Reliability of Left Ventricular Ejection Fraction from Three-Dimensional Echocardiography for Cardiotoxicity Onset Detection in Patients with Breast Cancer.

BACKGROUND: Cardiotoxicity is a well-known adverse effect of various chemotherapeutic agents that can be monitored by echocardiography. A decrease in left ventricular ejection fraction (LVEF) triggers consideration for therapy modification or interruption. The aim of this study was to evaluate how variability in LVEF estimates computed using three-dimensional echocardiography could influence cardiotoxicity onset detection. METHODS: One hundred eighty one patients with breast cancer treated with anthracycline and trastuzumab were analyzed. LVEF was computed using two commercial software packages. In a subgroup of 40 patients, three-dimensional echocardiographic data were reanalyzed to assess intra- and interobserver variability by two expert investigators using both packages. Global longitudinal strain (GLS) imaging was evaluated in 64 patients. RESULTS: End-diastolic volume, end-systolic volume, and LVEF measurements obtained applying the two software packages were in good agreement, with small bias and acceptable limits of agreement. Intra- and interobserver variability was smaller using one of the two software packages. However, for both packages, variability indexes were in the range of affecting LVEF estimates at a level that could lead to an inaccurate assessment of cardiac adverse effects of cancer therapeutic drugs. On the basis of LVEF, 11 of 181 patients (6.1%) had cardiotoxicity at 3-month follow-up. The absolute value of GLS was smaller in 16 of 64 patients (25%) thought to have cardiotoxicity on the basis of GLS results, including six of seven patients who had cardiotoxicity considering LVEF in this subgroup. CONCLUSIONS: Following clinical definition of cardiotoxicity onset, variability in LVEF computation by three-dimensional echocardiography could be a confounding factor for cardiotoxicity diagnosis, and different software packages should not be used interchangeably for LVEF monitoring. GLS confirms its predictive value for subsequent cardiotoxicity.

Myocardial perfusion: near-automated evaluation from contrast-enhanced MR images obtained at rest and during vasodilator stress.

PURPOSE: To develop and validate a technique for near-automated definition of myocardial regions of interest suitable for perfusion evaluation during vasodilator stress cardiac magnetic resonance (MR) imaging. MATERIALS AND METHODS: The institutional review board approved the study protocol, and all patients provided informed consent. Image noise density distribution was used as a basis for endocardial and epicardial border detection combined with nonrigid registration. This method was tested in 42 patients undergoing contrast material-enhanced cardiac MR imaging (at 1.5 T) at rest and during vasodilator (adenosine or regadenoson) stress, including 15 subjects with normal myocardial perfusion and 27 patients referred for coronary angiography. Contrast enhancement-time curves were near-automatically generated and were used to calculate perfusion indexes. The results were compared with results of conventional manual analysis, using quantitative coronary angiography results as a reference for stenosis greater than 50%. Statistical analyses included the Student t test, linear regression, Bland-Altman analysis, and κ statistics. RESULTS: Analysis of one sequence required less than 1 minute and resulted in high-quality contrast enhancement curves both at rest and stress (mean signal-to-noise ratios, 17±7 [standard deviation] and 22±8, respectively), showing expected patterns of first-pass perfusion. Perfusion indexes accurately depicted stress-induced hyperemia (increased upslope, from 6.7 sec(-1)±2.3 to 15.6 sec(-1)±5.9; P<.0001). Measured segmental pixel intensities correlated highly with results of manual analysis (r=0.95). The derived perfusion indexes also correlated highly with (r up to 0.94) and showed the same diagnostic accuracy as manual analysis (area under the receiver operating characteristic curve, up to 0.72 vs 0.73). CONCLUSION: Despite the dynamic nature of contrast-enhanced image sequences and respiratory motion, fast near-automated detection of myocardial segments and accurate quantification of tissue contrast is feasible at rest and during vasodilator stress. This technique, shown to be as accurate as conventional manual analysis, allows detection of stress-induced perfusion abnormalities.

An integrated framework to achieve interoperability in person-centric health management.

The need for high-quality out-of-hospital healthcare is a known socioeconomic problem. Exploiting ICT's evolution, ad-hoc telemedicine solutions have been proposed in the past. Integrating such ad-hoc solutions in order to cost-effectively support the entire healthcare cycle is still a research challenge. In order to handle the heterogeneity of relevant information and to overcome the fragmentation of out-of-hospital instrumentation in person-centric healthcare systems, a shared and open source interoperability component can be adopted, which is ontology driven and based on the semantic web data model. The feasibility and the advantages of the proposed approach are demonstrated by presenting the use case of real-time monitoring of patients' health and their environmental context.

3D dynamic position assessment of the coronary sinus lead in cardiac resynchronization therapy.

Although cardiac resynchronization therapy (CRT) is an effective treatment for chronic systolic heart failure with dyssynchrony, about one-third of patients do not respond favorably. The interaction between the pacing lead and the coronary sinus (CS) branches is of paramount importance for an effective resynchronization. Minor changes in lead position overtime could interfere with CRT mechanics, without affecting even biophysical parameters or ECG morphology. Although late post-implant CS lead dislodgement rate is consistent, lead movements have been little investigated and only with bi-dimensional methods. The aim of this study was (1) to develop a method for quantifying CS lead position in the 3D domain throughout the cardiac cycle and (2) to test it by comparing the CS lead position at implant and at follow-up, using chest fluoroscopy. Method performance, its accuracy and reproducibility were qualitatively and quantitatively assessed. Intra- and inter-observer percent discordance between trajectories were also computed. The accuracy of the procedure resulted in 0.3 ± 0.1 mm and its resolution was 0.5 mm. Intra- and inter-observer discordances were 2.2 ± 1.5 and 5.5 ± 3.6 mm, respectively. The proposed method for measuring the CS lead dynamic placement in 3D space seems accurate and reproducible. Investigating CS lead 3D dynamics could provide further insights into CRT mechanics.

A study of functional anatomy of aortic-mitral valve coupling using 3D matrix transesophageal echocardiography.

BACKGROUND: Mitral and aortic valves are known to be coupled via fibrous tissue connecting the two annuli. Previous studies evaluating this coupling have been limited to experimental animals using invasive techniques. The new matrix array transesophageal transducer provides high-resolution real-time 3D images of both valves simultaneously. We sought to develop and test a technique for quantitative assessment of mitral and aortic valve dynamics and coupling. METHODS AND RESULTS: Matrix array transesophageal (Philips iE33) imaging was performed in 24 patients with normal valves who underwent clinically indicated transesophageal echocardiography. Custom software was used to detect and track the mitral and aortic annuli in 3D space throughout the cardiac cycle, allowing automated measurement of changes in mitral and aortic valve morphology. Mitral annulus surface area and aortic annulus projected area changed reciprocally over time. Mitral annulus surface area was 8.0+/-2.1 cm(2) at end-diastole and decreased to 7.7+/-2.1 cm(2) in systole, reaching its maximum (10.0+/-2.2 cm(2)) at mitral valve opening. Aortic annulus projected area was 4.1+/-1.2 cm(2) at end-diastole, then increased during isovolumic contraction reaching its maximum (4.8+/-1.3 cm(2)) in the first third of systole and its minimum (3.6+/-1.0 cm(2)) during isovolumic relaxation. The angle between the mitral and aortic annuli was maximum (136+/-13 degrees ) at end-diastole and decreased to its minimum value (129+/-11 degrees ) during systole. CONCLUSIONS: This is the first study to report quantitative 3D assessment of the mitral and aortic valve dynamics from matrix array transesophageal images and describe the mitral-aortic coupling in a beating human heart. This ability may have impact on patient evaluation for valvular surgical interventions and prosthesis design.

Automated frame-by-frame endocardial border detection from cardiac magnetic resonance images for quantitative assessment of left ventricular function: validation and clinical feasibility.

PURPOSE: To develop a technique based on image noise distribution for automated endocardial border detection from cardiac magnetic resonance (CMR) images throughout the cardiac cycle, validate it, and test its clinical utility. MATERIALS AND METHODS: Images obtained in 36 patients were analyzed using custom software to obtain left ventricular (LV) volume throughout the cardiac cycle, end-systolic and end-diastolic LV volumes, and ejection fraction (EF). Validation against manually-traced endocardial boundaries included intertechnique comparisons of LV volumes, slice areas, and border positions. Then, the clinical feasibility of the dynamic automated analysis of LV function was tested in 14 patients with normal LV function, 12 patients with systolic dysfunction, and 10 patients with diastolic dysfunction. RESULTS: Analysis time for one cardiac cycle was <15 minutes. Intertechnique comparisons resulted in high correlation (r>0.96), small biases (volumes: -6 mL; EF: 4.6%) and narrow limits of agreement (volumes: 17.6 mL; EF: 9.2%). We found significant intergroup differences in multiple quantitative indices of systolic and diastolic function. CONCLUSION: Fast, automated, dynamic detection of LV endocardial boundaries is feasible and allows accurate quantification of LV size and function, which is potentially clinically useful for objective assessment of systolic and diastolic dysfunction.

Semi-automated analysis of dynamic changes in myocardial contrast from real-time three-dimensional echocardiographic images as a basis for volumetric quantification of myocardial perfusion.

AIMS: Despite the potential of real-time three-dimensional (3D) echocardiography (RT3DE) to assess myocardial perfusion, there is no quantification method available for perfusion analysis from RT3DE images. Such method would require 3D regions of interest (ROI) to be defined and adjusted frame-by-frame to compensate for cardiac translation and deformation. Our aims were to develop and test a technique for automated identification of 3D myocardial ROI suitable for translation-free quantification of myocardial videointensity over time, MVI(t), from contrast-enhanced RT3DE images. METHODS AND RESULTS: Twelve transthoracic RT3DE (Philips) data sets obtained in pigs during transition from no contrast to steady-state enhancement (Definity) were analysed using custom software. Analysis included: (i) semi-automated detection of left ventricular endo- and epicardial surfaces using level-set techniques in one frame to define a 3D myocardial ROI, (ii) rigid 3D registration to reduce translation and rotation, (iii) elastic 3D registration to compensate for deformation, and (iv) quantification of MVI(t) in the 3D ROI from the registered and non-registered data sets to assess the effectiveness of registration. For each MVI(t) curve we computed % variability during steady-state enhancement (100 x SD/mean) and goodness of fit (r2) to the indicator dilution equation MVI(t) = A[1-exp(-betat)]. Analysis of myocardial contrast throughout contrast inflow was feasible in all data sets. Three-dimensional registration improved MVI(t) curves in terms of both % variability (2.8 +/- 1.8 to 1.5 +/- 0.9%; P < 0.05) and goodness of fit (r2 from 0.79 +/- 0.2 to 0.90 +/- 0.1; P < 0.05). CONCLUSION: This is the first study to describe a new technique for semi-automated volumetric quantification of myocardial contrast from RT3DE images that includes registration and thus provides the basis for 3D measurement of myocardial perfusion.

Quantification of mitral apparatus dynamics in functional and ischemic mitral regurgitation using real-time 3-dimensional echocardiography.

Mitral regurgitation (MR) in dilated cardiomyopathy (DCM-MR) and MR in ischemic cardiomyopathy (ISC-MR) usually occurs as a result of mitral annulus (MA) dilatation and papillary muscle displacement secondary to global left ventricle remodelling. We propose a method to determine MA area and motion throughout the cardiac cycle and to define papillary muscle position in 3-dimensional space using real-time 3-dimensional echocardiography. Real-time 3-dimensional echocardiography was performed in 24 healthy individuals, and in 30 patients with DCM-MR (n = 15) or ISC-MR (n = 15). Significant intergroup differences were noted in MA surface area (control: 6.4 +/- 1.7 cm(2); DCM-MR: 11.1 +/- 2.6 cm(2); ISC-MR: 9.0 +/- 2.0 cm(2)) and in peak MA motion (control: 8.7 +/- 3.0 mm; DCM-MR: 3.4 +/- 1.7 mm; ISC-MR: 4.9 +/- 1.5 mm). In patients with DCM-MR, papillary muscle symmetry was preserved, whereas in patients with ISC-MR, papillary tethering lengths were unequal as a result of wall-motion abnormalities. Our methodology for dynamic volumetric measurements of the mitral apparatus allows better understanding of MR mechanisms.

Mathematical modeling and numerical simulation in maxillofacial virtual surgery.

Computer-based surgery simulation is a rapidly emerging and increasingly important area of research that combines a number of disciplines for the common purpose of improving healthcare. The objective of this article is to provide a virtual surgery tool for accurately planning the aesthetic impact of hard and soft tissue movements in dentoskeletal malocclusions. The approach proposed here allows direct interaction with a completely three-dimensional (3D) computed tomography (CT) model of a solid, highly detailed structure of the head to obtain a realistic prediction of soft tissue behavior. We studied 25 patients who had facial malformations pre- and postoperatively with 3D hard and soft tissue CT studies, and maxillary or mandibular osteotomies were simulated. The postoperative 3D CT and facial outcomes were compared with the simulations. In 80% of the cases studied, the simulation-predicted changes, when compared with the clinical outcomes, were within the tolerance level (2 mm) established by maxillofacial surgeons.

Improved reproducibility of right ventricular volumes and function estimation from cardiac magnetic resonance images using level-set models.

This study aims to assess whether an alternative method, that is based on volumetric surface detection (VoSD) without tracing and is totally free of geometric assumptions, can improve the reproducibility of right ventricular (RV) volume quantification from cardiac magnetic resonance (CMR) images, in comparison with a conventional disk-area technique. In a sample of 23 patients, with wide variability of RV end-diastolic volume (EDV: 47-131 ml), end-systolic volume (ESV: 20-76 ml), and ejection fraction (EF: 29-73%), using the standard method (Argus, Siemens) as the reference, the VoSD method showed good agreement for EDV, ESV, and EF estimations (correlation coefficient: 0.91, 0.94, and 0.94; Bland-Altman biases: 1 ml, 1 ml, and 0%; limits of agreement: +/-16 ml, +/-11 ml, and +/-11%, respectively). An analysis of the reproducibility of the two methods showed lower intraobserver variability for the VoSD method than for the conventional method, as evidenced by the coefficient of variability (CoV) values (2-6% vs. 8-15%; P < 0.05). In addition, the VoSD method showed improved interobserver reproducibility (7-10% vs. 8-15%), but the difference was statistically significant only for EF estimation variability (8 vs. 15%, P < 0.05). In conclusion, the newly developed VoSD technique allows accurate measurements of RV volumes and function, and appears to be more reproducible than the conventional methodology.

Mathematical modeling and numerical simulation in maxillo-facial virtual surgery (VISU).

Computer-based surgery simulation is a rapidly emerging and increasingly important area of research that combines a number of disciplines for the common purpose of improving healthcare. The objective of this paper is to provide a virtual surgery (VISU) tool for accurately planning the aesthetic impact of hard and soft tissue movements in dento-skeletal malocclusions. The approach proposed here allows direct interaction with a completely three-dimensional (3-D) computed tomography (CT) model of a solid, highly detailed structure of the head to obtain a realistic prediction of soft tissue behavior. We studied 25 patients who had facial malformations pre- and postoperatively with 3-D hard and soft tissue CT studies, and maxillary or mandibular osteotomies were simulated. The postoperative 3-D CT and facial outcomes were compared with the simulations. In 80% of the cases studied, the simulation-predicted changes, when compared with the clinical outcomes, were within the tolerance level (2 mm) established by maxillo-facial surgeons.

Quantification of regional left ventricular wall motion from real-time 3-dimensional echocardiography in patients with poor acoustic windows: effects of contrast enhancement tested against cardiac magnetic resonance.

OBJECTIVE: Regional left ventricular function can be assessed by real-time 3-dimensional echocardiography (RT3DE) in patients with good image quality. Our goals were to: (1) test the feasibility of RT3DE quantification of regional wall motion (RWM) in patients with poor acoustic windows who require contrast for endocardial visualization; and (2) validate these measurements against cardiac magnetic resonance (CMR) reference. METHODS: RT3DE datasets and CMR images were obtained in 24 patients. In 16 of 24 patients with suboptimal endocardial definition, RT3DE imaging was repeated with intravenous contrast and triggering at end systole and end diastole. RT3DE datasets were analyzed using custom software designed to semiautomatically detect and segment the endocardial surface and calculate RWM values. CMR images were analyzed using commercial software to obtain reference values for RWM. RESULTS: In 8 of 24 patients with good endocardial definition, RT3DE values of RWM correlated well with CMR (r = 0.73) with a small bias (-1.0 mm). In the remaining 16 patients, analysis of nonenhanced RT3DE datasets yielded lower correlation with CMR (r = 0.61) and a slightly greater bias (-1.5 mm). The agreement with CMR improved significantly (r = 0.76, bias -1.1 mm) with contrast enhancement. CONCLUSIONS: The agreement between RT3DE and CMR values of RWM is directly related to RT3DE image quality. In patients with poor acoustic windows, dual-triggered contrast enhancement improves the accuracy of RWM quantification to a level similar to that noted in patients with good images without contrast.

Volumetric quantification of global and regional left ventricular function from real-time three-dimensional echocardiographic images.

BACKGROUND: Real-time 3D echocardiographic (RT3DE) data sets contain dynamic volumetric information on cardiac function. However, quantification of left ventricular (LV) function from 3D echocardiographic data is performed on cut-planes extracted from the 3D data sets and thus does not fully exploit the volumetric information. Accordingly, we developed a volumetric analysis technique aimed at quantification of global and regional LV function. METHODS AND RESULTS: RT3DE images obtained in 30 patients (Philips 7500) were analyzed by use of custom software based on the level-set approach for semiautomated detection of LV endocardial surface throughout the cardiac cycle, from which global and regional LV volume (LVV)-time and wall motion (WM)-time curves were obtained. The study design included 3 protocols. In protocol 1, time curves obtained in 16 patients were compared point-by-point with MRI data (linear regression and Bland-Altman analyses). Global LVV correlated highly with MRI (r=0.98; y=0.99x+2.3) with minimal bias (1.4 mL) and narrow limits of agreement (+/-20 mL). WM correlated highly only in basal and midventricular segments (r=0.88; y=0.85x+0.7). In protocol 2, we tested the ability of this technique to differentiate populations with known differences in LV function by studying 9 patients with dilated cardiomyopathy and 9 normal subjects. All calculated indices of global and regional systolic and diastolic LV function were significantly different between the groups. In protocol 3, we tested the feasibility of automated detection of regional WM abnormalities in 11 patients. In each segment, abnormality was detected when regional shortening fraction was below a threshold obtained in normal subjects. The automated detection agreed with expert interpretation of 2D WM in 86% of segments. CONCLUSIONS: Volumetric analysis of RT3DE data is clinically feasible and allows fast, semiautomated, dynamic measurement of LVV and automated detection of regional WM abnormalities.

Maximum likelihood segmentation of ultrasound images with Rayleigh distribution.

This study presents a geometric model and a computational algorithm for segmentation of ultrasound images. A partial differential equation (PDE)-based flow is designed in order to achieve a maximum likelihood segmentation of the target in the scene. The flow is derived as the steepest descent of an energy functional taking into account the density probability distribution of the gray levels of the image as well as smoothness constraints. To model gray level behavior of ultrasound images, the classic Rayleigh probability distribution is considered. The steady state of the flow presents a maximum likelihood segmentation of the target. A finite difference approximation of the flow is derived, and numerical experiments are provided. Results are presented on ultrasound medical images as fetal echography and echocardiography.

Improved quantification of left ventricular volumes and mass based on endocardial and epicardial surface detection from cardiac MR images using level set models.

PURPOSE: The reproducibility of left ventricular (LV) volume and mass measurements based on subjective slice-by-slice tracing of LV borders is affected by image quality, and volume estimates are biased by geometric modeling. The authors developed a technique for volumetric surface detection (VoSD) and quantification of LV volumes and mass without tracing and geometric approximations. The authors hypothesized that this technique is accurate and more reproducible than the conventional methodology. METHODS: Images were obtained in 24 patients in 6 to 10 slices from LV base to apex (GE 1.5 T, FIESTA). Volumetric data were reconstructed, and endocardial and epicardial surfaces were detected using the level set approach. LV volumes were obtained from voxel counts and used to compute ejection fraction (EF) and mass. Conventional measurements (MASS Analysis) were used as a reference to test the accuracy of VoSD technique (linear regression, Bland-Altman). For both techniques, measurements were repeated to compute inter- and intra-observer variability. RESULTS: VoSD values resulted in high correlation with the reference values (EDV: r = 0.98; ESV: r = 0.99; EF: r = 0.91; mass: r = 0.98), with no significant biases (8 ml, 5 ml, 0.2% and -9 g) and narrow limits of agreement (SD: 13 ml, 10 ml, 6% and 9 g). Inter-observer variability of the VoSD technique was lower (range 3 to 5%) than that of the reference technique (5 to 11%; p < 0.05). Intra-observer variability was also lower (1 to 3% vs. 7 to 10%; p < 0.05). CONCLUSION: VoSD technique allows accurate measurements of LV volumes, EF, and mass, which are more reproducible than the conventional methodology.

Evolutionary partial differential equations for biomedical image processing.

We are presenting here a model for processing space-time image sequences and applying them to 3D echo-cardiography. The non-linear evolutionary equations filter the sequence with keeping space-time coherent structures. They have been developed using ideas of regularized Perona-Malik an-isotropic diffusion and geometrical diffusion of mean curvature flow type (Malladi-Sethian), combined with Galilean invariant movie multi-scale analysis of Alvarez et al. A discretization of space-time filtering equations by means of finite volume method is discussed in detail. Computational results in processing of 3D echo-cardiographic sequences obtained by rotational acquisition technique and by real-time 3D echo volumetrics acquisition technique are presented. Quantitative error estimation is also provided.

Left ventricular volume estimation for real-time three-dimensional echocardiography.

The application of level set techniques to echocardiographic data is presented. This method allows semiautomatic segmentation of heart chambers, which regularizes the shapes and improves edge fidelity, especially in the presence of gaps, as is common in ultrasound data. The task of the study was to reconstruct left ventricular shape and to evaluate left ventricular volume. Data were acquired with a real-time three-dimensional (3-D) echocardiographic system. The method was applied directly in the three-dimensional domain and was based on a geometric-driven scheme. The numerical scheme for solving the proposed partial differential equation is borrowed from numerical methods for conservation law. Results refer to in vitro and human in vivo acquired 3-D + time echocardiographic data. Quantitative validation was performed on in vitro balloon phantoms. Clinical application of this segmentation technique is reported for 20 patient cases providing measures of left ventricular volumes and ejection fraction.