ABSTRACT
T1 and T2 relaxation times and iron concentrations were measured in 24 specimens of gray matter from fresh human and monkey brains at magnetic fields from 0.05 to 1.5 Tesla. Three different effects were found that correlate with iron content: a T1-shortening that falls off somewhat at high fields, a T2-shortening that is field-independent and thus important at low fields, and a contribution to 1/T2 that increases linearly with field strength. This linear field dependence has been seen only in ferritin and other ferric oxyhydroxide particles. Our results are in agreement with in vivo MRI studies and are generally consistent with values for ferritin solution, except for differences such as clustering of ferritin in tissue. A cerebral cavernous hemangioma specimen showed similar T2-shortening, but with a 2.7 times larger magnitude, attributed to larger clusters of hemosiderin in macrophages. The dependence on interecho time 2 tau was measured in three brains; 1/T2 increased significantly for tau up to 32 ms, as expected from the size of the ferritin clusters. These findings support the theory that ferritin iron is the primary determinant of MRI contrast in normal gray matter.
Subject(s)
Brain/metabolism , Iron/metabolism , Magnetic Resonance Imaging/methods , Magnetic Resonance Spectroscopy/methods , Adult , Animals , Brain Mapping , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Female , Ferritins/metabolism , Hemangioma, Cavernous/metabolism , Hemangioma, Cavernous/pathology , Humans , Macaca mulatta , Male , Middle Aged , Reference ValuesABSTRACT
A retrospective analysis of 158 T1-weighted and T2-weighted MRI scans of normal brains at 0.5 and 1.5 Tesla was performed. Signal intensities in the frontal cortex, caudate nucleus, putamen, and globus pallidus were divided by those of frontal white matter; and these gray/white ratios were correlated with iron concentration, estimated from the anatomical region and age of the patient. Intraregional plots were also made of gray/white ratio versus age for the 1.5 Tesla scans. The changes in both T1-weighted and T2-weighted ratios were consistent with the hypothesis that 1/T1 and 1/T2 vary linearly with iron concentration, and the corresponding coefficients, determined separately from the interregional and intraregional plots, were generally in agreement. Furthermore, the variability of the MRI ratios at 1.5 Tesla was consistent with expected iron variability except for the cortex, in which partial volume errors due to sulci and white matter caused increased variations. The MRI results agreed well with in vitro data on T1 and T2 in tissue specimens and with other MRI studies. When compared with T1 and T2 in ferritin solution, a significant "tissue relaxation enhancement" was found, attributable to slower diffusion and clustering of ferritin in tissue.
Subject(s)
Brain/metabolism , Brain/pathology , Iron/metabolism , Magnetic Resonance Imaging/methods , Adult , Age Factors , Child, Preschool , Epilepsy/metabolism , Epilepsy/pathology , Evaluation Studies as Topic , Ferritins/administration & dosage , Humans , Magnetic Resonance Spectroscopy , Models, Theoretical , Periaqueductal Gray/metabolism , Periaqueductal Gray/pathology , Reference Values , Reproducibility of Results , Retrospective StudiesABSTRACT
T2 was measured in samples of human blood and monkey brain over a field range of 0.02-1.5 Tesla, with variable interecho times, and was compared with previous data on ferritin solutions (taken with the same apparatus). 1/T2 in deoxygenated blood increased quadratically with field strength, as noted previously, but in brain gray matter the increase was linear, as also was the case in ferritin solution. In both deoxygenated blood and gray matter, 1/T2 increased with interecho time, but appeared to level off at times around 50 msec, as expected from the theory of diffusion through magnetic gradients. Diffusion times estimated by using the chemical exchange approximation were 3.4 msec for deoxygenated blood and 5.7 msec for the globus pallidus. The quadratic field dependence in blood is consistent with this same theory, but the linear dependence in brain tissue and in ferritin solutions remains unexplained.
Subject(s)
Blood , Brain Chemistry , Ferritins , Magnetic Resonance Imaging/methods , Animals , Humans , Macaca mulattaABSTRACT
A protein-encaged superparamagnetic iron oxide has been developed and characterized by using horse spleen apoferritin as a novel bioreactive environment. The roughly spherical magnetoferritin molecules, 120 A in diameter, are composed of a monocrystalline maghemite or magnetite core 73 A +/- 14 in diameter. Except for the additional presence of iron-rich molecules of higher molecular weight, the appearance and molecular weight (450 kd) of magnetoferritin are identical to that of natural ferritin; the molecules are externally indistinguishable from their precursor, with a pI (isoelectric point) in the range 4.3-4.6. The measured magnetic moment of the superparamagnetic cores is 13,200 Bohr magnetons per molecule, with T1 and T2 relaxivities (r1 and r2) of 8 and 175 L.mmol-1 (Fe).sec-1, respectively, at body temperature and clinical field strengths. The unusually high r2/r1 ratio of 22 is thought to arise from ideal core composition, with no evidence of crystalline paramagnetic inclusions. T2 relaxation enhancement can be well correlated to the field-dependent molecular magnetization, as given by the Langevin magnetization function, raised to a power in the range 1.4-1.6. With its nanodimensional biomimetic protein cage as a rigid, convenient matrix for complexing a plethora of bioactive substances, magnetoferritin may provide a novel template for specific targeting of selected cellular sites.