Wanida Chua-anusorn

Structural and magnetic properties of nanoscale iron oxide particles synthesized in the presence of dextran or polyvinyl alcohol

Magnetite/maghemite nanoparticles were synthesized in the presence of either dextran or polyvinyl alcohol, yielding cluster- and necklace-like aggregates, respectively. Magnetization, Mossbauer spectroscopy, and microscopy measurements indicate that the arrangement of the particles within the aggregates affects the magnetic properties of the particles resulting in smaller particles in the clusters having higher superparamagnetic blocking temperatures than larger particles in the necklaces.

Measurement and Mapping of Liver Iron Concentrations Using Magnetic Resonance Imaging

Abstract: Measurement of liver iron concentration (LIC) is an important clinical procedure in the management of transfusional iron overload with iron chelation. LIC gives an indication of over‐ or underchelation. Although chemical assay of needle biopsy samples from the liver has been considered the “gold standard” of LIC measurement, needle biopsy sampling errors can be surprisingly large owing to the natural spatial variation of LIC throughout the liver and the small size of biopsy specimens. A magnetic resonance imaging technique has now been developed that enables safe noninvasive measurement and imaging of LIC with a known accuracy and precision. Measurements of LIC can be made over the range of LIC encountered in clinical practice. The technique is based on the measurement and imaging of proton transverse relaxation rates (R2) within the liver. The R2 imaging technique can be implemented on most clinical 1.5‐T MRI instruments, making it readily available to the clinical community.

Proton transverse relaxation rate (R2) images of iron‐loaded liver tissuepping local tissue iron concentrations with MRI

Proton transverse relaxation rate (R2) imaging measurements were made on post mortem iron‐loaded human liver tissue samples (both intact and dissected into approximately 1‐cm cubes) from a single subject. Iron concentrations for the dissected samples as measured by atomic absorption spectrometry varied from 10.8 to 23.3 mg Fe.g−1 dry tissue. A significant linear correlation between the mean R2 and iron concentration of each sample was found (r = 0.95). In addition, regions of liver tissue with micronodular cirrhosis exhibited lower R2 values, corresponding to the displacement of iron by fibrotic septa. The cirrhotic tissue was clearly identified as a separate peak in the R2 distribution of the tissue. The relaxivity of the iron did not appear to depend on the microarchitecture of the tissue. Magn Reson Med 49:572–575, 2003.

Low-frequency low-field magnetic susceptibility of ferritin and hemosiderin

Low-frequency low-field magnetic susceptibility measurements were made on four samples of mammalian tissue iron oxide deposits. The samples comprised: (1) horse spleen ferritin; (2) dugong liver hemosiderin; (3) thalassemic human spleen ferritin; and (4) crude thalassemic human spleen hemosiderin. These samples were chosen because Mössbauer spectroscopic measurements on the samples indicated that they exemplified the variation in magnetic and mineral structure found in mammalian tissue iron oxide deposits. The AC-magnetic susceptometry yielded information on the magnetization kinetics of the four samples indicating samples 1, 2, and 3 to be superparamagnetic with values of around 10(11) s(-1) for the pre-exponential frequency factor in the Néel-Arrhenius equation and values for characteristic magnetic anisotropy energy barriers in the range 250-400 K. Sample 4 was indicated to be paramagnetic at all temperatures above 1.3 K. The AC-magnetic susceptometry data also indicated a larger magnetic anisotropy energy distribution in the dugong liver sample compared with samples 1 and 3 in agreement with previous Mössbauer spectroscopic data on these samples. At temperatures below 200 K, samples 1-3 exhibited Curie-Weiss law behavior, indicating weak particle-particle interactions tending to favor antiparallel alignment of the particle magnetic moments. These interactions were strongest for the dugong liver hemosiderin, possibly reflecting the smaller separation between mineral particles in this sample. This is the first magnetic susceptometry study of hemosiderin iron deposits and demonstrates that the AC-magnetic susceptometry technique is a fast and informative method of studying such tissue iron oxide deposits.

Bi-exponential proton transverse relaxation rate (R2) image analysis using RF field intensity-weighted spin density projection: potential for R2 measurement of iron-loaded liver

A bi-exponential proton transverse relaxation rate (R(2)) image analysis technique has been developed that enables the discrimination of dual compartment transverse relaxation behavior in systems with rapid transverse relaxation enhancement. The technique is particularly well suited to single spin-echo imaging studies where a limited number of images are available for analysis. The bi-exponential R(2) image analysis is facilitated by estimation of the initial proton spin density signal within the region of interest weighted by the RF field intensities. The RF field intensity-weighted spin density map is computed by solving a boundary value problem presented by a high spin density, long T(2) material encompassing the region for analysis. The accuracy of the bi-exponential R(2) image analysis technique is demonstrated on a simulated dual compartment manganese chloride phantom system with relaxation rates and relative population densities between the two compartments similar to the bi-exponential transverse relaxation behavior expected of iron loaded liver. Results from analysis of the phantoms illustrate the potential of bi-exponential R(2) image analysis with RF field intensity-weighted spin density projection for quantifying transverse relaxation enhancement as it occurs in liver iron overload.

The form of iron oxide deposits in thalassemic tissues varies between different groups of patients: a comparison between Thai β-thalassemia/hemoglobin E patients and Australian β-thalassemia patients

Mössbauer spectra of 12 beta-thalassemia/hemoglobin E spleen samples from Thai patients who had not received multiple blood transfusions and chelation therapy and seven beta-thalassemia spleen samples from Australian patients who had received multiple blood transfusions and chelation therapy were recorded with sample temperatures of 78 K. Each spectrum was found to consist of a superposition of a relatively intense central doublet characteristic of high-spin Fe(III), a low intensity sextet of peaks due to magnetic hyperfine-field splitting, and occasionally a doublet that could be attributed to heme iron. A significant (P=0.01) difference (Kolmogorov-Smirnov statistic of 0.71) between the distributions of sextet signal intensity as a fraction (Fs) of the total non-heme iron Mössbauer spectral signal for the two groups of patients was detected. The distribution of Fs for the Thai beta-thalassemia/hemoglobin E spleens had a mean value of 0.128 (S.D. 0.035) while that for the Australian beta-thalassemia spleens had a mean of 0.27 (S.D. 0.12). No significant difference between the distributions of non-heme iron concentrations in the tissues for the two groups of patients was detected by atomic absorption spectrometry. This study shows that the Australian beta-thalassemia patients had a higher fraction of their non-heme spleen iron in a goethite-like form than the Thai beta-thalassemia/Hb E patients.

Detection limits for ferrimagnetic particle concentrations using magnetic resonance imaging based proton transverse relaxation rate measurements

A clinical magnetic resonance imaging (MRI) system was used to measure proton transverse relaxation rates (R2) in agar gels with varying concentrations of ferrimagnetic iron oxide nanoparticles in a field strength of 1.5 T. The nanoparticles were prepared by coprecipitation of ferric and ferrous ions in the presence of either dextran or polyvinyl alcohol. The method of preparation resulted in loosely packed clusters (dextran) or branched chains (polyvinyl alcohol) of particles containing of the order of 600 and 400 particles, respectively. For both methods of particle preparation, concentrations of ferrimagnetic iron in agar gel less than 0.01 mg ml(-1) had no measurable effect on the value of R2 for the gel. The results indicate that MRI-based R2 measurements using 1.5 T clinical scanners are not quite sensitive enough to detect the very low concentrations of nanoparticulate biogenic magnetite reported in human brain tissue.

The effect of histological processing on the form of iron in iron-loaded human tissues

Iron-loaded human spleen tissue was immersed in neutral buffered formalin over a period of 200 days. Over the first 60 days, iron leached steadily from the tissue until 3% had been lost. Thereafter, no further iron leaching was detected. Comparisons of Mossbauer spectra of freeze-dried tissue and tissue freeze-dried after immersion in formalin for 200 days showed no evidence of chemical transformation of the iron remaining in the tissue. The spectra indicated a difference in the heme-iron to non-heme iron ratio between the two samples probably reflecting inhomogeneity of the ratio throughout the spleen as measured on the centimetre scale. Mossbauer spectra of freeze-dried samples of iron-loaded human liver and pancreas tissue were compared with those for samples from the same patient that had been processed by routine hospital procedures for histology and archival. These spectra showed no evidence for chemical transformation of the iron present in the tissues. These results demonstrate that it is feasible to use archived fixed and embedded human tissue samples for studies aimed at gauging the relative fraction of goethite-like hemosiderin present in the tissue.

Mössbauer spectroscopic study of the forms of iron in normal human liver and spleen tissue

Mössbauer spectra of 12 normal human spleen and 12 normal human liver samples (post mortem) from Australia and Thailand have been recorded at 78 K. The spectra show the presence of iron in the form of ferrihydrite, together with some deoxyhemoglobin and methemoglobin in some samples. The spectra were used in conjunction with elemental analysis to calculate the non-heme iron concentrations in the tissues. The mean non-heme iron concentration in the Thai livers was significantly less than that for the Australian samples. The goethite-like form of hemosiderin that has been observed in some pathological tissues was not detected.

Infrared spectroscopic studies of nanoscale iron oxide deposits isolated from human thalassemic tissues

Ferritin and hemosiderin isolated from human thalassemic tissues have been characterized by infrared spectroscopy. Spectral features due to both the organic components and the inorganic iron oxyhydroxide have been identified. In particular, spectral evidence for the presence of the goethite (alpha-FeOOH) form of hemosiderin has been obtained in the < 800 cm(-1) range. Various treatments of the hemosiderin isolates result in only small changes in the infrared spectrum indicating the close association of the organic components with the nanoscale iron particles present.