Variable‐field relaxometry of iron‐containing human tissues: a preliminary study

Abstract

Excess iron is found in brain nuclei from neurodegenerative patients (with Parkinson's, Alzheimer's and Huntington's diseases) and also in the liver and spleen of cirrhosis, hemochromatosis and thalassaemia patients. Ferritin, the iron-storing protein of mammals, is known to darken T(2)-weighted MR images. Understanding NMR tissue behavior may make it possible to detect those diseases, to follow their evolution and finally to establish a protocol for non-invasive measurement of an organ's iron content using MRI methods. In this preliminary work, the MR relaxation properties of embalmed iron-containing tissues were studied as well as their potential correlation with the iron content of these tissues. Relaxometric measurements (T(1) and T(2)) of embalmed samples of brain nuclei (caudate nucleus, dentate nucleus, globus pallidus, putamen, red nucleus and substantia nigra), liver and spleen from six donors were made at different magnetic fields (0.00023-14 T). The influence of the inter-echo time on transverse relaxation was also studied. Moreover, iron content of tissues was determined by inductively coupled plasma atomic emission spectroscopy. In brain nuclei, 1/T(2) increases quadratically with the field and depends on the inter-echo time in CPMG sequences at high fields, both features compatible with an outer sphere relaxation theory. In liver and spleen, 1/T(2) increases linearly with the field and depends on the inter-echo time at all fields. In our study, a correlation between 1/T(2) and iron concentration is observed. Explaining the relaxation mechanism for these tissues is likely to require a combination of several models. The value of 1/T(2) at high field could be used to evaluate iron accumulation in vivo. In the future, confirmation of those features is expected to be achieved from measurements of fresh (not embalmed) human tissues.

Neurodegenerative diseases and therapeutic strategies using iron chelators

“…[25] Since the majority of patients with neurodegenerative disease will have normal iron homeostasis, low doses of the chelator need to be used to minimise side effects. The MRI technique T2* has been extensively used to monitor changes in the iron content of specific brain regions, which appears at best to be semiquantitative, the results being influenced by differences in crystal structure and/or unequal ferritin clustering in these specific brain regions as well as by size of the magnetic particle [26]. The chemical structures of three iron chelators which have been approved for clinical use in the treatment of beta-thalassaemia, desferrioxamine, deferiprone and desferasirox are shown in Figure 2.…”

Quantitative Magnetic Resonance Imaging of the Brain : Applications for Tissue Segmentation and Multiple Sclerosis

“…T1 in the brain is mainly influenced by water concentration (63,64,(73)(74)(75), but also by iron concentration (76)(77)(78)(79). T2 in the brain is mainly affected by different tissue water environments (70,71), such as water inside cells, extracellular water and water between the myelin sheets, but T2 is also affected by iron concentration (79)(80)(81)(82). The relative sizes of each tissue water environment, as well as exchange rate among these, affects the T2 relaxation, especially when only one T2 component is estimated.…”

“…Another process that affects both T1 and T2 relaxation in the brain is the iron concentration (76)(77)(78)(79)(80)(81)(82). Deep GM structures are particularly rich in iron (79,81,92).…”

“…Deep GM structures are particularly rich in iron (79,81,92). Furthermore, iron accumulates with age (80,93) and is abnormal in diseases such as Alzheimer's disease (94), Hallevorden-Spatz syndrome (95), Parkinson's disease (96)(97)(98), and MS (99-104).…”

“…That is the dependency on main magnetic field strength, which directly affects the measured R1 and R2 rates (79,81,135). In general, R1 and R2 decrease when the main magnetic field is increased; this relation is complex and depends on tissue composition.…”