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• W2078131437 abstract "Conventionally, echocardiographic assessment of cardiac function is based on two-dimensional ultrasound quantification of changes in cardiac chamber size or Doppler assessment of blood flow. Global indices of function, such as cardiac output, ejection fraction and fractional shortening, are then derived from these measures in order to estimate myocardial function. In this issue of the Journal, Gardiner et al.1 investigate the long-term effect of twin-to-twin transfusion syndrome (TTTS), and subsequent treatment, on cardiac function at age 10 years. In addition to traditional M-mode and Doppler assessments of cardiac function, they present more novel myocardial deformation, or ‘strain’, imaging-derived measures based on speckle-tracking ultrasound techniques. What can these measures contribute? In the last decade, there have been huge advances in echocardiographic imaging technology and processing. These developments have resulted in the advent of imaging approaches that can track myocardial deformation during the cardiac cycle. In particular, quantification of how much the myocardium ‘thickens’ or ‘thins’ allows measurement of myocardial ‘strain’. Strain is the deformation of an object relative to its original size and is therefore a dimensionless quantity2. Lengthening of an object is represented by positive values and shortening by negative values. Strain rate is the speed at which the deformation occurs. These measures provide a non-invasive surrogate measure of contractility of the myocardium and therefore potentially a more physiologically and mechanically correct representation of myocardial function during the cardiac cycle than does traditional assessment. As these measures are specific to particular areas, they can be used to generate both global and regional measures of myocardial function3, which allows insight into interactions between different segments of the myocardium in pathological conditions. Traditional ultrasound techniques, such as gray-scale M-mode recordings, can offer some information on wall thickening and thinning, but this is limited to deformation aligned with the ultrasound beam that involves the whole thickness of the wall and only at a single position within the heart4. The advent of tissue Doppler imaging (TDI), which uses frequency shifts in ultrasound waves to calculate velocity, similar to conventional Doppler techniques but within ranges seen in the myocardium, allowed more precise measures of strain5. This is because TDI can be used to track motion of specific points within the myocardium and, with the help of offline analysis tools, global and regional strain and strain-rate values can be derived. The technique works at the high temporal resolution required for assessment of velocity and strain rates but is angle-dependent, as only motion towards, or away from, the transducer can be tracked. The major development that simplified acquisition of myocardial deformation measures was ‘speckle tracking’. When an ultrasound beam strikes myocardial features, an inherent ‘speckle’ pattern is generated that can be seen within the ultrasound image and is constant within the myocardium over time. These bright myocardial areas can be tracked frame-by-frame using specific image-processing algorithms. By studying the relative position of different speckles, the thickening and thinning of the myocardium can then be quantified with high spatial resolution6. A major advantage is that it is not angle- or direction-dependent. Similar concepts have been used to measure strain with other imaging modalities. For instance, areas of the myocardium can be marked artificially using magnetic resonance to generate ‘tags’ that can be tracked during the cardiac cycle3, 7, 8. However, ultrasonography has the advantages of accessibility and low cost, combined with real-time capability, safety and operator comfort and experience9. Image quality is important for accurate speckle tracking and chamber foreshortening can result in overestimation of strain. Low frame rates can also result in tracking failure, and improvement of tracking algorithms is a major area of development. There are several different commercially available speckle-tracking software applications with their own individual algorithms for tracking speckles. As a result, absolute measures are not always comparable between manufacturers and results vary with choice of equipment for acquisition and analysis2. Nevertheless, speckle tracking has been validated against sonomicrometry, which involves the tracking of small, artificial beads, implanted within the myocardium10, and is comparable to magnetic resonance imaging (MRI)10, 11 as well as TDI12 in the adult population. The introduction of three-dimensional echocardiography has also made it possible to measure deformation in all three axes of the heart (radial, longitudinal and circumferential), within a single cardiac cycle, a method that enhances the possibility to measure more complex myocardial functional parameters such as ‘twist’ and ‘torsion’11, 13-15. Ultrasound-based cardiac strain analysis has been applied to many conditions in the adult population. These include coronary artery disease16, volume overload in the context of valvular disease7, pressure overload in hypertension17 and genetic cardiomyopathies18. These studies demonstrate that subtle changes in myocardial deformation usually precede gross changes in function assessed by conventional volumetric measures and therefore may provide useful early diagnostic and prognostic information. However, the data acquisition approaches and software tools for post-processing and analysis of strain parameters were developed and refined for the adult heart. Therefore, the reliability of the algorithms in younger populations, for example neonates, in whom the heart is much smaller with thinner myocardium and who have a much faster heart rate, is unclear. Figure 1 demonstrates the distinct appearances of strain curves derived in adults compared with neonates and fetuses. Fetal imaging has particular additional, unique challenges, such as: the orientation of the fetus relative to the ultrasound beam; variations in distance between fetus and transducer; variations in imaging quality related to maternal adiposity, oligohydramnios or an anterior placenta; as well as maternal and fetal movement during the cardiac cycle (Table 1). With no direct access to the fetus, electrocardiographic (ECG) registration is not currently possible and invasive validation studies to assess the reliability of strain technology are not feasible. Some of these problems are now being overcome; for example, a dummy ECG can be generated by manual indication of the onset of the cardiac cycle based on mitral valve motion19 or M-mode recordings20. In addition, high frame-rate acquisitions should improve the reliability of results, and recent studies have shown that measures of cardiac deformation using TDI and speckle tracking are feasible and reproducible in the fetus19-21. These novel strain technologies have now been used to investigate pathological states in the fetus and child. Results vary between conditions, for example, hypoplastic left heart syndrome and Ebstein's anomaly have been shown to be associated with abnormal strain patterns22-24, whereas strain values were normal in cases of tetralogy of Fallot, double outlet right ventricle and atrial septal defects23, 24. One study reported a reduction in right ventricular systolic strain in the recipient twin in TTTS25, although cardiovascular function has not been shown to be a useful prognostic marker in this condition26. As the techniques are applied more widely, in larger groups and in other conditions known to affect fetal and pediatric cardiac function, such as cardiomyopathies, their additional diagnostic and prognostic value will be clarified. We already know from studies in adults that certain factors during the perinatal period are relevant to long-term changes in myocardial strain and, thereby, adult cardiovascular health. Recent MRI studies have shown that preterm delivery and maternal pre-eclampsia, as well as short-term interventions, such as intravenous lipid therapy, are associated with reductions in cardiovascular strain in young adulthood27-29. It may well be that these changes emerge during fetal and neonatal life, as ventricular strain has been demonstrated to alter when there is preterm rupture of membranes associated with intra-amniotic infection30 and both systolic and diastolic myocardial deformation have been shown to be altered with early-onset fetal growth restriction (FGR) before more traditional measures of function, such as the Doppler waveform in the ductus venosus, become abnormal31-33. In addition, a proportion of fetuses with late-onset FGR have been found using TDI to have subclinical cardiac dysfunction34 and abnormalities in cardiac strain have been shown to persist into early childhood in cases of FGR35. Ultrasound speckle tracking has generated interesting opportunities for relatively simple assessment of early, subtle changes in both global and regional myocardial deformation that are evident before gross changes in volumetric measures of function are detected. However, the techniques and tracking algorithms have been developed for adult populations and, even in this setting, problems with standardization exist. Therefore, work is required to establish protocols and algorithms to allow feasible, reproducible and repeatable image acquisition in the infant and fetus. Strain is known to vary with age, development and gender3; therefore, greater knowledge of how strain and strain-rate parameters vary throughout gestation will help in interpreting the impact on cardiac function of perinatal exposures or interventions. Nevertheless, deformation imaging has the potential to provide valuable insights into how a wide range of diseases and conditions influence the myocardium, and this could aid early diagnosis, prognosis and monitoring and enable timely intervention, to modify long-term risk. Work within the research group is supported by grants to Professor Paul Leeson from the British Heart Foundation (FS/11/65/28865). Additional grants have been received from the Engineering and Physical Sciences Research Council, National Institute for Health Research Oxford Biomedical Research Centre and Oxford British Heart Foundation Centre for Research Excellence." @default.
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• W2078131437 title "Assessment of cardiac function from fetal to adult life with myocardial deformation imaging" @default.
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