Association of iron overload based quantitative T2* MRI technique and carotid intima-media thickness in patients with beta-thalassemia: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Body iron status has been implicated in atherosclerotic cardiovascular disease. The main hypothesis is that high iron status is associated with increased risk of atherosclerosis. We investigated the potential role of iron as an additional risk factor promoting atherosclerosis among beta-thalassemic patients.</p> <p>Methods</p> <p>In this cross-sectional study, the liver iron load was assessed by quantitative T2* MRI technique and intima-media thickness (IMT) of the common carotid artery by high-resolution ultrasound among 119 patients (62 male, 57 female) with beta-thalassemia (major and intermediate) whose age ranged from 10 to 50 years with a mean of 25.6 years. The patients were divided into three groups according to the severity of iron loading, obtained by T2*MRI technique: group I (normal), group II (mild) and group III (moderate and severe) iron load.</p> <p>For elimination of the effect of age on carotid IMT values, the patients also were divided into four age groups (10-19 y, 20-29 y, 30-39 y and 40-50 y). Mean carotid IMT based on the severity of iron loading were compared at different age groups, using one way ANOVA analysis for assessing the effect of iron loading on carotid IMT. Pearson's coefficient of correlation were used to assess the degree of correlation between studied variables (liver T2*, IMT, age).</p> <p>Results</p> <p>There were significant differences in mean carotid IMT based on the severity of iron loading at different age groups, with P = 0.003 at 20-29 y, P = 0.006 at 30-39 y and p = 0.037 at 40-50 y. Age (p = 0.001) and liver T2*(p = 0.003) had significant correlation with mean carotid IMT independently.</p> <p>At the age group of 10-19 years, there were not significant differences in mean carotid IMT based on the liver iron loading (p = 0.661).</p> <p>No significant differences also are seen in mean carotid IMT between male and female (p = 0.41).</p> <p>Conclusions</p> <p>This study identified a relationship between body iron status and carotid IMT. This relationship support to the hypothesis of a link between body iron load and atherosclerosis.</p

Magn Reson Med

PurposeTo determine whether systematic differences were present between myocardial R2* values obtained with two different decay models: truncation and exponential-plus-constant (Exp-C).MethodsSingle-center cohorts were used to compare black and bright blood sequences separately and a multi-center cohort of mixed bright and black blood studies was used to assess the generalizability. Truncated exponential estimates were calculated with CMRTools that uses a single region of interest (ROI) method. Exp-C estimates were calculated using a pixelwise approach.ResultsNo differences could be distinguished based upon whether a white or black blood sequence was examined. The two fitting algorithms gave similar R2* values, with R-squared values exceeding 0.997 and CoV of 3\u20134%. Results using the pixelwise method yielded a small systematic bias (~3%) that became apparent in patients with severe iron deposition. This disparity disappeared when Exp-C fitting was used on a single ROI suggesting that the use of pixelwise mapping was responsible for the bias. In the multicenter cohort the strong agreement between the two fitting approaches was reconfirmed.ConclusionCardiac R2* values are independent of the signal model used for its calculation over clinically relevant ranges. Clinicians can compare results among centers using these disparate approaches with confidence.RC1 HL099412/HL/NHLBI NIH HHS/United StatesRR00043-43/RR/NCRR NIH HHS/United States1 U01 DD000309-1/DD/NCBDD CDC HHS/United StatesR01 HL075592/HL/NHLBI NIH HHS/United StatesM01 RR000043/RR/NCRR NIH HHS/United StatesU01 DD000309/DD/NCBDD CDC HHS/United States1 R01 HL075592-01A1/HL/NHLBI NIH HHS/United States2015-08-01T00:00:00Z24123261PMC42930216525vault:139

Longitudinal follow‐up of patients with thalassaemia intermedia who started transfusion therapy in adulthood: a cohort study

SummaryWe longitudinally evaluated the effects of regular blood transfusions (BTs), in the real‐life context of the Myocardial Iron Overload in Thalassaemia network, in patients with thalassaemia intermedia (TI). We considered 88 patients with TI (52 females) who started regular BTs after the age of 18 years. Magnetic resonance imaging was used to quantify iron overload and biventricular function. For 56·8% of the patients there were more than two indications for the transition to regular BTs, with anaemia present in 94·0% of the cases. A significant decrease in nucleated red blood cells, platelets, lactate dehydrogenase, bilirubin, and uric acid levels was detected 6 months after starting regular BTs. After the transition to the regular BT regimen there was a significant increase only in the frequency of hypothyroidism and osteopenia, and a significant decrease in liver iron and cardiac index. The percentage of chelated patients increased significantly after starting regular BTs. The decision to regularly transfuse patients with TI may represent a way to prevent or slow down the natural progression of the disease, despite the more complex initial management

A: Deferasirox, deferiprone and desferrioxamine treatment in thalassemia major patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging. Haematologica 2011; 96

Background Oral deferiprone was suggested to be more effective than subcutaneous desferrioxamine for removing heart iron. Oral once-daily chelator deferasirox has recently been made commercially available but its long-term efficacy on cardiac iron and function has not yet been established. Our study aimed to compare the effectiveness of deferasirox, deferiprone and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function in thalassemia major patients by means of quantitative magnetic resonance imaging. Design and Methods From the first 550 thalassemia subjects enrolled in the Myocardial Iron Overload in Thalassemia network, we retrospectively selected thalassemia major patients who had been receiving one chelator alone for longer than one year. We identified three groups of patients: 24 treated with deferasirox, 42 treated with deferiprone and 89 treated with desferrioxamine. Myocardial iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron concentrations were measured by T2* multiecho technique. Results The global heart T2* value was significantly higher in the deferiprone (34±11ms) than in the deferasirox (21±12 ms) and the desferrioxamine groups (27±11 ms) (P=0.0001). We found higher left ventricular ejection fractions in the deferiprone and the desferrioxamine versus the deferasirox group (P=0.010). Liver iron concentration, measured as T2* signal, was significantly lower in the desferrioxamine versus the deferiprone and the deferasirox group (P=0.004). Conclusions The cohort of patients treated with oral deferiprone showed less myocardial iron burden and better global systolic ventricular function compared to the patients treated with oral deferasirox or subcutaneous desferrioxamine. Key words: thalassemia, iron chelation therapy, cardiac magnetic resonance imaging. Citation: Pepe A, Meloni A, Capra M, Cianciulli P, Prossomariti L, Malaventura C, Putti MC, Lippi A, Romeo MA, Bisconte MG, Filosa A, Caruso V, Quarta A, Pitrolo L, Missere M, Midiri M, Rossi G, Positano V, Lombardi M, and Maggio A. Deferasirox, deferipron

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

Data Mining of Biomedical Databases

Data mining can be defined as the nontrivial extraction of implicit, previously unknown and potentially useful information from data. This thesis is focused on Data Mining in Biomedicine, representing one of the most interesting fields of application. Different kinds of biomedical data sets would require different data mining approaches. Two approaches are treated in this thesis, divided in two separate and independent parts. The first part deals with Bayesian Networks, representing one of the most successful tools for medical diagnosis and therapies follow-up. Formally, a Bayesian Network (BN) is a probabilistic graphical model that represents a set of random variables and their conditional dependencies via a directed acyclic graph. An algorithm for Bayesian network structure learning that is a variation of the standard search-and-score approach has been developed. The proposed approach overcomes the creation of redundant network structures that may include non significant connections between variables. In particular, the algorithm finds which relationships between the variables must be prevented, by exploiting the binarization of a square matrix containing the mutual information (MI) among all pairs of variables. Four different binarization methods are implemented. The MI binary matrix is exploited as a pre-conditioning step for the subsequent greedy search procedure that optimizes the network score, reducing the number of possible search paths in the greedy search procedure. This approach has been tested on four different datasets and compared against the standard search-and-score algorithm as implemented in the DEAL package, with successful results. Moreover, a comparison among different network scores has been performed. The second part of this thesis is focused on data mining of microarray databases. An algorithm able to perform the analysis of Illumina microRNA microarray data in a systematic and easy way has been developed. The algorithm includes two parts. The first part is the pre-processing, characterized by two steps: variance stabilization and normalization. Variance stabilization has to be performed to abrogate or at least reduce the heteroskedasticity while normalization has to be performed to minimize systematic effects that are not constant among different samples of an experiment and that are not due to the factors under investigation. Three alternative variance stabilization strategies and three alternative normalization approaches are included. So, considering all the possible combinations between variance stabilization and normalization strategies, 9 different ways to pre-process the data are obtained. The second part of the algorithm deals with the statistical analysis for the differential expression detection. Linear models and empirical Bayes methods are used. The final result is the list of the microRNAs significantly differentially-expressed in two different conditions. The algorithm has been tested on three different real datasets and partially validated with an independent approach (quantitative real time PCR). Moreover, the influence of the use of different preprocessing methods on the discovery of differentially expressed microRNAs has been studied and a comparison among the different normalization methods has been performed. This is the first study comparing normalization techniques for Illumina microRNA microarray data

Evaluation of a web-based network for reproducible T2*MRI assessment of iron overload in thalassemia RID A-6953-2008

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 951 km to 387 km. 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. (C) 2009 Elsevier Ireland Ltd. All rights reserved

Studio,sviluppo e validazione di un algoritmo di clustering multidimensionale per la segmentazione di immagini di risonanza magnetica multiecho.

Il lavoro di tesi svolto ha avuto lo scopo di ricercare un algoritmo di segmentazione automatica applicabile a dati di risonanza magnetica multispettrali (multiparametrici e/o multiecho)e di applicarlo ad immagini RM cardiache multiecho finalizzate alla valutazione del sovraccarico di ferro cardiaco in pazienti talassemici