Contrast echocardiography for cardiac quantifications

The indicator-dilution-theory for cardiac quantifications has always been limited in practice by the invasiveness of the available techniques. However, the recent introduction of stable ultrasound contrast agents opens new possibilities for indicator dilution measurements. This study describes a new and successful approach to overcome this invasiveness issue. We show a novel approach for minimally invasive quantification of several cardiac parameters based on the dilution of ultrasound contrast agents. A single peripheral injection of an ultrasound contrast agent bolus can result in the simultaneous assessment of cardiac output, pulmonary blood volume, and left and right ventricular ejection fraction. The bolus passage in different sites of the central circulation is detected by an ultrasound transducer. The detected acoustic (or video) intensities are processed and several indicator dilution curves are measured simultaneously. To this end, we exploit that for low concentrations the relation between contrast concentration and acoustic backscatter is approximately linear. The Local Density Random Walk Model is used to fit and interpret the indicator dilution curves for cardiac output, pulmonary blood volume, and ejection fraction measurements. Two fitting algorithms based either on a multiple linear regression in the logarithmic domain or on the solution of the moment equations are developed. The indicator dilution system can be also interpreted as a linear system and, therefore, characterized by an impulse response function. An adaptive Wiener deconvolution filter is implemented for robust dilution system identification. For ejection fraction measurements, the atrial and ventricular indicator dilution curves are measured and processed by the deconvolution filter, resulting in the estimate of the left ventricle dilution-system impulse response. This curve can be fitted and interpreted by a mono-compartment exponential model for the ejection fraction assessment. The proposed deconvolution filter is also used for the identification of the dilution system between right ventricle and left atrium. The Local Density Random Walk Model fit of the estimated impulse response allows the pulmonary blood volume assessment. Both cardiac output and pulmonary blood volume measurements are validated in vitro with accurate results (correlation coefficients larger than 0.99). The Pulmonary blood volume measurement feasibility is also tested in humans with promising results. The ejection fraction measurement is validated in-vivo. The impulse response approach allows accurate left ventricle ejection fraction estimates. Comparison with echocardiographic bi-plane measurements shows a correlation coefficient equal to 0.93. A dedicated image segmentation algorithm for videodensitometry has also been developed for automating the determination of regions of interest. The resulting algorithm has been integrated with the indicator dilution analysis system. The automatic determination of the measurement region results in improved dilution-curve signal-to-noise ratios. In conclusion, this study proves that quantification of cardiac output, pulmonary blood volume, and left and right ventricular ejection fraction by dilution of ultrasound contrast agents is feasible and accurate. Moreover, the proposed methods are applicable in different contexts (e.g., magnetic resonance imaging) and for different types of measurements, leading to a broad range of applications

Videodensitometric methods for cardiac output measurements

Cardiac output is often measured by indicator dilution techniques, usually based on dye or cold saline injections. Developments of more stable ultrasound contrast agents (UCA) are leading to new noninvasive indicator dilution methods. However, several problems concerning the interpretation of dilution curves as detected by ultrasound transducers have arisen. This paper presents a method for blood flow measurements based on UCA dilution. Dilution curves are determined by real-time densitometric analysis of the video output of an ultrasound scanner and are automatically fitted by the Local Density Random Walk model. A new fitting algorithm based on multiple linear regression is developed. Calibration, that is, the relation between videodensity and UCA concentration, is modelled by in vitro experimentation. The flow measurement system is validated by in vitro perfusion of SonoVue contrast agent. The results show an accurate dilution curve fit and flow estimation with determination coefficient larger than 0.95 and 0.99, respectively

Pregnancy monitoring

International audienc

Observed cumulative time delay between second harmonic and fundamental component of pressure wave fields propagating through ultrasound contrast agentss

Several studies on the propagation velocity of pressure wave fields through ultrasound contrast agents (UCAs) have been reported in the literature. However, the variation of propagation velocity between the fundamental and the second harmonic component generated during the propagation of ultrasound through UCAs has, to our knowledge, not been studied yet. To this scope, dedicated transmission and backscattering measurements of pressure wave fields propagating through SonoVue and Definity contrast agents, are analyzed. Results show the occurrence of a cumulative delay between the time signals related to the second harmonic and fundamental component, suggesting a smaller propagation velocity for the second harmonic as compared to the fundamental component. Moreover, this time delay increases with increasing UCA concentration and propagation path length of ultrasound trough microbubbles, depends on mechanical index and frequency, and, most importantly, is not observed in the absence of UCAs. These results may be relevant to contrast-enhanced ultrasonography, opening up to new possibilities to increase contrast-to-tissue ratios and to quantify UCA concentration

Identification of ultrasound-contrast-agent dilution systems for ejection fraction measurements

Left ventricular ejection fraction is an important cardiac-efficiency measure. Standard estimations are based on geometric analysis and modeling; they require time and experienced cardiologists. Alternative methods make use of indicator dilutions, but they are invasive due to the need for catheterization. This study presents a new minimally invasive indicator dilution technique for ejection fraction quantification. It is based on a peripheral injection of an ultrasound contrast agent bolus. Left atrium and left ventricle acoustic intensities are recorded versus time by transthoracic echocardiography. The measured curves are corrected for attenuation distortion and processed by an adaptive Wiener deconvolution algorithm for the estimation of the left ventricle impulse response, which is interpolated by a monocompartment exponential model for the ejection fraction assessment. This technique measures forward ejection fraction, which excludes regurgitant volumes. The feasibility of the method was tested on a group of 20 patients with left ventricular ejection fractions going from 10% to 70%. The results are promising and show a 0.93 correlation coefficient with echographic bi-plane ejection fraction measurements. A more extensive validation as well as an investigation on the method applicability for valve insufficiency and right ventricular ejection fraction quantification will be an object of future study

Towards dynamic contrast specific ultrasound tomography

We report on the first study demonstrating the ability of a recently-developed, contrast-enhanced, ultrasound imaging method, referred to as cumulative phase delay imaging (CPDI), to image and quantify ultrasound contrast agent (UCA) kinetics. Unlike standard ultrasound tomography, which exploits changes in speed of sound and attenuation, CPDI is based on a marker specific to UCAs, thus enabling dynamic contrast-specific ultrasound tomography (DCS-UST). For breast imaging, DCS-UST will lead to a more practical, faster, and less operator-dependent imaging procedure compared to standard echo-contrast, while preserving accurate imaging of contrast kinetics. Moreover, a linear relation between CPD values and ultrasound second-harmonic intensity was measured (coefficient of determination = 0.87). DCS-UST can find clinical applications as a diagnostic method for breast cancer localization, adding important features to multi-parametric ultrasound tomography of the breast.</p

Fetal movement quantification by fetal vectrocardiography: a preliminary study.

Fetal movement is a valuable source of information to monitor the neurological development of the fetus and assess fetal health. Currently, fetal movement can be assessed by the mother or detected by analysis of ultrasound images. Long-term monitoring of movement is complicated with both these methods as maternal self-assessment has a relatively poor sensitivity and specificity and automatic analysis of ultrasound images is not available. Moreover, ultrasound transducers transmit energy into the body, potentially endangering fetal health. In this paper, an alternative method for fetal movement monitoring is presented. This method operates by estimating and analyzing the fetal vectorcardiogram (VCG) from non-invasive recordings on the maternal abdomen. The determined fetal movement is compared with that assessed from a simultaneously performed ultrasound recording; the results of the presented method are consistent with the ultrasound images. In addition, the presented method enables quantification of the rotation angles by means of analysis of the rotation matrix between consecutive fetal VCGs, providing a tool for long-term monitoring of fetal movement with increased specificity

On the distinct differences in autonomic regulation between pregnant and non-pregnant women:a heart rate variability analysis

Objective. Appropriate adaptation of the maternal autonomic nervous system to progressing gestation is essential to a healthy pregnancy. This is partly evidenced by the association between pregnancy complications and autonomic dysfunction. Therefore, assessing maternal heart rate variability (HRV)—a proxy measure for autonomic activity—may offer insights into maternal health, potentially enabling the early detection of complications. However, identifying abnormal maternal HRV requires a thorough understanding of normal maternal HRV. While HRV in women of childbearing age has been extensively investigated, less is known concerning HRV during pregnancy. Subsequently, we investigate the differences in HRV between healthy pregnant women and their non-pregnant counterparts. Approach. We use a comprehensive suite of HRV features (assessing sympathetic and parasympathetic activity, heart rate (HR) complexity, HR fragmentation, and autonomic responsiveness) to quantify HRV in large groups of healthy pregnant (n = 258) and non-pregnant women (n = 252). We compare the statistical significance and effect size of the potential differences between the groups. Main results. We find significantly increased sympathetic and decreased parasympathetic activity during healthy pregnancy, along with significantly attenuated autonomic responsiveness, which we hypothesize serves as a protective mechanism against sympathetic overactivity. HRV differences between these groups typically had a large effect size (Cohen’s d &gt; 0.8), with the largest effect accompanying the significantly reduced HR complexity and altered sympathovagal balance observed in pregnancy (Cohen’s d &gt; 1.2). Significance. Healthy pregnant women are autonomically distinct from their non-pregnant counterparts. Subsequently, assumptions based on HRV research in non-pregnant women cannot be readily translated to pregnant women.</p