Daniele De Marchi

Multislice multiecho T2* cardiovascular magnetic resonance for detection of the heterogeneous distribution of myocardial iron overload

To assess the tissue iron concentration of the left ventricle (LV) using a multislice, multiecho T2* MR technique and a segmental analysis.

Early Hypertension Is Associated With Reduced Regional Cardiac Function, Insulin Resistance, Epicardial, and Visceral Fat

Mild-to-moderate hypertension is often associated with insulin resistance and visceral adiposity. Whether these metabolic abnormalities have an independent impact on regional cardiac function is not known. The goal of this study was to investigate the effects of increased blood pressure, insulin resistance, and ectopic fat accumulation on the changes in peak systolic circumferential strain. Thirty-five male subjects (age: 47±1 years; body mass index: 28.4±0.6 kg.m−2; mean±SEM) included 13 with normal blood pressure (BP: 113±5/67±2 mm Hg), 13 with prehypertension (BP: 130±1/76±2 mm Hg), and 9 newly diagnosed with essential hypertension (BP: 150±2/94±2 mm Hg) who underwent cardiac magnetic resonance tissue tagging (MRI) and MRI quantitation of abdominal visceral and epicardial fat. Glucose tolerance, on oral glucose tolerance test, and insulin resistance were assessed along with the serum lipid profile. All of the subjects had normal glucose tolerance, left- and right-ventricular volumes, and ejection fraction. Across the BP groups, left ventricular mass tended to increase, and circumferential shortening was progressively reduced at basal, midheart, and apical segments (on average, from −17.0±0.5% in normal blood pressure to −15.2±0.7% in prehypertension to −13.6±0.8% in those newly diagnosed with essential hypertension; P=0.004). Reduced circumferential strain was significantly associated with raised BP independent of age (r=0.41; P=0.01) and with epicardial and visceral fat, serum triglycerides, and insulin resistance independent of age and BP. In conclusion, regional left ventricular function is already reduced at the early stages of hypertension despite the normal global cardiac function. Insulin resistance, dyslipidemia, and ectopic fat accumulation are associated with reduced regional systolic function.

Evaluation of the efficacy of oral deferiprone in β-thalassemia major by multislice multiecho T2

Abstract:  Objectives: Oral deferiprone (L1) appears to be promising in the treatment of β‐thalassemia major (TM) patients. T2* magnetic resonance imaging (MRI) with a single measurement in the mid‐ventricular septum was validated as a quantitative evaluation of myocardial iron overload. Previous studies suggested a marked heterogeneity of iron distribution in the myocardium. We set up a multislice multiecho T2* MRI for the detection of this heterogeneity. The aim of our study was to investigate differences between the L1 vs. the subcutaneous desferrioxamine (DF)‐treated patients using this new approach.Methods: Thirty‐six β‐TM patients (age 29 ± 8 yr) underwent MRI. Eighteen patients received long‐term L1, and 18 other patients matched for age and sex received DF. T2* multiecho sequences on three short axis views of the left ventricle were obtained and analyzed by custom‐made software. In each slice, the myocardium was automatically segmented into four segments. Cine‐dynamic images were also obtained to evaluate biventricular function.Results: For multislice T2* technique, the coefficient of variation for intra‐ and inter‐observer, and inter‐study reproducibility was 3.9%, 4.7%, and 5.5%, respectively. The global heart T2* value was significantly higher in the L1 vs. DF group (35 ± 7 vs. 27 ± 2 ms; P = 0.02). The number of segments with normal T2* value (>20 ms) was significantly higher in the L1 vs. the DF group (11 ± 1 vs. 8 ± 5 segments; P = 0.03). We did not detect significant differences in biventricular function parameters.Conclusions: This new approach confirms that L1 could be more effective than DF in removal of myocardial iron.

Improved T2* assessment in liver iron overload by magnetic resonance imaging

In the clinical MRI practice, it is common to assess liver iron overload by T2* multi-echo gradient-echo images. However, there is no full consensus about the best image analysis approach for the T2* measurements. The currently used methods involve manual drawing of a region of interest (ROI) within MR images of the liver. Evaluation of a representative liver T2* value is done by fitting an appropriate model to the signal decay within the ROIs vs. the echo time. The resulting T2* value may depend on both ROI placement and choice of the signal decay model. The aim of this study was to understand how the choice of the analysis methodology may affect the accuracy of T2* measurements. A software model of the iron overloaded liver was inferred from MR images acquired from 40 thalassemia major patients. Different image analysis methods were compared exploiting the developed software model. Moreover, a method for global semiautomatic T2* measurement involving the whole liver was developed. The global method included automatic segmentation of parenchyma by an adaptive fuzzy-clustering algorithm able to compensate for signal inhomogeneities. Global liver T2* value was evaluated using a pixel-wise technique and an optimized signal decay model. The global approach was compared with the ROI-based approach used in the clinical practice. For the ROI-based approach, the intra-observer and inter-observer coefficients of variation (CoVs) were 3.7% and 5.6%, respectively. For the global analysis, the CoVs for intra-observers and inter-observers reproducibility were 0.85% and 2.87%, respectively. The variability shown by the ROI-based approach was acceptable for use in the clinical practice; however, the developed global method increased the accuracy in T2* assessment and significantly reduced the operator dependence and sampling errors. This global approach could be useful in the clinical arena for patients with borderline liver iron overload and/or requiring follow-up studies.

Multicenter validation of the magnetic resonance t2* technique for segmental and global quantification of myocardial iron

To assess the transferability of the magnetic resonance imaging (MRI) multislice multiecho T2* technique for global and segmental measurement of iron overload in thalassemia patients.

Is the genotoxic effect of magnetic resonance negligible? Low persistence of micronucleus frequency in lymphocytes of individuals after cardiac scan.

Magnetic resonance imaging is a diagnostic technique widely used in medicine and showing a growing impact in cardiology. Biological effects associated to magnetic resonance electromagnetic fields have received far little attention, but it cannot be ruled out that these fields can alter DNA structure. The present study aimed at to identify possible DNA damage induced by magnetic resonance scan in humans. Lymphocyte cultures from healthy subjects had been exposed into magnetic resonance device for different times and under different variable magnetic exposure in order to build dose-effect curves, using micronuclei induction as biological marker. Replicate cultures were also left for 24h at room temperature before stimulation, to verify possible damage recovery. Furthermore, micronuclei induction and recovery up to 120h have been also evaluated in circulating lymphocytes of individuals after cardiac scan. A dose-dependent increase of micronuclei frequency was observed in vitro. However after 24h, the frequency returns to control value when the exposure is within diagnostic dosage. After in vivo scan, a significant increase in micronuclei is found till 24h, after the frequencies slowly return to control value.

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 patients comfort, assessed as the mean distance from the patient home locations to the MRI centers, significantly increased during the networks 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.

Single region of interest versus multislice T2* MRI approach for the quantification of hepatic iron overload

To evaluate the effectiveness of the single ROI approach for the detection of hepatic iron burden in thalassemia major (TM) patients in respect to a whole liver measurement.

Multislice multiecho T2* cardiac magnetic resonance for the detection of heterogeneous myocardial iron distribution in thalassaemia patients

The present study investigated myocardial T2* heterogeneity in thalassaemia major (TM) patients by cardiac magnetic resonance (CMR), to determine whether is related to inhomogeneous iron overload distribution. A total of 230 TM patients consecutively referred to our laboratory were studied retrospectively. Three short‐axis views (basal, medium and apical) of the left ventricle (LV) were obtained by multislice multiecho T2* CMR. T2* segmental distribution was mapped on a 16‐segment LV model. The level of heterogeneity of the T2* segmental distribution, evaluated by the coefficient of variation (CoV), was compared with that of a surrogate data set, to determine whether the inhomogeneous segmental distribution of T2* could be generated by susceptibility artefacts. Susceptibility artefacts offer an explanation for the T2* heterogeneity observed in patients without iron overload. In subjects with global T2* below the lower limit of the normal, T2* heterogeneity increased abruptly which could not be explained by artefactual effects. Some segmental T2* values were below and others above the limit of normal threshold (20 ms) in 104 (45%) TM patients. Among these patients, 74% showed a normal T2* global value. In conclusion, a true heterogeneity in the iron overload distribution may be present in TM patients. Heterogeneity seemingly appears in the borderline myocardial iron and stabilizes at moderate to severe iron burden. Copyright

Severe Mechanical Dyssynchrony Causes Regional Hibernation-Like Changes in Pigs With Nonischemic Heart Failure

BACKGROUND Sustained left ventricular (LV) dyssynchrony can lead to heart failure (HF) in the absence of coronary artery stenosis. We tested whether myocardial hibernation underlies the LV functional impairment caused by high-frequency pacing, an established model of nonischemic dilated cardiomyopathy. METHODS AND RESULTS Regional LV contractile and perfusion reserve were assessed by magnetic resonance imaging, respectively, as end-systolic wall thickening (LVESWT) and myocardial perfusion reserve index (MPRI) at rest and during low-dose dobutamine stress (LDDS, 10 microg.kg.min intravenously for 10minutes) in failing minipigs (n=8). LV tissue was analyzed for glycogen deposits and other molecular hallmarks of hibernation. LDDS caused a marked increase in LVESWT (27+/-2.98 vs. 7.15+/-3 %, P < .05) and MPRI (2.1+/-0.5 vs. 1.3+/-0.3 P < .05) in the region that was activated first (pacing site) compared with the opposite region. Myocardial glycogen content was markedly increased in the pacing site (P < .05 vs. opposite region). In addition, gene expression of glycogen phosphorylase was reduced in pacing site compared with opposite regions (0.71+/-0.1 vs. 1.03+/-0.3, P < .05), whereas that of hexokinase type II was globally reduced by 83%. CONCLUSIONS The combination of high heart rate and sustained dyssynchronous LV contraction causes asymmetrical myocardial hibernation, in absence of coronary artery stenosis.