Hepatic Iron - MRI Investigation

11/23/2005

Question:  How useful is MRI in the investigation of hepatic iron stores, especially hepatic iron overload?

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15256427.ui or 15117445.ui or 15070565.ui or 14717788.ui or 12165905.ui or 10405746.ui or 10206461.ui or 9389689.ui or 2298350.ui or 3964933.ui

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15256427[PMID] OR 15117445[PMID] OR 15070565[PMID] OR 14717788[PMID] OR 12165905[PMID] OR 10405746[PMID] OR 10206461[PMID] OR 9389689[PMID] OR 2298350[PMID] OR 3964933[PMID]

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Unique Identifier [PMID]: 15256427

Authors: St Pierre TG. Clark PR. Chua-anusorn W. Fleming AJ. Jeffrey GP. Olynyk JK. Pootrakul P. Robins E. Lindeman R.

Institution: School of Physics, University of Western Australia, Perth, Australia. stpierre@physics.uwa.edu.au

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

Source: Blood. 105(2):855-61, 2005 Jan 15.

Abstract: Measurement 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%.

Publication Type: Clinical Trial. Journal Article.

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Unique Identifier [PMID]: 15117445

Authors: Johnston JD.

Institution: Queen Elizabeth Hospital, London, UK.

Title: Non-invasive assessment of hepatic iron stores by MRI.

Source: Annals of Clinical Biochemistry. 41(Pt 3):254, 2004 May.

Publication Type: Journal Article.

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Unique Identifier [PMID]: 15070565

Authors: Gandon Y. Olivie D. Guyader D. Aube C. Oberti F. Sebille V. Deugnier Y.

Institution: Federation d'Imagerie Medicale, CHU Pontchaillou, Rennes, France. yves.gandon@chu-rennes.fr

Title: Non-invasive assessment of hepatic iron stores by MRI.[see comment].

Comments Comment in: Lancet. 2004 Jan 31;363(9406):341-2; PMID: 15070558

Source: Lancet. 363(9406):357-62, 2004 Jan 31.

Abstract: BACKGROUND: MRI has been proposed for non-invasive detection and quantification of liver iron content, but has not been validated as a reproducible and sensitive method, especially in patients with mild iron overload. We aimed to assess the accuracy of a simple, rapid, and easy to implement MRI procedure to detect and quantify hepatic iron stores. METHODS: Of 191 patients recruited, 17 were excluded and 174 studied, 139 in a study group and 35 in a validation group. All patients underwent both percutaneous liver biopsy with biochemical assessment of hepatic iron concentration (B-HIC) and MRI of the liver with various gradient-recalled-echo (GRE) sequences obtained with a 1.5 T magnet. Correlation between liver to muscle (L/M) signal intensity ratio and liver iron concentration was calculated. An algorithm to calculate magnetic resonance hepatic iron concentration (MR-HIC) was developed with data from the study group and then applied to the validation group. FINDINGS: A highly T2-weighted GRE sequence was most sensitive, with 89% sensitivity and 80% specificity in the validation group, with an L/M ratio below 0.88. This threshold allowed us to detect all clinically relevant liver iron overload greater than 60 micromol/g (normal value <36 micromol/g). With other sequences, an L/M ratio less than 1 was highly specific (>87%) for raised hepatic iron concentration. With respect to B-HIC range analysed (3-375 micromol/g), mean difference and 95% CI between B-HIC and MR-HIC were quite similar for study and validation groups (0.8 micromol/g [-6.3 to 7.9] and -2.1 micromol/g [-12.9 to 8.9], respectively). INTERPRETATION: MRI is a rapid, non-invasive, and cost effective technique that could limit use of liver biopsy to assess liver iron content. Our MR-HIC algorithm is designed to be used on various magnetic resonance machines.

Publication Type: Journal Article.

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Unique Identifier [PMID]: 14717788

Authors: Ooi GC. Khong PL. Chan GC. Chan KN. Chan KL. Lam W. Ng I. Ha SY.

Institution: Department of Diagnostic Radiology, The University of Hong Kong, Room 405/Block K, Queen Mary Hospital, Hong Kong SAR, China. cgooi@hkucc.hku.hk

Title: Magnetic resonance screening of iron status in transfusion-dependent beta-thalassaemia patients.

Source: British Journal of Haematology. 124(3):385-90, 2004 Feb.

Abstract: The clinical utility of dual sequence (T1- and T2-weighted) magnetic resonance (MR) imaging in estimating liver iron concentration (LIC) in 32 transfusion-dependent beta-thalassaemia major (24 females; age 18.5+/-5.9 years) patients on desferrioxamine was evaluated. Signal intensity ratios (SIR) between liver, spleen and pancreas to psoas muscle were determined on both sequences. Relationships between clinical and MR parameters, and accuracy of SIR thresholds in determining adequacy of chelation from LIC were analysed. Liver T1- and T2-SIR were related to LIC (P < 0.001). T1-SIR < 0.60 predicted severe iron overload (LIC > 15 mg/g) with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 100%, 87%, 33% and 100% respectively. T2-SIR < 0.1 yielded 100% sensitivity, 93% specificity, 50% PPV and 100% NPV. T1-SIR > or = 1.1 predicted LIC < 7 mg/g with 69% sensitivity, 88% specificity, 85% PPV and 74% NPV. T2-SIR > or = 0.20 yielded 56.5% sensitivity, 94% specificity, 90% PPV and 71% NPV. LIC correlated with liver T1-SIR, liver T2-SIR and serum ferritin (r = -0.76, -0.65, 0.47, respectively; P < 0.01). Serum ferritin was inversely related to liver T1-SIR, liver T2-SIR and spleen T2-SIR (r = -0.35, -0.43, -0.40, respectively; P < 0.05). Mean total transfusion burden was not related to any MR parameter. Although neither MR sequence was a highly accurate predictor of LIC, SIR thresholds are useful to determine presence of iron overload and adequacy of chelation treatment.

Publication Type: Journal Article.

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Unique Identifier [PMID]: 10405746

Authors: Bonkovsky HL. Rubin RB. Cable EE. Davidoff A. Rijcken TH. Stark DD.

Institution: Dept of Medicine, University of Massachusetts Medical School, Worcester, USA. Herbert.Bonkovsky@ummhc.org

Title: Hepatic iron concentration: noninvasive estimation by means of MR imaging techniques.

Source: Radiology. 212(1):227-34, 1999 Jul.

Abstract: PURPOSE: To identify a magnetic resonance (MR) imaging method sufficiently sensitive and specific in the estimation of hepatic iron content to obviate liver biopsy. MATERIALS AND METHODS: Thirty-eight patients underwent percutaneous needle biopsy of the liver with chemical measurement of the hepatic iron concentration and hepatic MR imaging with several spin-echo and gradient-recalled-echo (GRE) techniques. Correlations between MR imaging parameters and the hepatic iron concentration were determined. RESULTS: Inverse curvilinear relationships were noted between several MR parameters and hepatic iron concentrations. GRE sequences with short repetition and echo times were more accurate and precise than spin-echo sequences for the estimation of hepatic iron concentration. A GRE sequence with a repetition time of 18 msec, an echo time of 5 msec, and a flip angle of 10 degrees showed close correlation between the hepatic iron concentration and the natural logarithm of the ratio of the signal intensity of liver to the SD of background noise (r = -0.94) and low coefficient of variation (12%). CONCLUSION: MR imaging with these parameters is a rapid, noninvasive, and accurate modality for estimation of hepatic iron concentration; it is sufficiently accurate and precise to obviate liver biopsy for the purpose of measuring hepatic iron concentration.

Publication Type: Journal Article.

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Unique Identifier [PMID]: 10206461

Authors: Papakonstantinou O. Kostaridou S. Maris T. Gouliamos A. Premetis E. Kouloulias V. Nakopoulou L. Kattamis C.

Institution: Department of Diagnostic Radiology, Areteion Hospital, Athens University, Greece.

Title: Quantification of liver iron overload by T2 quantitative magnetic resonance imaging in thalassemia: impact of chronic hepatitis C on measurements.

Source: Journal of Pediatric Hematology/Oncology. 21(2):142-8, 1999 Mar-Apr.

Abstract: PURPOSE: Measurement of liver T2 values seems to be an accurate and sensitive magnetic resonance imaging (MRI) method for the quantification of liver hemosiderosis in multiple transfused patients with thalassemia. Because many of these patients have coexistent chronic hepatitis C virus (HCV) infection, the effect of inflammatory changes on liver T2 values was assessed. MATERIALS AND METHODS: Liver MRI studies of 35 HCV+ and 17 HCV- patients with beta-thalassemia, 9 HCV+ patients without thalassemia, and 10 healthy controls of the same age range (13 to 32 years) were reviewed. Iron status was assessed by serum ferritin in all patients, and determination of liver iron concentration (LIC) was available in 16 HCV+ patients with thalassemia. Histologic activity index (HAI) and grades of siderosis were evaluated in all HCV+ patients with thalassemia. RESULTS: Patients with thalassemia had significantly lower T2 values (P < 0.0001) than subjects without thalassemia, whereas no difference existed between HCV+ patients without thalassemia and healthy controls. In HCV+ patients, LIC correlated more nearly with T2 values (r = 0.93) than with serum ferritin (r = 0.73). T2 values were not influenced by HAI score or fibrosis. CONCLUSION: Liver T2 values were found to be more accurate than serum ferritin in predicting liver iron overload and were not influenced by the presence of chronic hepatitis C. Therefore, MRI could serve as a noninvasive alternative to liver biopsy for the quantification of hemosiderosis in HCV+ patients with thalassemia.

Publication Type: Journal Article.

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Unique Identifier [PMID]: 9389689

Authors: Angelucci E. Giovagnoni A. Valeri G. Paci E. Ripalti M. Muretto P. McLaren C. Brittenham GM. Lucarelli G.

Institution: Divisione Ematologica e Centro Trapianto Midollo Osseo di Muraglia, Azienda Ospedale di Pesaro, Pesaro, Italy.

Title: Limitations of magnetic resonance imaging in measurement of hepatic iron.

Source: Blood. 90(12):4736-42, 1997 Dec 15.

Abstract: To evaluate the usefulness of magnetic resonance imaging for the quantitative determination of hepatic iron, we examined 43 patients with thalassemia major and assessed the influence of pathologic changes in the liver on the precision of estimates of the hepatic iron concentration. Tissue signal intensities were measured from magnetic resonance T1-weighted images derived from gradient-echo (GE) pulse sequences and the ratio of the signal intensity of liver to muscle calculated. By excluding patients (n = 9) having a signal intensity ratio (SIR) less than or equal to 0.2, a linear relationship with hepatic iron was found and subsequent analyses were limited to these 34 patients. In 27 patients with hepatic fibrosis, an overall correlation of -0.848 was found between hepatic iron and SIR. By contrast, in the seven patients with no fibrosis, the correlation coefficient (-0.993) was significantly greater (P < .0001). Despite the differences in correlation, the regression line between hepatic iron and SIR for the patients with no fibrosis did not differ significantly with respect to either slope or intercept from that of the patients with fibrosis. Thus, the presence of fibrosis did not seem to affect the pattern of the relationship between hepatic iron and the SIR, but rather to increase the variability of the relationship. Clinically, the presence of fibrosis makes estimates of hepatic iron derived from magnetic resonance imaging so variable as to be of little practical use in the management of transfusional iron overload.

Publication Type: Journal Article.

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Unique Identifier [PMID]: 2298350

Authors: Chezmar JL. Nelson RC. Malko JA. Bernardino ME.

Institution: Department of Radiology, Emory University School of Medicine, Atlanta, Georgia.

Title: Hepatic iron overload: diagnosis and quantification by noninvasive imaging.

Source: Gastrointestinal Radiology. 15(1):27-31, 1990.

Abstract: The diagnostic efficacy of magnetic resonance (MR) and computed tomography (CT) for detection and quantification of hepatic iron was assessed in a series of patients under investigation for clinical or biochemical evidence of hepatic iron overload. Thirty patients underwent MR imaging (SE 30,60/1000 or SE 30,60/2000) at 0.5 Tesla with calculation of hepatic T2 and liver to paraspinous muscle signal intensity ratios. Twenty-nine patients also had measurement of hepatic attenuation on noncontrast CT images. Results of these imaging studies were correlated in all patients with quantitative iron determination from liver biopsy specimens. The best predictor of liver iron among parameters studied was the ratio of the signal intensities of liver and paraspinous muscle (L/M) on a SE 60/1000 sequence. Both MR using L/M ratios and CT were sensitive methods for detection of severe degrees of hepatic iron overload with 100% of patients with hepatic iron on biopsy greater than 600 micrograms/100 mg liver dry weight detected on the basis of L/M less than 0.6 or CT attenuation greater than 70 Hounsfield units (HU). The MR parameter, however, was more specific than CT (100 vs 50%) and showed a higher degree of correlation with quantitated hepatic iron from biopsy. T2 measurements showed poor correlation with hepatic iron, due to difficulty in obtaining precise T2 measurements in vivo when the signal intensity is low. None of the parameters utilized was sensitive for detecting mild or moderate degrees of hepatic iron overload. We conclude that MR and CT are sensitive techniques for noninvasive detection of severe hepatic iron overload, with MR providing greater specificity than CT.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication Type: Journal Article.

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Unique Identifier [PMID]: 3964933

Authors: Stark DD. Moseley ME. Bacon BR. Moss AA. Goldberg HI. Bass NM. James TL.

Title: Magnetic resonance imaging and spectroscopy of hepatic iron overload.

Source: Radiology. 154(1):137-42, 1985 Jan.

Abstract: Experimental animals that had been given excess iron in their diet were studied by magnetic resonance (MR) imaging in vivo and by magnetic resonance (MR) spectroscopy in vitro. Hepatic iron overload in patients with transfusional iron excess was studied by MR imaging, and isolated iron protein fractions were studied in vitro by MR spectroscopy. The spin echo image intensity of livers with iron overload was decreased because of the extreme decreases in T2 compared with normal; T1 was decreased only moderately. The relaxation rates 1/T2 and 1/T1 both showed a linear relationship to hepatic iron levels. Ferritin solutions showed moderate decreases in T2 and mild decreases in T1. The T2 relaxivity of ferritin, which is due to the iron core rather than the apoferritin protein shell, does not appear sufficient to account for the extreme decrease in T2 observed in hepatic iron overload. Low molecular weight cytosol iron is present in lower concentrations than ferritin but potentially has much greater relaxivity and may contribute to the MR findings. These techniques may be useful in other studies of iron metabolism.

Publication Type: Journal Article.