Combined Brain-Heart Imaging in Takotsubo Syndrome: Towards a Holistic Patient Assessment.

Takotsubo syndrome (TTS) is a type of cardiomyopathy usually precipitated by either emotional or physical stress and potentially leading to reversible heart failure. There is emerging evidence indicating an interaction between the brain and the heart in patients with TTS. Nevertheless, these new insights are not reflected in the current clinical approach to TTS. The application of novel and existing imaging modalities for the evaluation of brain-heart interactions is an interesting approach that could potentially augment diagnostic and prognostic yield, as well as improve our pathophysiologic understanding in the context of TTS. In this opinion piece, we discuss the evidence supporting a brain-heart interaction in patients with TTS and discuss how a combined evaluation of brain-heart interactions could potentially be implemented.

Multiparametric Cardiac Magnetic Resonance Assessment in Sickle Beta Thalassemia.

Cardiac involvement in sickle beta thalassemia (Sß-thal) patients has been poorly investigated. We aimed to evaluate cardiac function and myocardial iron overload by cardiovascular magnetic resonance (CMR) in patients with Sß-thal. One-hundred and eleven Sß-thal patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network were studied and compared with 46 sickle cell anemia (SCA) patients and with 111 gender- and age- matched healthy volunteers. Cine images were acquired to quantify biventricular function. Myocardial iron overload (MIO) was assessed by the T2* technique, while macroscopic myocardial fibrosis was evaluated by the late gadolinium enhancement (LGE) technique. In Sß-thal and SCA patients, the morphological and functional CMR parameters were not significantly different, except for the left atrial area and left ventricular (LV) stroke volume, indexed by body surface area (p = 0.023 and p = 0.048, respectively), which were significantly higher in SCA patients. No significant differences between the two groups were found in terms of myocardial iron overload and macroscopic myocardial fibrosis. When compared to healthy subjects, Sß-thal patients showed significantly higher bi-atrial and biventricular parameters, except for LV ejection fraction, which was significantly lower. The CMR analysis confirmed that Sß-thal and SCA patients are phenotypically similar. Since Sß-thal patients showed markedly different morphological and functional indices from healthy subjects, it would be useful to identify Sß-thal/SCA-specific bi-atrial and biventricular reference values.

Impact of the COVID-19 Pandemic on Iron Overload Assessment by MRI in Patients with Hemoglobinopathies: The E-MIOT Network Experience.

BACKGROUND: The E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) project is an Italian Network assuring high-quality quantification of tissue iron overload by magnetic resonance imaging (MRI). We evaluated the impact of the COVID-19 pandemic on E-MIOT services. METHODS: The activity of the E-MIOT Network MRI centers in the year 2020 was compared with that of 2019. A survey evaluated whether the availability of MRI slots for patients with hemoglobinopathies was reduced and why. RESULTS: The total number of MRI scans was 656 in 2019 and 350 in 2020, with an overall decline of 46.4% (first MRI: 71.7%, follow-up MRI: 36.9%), a marked decline (86.9%) in the period March-June 2020, and a reduction in the gap between the two years in the period July-September. A new drop (41.4%) was recorded in the period October-December for two centers, due to the general reduction in the total amount of MRIs/day for sanitization procedures. In some centers, patients refused MRI scans for fear of getting COVID. Drops in the MRI services >80% were found for patients coming from a region without an active MRI site. CONCLUSIONS: The COVID-19 pandemic had a strong negative impact on MRI multi-organ iron quantification, with a worsening in the management of patients with hemoglobinopathies.

Consensus on the assessment of systemic sclerosis-associated primary heart involvement: World Scleroderma Foundation/Heart Failure Association guidance on screening, diagnosis, and follow-up assessment.

Introduction: Heart involvement is a common problem in systemic sclerosis. Recently, a definition of systemic sclerosis primary heart involvement had been proposed. Our aim was to establish consensus guidance on the screening, diagnosis and follow-up of systemic sclerosis primary heart involvement patients. Methods: A systematic literature review was performed to investigate the tests used to evaluate heart involvement in systemic sclerosis. The extracted data were categorized into relevant domains (conventional radiology, electrocardiography, echocardiography, cardiac magnetic resonance imaging, laboratory, and others) and presented to experts and one patient research partner, who discussed the data and added their opinion. This led to the formulation of overarching principles and guidance statements, then reviewed and voted on for agreement. Consensus was attained when the mean agreement was ⩾7/10 and of ⩾70% of voters. Results: Among 2650 publications, 168 met eligibility criteria; the data extracted were discussed over three meetings. Seven overarching principles and 10 guidance points were created, revised and voted on. The consensus highlighted the importance of patient counseling, differential diagnosis and multidisciplinary team management, as well as defining screening and diagnostic approaches. The initial core evaluation should integrate history, physical examination, rest electrocardiography, trans-thoracic echocardiography and standard serum cardiac biomarkers. Further investigations should be individually tailored and decided through a multidisciplinary management. The overall mean agreement was 9.1/10, with mean 93% of experts voting above 7/10. Conclusion: This consensus-based guidance on screening, diagnosis and follow-up of systemic sclerosis primary heart involvement provides a foundation for standard of care and future feasibility studies that are ongoing to support its application in clinical practice.

Tumor Diagnosis and Treatment: Imaging Assessment.

At present, oncologic imaging is crucial for clinical decision-making [...].

Estimation of pancreatic R2* for iron overload assessment in the presence of fat: a comparison of different approaches.

OBJECTIVES: To propose a method for estimating pancreatic relaxation rate, R2*, from conventional multi-echo MRI, based on the nonlinear fitting of the acquired magnitude signal decay to MR signal models that take into account both the signal oscillations induced by fat and the different R2* values of pancreatic parenchyma and fat. MATERIALS AND METHODS: Single-peak fat (SPF) and multi-peak fat (MPF) models were introduced. Single-R2* and dual-R2* assumptions were considered as well. Analyses were conducted on simulated data and 20 thalassemia major patients. RESULTS: Simulations revealed the ability of the MPF model to correctly estimate the R2* value in a large range of fat fractions and R2* values. From the comparison between the results obtained with a single R2* value for water and fat and the dual-R2* approach, the latter is more accurate in both water R2* and fat fraction estimation. In patient's data analysis, a strong concordance was found between SPF and MPF estimated data with measurements done with manual signal correction and from fat-saturated images. The MPF method showed better reproducibility. CONCLUSION: The MPF dual-R2* approach improves reproducibility and reduces image analysis time in the assessment of pancreatic R2* value in patients with iron overload.

Non-compact myocardium assessment by cardiac magnetic resonance: dependence on image analysis method.

To compare image analysis methods for the assessment of left ventricle non-compaction from cardiac magnetic resonance (CMR) imaging. CMR images were analyzed in 20 patients and 10 normal subjects. A reference model of the MR signal was introduced and validated based on image data. Non-compact (NC) myocardium size and distribution were assessed by tracing a single, continuous contour delimiting trabeculated region (Jacquier) or by one-by-one selection of trabeculae (Grothoff). The global non-compact/compact (NC/C) ratio, the NC mass, and the segmental NC/C ratio were assessed. Results were compared with the reference model. A significant difference between Grothoff and Jacquier approaches in the estimation of NC/C ratio (32.08 ± 6.63 vs. 19.81 ± 5.72, p < 0.0001) and NC mass (26.59 ± 8.36 vs. 14.15 ± 5.73 g/m2, p < 0.0001) was found. The Grothoff approach better matches the expected signal distribution. Inter-observer reproducibility of both Grothoff and Jacquier methods was adequate (9.71 and 8.22%, respectively) with no significant difference between observers. Jacquier and Grothoff approaches are not interchangeable so that specific diagnostic thresholds should be used for different image analysis methods. Grothoff method seems to better capture the true extension of trabeculated tissue.

Cost-Utility Analysis of Three Iron Chelators Used in Monotherapy for the Treatment of Chronic Iron Overload in ß-Thalassaemia Major Patients: An Italian Perspective.

PURPOSE: Deferiprone (DFP), deferasirox (DFX) and deferoxamine (DFO) are used in thalassaemia major (TM) patients to treat chronic iron overload. We evaluated the cost-effectiveness of DFP, compared with DFX and DFO monotherapy, from an Italian healthcare system perspective. METHODS: A Markov model was used over a time horizon of 5 years. Italian-specific cost data were combined with Italian efficacy data. Costs and quality-adjusted life years (QALYs) were calculated for each treatment, with cost-effectiveness expressed as cost per QALY. RESULTS: In all scenarios modelled, DFP was the dominant treatment strategy. Sensitivity analyses showed that DFP dominated the other treatments with a >99% likelihood of being cost-effective against DFX and DFO at a willingness to pay threshold of €20,000 per QALY. CONCLUSIONS: DFP was the dominant and most cost-effective treatment for managing chronic iron overload in TM patients. Its use can result in substantial cost savings for the Italian healthcare system.

Clinical recommendations of cardiac magnetic resonance, Part I: ischemic and valvular heart disease: a position paper of the working group 'Applicazioni della Risonanza Magnetica' of the Italian Society of Cardiology.

Cardiac magnetic resonance (CMR) has emerged as a reliable and accurate diagnostic tool for the evaluation of patients with cardiac disease in several clinical settings and with proven additional diagnostic and prognostic value compared with other imaging modalities. This document has been developed by the working group on the 'application of CMR' of the Italian Society of Cardiology to provide a perspective on the current state of technical advances and clinical applications of CMR and to inform cardiologists on how to implement their clinical and diagnostic pathways with the inclusion of this technique in clinical practice. The writing committee consisted of members of the working group of the Italian Society of Cardiology and two external peer reviewers with acknowledged experience in the field of CMR.

Quantitative T2* magnetic resonance imaging for renal iron overload assessment: normal values by age and sex.

PURPOSE: Few studies of renal iron content have been performed with multiecho gradient-echo (ME-GRE) T2* magnetic resonance imaging (MRI). We assessed the feasibility and reproducibility of ME-GRE T2* MRI for measuring regional and global renal T2* values, and established the lower limits of normal in healthy subjects, also correlating the measured values with age and sex. METHODS: Twenty consecutive healthy subjects (13 men and 7 women, mean age 29.1 ± 7.2 years, range 19-42 years) underwent MRI examinations using a 1.5 T magnet and an ME-GRE T2* sequence. For each kidney, T2* was measured in anterior, posterolateral, and posteromedial renal parenchymal regions. The mean T2* value was calculated as the average of the two kidneys T2* values. RESULTS: For the mean kidney T2* value, the coefficients of variation for intra- and inter-operator reproducibility were 1.76% and 6.23%, respectively. The lower limit of normal for the mean kidney T2* value was 31 ms (median 51.39 ± 10.09). There was no significant difference between left and right kidney T2* values (p = 0.578). No significant correlation was found between T2* values and subjects' age or sex. CONCLUSIONS: Renal ME-GRE T2* appears to be a feasible and reproducible technique. The renal T2* values showed no dependence on sex or age.

Assessment of atrial diastolic function in patients with hypertrophic cardiomyopathy by cine magnetic resonance imaging.

PURPOSE: This study was conducted to assess the role of atrial function by cardiac magnetic resonance (CMR) for the evaluation of diastolic physiology in patients with hypertrophic cardiomyopathy (HCM) compared to healthy controls. MATERIALS AND METHODS: We enrolled 23 consecutive patients affected by HCM and 43 healthy subjects as age-matched control cases (CC). CMR was performed through acquisition of cine steady-state free precession sequences using a 1.5-T scanner. Image postprocessing was carried out using Tracking Tool software. RESULTS: Atrial volumes were significantly higher in patients with HCM compared to CC: maximum atrial volume (p = 0.007) and minimum atrial volume (p = 0.01). A statistically significant difference was also observed in atrial ejection fraction in patients with HCM (p < 0.0001). The atrial volume curves defined as cavity volume over time (dV/t) showed significant differences: early atrial peak emptying rate (PERE) (maximum rate of emptying independent of atrial contraction) in HCM was -146 ± 53 ml/s versus -227 ± 86 ml/s in CC (p < 0.0001); active atrial peak emptying rate (PERA) (maximum rate of emptying secondary to atrial contraction) in HCM was -256 ± 80 ml/s versus -216 ± 104 ml/s in CC (p = 0.05); the atrial PER E/A ratio in HCM was 0.6 ± 0.2 versus 1.05 ± 0.5 in CC (p < 0.0001). CONCLUSIONS: This study demonstrated that in HCM patients with early diastolic dysfunction the parameters of left atrial function assessed by CMR are impaired before the ventricular diastolic indexes such as the early peak filling rate and the active peak filling rate.

Regional and global pancreatic T*2 MRI for iron overload assessment in a large cohort of healthy subjects: normal values and correlation with age and gender.

Multiecho gradient-echo T*2 magnetic resonance imaging is a well-established technique for iron overload assessment but there are few reports concerning the pancreas. The aim of this work was to assess the feasibility and reproducibility of the magnetic resonance imaging for measuring pancreatic regional and global T*2 values, to establish the lower limit of normal in a large cohort of healthy subjects and to correlate the measured values with age and gender. One hundred and twenty healthy subjects (61 males, 51±17 years) underwent magnetic resonance imaging (1.5T) using a multiecho gradient-echo T*2 sequence. T*2 measurements were performed in pancreatic head, body, and tail. The global value was calculated as the mean. Measurement of pancreatic T*2 values was feasible in all subjects. For the T*2 global value the coefficient of variation for intraoperator and interoperator reproducibility were 7.7% and 13%, respectively. The global T*2 values ranged from 24 to 52 ms with the lower limit of normal of 26 ms. There were no significant differences among the regional pancreatic T*2 values. No significant correlation was found between T*2 and patient age or gender. In conclusion, pancreatic T*2 measurements appear to be feasible, reproducible, nontime-consuming and reliable. Gender- and age-related differences concerning pancreatic T*2 were not found.

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.

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.