Calibration of Improved T2* Method for the Estimation of Liver Iron Concentration in Transfusional Iron Overload.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2004-2004 ◽  
Author(s):  
Maciej W Garbowski ◽  
John-Paul Carpenter ◽  
Gillian Smith ◽  
Dudley J Pennell ◽  
John B Porter
Keyword(s):  
Liver Biopsy ◽  
Iron Concentration ◽  
Cardiovascular Imaging ◽  
Breath Hold ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Single Breath ◽  
Single Breath Hold ◽  
Tissue Iron ◽  
The Relationship

Abstract Abstract 2004 Poster Board I-1026 Background and rationale Non-invasive estimation of tissue iron concentration is being used increasingly to follow responses to chelation therapy. Magnetic resonance (MR) T2* was originally developed to estimate myocardial iron but the first description of the myocardial T2* method also demonstrated a clear relationship between liver T2* and liver iron concentration (LIC) measured by biopsy (Anderson, Eur Heart J 2001). The inclusion of liver analysis at this time was intended mainly to show the relationship of T2* to tissue iron rather than as a standard method for LIC measurement, particularly as the echo times used were too long to measure the high iron levels commonly found in the liver. Since this work, other MR methods such as the R2 technique (St. Pierre, Blood 2004) have been specifically validated to measure LIC. However, if T2* could be validated and calibrated appropriately for LIC, it may be convenient to measure liver and heart iron at the same time using this rapid technique. Since the initial calibration of the T2* method, there have been major improvements in scanner technology and hardware. In the original paper, eight different echo times were acquired (TE 2.2- 20.1ms), each of which required a separate breath-hold with important implications for image registration regarding the measurement of T2*. Much shorter, more closely spaced echo times are now possible in a single breath-hold which makes the calculation of T2* more accurate, especially at higher liver iron concentrations where T2* is short. Methods: A large cohort of patients at UCLH have had liver biopsies as part of iron chelation studies on Deferasirox, while continuing to be monitored by T2* of both heart and liver. Data pairs for LIC calibration curve plots were chosen as nested values by shortest biopsy-to-MR time lapse criterion (±75 days) from all biopsy and hepatic T2* results. Liver biopsy iron was measured in a single central laboratory in Rennes, France (Clinique des Maladies du Foie [Clinic for Hepatic Illnesses], Center Hospitalier Universitaire) on paraffin embedded sections as previously described (Soriano-Cubells MJ, Atomic Spectrosc. 1984). All MR scans were performed on a 1.5T Sonata MR scanner (Siemens, Germany) using a 4-channel anterior phased array coil at Royal Brompton Hospital, London. A transverse slice through the centre of the liver was imaged using a multi-echo single breath-hold gradient echo T2* sequence with a range of echo times (TE 0.93-16.0ms). T2* decay was measured using Thalassaemia tools (Cardiovascular Imaging Solutions, London, UK) from a region of interest (ROI) in an area of homogeneous liver tissue, avoiding blood vessels and other sources of artefact. To account for background noise, a truncation method was used for curve-fitting (He, Magn Reson Med 2008). All T2* measurements were performed in triplicate by 2 independent observers choosing three separate ROIs to analyse. The ROIs were chosen to be as large as possible in three separate areas of the liver (anterior, mid/lateral and posterior). Spearman correlation method was used to estimate the degree of relationship between biopsy LIC and hepatic R2* (1/T2*) values, both of which showed positive skew. Results and conclusions: 61 patients had both liver biopsy and liver MR measurements undertaken. However, only 18 had biopsies within 75 days of MR T2* measurement and these are the patients included in the following analysis. There is a linear relationship between biopsy LIC and the reciprocal of T2* (R2*), given by: LIC = 0.03 x R2* + 0.74 (R2=0.96 p<0.0001, slope 95% CI 0.027-0.033, with y intercept CI -0.73 to 2.2). The 95% confidence intervals for the linear regression line were calculated from the SEM and are shown as the broken lines (Figure 1). Staging of fibrosis/cirrhosis provided in biopsy reports was not found to significantly affect regression analysis contrary to previous studies. The inset shows the relationship between T2* and biopsy LIC. The new calibration shows acceptable linearity and reproducibility over an LIC range up to 30mg/g dry weight and gives LIC values approximately 1.94 times higher than the original method reported by Anderson. Comparison of these values with those obtained by SQUID and Ferriscan would also be of interest. Disclosures: Pennell: Cardiovascular Imaging SOlutions, London, UK: Director.

Myocardial iron overload

2018 ◽  
pp. 364-374
Author(s):  
John P Carpenter ◽  
John C Wood ◽  
Dudley J Pennell
Keyword(s):  
Heart Failure ◽  
Iron Overload ◽  
Iron Concentration ◽  
Left Ventricular ◽  
Breath Hold ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Single Breath ◽  
Developing Heart ◽  
Cost Efficient

The heart is the target lethal organ in thalassaemia major. Cardiovascular magnetic resonance (CMR) measures iron using the magnetic relaxation time T2*. This allows comparison with the left ventricular function and conventional iron measurements such as liver iron and serum ferritin. The single breath-hold cardiac-gated CMR acquisition takes only 15 seconds, making it cost-efficient and relevant to developing countries. Myocardial T2* of <20 ms (increased iron) correlates with reduced left ventricular ejection fraction, but poor correlation exists with ferritin and liver iron, indicating poor capability to assess future risk. Myocardial T2* of <10 ms is present in >90% of thalassaemia patients developing heart failure, and approximately 50% of patients with T2* of <6 ms will develop heart failure within 1 year without intensified treatment. The technique is validated and calibrated against human heart iron concentration. The treatment for iron overload is iron chelation, and three major trials have been performed for the heart. The first trial showed deferiprone was superior to deferoxamine in removing cardiac iron. The second trial showed a combination therapy of deferiprone with deferoxamine was more effective than deferoxamine monotherapy. The third trial showed that deferasirox was non-inferior to deferoxamine in removing cardiac iron. Each drug in suitable doses can be used to remove cardiac iron, but their use depends on clinical circumstances. Other combination regimes are also being evaluated. Use of T2*, intensification of chelation treatment, and use of deferiprone are associated with reduced mortality (a reduction in deaths by 71% has been shown in the United Kingdom). The use of T2* and iron chelators in the heart has been summarized in recent American Heart Association guidelines.

Inter-Site Validation of a Single Breath Hold T2* MR Technique for Heart and Liver Iron Measurement.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3830-3830 ◽  
Author(s):  
Paul Kirk ◽  
Lisa J. Anderson ◽  
Mark A. Tanner ◽  
Renzo Galanello ◽  
Gildo Matta ◽  
...  
Keyword(s):  
Coefficient Of Variation ◽  
Breath Hold ◽  
Iron Loading ◽  
Myocardial Iron ◽  
Thalassaemia Major ◽  
Liver Iron ◽  
Single Breath ◽  
Single Breath Hold ◽  
Average Coefficient ◽  
Siemens Sonata

Abstract Background Approximately 60,000 people are born with thalassaemia major every year. The average life expectancy of thalassaemia major patients is 35 years due to iron overload Cardiomyopathy. The cardiomyopathy is reversible when treated early, but once heart failure is established it is often rapidly progressive, and unresponsive to treatment. The single breath hold (SBH) T2* technique has been validated as the most robust and reproducible non-invasive measurement of myocardial and iron load. Our aim in this study was to validate the transferability and reproducibility of this technique in different scanners worldwide. Methods We aim to compare the reproducibility in six different sites worldwide as part of an NIH funded grant (R01-DK66084-01). So far, two of these sites have been validated: Singapore (Siemens Sonata, 1.5T scanner) and Cagliari, Italy (GE Signa, 1.5 T scanner). At both validation sites, 10 patients were scanned for heart and liver T2*, and scans were repeated for interstudy reproducibility. All patients then flew to London to be rescanned on our reference Siemens Sonata scanner. Results Of the 20 patients scanned, 70% had myocardial iron loading (T2* <20ms) and in 10% the myocardial iron loading was severe. Liver iron loading was present in 65% of patients and in 30% this was severe. The coefficient of variation (COV) for the heart T2* measurements between the local sites and London was 5.9% and 4.9% yielding an average coefficient of variation across both sites of 5.4% (figure 1). The coefficient of variation (COV) for the liver T2* measurements between the local sites and London was 11.3% and 3.9% yielding an average coefficient of variation across both sites of 7.6% (figure 2). There was no significant correlation between liver and myocardial loading. Conclusion These are the first data demonstrating the transferability of the SBH T2* technique and the clinical validation from the 2 collaborating centers were excellent for both heart and liver measurements. Further MR sites confirmed for validation include Children’s Hospital of Philadelphia (USA); Ramathibodi Hospital, Bangkok (Thailand); and Chinese University Hong Kong. Figure 1 Figure 1. Figure 2 Figure 2.

Liver Iron Concentration Estimates by R2* Are More Robust Than by Ferriscan During Rapid Changes in Iron Burden

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5296-5296
Author(s):  
John C Wood ◽  
Amber Jones ◽  
Hugh Y Rienhoff ◽  
Ellis J. Neufeld
Keyword(s):  
Liver Biopsy ◽  
Research Funding ◽  
Iron Concentration ◽  
Drug Consumption ◽  
Dose Titration ◽  
Outcome Variable ◽  
Gradient Echo ◽  
Liver Iron ◽  
Body Iron ◽  
Tissue Iron

Abstract Abstract 5296 Introduction: MRI assessment of LIC concentration is increasing utilized as the primary outcome variable of clinical trials for iron chelation. The MRI parameters R2 and R2* can both be used for this purpose but have slightly different sensitivities to the scale and distribution of tissue iron deposits. As a result, these techniques may provide significantly disparate results in any given patient and may diverge following abrupt changes in chelation therapy. It is not practical, nor ethical, to use liver biopsy to validate R2 and R2* LIC measures on a short time scale. Thus, we used calculations of chelator molar efficiency to determine whether predicted changes in LIC were consistent with the known iron balance assessed by transfusional burden and drug consumption. Methods: The Phase II trial of FBS701, a novel oral iron chelator, measured LIC by both R2 and R2* at screening, 12 weeks, and 24 weeks of therapy; nine thalassemia centers participated in 7 countries. 51 individuals completed 24 weeks of treatment. Liver R2 was collected and analyzed using a FDA-approved protocol and a commercial vendor (Ferriscan Resonance Health, Australia). Liver R2* was measured using gradient echo sequences with minimum echo times ranging from 1.0–1.2 ms. All gradient echo images were transferred to a central core laboratory for R2* calculation using a three component decay model (exponential + offset). Only patients with LIC values between 3 and 30 mg/g by Ferriscan LIC were allowed to participate. Transfusional iron burden was calculated from transfusional volumes documented for six months prior to entering the study and corrected for hematocrit. Change in total body iron was calculated using the Angelucci equation. Chelator efficiency was calculated using the net change in body iron concentration by drug consumption, calculated on a molar basis, to yield a unit-less number; drug concentration was divided by two to account for the chelator-iron stoichiometry. Observed changes in LIC were judged to be erroneous if they produced an estimated chelator efficiency greater than one or less than zero. We also assume that the efficiency between 0–12 weeks and 12–24 weeks should be comparable; the variance between these two values was used as an independent metric of Ferriscan, robustness for LIC measurement. Results: Figure 1 demonstrates the calculated chelator efficiency from 12–24 weeks versus 0–12 weeks, using LIC values calculated by Ferriscan(open circles) and by R2* (solid dots). The solid line indicates the line of identity and the inset box represents the physiologically possible range. 19/95 Ferriscan LIC measurements were physiologically impossible compared with 5/95 R2* LIC measurements (p=0.004 by Fischer's exact test). Ferriscan 12–24 week efficiency measurements were uncorrelated with Ferriscan 0–12 week measurements and generally strayed a greater distance from the line of identity, with a three-fold larger mean-squared error (0.375 versus 0.126) than for efficiencies calculated using R2*. Discussion: Both R2 and R2* are biopsy-validated, clinically accepted tools for noninvasive LIC estimation and can be used to track liver iron on a long-term basis. However, the ability of these techniques to accurately track short-term changes (below 1 year) has never been studied; such changes may be important for rapid dose-titration. In this study, Ferriscan LIC estimates were inconsistent with measured iron-balance, producing many nonphysiologic estimates of chelator efficiency and poor consistency between observations at three-month intervals. It is not known whether this represents an intrinsic property of R2 measurements, caused by undue sensitivity to microscopic iron particle distribution, or a limitation specific to the Ferriscan processing. However, given the previously published success of the Ferriscan technique with respect to liver biopsy when assessed on longer time-scales, we believe that these data represent a disequilibrium phenomenon, i.e., that R2 measurements are transiently inaccurate following an abrupt chelation change. Longer-term studies will be necessary to test this hypothesis. Nonetheless, caution should be used in trying to interpret Ferriscan results at intervals of six months or less. R2* LIC measurements are intrinsically less sensitive to changes in tissue iron distribution and more accurate reflections of iron balance at shorter time intervals. Disclosures: Wood: Novartis: Research Funding; Ferrokin Biosciences: Consultancy; Cooleys Anemia Foundation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Jones:Ferrokin BioSciences: Employment. Rienhoff:Ferrokin BioSciences: Employment, Equity Ownership. Neufeld:Ferrokin BioSciences: Research Funding; Novartis: Research Funding.

Liver Iron Concentration By MRI In Chronically Transfused Children With Sickle Cell Anemia In The Twitch Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 780-780
Author(s):  
John C. Wood ◽  
Zora R. Rogers ◽  
Isaac Odame ◽  
Janet Kwiatkowski ◽  
Margaret Lee ◽  
...  
Keyword(s):  
Iron Overload ◽  
Research Funding ◽  
Iron Concentration ◽  
Altman Analysis ◽  
Liver Iron Concentration ◽  
Limits Of Agreement ◽  
Advisory Committees ◽  
Liver Iron ◽  
Markers Of Inflammation ◽  
Tissue Iron

Abstract Introduction Chronic transfusion therapy represents the standard of care for sickle cell anemia (SCA) patients with abnormal transcranial Doppler (TCD) ultrasound or prior stroke. While effective, monthly transfusions produce iron overload and toxicity if not controlled with chelation therapies. Liver iron concentration (LIC) is a powerful surrogate for total body iron stores. Unfortunately, liver biopsy is not suited for longitudinal analysis because it is invasive, expensive, and prone to sampling variability. MRI transverse relaxation rates, R2 and R2*, are highly correlated with LIC and have mostly supplanted liver biopsy for iron quantification in clinical practice and clinical trials. Since R2 and R2* have different sensitivity to the size and scale of tissue iron distribution, we compared the agreement of LIC values predicted by R2 and R2* in children with SCA and transfusional iron overload from the prospective multicenter TCD with Transfusions Changing to Hydroxyurea (TWiTCH) trial (ClinicalTrials.gov; NCT01425307). Methods 133 patients underwent LIC assessment using both R2 and R2* techniques at 22 MRI sites. All sites used 1.5 Tesla magnets and torso phased array coils. Images for R2 measurements were collected on validated scanners and analyzed centrally according to the FerriScan” protocol (Resonance Health, Western Australia, see St Pierre, T.G., et al. Blood,105, 855-861, 2005). Images for R2* assessment were collected using multiple-echo gradient echo sequences (see Wood, J.C., et al. Blood,106, 1460-1465, 2005). Images were analyzed centrally at Children's Hospital Los Angeles, using an exponential-plus-constant fit to the signal decay. Bland-Altman analysis on log-transformed LIC values was used to test agreement between LICR2 and LICR2*; the residuals of this relationship were probed for association with transfusion/chelation history, markers of inflammation, and markers of hemolysis. Results Figure 1A illustrates the scattergram between LICR2* and LICR2. The variance of the disagreement between the two techniques increases with LIC, so log-transformation was performed prior to Bland Altman analysis. LICR2* was systematically higher than LICR2 below about 5 mg Fe/g dw and systematically lower above 5 mg Fe/g dw. Bland Altman comparison of the log-transformed data (Figure 1B) reveals a downward trend (r2 of 0.203, p<0.0001). After correcting for the trend, 95% limits of agreement were -0.42 to 0.42, translating to 95% limits of agreement of the ratio of the two LIC measurements of 0.66 to 1.52. After controlling for mean log LIC, differences in log LIC values were not associated with transfusion or chelation history, markers of inflammation, or markers of hemolysis. Discussion Systematic bias is present between LICR2 and LICR2* in a cohort of children with SCA and transfusional iron overload. Even after correcting these differences, LICR2 and LICR2* also demonstrate significant intrasubject variability, comparable to the error both techniques displayed with respect to biopsy, precluding use of these metrics interchangeably. This implies that LICR2 and LICR2* have potentially clinically significant deviations from true LIC. Rather than sampling or MRI measurement errors, which are consistently < 10% in multiple studies, these disparities likely reflect calibration bias introduced by intersubject differences in tissue iron distribution. Longitudinal LIC determination should lessen their impact, however, and the changes in LIC predicted by R2 and R2* will be compared using one and two year data from the TWiTCH trial. Disclosures: Wood: Novartis: Honoraria; Apopharma: Honoraria, Patents & Royalties; Shire: Consultancy, Research Funding. Off Label Use: Hydroxyurea is FDA-approved for use in adults but not children. Kwiatkowski:Shire: Consultancy; Resonance Health: Research Funding. St. Pierre:Resonance Health Ltd: Consultancy, Equity Ownership, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Assessing Bone Quality Using Trabecular Bone Score in Patients with Hemoglobinopathies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3629-3629
Author(s):  
Melissa Cervantes ◽  
Ashutosh Lal ◽  
Anne M Marsh ◽  
Ellen B. Fung
Keyword(s):  
Bone Mass ◽  
Bone Quality ◽  
Trabecular Bone Score ◽  
Iron Concentration ◽  
Healthy Controls ◽  
Low Bone Mass ◽  
Liver Iron Concentration ◽  
Mineral Density ◽  
Liver Iron ◽  
The Relationship

Abstract Introduction: Osteoporosis is characterized by a decrease in bone mass and density with enlarged trabecular space resulting in porosity and bone fragility. It has been described in as many as 70 to 80% of adults with thalassemia (Thal) and sickle cell disease (SCD). Though assessment by DXA scan is now part of routine clinical practice, bone quality has been poorly characterized, particularly in SCD. Trabecular bone score (TBS) is a new textural analysis of lumbar spine DXA scans that reflects bone microarchitecture, shown to be highly predictive of fracture in adults. The objectives of this study were 1) to determine the prevalence of poor bone quality as assessed by TBS in patients with Thal and SCD, compared to healthy individuals and 2) to assess the relationship between bone quality and clinical predictors (age, transfusion status, liver iron concentration, diet, BMI, endocrinopathies). Methods: A retrospective chart review was conducted in patients > 10 years and > 40 Kg with Thal or SCD who had a spine bone mineral density (BMD) scan performed in the previous 5 years. Patients had on average 1.7±0.9 spine scans during the collection period (range 1-5); all scans were reanalyzed using the TBS software (Insight, MediMaps v2.2, France). Optimal bone quality was defined as TBS >1.35; subnormal TBS= 1.34-1.20; abnormal <1.20. Liver iron concentration (LIC) was assessed by SQUID. Data from healthy controls without Thal or SCD were collected from previously completed research studies. Statistical analysis was performed using STATA, v. 9.0 (College Station, TX). This study was approved by the Institutional Review Board at UCSF Benioff Children's Hospital Oakland. Results: Data from 251 patients were abstracted which included, 162 females, 173 adults; 81 Thal, 102 SCD, and 68 healthy controls. Thal patients were older than SCD or controls (29.7 vs. 23.8, 25.8 years, p<0.05) and had lower LIC (2303 vs. 3014 µg Fe/g wet wt., p=0.004) but higher incidence of hypogonadism (31% vs. 1%, p<0.001). No differences were observed in vitamin D status, fracture history or family history of osteoporosis. On average, Thal patients had greater deficits in spine BMD Z-score (-2.1±1.2, Mean±SD), as compared to SCD (-1.0±1.5) and controls (-0.1±0.8), as well as a higher prevalence of abnormal bone quality by TBS (29.7%) vs. 12.2% in SCD, 4.6% in control, (p<0.001). TBS was positively correlated with BMD (r=0.7, p<0.001) and negatively correlated with age (r=-0.28, p<0.001). After controlling for age, BMI, hypogonadism and diagnosis, LIC was negatively associated with bone quality (r=0.30, p=0.001). Conclusions: These data support the relationship between reduced bone mass and bone quality in adult and adolescent patients with hemoglobinopathies. Older patients with low bone mass appear to be at particular risk for abnormal bone quality. TBS may be a valuable clinical tool in the assessment of true fracture risk in this group of patients with extremely low bone mineral density. However, future research is needed to develop models that include BMD and TBS for prediction of absolute fracture risk and need for treatment of low bone mass in patients with hemoglobinopathies. Disclosures No relevant conflicts of interest to declare.

Does liver biopsy overestimate liver iron concentration?

Blood ◽  
2006 ◽  
Vol 108 (5) ◽  
pp. 1775-1776 ◽  
Author(s):  
Roland Fischer ◽  
Paul Harmatz ◽  
Peter Nielsen
Keyword(s):  
Liver Biopsy ◽  
Iron Concentration ◽  
Liver Iron Concentration ◽  
Liver Iron

Semi-Quantitative Assessment of Hemosiderin Distribution Accurately Reflects Reductions in Liver Iron Concentration Following Therapy with Deferasirox (Exjade®, ICL670) or Deferoxamine in Patients with Transfusion-Dependent Anemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2708-2708 ◽  
Author(s):  
Yves Deugnier ◽  
Bruno Turlin ◽  
Martine Ropert ◽  
Mohamed Bejaoui ◽  
Miranda Athanassiou-Metaxa ◽  
...  
Keyword(s):  
Liver Biopsy ◽  
Liver Tissue ◽  
Quantitative Assessment ◽  
Chelation Therapy ◽  
Iron Concentration ◽  
Reference Standard ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Functional Areas ◽  
The Impact

Abstract Introduction: Direct biochemical measurement of liver iron from biopsy is the reference standard for determining liver iron concentration (LIC) and therefore the efficacy of chelation therapy. Semi-quantitative assessment of liver iron using Prussian blue stained tissue sections has, however, also been shown to correlate with LIC in patients with non-transfusional hemosiderosis. Aim: To determine the value of semi-quantitative liver iron measurement as an indicator of LIC in patients with transfusion-dependent anemia treated with reference standard therapy deferoxamine (DFO) or the investigational once-daily, oral iron chelator deferasirox. The differential involvement of hepatocytes and macrophages in the storage of excess iron was also assessed. Methods: During the deferasirox registration studies, semi-quantitative determination of liver tissue iron score (TIS) was performed in all patients who underwent liver biopsy; these data were compared with other markers of iron overload such as LIC and serum ferritin. In Studies 0107 and 0108, 454 patients with β-thalassemia and 101 patients with β-thalassemia or rare anemias (MDS, DBA and others) underwent liver biopsy at the start of the study and again after 1 year of chelation therapy with deferasirox (Study 0107, n=224 and all patients of 0108) or DFO (Study 0107 only, n=230). Patients analyzed in Study 0108 had β-thalassemia (n=61) or rare anemias (n=40). Results: There was a good correlation between semi-quantitative and quantitative liver iron measurements in all patient populations (R≥0.80, Pearson correlation coefficient). Baseline and change from baseline TIS and LIC are given in Table 1. These changes were dose-dependent, with the greatest decrease observed in patients treated with the highest deferasirox dose (30 mg/kg: TIS decreased from 34.3 ± 7.7 to 25.9 ± 11.2, n=107, in Study 0107; and from 35.3 ± 7.6 to 29.2 ± 10.3, n=78, in Study 0108). Further analyses demonstrated that both deferasirox and DFO were active in removing iron from different functional areas of liver tissue (hepatocytic, sinusoidal and portal areas). Table 1. Overall TIS and LIC changes after 1 year of treatment Study 0107 Study 0108 DFO Deferasirox β-thalassemia Rare anemias (n=230) (n=224) (n=61) (n=40) *Mean ± SD TIS* - Baseline 24.0 ± 10.3 25.3 ± 11.2 29.9 ± 10.9 34.1 ± 9.2 - Change from baseline −2.4 ± 11.2 −3.5 ± 7.1 −4.8 ± 11.2 −6.2 ± 10.1 LIC, mg Fe/g dw* - Baseline 14.5 ± 9.6 15.7 ± 10.1 21.2 ± 10.9 22.8 ± 9.4 - Change from baseline −3.0 ± 8.8 −3.2 ± 5.7 −5.8 ± 9.1 −5.5 ± 7.5 Conclusions: Semi-quantitative iron assessment clearly correlates with quantitative iron measurement. The impact of iron chelation therapy on iron deposits was seen in all functional areas of the liver, with the highest decrease observed in patients treated with deferasirox.

Precision of Multi-Echo CMR for Myocardial Iron Overload Evaluation Is Dependent From MR Sequence Design

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5169-5169
Author(s):  
Antonella Meloni ◽  
incenzo Positano ◽  
Alessia Pepe ◽  
Dell'Amico Maria Chiara ◽  
Luca Menichetti ◽  
...  
Keyword(s):  
Iron Overload ◽  
Conflicts Of Interest ◽  
Iron Concentration ◽  
Breath Hold ◽  
Myocardial Iron ◽  
Single Breath ◽  
Single Breath Hold ◽  
Values Assessment ◽  
Value Determination ◽  
Almost All

Abstract Abstract 5169 Introduction. T2* multiecho cardiovascular magnetic resonance (CMR) is largely used to assess iron overload in heart because of the established inverse relationship between the T2* value and the iron concentration in tissues (Wood JC et al, Hemoglobin 2008). The decay of CMR signal is sampled at several echo times (TEs) and the T2* is inferred by fitting the decay curve to an appropriate model (Positano V et al, NMR in Biomed 2007). Our aim was to quantify the reliance on TEs of the expected error in T2* value determination. Methods. The Cramer-Rao lower bounds theory (CRLB) was used. CRLB provide a fundamental limit to the accuracy in determination of the T2* value from experimental data in dependence of SNR at signal samples. CRLB were evaluated for a commonly used multi-echo sequence with the first TE equal to the minimum achievable (1.4-2 ms), ΔTE of about 2.3 ms to minimize the fat-water interface artifacts, 10 echoes to assure acquisition in a single breath-hold. Results. Percent error in T2* values assessment was lower than 10% in the range of clinical interest, with the exception of very low T2* values. Precision in measurement of low T2* values is strongly dependent on the value of the first TE, that is limited by the used scanner. T2* values greater than 1.8 ms and 1.5 ms can be assessed with an error below 20% using a first TE of 2 ms and 1.5 ms, respectively (see Figure). Conclusions. T2* multiecho sequences used in clinical practice assure an acceptable precision for T2* values ≥ 2 ms, depending from the used hardware. This limit includes almost all patients with hemochromatosis or hemosiderosis in country where the patients can be well managed. For patients with very high myocardial iron overload sequences with lower minimum echo time and/or lower echoes interval may be useful. Disclosures: No relevant conflicts of interest to declare.

Is Ferriscan - a Useful Tool for Diagnosing and Monitoring Tissue Iron Load after Acute Iron Intoxication?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4828-4828
Author(s):  
Mohamed A. Yassin ◽  
Ashraf Tawfiq Soliman ◽  
Abdulqadir Nashwan ◽  
Abbas Moustafa ◽  
Sandra Abousamaan
Keyword(s):  
Iron Overload ◽  
Serum Iron ◽  
Iron Concentration ◽  
Iron Toxicity ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Body Iron ◽  
Elemental Iron ◽  
Iron Stores ◽  
Tissue Iron

Abstract Almost 16,000 iron exposures annually are reported in children less than six years of age in the United States. Deferoxamine is the iron-chelating agent of choice. Deferoxamine binds absorbed iron, and the iron-deferoxamine complex is excreted in the urine. Indications for treatment include shock, altered mental status, persistent GI symptoms, metabolic acidosis, pills visible on radiographs, serum iron level greater than 500 µg/dL, or estimated dose greater than 60 mg/kg of elemental iron. No clear end point of therapy is distinguished. Infusion of deferoxamine for 6-12 hours has been suggested for moderate toxicity. For severe toxicity, administer deferoxamine for 24 hours. Because these end points are arbitrary, observe the patient for the recurrence of toxicity 2-3 hours after the deferoxamine has been stopped. Complications of iron toxicity include the following: Infection with Yersinia enterocolitica, acute respiratory distress syndrome (ARDS) and fulminant hepatic failure, hepatic cirrhosis, pyloric or duodenal stenosis. Systemic toxicity is expected with an ingestion of 60 mg/kg. Ingestion of more than 250 mg/kg of elemental iron is potentially lethal. Although a low serum ferritin is an accurate measure of iron deficiency, there is no accurate serum or plasma marker for acute body-iron overload. Serum iron concentration and transferrin saturation do not quantitatively reflect body iron. Stores and should therefore not be used as surrogate markers of tissue iron overload. Liver iron concentration provides the best measure of total body iron stores and is a validated predictor of the risks a particular patient faces from the complications of iron toxicity. Several imaging noninvasive techniques are available for measuring liver iron concentration (LIC) . There are two validated MRI methods for quantitating the liver iron burden: the FerriScan and T2 methods. The noninvasive R2-MRI technique (FerriScan) is highly sensitive and specific for estimating LIC and is approved by the Food and Drug Administration for routine clinical use. However, it was not used to diagnose and monitor LIC in cases of acute iron intoxication. This 27 year old female nurse by profession self-referred to hematology clinic for evaluation of Iron overload after self injecting herself with 20 ampoules of IV iron Ferro sac (each ampoule containing 200 mg of iron, (4000 mg elemental iron, 60 mg/kg) . Her CBC on presentation showed Hb of 12.5 g/dl her baseline Hb 9 g/dl with serum iron of 28 (NR 9.0 - 30.4 umol/L) ,TIBC of 42 NR(45 - 80 umol/L ), ferritin 1001 (NR 24-336 mcg/l) Her clinical exam was unremarkable. Her MRI showed severe iron overload. 9 mg /g dray tissue (NR 0.17-1.8) Patient received chelation with deferasirox at dose of 30 mg /kg for 6 months when her ferriscan showed almost normal LIC of 2 mg /g dry tissue. This case report showed the value of ferriscan in diagnosing the degree of tissue iron overload and in monitoring chelation to a safe level of hepatic iron content. Disclosures No relevant conflicts of interest to declare.

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