Jan D'hooge

Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging

Recognizing the critical need for standardization in strain imaging, in 2010, the European Association of Echocardiography (now the European Association of Cardiovascular Imaging, EACVI) and the American Society of Echocardiography (ASE) invited technical representatives from all interested vendors to participate in a concerted effort to reduce intervendor variability of strain measurement. As an initial product of the work of the EACVI/ASE/Industry initiative to standardize deformation imaging, we prepared this technical document which is intended to provide definitions, names, abbreviations, formulas, and procedures for calculation of physical quantities derived from speckle tracking echocardiography and thus create a common standard.

Strain Rate Imaging Detects Early Cardiac Effects of Pegylated Liposomal Doxorubicin as Adjuvant Therapy in Elderly Patients with Breast Cancer

OBJECTIVE Cardiac toxicity remains an important side effect of anthracyclines. New drug formulations (eg, pegylated liposomal doxorubicin [PL-DOX]) seem to be a successful strategy for reducing it. Changes in cardiac function induced by early chemotherapy, however, are subtle and difficult to quantitate by conventional imaging methods. Doppler myocardial imaging-based velocity, strain, and strain rate measurements have been shown to sensitively quantify abnormalities in cardiac function in other settings. DESIGN We evaluated the feasibility and sensitivity of strain rate imaging compared with conventional echocardiography in detecting cardiac effects of PL-DOX therapy in elderly patients with cancer. In a pilot study, we examined 16 elderly women (age 69.8 +/- 3.1 years) with breast cancer receiving 6 cycles of PL-DOX. Conventional and Doppler myocardial imaging echocardiography were obtained at baseline and after 3 and 6 cycles of treatment. Segmental peak systolic longitudinal and radial velocity, strain, and strain rate were measured. RESULTS Left ventricular dimensions, ejection fraction, and systolic myocardial velocity did not change throughout the follow-up. In contrast, a significant reduction in longitudinal and radial strain and strain rate was found after 6 cycles (longitudinal strain -18.8% +/- 2.8% vs -22.7% +/- 2.8%, P < .001 vs baseline and P = .001 vs after 3 cycles; radial strain 32.3% +/- 8.1% vs 50.1% +/- 11.6%, P < .001 vs baseline). Changes in radial function appeared earlier and were more pronounced than in longitudinal direction. CONCLUSION In contrast with conventional echocardiography and myocardial velocity measurements, myocardial deformation parameters allowed detecting subtle changes in longitudinal and radial left ventricular function after 6 cycles of PL-DOX. We suggest that Doppler-based myocardial deformation imaging should be used for cardiac function monitoring during chemotherapy.

Definitions for a common standard for 2D speckle tracking echocardiography: consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging.

Recognizing the critical need for standardization in strain imaging, in 2010, the European Association of Echocardiography (now the European Association of Cardiovascular Imaging, EACVI) and the American Society of Echocardiography (ASE) invited technical representatives from all interested vendors to participate in a concerted effort to reduce intervendor variability of strain measurement. As an initial product of the work of the EACVI/ASE/Industry initiative to standardize deformation imaging, we prepared this technical document which is intended to provide definitions, names, abbreviations, formulas, and procedures for calculation of physical quantities derived from speckle tracking echocardiography and thus create a common standard.

Left ventricular strain and strain rate in a general population

AIMS Strain and strain rate (SR) are measures of deformation that reflect left ventricular (LV) function. To our knowledge, no previous study described these indexes in a general population. We therefore described peak-systolic strain and SR of the LV in the general population and derived diagnostic thresholds for these measurements in a healthy subgroup. METHODS AND RESULTS In 480 subjects enrolled in a family-based population study (50.5% women; mean age, 50.5 years; 37.2% hypertensive), we measured: (i) end-systolic longitudinal strain and peak-systolic SR from the basal portion of the LV inferior and inferolateral free walls; (ii) radial deformation of the LV inferolateral wall. Longitudinal (mean, 22.9%) and radial (59.2%) strain and longitudinal (1.31 s(-1)) and radial (3.40 s(-1)) SR decreased with age (P </= 0.007). Longitudinal and radial strain independently decreased (P </= 0.006) with relative wall thickness (RWT), longitudinal strain with the waist-to-hip ratio, and radial strain with body weight. In contrast, LV ejection fraction increased (P </= 0.0001) with age and RWT. Longitudinal and radial stain rate increased with heart rate (P </= 0.05). In healthy subgroup (n = 236), the fifth percentiles were 18.4 and 44.3%, and 0.99 and 2.43 s(-1), for longitudinal and radial strain and SR, respectively. CONCLUSION We explored the early signs of LV systolic dysfunction in a general population, using tissue Doppler imaging technique. LV strain and SR decrease with age, body weight, central obesity, and RWT. Our current study resulted in the proposal for diagnostic thresholds for strain and SR, based on a healthy subgroup recruited via random sampling of the population.

Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction

The matricellular protein SPARC (secreted protein, acidic and rich in cysteine, also known as osteonectin) mediates cell–matrix interactions during wound healing and regulates the production and/or assembly of the extracellular matrix (ECM). This study investigated whether SPARC functions in infarct healing and ECM maturation after myocardial infarction (MI). In comparison with wild-type (WT) mice, animals with a targeted inactivation of SPARC exhibited a fourfold increase in mortality that resulted from an increased incidence of cardiac rupture and failure after MI. SPARC-null infarcts had a disorganized granulation tissue and immature collagenous ECM. In contrast, adenoviral overexpression of SPARC in WT mice improved the collagen maturation and prevented cardiac dilatation and dysfunction after MI. In cardiac fibroblasts in vitro, reduction of SPARC by short hairpin RNA attenuated transforming growth factor β (TGF)–mediated increase of Smad2 phosphorylation, whereas addition of recombinant SPARC increased Smad2 phosphorylation concordant with increased Smad2 phosphorylation in SPARC-treated mice. Importantly, infusion of TGF-β rescued cardiac rupture in SPARC-null mice but did not significantly alter infarct healing in WT mice. These findings indicate that local production of SPARC is essential for maintenance of the integrity of cardiac ECM after MI. The protective effects of SPARC emphasize the potential therapeutic applications of this protein to prevent cardiac dilatation and dysfunction after MI.

Three-Dimensional Cardiac Strain Estimation Using Spatio–Temporal Elastic Registration of Ultrasound Images: A Feasibility Study

Current ultrasound methods for measuring myocardial strain are often limited to measurements in one or two dimensions. Cardiac motion and deformation however are truly 3-D. With the introduction of matrix transducer technology, 3-D ultrasound imaging of the heart has become feasible but suffers from low temporal and spatial resolution, making 3-D strain estimation challenging. In this paper, it is shown that automatic intensity-based spatio-temporal elastic registration of currently available 3-D volumetric ultrasound data sets can be used to measure the full 3-D strain tensor. The method was validated using simulated 3-D ultrasound data sets of the left ventricle (LV). Three types of data sets were simulated: a normal and symmetric LV with different heart rates, a more realistic asymmetric normal LV and an infarcted LV. The absolute error in the estimated displacement was between 0.47 plusmn0.23 and 1.00 plusmn0.59 mm, depending on heart rate and amount of background noise. The absolute error on the estimated strain was 9%-21% for the radial strain and 1%-4% for the longitudinal and circumferential strains. No large differences were found between the different types of data sets. The shape of the strain curves was estimated properly and the position of the infarcts could be identified correctly. Preliminary results on clinical data taken in vivo from three healthy volunteers and one patient with an apical aneurism confirmed these findings in a qualitative manner as the strain curves obtained with the proposed method have an amplitude and shape similar to what could be expected.

Left ventricular strain and strain rate: characterization of the effect of load in human subjects.

AIMS Left ventricular (LV) strain and strain rate have been proposed as novel indices of systolic function; however, there are limited data about the effect of acute changes on these parameters. METHODS AND RESULTS Simultaneous Millar micromanometer LV pressure and echocardiographic assessment were performed on 18 patients. Loading was altered sequentially by the administration of glyceryl trinitrate (GTN) and saline fluid loading. Echocardiographic speckle tracking imaging was used to quantify the peak systolic strain (S) and peak systolic strain rate (SR S) and dp/dt max was recorded from the micromanometer data. GTN administration decreased preload (LV end diastolic pressure [LVEDP]: 15.7 vs. 8.4 mmHg, P < 0.001) and afterload (end systolic wall stress: 74 vs. 43 x 10(3)dyn/cm(2), P < 0.001). Administration of fluid increased preload (LVEDP: 11.3 vs. 18.1 mmHg, P < 0.001) and increased wall stress (53 vs. 62 x 10(3)dyn/cm(2), P < 0.003). Administration of GTN resulted in increased circumferential SR S (-1.2 vs. -1.7s(-1), P < 0.01) and longitudinal SR S (-0.9 vs. -1.0 s(-1), P < 0.001). The administration of fluid resulted in decreased circumferential SR S (-1.5 vs. -1.3s(-1), P < 0.01) and longitudinal SR S (-1.0 vs. -0.9s(-1), P < 0.01). As preload and afterload increased, decrease in circumferential SR S (r = 0.63, P < 0.001; r = 0.56, P<0.001) and longitudinal SR S were observed (r = 0.42, P < 0.003; r = 0.49 P < 0.001). CONCLUSION Circumferential and longitudinal peak strain and systolic strain rate are sensitive to acute changes in load, an important factor that needs to be considered in their application as indices of systolic function.

Ultrastructural and Functional Remodeling of the Coupling Between Ca2+ Influx and Sarcoplasmic Reticulum Ca2+ Release in Right Atrial Myocytes From Experimental Persistent Atrial Fibrillation

Rationale: Persistent atrial fibrillation (AF) has been associated with structural and electric remodeling and reduced contractile function. Objective: To unravel mechanisms underlying reduced sarcoplasmic reticulum (SR) Ca2+ release in persistent AF. Methods: We studied cell shortening, membrane currents, and [Ca2+]i in right atrial myocytes isolated from sheep with persistent AF (duration 129±39 days, N=16), compared to matched control animals (N=21). T-tubule density, ryanodine receptor (RyR) distribution, and local [Ca2+]i transients were examined in confocal imaging. Results: Myocyte shortening and underlying [Ca2+]i transients were profoundly reduced in AF (by 54.8% and 62%, P<0.01). This reduced cell shortening could be corrected by increasing [Ca2+]i. SR Ca2+ content was not different. Calculated fractional SR Ca2+ release was reduced in AF (by 20.6%, P<0.05). Peak Ca2+ current density was modestly decreased (by 23.9%, P<0.01). T-tubules were present in the control atrial myocytes at low density and strongly reduced in AF (by 45%, P<0.01), whereas the regular distribution of RyR was unchanged. Synchrony of SR Ca2+ release in AF was significantly reduced with increased areas of delayed Ca2+ release. Propagation between RyR was unaffected but Ca2+ release at subsarcolemmal sites was reduced. Rate of Ca2+ extrusion by Na+/Ca2+ exchanger was increased. Conclusions: In persistent AF, reduced SR Ca2+ release despite preserved SR Ca2+ content is a major factor in contractile dysfunction. Fewer Ca2+ channel–RyR couplings and reduced efficiency of the coupling at subsarcolemmal sites, possibly related to increased Na+/Ca2+ exchanger, underlie the reduction in Ca2+ release.

Recommendations of the European Association of Echocardiography How to use echo-Doppler in clinical trials: different modalities for different purposes

The European Association of Echocardiography (EAE) has developed the present recommendations to assist clinical researchers in the design, implementation, and conduction of echocardiographic protocols for clinical trials and to guarantee their quality. Clinical trials should be designed and conducted based on the knowledge of the pathophysiology of the clinical condition studied, the technical characteristics of the echo-Doppler modalities, and the variability of the tested parameters. These procedures are important to choose the most reliable and reproducible techniques and parameters. Quality assurance must be guaranteed by adequate training of peripheral site operators to obtain optimal echo-Doppler data and by using a core laboratory for accurate and reproducible data analysis.

A fast convolution-based methodology to simulate 2-Dd/3-D cardiac ultrasound images

This paper describes a fast convolution-based methodology for simulating ultrasound images in a 2-D/3-D sector format as typically used in cardiac ultrasound. The conventional convolution model is based on the assumption of a space-invariant point spread function (PSF) and typically results in linear images. These characteristics are not representative for cardiac data sets. The spatial impulse response method (IRM) has excellent accuracy in the linear domain; however, calculation time can become an issue when scatterer numbers become significant and when 3-D volumetric data sets need to be computed. As a solution to these problems, the current manuscript proposes a new convolution-based methodology in which the data sets are produced by reducing the conventional 2-D/3-D convolution model to multiple 1-D convolutions (one for each image line). As an example, simulated 2-D/3-D phantom images are presented along with their gray scale histogram statistics. In addition, the computation time is recorded and contrasted to a commonly used implementation of IRM (Field II). It is shown that COLE can produce anatomically plausible images with local Rayleigh statistics but at improved calculation time (1200 times faster than the reference method).