Use of portable X-ray fluorescence (PXRF) in vivo as an alternative technique for the assessment of iron levels in patients with thalassemia and hemochromatosis.

This work investigated the viability of the portable x-ray fluorescence (PXRF) technique as a means of measuring iron levels in patients suffering from thalassemia major (beta-thalassemia) and hereditary hemochromatosis (HH or Haemochromatosis) or other iron-overload conditions. Measurements were conducted at the University Hospital Blood Center and in the Laboratory of Applied Nuclear Physics at the State University of Londrina, Brazil. One thalassemia major patient and four healthy people were grouped. A PXRF system consisting of a Pu x-ray source and a SiPIN diode detector was used for measurements in vivo on the hand of each patient. The measuring system was calibrated with phantoms of aqueous solution doped with 15 to 150 ppm of iron. The duration of each measurement was 50 s. The detection limit (LLD) reached for iron was 13 ppm. The radiation dose on the skin was 10 mSv. The thalassemia patient presented 74 ± 6 ppm of iron, whereas the healthy people presented an average of 53 ± 5 ppm of iron. The results are in accord with the literature, which shows iron levels in the skin to be between 15 - 60 ppm for healthy people and between 70 - 150 ppm for thalassemia major patients. This work concluded that it is viable to apply the XRF methodology to follow thalassemia major and HH patients.

Assessment of iron overload with T2* magnetic resonance imaging.

T2* is a magnetic relaxation property of any tissue and is inversely related to intracellular iron stores. Measurement is simple, quick, and robust and has high reproducibility. The ability to measure ventricular function plus T2* in the heart and liver during the same scan has revolutionized the understanding of iron storage disease and the management of the iron-loaded patient. The early findings using T2* challenged conventional teachings, and both the technique and the findings were initially viewed with scepticism. However, after a decade of work in validating, calibrating, and expanding access to this method, it is now accepted as the method of choice for tissue iron assessment. In the UK, where T2* measurement was first used in the clinical care of patients with thalassemia major, a large and significant fall in mortality has been seen in this patient group.

Assessment of cardiac iron by MRI susceptometry and R2* in patients with thalassemia.

A magnetic resonance imaging cardiac magnetic susceptometry (MRI-CS) technique for assessing cardiac tissue iron concentration based on phase mapping was developed. Normal control subjects (n=9) and thalassemia patients (n=13) receiving long-term blood transfusion therapy underwent MRI-CS and MRI measurements of the cardiac relaxation rate R2*. Using MRI-CS, subepicardium and subendocardium iron concentrations were quantified exploiting the hemosiderin/ferritin iron specific magnetic susceptibility. The average of subepicardium and subendocardium iron concentrations and R2* of the septum were found to be strongly correlated (r=0.96, P<.0001), and linear regression analysis yielded CIC (microg Fe/g(wet tissue))=(6.4+/-0.4).R2* (septum) (s(-1)) - (120+/-40). The results demonstrated that septal R2* indeed measures cardiac iron level.

Evaluation of a web-based network for reproducible T2* MRI assessment of iron overload in thalassemia.

PURPOSE: To build and evaluate a national network able to improve the care of thalassemia, a genetic disorder in haemoglobin synthesis often associated with iron accumulation in a variety of organs, due to the continuous blood transfusions. METHODS: The MIOT (Myocardial Iron Overload in Thalassemia) network is constituted by thalassemia and magnetic resonance imaging (MRI) centers. Thalassemia centers are responsible for patient recruitment and collection of anamnestic and clinical data. MRI centers have been equipped with a standardized acquisition technique and an affordable workstation for image analysis. They are able to perform feasible and reproducible heart and liver iron overload assessments for a consistent number of thalassemia patients in a robust manner. All centers are linked by a web-based network, configured to collect and share patient data. RESULTS: On 30th March 2008, 695 thalassemia patients were involved in the network. The completion percentage of the patient records in the database was 85+/-6.5%. Six hundred and thirteen patients (88%) successfully underwent MRI examination. Each MRI center had a specific absorption capacity that remained constant over time, but the network was capable of sustaining an increasing number of patients due to continuous enrollment of new centers. The patient's comfort, assessed as the mean distance from the patient home locations to the MRI centers, significantly increased during the network's evolution. CONCLUSION: The MIOT network seems to be a robust and scalable system in which T2* MRI-based cardiac and liver iron overload assessment is available, accessible and reachable for a significant and increasing number of thalassemia patients in Italy (about 420 per year), reducing the mean distance from the patient locations to the MRI sites from 951km to 387km. A solid, wide and homogeneous database will constitute an important scientific resource, shortening the time scale for diagnostic, prognostic and therapeutical evidence-based research on the management of thalassemia disease.

MRI assessment of liver iron content in thalassamic patients with three different protocols: comparisons and correlations.

Our aim was to assess liver iron content, in thalassaemic patients, by using three different MR protocols and compare their data. Ninety-four thalassaemic patients (44 M and 50 F, mean age 25.82 +/- 8.3 yrs), were enrolled in the study. In each patient, three measurements of the liver iron content were performed, with the use of a single imager, equipped with a 1.5 Tesla magnet. Liver R2* was measured on gradient-echo sequence. Calculation of MR-HIC values was based on an algorithm using liver to muscle (L/M) ratios in five axial gradient-echo sequences. Finally, determination of liver R2 employed a 16-echo, spin-echo pulse sequence. Additionally, myocardial R2* value was determined for each patient. Results showed that all three magnetic resonance imaging (MRI) methods were highly correlated to each other and significantly correlated to serum ferritin concentrations. Liver R2 method showed an increased sensitivity in detecting liver iron contents in the upper range. No correlation occurred between each liver MRI parameter and myocardial R2* values. Finally, we managed to provide formulae for equating values obtaining with any of these three MRI methods.

Practical implications of liver and heart iron load assessment by T2*-MRI in children and adults with transfusion-dependent anemias.

This study examined the relationship between hepatic and myocardial iron concentration, assessed by T2*-MRI in 66 patients (3-82 years) with transfusion-dependent anemias and thalassemia intermedia, to determine whether hepatic iron levels alone suffice for chelation adjustments. We found a poor correlation between hepatic and myocardial iron (r = 0.10, P = 0.43) and identified a subgroup (14%) with increased myocardial iron without a matched degree of hepatic hemosiderosis. Left ventricular ejection fraction was insensitive for detecting elevated myocardial iron. These findings were present in both adult and pediatric patients. We recommend therapeutic monitoring of iron burden by evaluation of both liver and myocardial iron with T2*-MRI.

Assessment of cardiac and hepatic iron overload in thalassaemic patients by magnetic resonance: a four year observational study.

In this study, we present results of the determination of cardiac and hepatic iron overload in patients with thalassaemia by means of a non-invasive method based on magnetic resonance. The procedure was applied for a period of four years to a group of patients followed in the Thalassemia Centre of our hospital. The gathered data were stratified to indicate groups of patients with mild, moderate and severe hepatic iron overload. We also studied cardiac iron overload and related it to the ejection fraction. In addition, we addressed the issue of replacement of the resonance equipment with a change in the intensity of the magnetic field from 1 to 1.5 T. The calibration on the new equipment was carried out using a set of MnCl2 standard solutions. The results demonstrated the possibility of using the algorithms reported in the literature and thus the "portability" of the procedure on equipment of the same type. The study has confirmed the usefulness of this non-invasive procedure for the monitoring of the iron load in patients with thalassaemia and the possibility of its use on resonance installations in clinical use.

A robust method for assessment of iron overload in liver by magnetic resonance imaging.

Assessment of iron overload in liver by T2* magnetic resonance imaging (MRI) is a widely used clinical procedure. In the common clinical practice, measurement is performed locally by manually drawing a small region of interest in liver. This procedure may be affected by a noticeable intra- and inter-observer variability. In this study, a new approach is proposed that performs a global semiautomatic measurement of T2* involving the whole liver extension. Parenchyma is automatically segmented by an adaptive fuzzy-clustering algorithm. The liver T2* global value is evaluated using a pixel-wise approach by introducing an appropriate signal decay model. The proposed method was tested on a synthetic software model and on MR images acquired from 30 thalassemia major patients. The methods was demonstrated to increase the measure precision in T2* assessment and to significantly reduce the intra- and inter-observer variability.

Clinical research: a tale of two studies.

Threats to the status of clinical research have been well documented in the past three decades, and the National Institutes of Health and the Congress have done much to alleviate them. But the relationships of academic investigators and pharmaceutical companies remain a treacherous area. This vital nexus, on which so much progress depends, must be carefully maintained. In this paper I present two examples of academic/pharmaceutical company collaborations, both in search of a similar drug. The cases illustrate both some important hazards and accomplishments of clinical research.

Non-invasive myocardial iron assessment in thalassaemic patients. T2 relaxometry and magnetization transfer ratio measurements.

PURPOSE: To compare T2 relaxometry and magnetization transfer ratio (MTR) measurements of myocardial tissue in normal volunteers and thalassaemic patients for assessment of the myocardial iron levels. MATERIAL AND METHODS: All examinations were done on a 1 T MR system using a multi-echo spin-echo sequence with 8 echoes for T2 measurements and a gradient echo sequence for MTR measurements. Diastolic cardiac triggering was used in both sequences. Ten patients and 10 normal subjects were included in the study. T2 and MTR measurements were correlated with serum ferritin levels. RESULTS: Regression analysis between T2 and MTR measurements and ferritin demonstrated a reversed linear relationship, (r=-0.932, p<0.05) and (r= -0.824, p<0.05), respectively. Mean T2 relaxation time and mean MTR of the normal subjects (57.95+/-4.9 ms and 43.70+/-3.3%) was significantly higher than that of the thalassaemic patients (38.8+/-6.2 ms and 26.40+/-6.1%) (p<0.01), respectively. CONCLUSION: MTR measurements can be used to complement T2 measurements for non-invasive myocardial iron assessment.

Assessment of liver iron overload in thalassemic patients by MR imaging.

The use of MR imaging has been proposed for the assessment of the hepatic iron overload in transfusion-dependent thalassemic patients treated with desferrioxamine. The aim of the study was to correlate serum ferritin levels and MR signal intensity of the liver parenchyma. Results on 12 patients showed that the ratios between the signal intensity of liver parenchyma and muscle and fat are promising parameters for predicting iron overload.

Computed tomographic assessment of vertebral bone mineral in childhood.

Quantitative computed tomography (QCT) was used to assess trabecular bone mineral concentration in the vertebrae of 132 children, 45 with suspected disorder of bone mineralisation, 54 with thalassaemia and 37 controls. The range for bone mineral concentration in controls, expressed as equivalent K2HPO4 concentrations, was 90-190 mg cm-3. Abnormally low values were seen in all untreated children with idiopathic juvenile osteoporosis, 3/9 steroid recipients, and three patients with osteogenesis imperfecta. Abnormally high values were seen in 10/14 chronic renal failure patients. Comparison of the single and dual-energy methods showed that the single energy method, which has a lower radiation dose and is less prone to error from movement artifact, is satisfactory in most paediatric applications.