Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance

AbstractMeasurement of liver iron concentration (LIC) is necessary for a range of iron-loading disorders such as hereditary hemochromatosis, thalassemia, sickle cell disease, aplastic anemia, and myelodysplasia. Currently, chemical analysis of needle biopsy specimens is the most common accepted method of measurement. This study presents a readily available noninvasive method of measuring and imaging LICs in vivo using clinical 1.5-T magnetic resonance imaging units. Mean liver proton transverse relaxation rates (R2) were measured for 105 humans. A value for the LIC for each subject was obtained by chemical assay of a needle biopsy specimen. High degrees of sensitivity and specificity of R2 to biopsy LICs were found at the clinically significant LIC thresholds of 1.8, 3.2, 7.0, and 15.0 mg Fe/g dry tissue. A calibration curve relating liver R2 to LIC has been deduced from the data covering the range of LICs from 0.3 to 42.7 mg Fe/g dry tissue. Proton transverse relaxation rates in aqueous paramagnetic solutions were also measured on each magnetic resonance imaging unit to ensure instrument-independent results. Measurements of proton transverse relaxivity of aqueous MnCl2 phantoms on 13 different magnetic resonance imaging units using the method yielded a coefficient of variation of 2.1%.

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High-Resolution CMRO2 Mapping in Rat Cortex: A Multiparametric Approach to Calibration of BOLD Image Contrast at 7 Tesla

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200005000-00012 ◽

2000 ◽

Vol 20 (5) ◽

pp. 847-860 ◽

Cited By ~ 69

Author(s):

Ikuhiro Kida ◽

Richard P. Kennan ◽

Douglas L. Rothman ◽

Kevin L. Behar ◽

Fahmeed Hyder

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Spin Echo ◽

7 Tesla ◽

Relaxation Rates ◽

Resonance Imaging ◽

Gradient Echo ◽

Transverse Relaxation ◽

Physiologic Parameters ◽

Spin Echo Sequences

The blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) method, which is sensitive to vascular paramagnetic deoxyhemoglobin, is dependent on regional values of cerebral metabolic rate of oxygen utilization (CMRO2), blood flow (CBF), and volume (CBV). Induced changes in deoxyhemoglobin function as an endogenous contrast agent, which in turn affects the transverse relaxation rates of tissue water that can be measured by gradient-echo and spin-echo sequences in BOLD fMRI. The purpose here was to define the quantitative relation between BOLD signal change and underlying physiologic parameters. To this end, magnetic resonance imaging and spectroscopy methods were used to measure CBF, CMRO2, CBV, and relaxation rates (with gradient-echo and spin-echo sequences) at 7 Tesla in rat sensorimotor cortex, where cerebral activity was altered pharmacologically within the autoregulatory range. The changes in tissue transverse relaxation rates were negatively and linearly correlated with changes in CBF, CMRO2, and CBV. The multiparametric measurements revealed that CBF and CMRO2 are the dominant physiologic parameters that modulate the BOLD fMRI signal, where the ratios of (ΔCMRO2/CMRO2)/(ΔCBF/CBF) and (ΔCBV/CBV)/(ΔCBF/CBF) were 0.86 ± 0.02 and 0.03 ± 0.02, respectively. The calibrated BOLD signals (spatial resolution of 48 μL) from gradient-echo and spin-echo sequences were used to predict changes in CMRO2 using measured changes in CBF, CBV, and transverse relaxation rates. The excellent agreement between measured and predicted values for changes in CMRO2 provides experimental support of the current theory of the BOLD phenomenon. In gradient-echo sequences, BOLD contrast is affected by reversible processes such as static inhomogeneities and slow diffusion, whereas in spin-echo sequences these effects are refocused and are mainly altered by extravascular spin diffusion. This study provides steps by which multiparametric MRI measurements can be used to obtain high-spatial resolution CMRO2 maps.

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Correlation of liver iron concentration determined by R2 magnetic resonance imaging with serum ferritin in patients with thalassemia intermedia

Haematologica ◽

10.3324/haematol.13098 ◽

2008 ◽

Vol 93 (10) ◽

pp. 1584-1586 ◽

Cited By ~ 79

Author(s):

A. Taher ◽

F. El Rassi ◽

H. Isma'eel ◽

S. Koussa ◽

A. Inati ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Serum Ferritin ◽

Iron Concentration ◽

Thalassemia Intermedia ◽

Resonance Imaging ◽

Liver Iron Concentration ◽

Liver Iron

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Quantitative liver iron measurement by magnetic resonance imaging: in vitro and in vivo assessment of the liver to muscle signal intensity and the R2* methods

Magnetic Resonance Imaging ◽

10.1016/j.mri.2008.01.028 ◽

2008 ◽

Vol 26 (8) ◽

pp. 1175-1182 ◽

Cited By ~ 27

Author(s):

Johanna M. Virtanen ◽

Markku E. Komu ◽

Riitta K. Parkkola

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Signal Intensity ◽

Resonance Imaging ◽

Liver Iron ◽

In Vivo Assessment

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Chelation use and iron burden in North American and British thalassemia patients: a report from the Thalassemia Longitudinal Cohort

Blood ◽

10.1182/blood-2011-04-344507 ◽

2012 ◽

Vol 119 (12) ◽

pp. 2746-2753 ◽

Cited By ~ 54

Author(s):

Janet L. Kwiatkowski ◽

Hae-Young Kim ◽

Alexis A. Thompson ◽

Charles T. Quinn ◽

Brigitta U. Mueller ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Clinical Care ◽

Iron Concentration ◽

Dry Weight ◽

Combination Therapies ◽

Resonance Imaging ◽

Liver Iron ◽

Organ Specific

Abstract Morbidity and mortality in thalassemia are associated with iron burden. Recent advances in organ-specific iron imaging and the availability of oral deferasirox are expected to improve clinical care, but the extent of use of these resources and current chelation practices have not been well described. In the present study, we studied chelation use and the change in iron measurements in 327 subjects with transfusion-dependent thalassemia (mean entry age, 22.1 ± 2.5 years) from 2002-2011, with a mean follow-up of 8.0 years (range, 4.4-9.0 years). The predominant chelator currently used is deferasirox, followed by deferoxamine and then combination therapies. The use of both hepatic and cardiac magnetic resonance imaging increased more than 5-fold (P < .001) during the study period, leading to an 80% increase in the number of subjects undergoing liver iron concentration (LIC) measurements. Overall, LIC significantly improved (median, 10.7 to 5.1 mg/g dry weight, P < .001) with a nonsignificant improvement in cardiac T2* (median, 23.55 to 34.50 ms, P = .23). The percentage of patients with markers of inadequate chelation (ferritin > 2500 ng/mL, LIC > 15 mg/g dry weight, and/or cardiac T2* < 10 ms) also declined from 33% to 26%. In summary, increasing use of magnetic resonance imaging and oral chelation in thalassemia management has likely contributed to improved iron burden.

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