitative MRI
- brain iron
- myelin
- contrast generation
- postmortem
- relaxation rate mapping
- phase imaging
- quantitative susceptibility mapping
