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

Pierre, Timothy G. St.; Clark, Paul; Chua‐anusorn, Wanida; Fleming, Adam; Jeffrey, Gary P.; Olynyk, John K.; Pootrakul, Pensri; Robins, Erin; Lindeman, Robert

doi:10.1182/blood-2004-01-0177

Cited by 813 publications

(864 citation statements)

References 42 publications

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“…Moreover, every new noninvasive technology able to quantitate liver iron concentration should be validated versus the above defined good quality biopsies reporting determination coefficient (R 2 ) with a 95% confidence prediction interval sufficiently narrow to be inside the well-known liver iron concentration thresholds predicting tissue damage and death. As far as we are aware, only liver MRI R2 and R2* presented this evidence but not for the whole possible ranges of liver iron concentration [2].…”

Section: Discussionmentioning

confidence: 82%

“…Determination of liver iron concentration (LIC) is essential to predict iron related tissue damage and disease and to guide chelation therapy [1]. Nowadays, only two validated noninvasive methods are available (MRI-R2 and R2*) [2] and liver biopsy continues to be the gold standard for hepatic iron determination. However, concern has been raised on the capability of the determination of iron concentration in a single hepatic biopsy sample to represent the entire parenchyma iron concentration [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Reproducibility of liver iron concentration measured on a biopsy sample: A validation study in vivo

et al. 2014

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Determination of liver iron concentration is essential to predict iron related tissue damage and to guide chelation therapy. To assess the reliability of a single biopsy iron concentration determination in representing the whole liver iron concentration, we conducted a prospective study performing two immediately successive liver biopsies from 61 noncirrhotic, iron overloaded thalassemia patients, directing the needle to different direction from the same skin cut. The correlation among sample biopsies was determined by both regression analysis and the Bland-Altman method. The results showed that overall correlation between the two samples was high (Pearson's coefficient of correlation r 5 0.970, P < 0.0001; 95% CI 0.951-0.981; R 2 5 0.941). To evaluate if sample dimension had an impact on the analysis we analyzed separately biopsy couples were both sample gross weight were 1 mg dry weight (n 5 16) from the others [one or both had a specimen gross weight <1 mg dry weight (n 5 45)]. In the first case, correlation coefficient r was equal to 0.998 (P < 0.0001; 95% CI: 0.995-0.999; R 2 5 0.996) while in the latter was 0.960 (P < 0.0001; 95% CI: 0.928-0.977; R 2 5 0.921). In no instance second specimen prediction interval was outside the interval implying different prognostic and therapeutic decision if both liver samples gross weight were 1 mg dry weight. The Bland-Altman plot analysis showed the same trend observed using Pearson's correlation coefficient in the analyzed sample categories. Hepatic iron concentration determined in "good quality" biopsy specimen (i.e. sample gross weight 1 mg dry weight) is a reliable indicator of whole liver iron concentration.

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Section: Discussionmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Reproducibility of liver iron concentration measured on a biopsy sample: A validation study in vivo

et al. 2014

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“…The most widely used R2 technique, FerriscanV R , uses standardized spin echo acquisitions and analysis techniques [4] through a FDA-approved, commercial protocol (Resonance Health, Western Australia). Ferriscan was originally validated to liver biopsy in 105 subjects [4], and the calibration reaffirmed in a subsequent test sample of 233 subjects [5].…”

Section: Introductionmentioning

confidence: 99%

R2 and R2* are equally effective in evaluating chronic response to iron chelation

et al. 2014

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MRI relaxometry (R2, R2*) has generally replaced liver biopsy for estimation of liver iron stores in response to iron chelation, but there have been no longitudinal studies comparing R2 and R2* techniques. We use R2 and R2* liver iron concentration (LIC) estimates, transfusional iron burdens, and drug compliance data to calculate iron chelation efficiency (ICE) in patients undergoing a Phase II trial of SPD602. Fifty-one patients underwent a baseline examination, 39 patients completed 1 year, and 26 patients completed 2 years. Baseline LIC R2 and LIC R2* estimates were unbiased, but had limits of agreement exceeding 50%, suggesting that these techniques cannot be interchanged with one another in the same patient. However, ICE estimates across the two techniques compared more favorably, with r 2 values reaching 0.89 at 2 years. 95 confidence intervals for efficiency estimates were 0.0 6 4.1%. These data indicate that clinical trial and clinical effectiveness data calculated using LIC R2 and LIC R2* estimates can be compared to one another, even though LIC estimates may be disparate on cross-sectional analysis. While the choice of MRI assessment technique for clinical trials and for clinical management depends on many logistical considerations, one can have confidence comparing conclusions on clinical effectiveness.

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“…Subsequent revalidation of the method on the basis of 223 patients [23] showed a certain range of the results with an average deviation compared to liver biopsy of 35 %. In contrast to the nonlinear relationship between R 2 and liver iron content in a range of up to 40 mg/g dry weight stated in the studies by St. Pierre et al [20,23], Wood showed a linear course (as is theoretically to be expected), but only for a maximum liver iron concentration of up to 30 mg/g dry weight ( fig. 2 in ref.…”

Section: Spin-echo Sequencementioning

confidence: 58%

“…Historically used first [12,13], this method was then further developed by St. Pierre [20] on the basis of the data of 40 patients into a validated, FDA-approved, CE-certified, feebased method under the name Ferriscan ® . The method is based on the fact that the liver signal decreases as the echo time (TE) increases as shown in • ▶ Fig.…”

Section: Spin-echo Sequencementioning

confidence: 99%

Noninvasive MRI-Based Liver Iron Quantification: Methodic Approaches, Practical Applicability and Significance

Wunderlich

Cario²,

Juchems

et al. 2016

Fortschr Röntgenstr

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Pathophysiology of iron overload ▼Normal iron content plays an important role in the physiological processes of the human body. A disturbance to the precisely regulated iron metabolism system has serious consequences. Therefore, for example, iron overload results in oxidative damage to membrane lipids and proteins and in DNA damage that can cause mitochondrial and lysosomal dysfunction, changes in gene expression, and changes in tumor suppressor genes (p53). Organ damage due to iron overload primarily affects the heart and liver as well as the endocrine organs, i. e., the pituitary gland, pancreas, thyroid, parathyroid, and gonads [1]. Cardiac insufficiency and arrhythmia as a result of myocardial siderosis are the most Abstract ▼Due to the dependence of transverse relaxation times T 2 and T 2 * on tissue iron content, MRI offers different options for the determination of iron concentration. These are the timeconsuming spin-echo sequence as well as the gradient-echo sequence. For the latter, several data analysis approaches have been proposed, with different requirements for acquisition and post-processing: the mathematically challenging R 2 * analysis and the signal-intensity ratio method with its high demand on the signal homogeneity of MR images. Furthermore, special procedures currently under evaluation are presented as future prospects: quantitative susceptibility imaging, as a third approach for analyzing gradient echo data, and multicontrast spin-echo using repeated refocusing pulses. MR theory, as far as needed for understanding the methods, is briefly depicted.

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

Cited by 813 publications

References 42 publications

Reproducibility of liver iron concentration measured on a biopsy sample: A validation study in vivo

Reproducibility of liver iron concentration measured on a biopsy sample: A validation study in vivo

R2 and R2* are equally effective in evaluating chronic response to iron chelation

Noninvasive MRI-Based Liver Iron Quantification: Methodic Approaches, Practical Applicability and Significance

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