Imaging inflammation in atherosclerotic plaques, targeting SST2 with [111In]In-DOTA-JR11.

BACKGROUND: Imaging Somatostatin Subtype Receptor 2 (SST2) expressing macrophages by [DOTA,Tyr3]-octreotate (DOTATATE) has proven successful for plaque detection. DOTA-JR11 is a SST2 targeting ligand with a five times higher tumor uptake than DOTATATE, and holds promise to improve plaque imaging. The aim of this study was to evaluate the potential of DOTA-JR11 for plaque detection. METHODS AND RESULTS: Atherosclerotic ApoE-/- mice (n = 22) fed an atherogenic diet were imaged by SPECT/CT two hours post injection of [111In]In-DOTA-JR11 (~ 200 pmol, ~ 50 MBq). In vivo plaque uptake of [111In]In-DOTA-JR11 was visible in all mice, with a target-to-background-ratio (TBR) of 2.23 ± 0.35. Post-mortem scans after thymectomy and ex vivo scans of the arteries after excision of the arteries confirmed plaque uptake of the radioligand with TBRs of 2.46 ± 0.52 and 3.43 ± 1.45 respectively. Oil red O lipid-staining and ex vivo autoradiography of excised arteries showed [111In]In-DOTA-JR11 uptake at plaque locations. Histological processing showed CD68 (macrophages) and SST2 expressing cells in plaques. SPECT/CT, in vitro autoradiography and immunohistochemistry performed on slices of a human carotid endarterectomy sample showed [111In]In-DOTA-JR11 uptake at plaque locations containing CD68 and SST2 expressing cells. CONCLUSIONS: The results of this study indicate DOTA-JR11 as a promising ligand for visualization of atherosclerotic plaque inflammation.

Imaging of inflammatory cellular protagonists in human atherosclerosis: a dual-isotope SPECT approach.

PURPOSE: Atherosclerotic plaque development and progression signifies a complex inflammatory disease mediated by a multitude of proinflammatory leukocyte subsets. Using single photon emission computed tomography (SPECT) coupled with computed tomography (CT), this study tested a new dual-isotope acquisition protocol to assess each radiotracer's capability to identify plaque phenotype and inflammation levels pertaining to leukocytes expressing leukocyte function-associated antigen-1 (LFA-1) and the leukocyte subset of proinflammatory macrophages expressing somatostatin receptor subtype-2 (SST2). Individual radiotracer uptake was quantified and the presence of corresponding immunohistological cell markers was assessed. METHODS: Human symptomatic carotid plaque segments were obtained from endarterectomy. Segments were incubated in dual-isotope radiotracers [111In]In-DOTA-butylamino-NorBIRT ([111In]In-Danbirt) and [99mTc]Tc-[N0-14,Asp0,Tyr3]-octreotate ([99mTc]Tc-Demotate 2) before scanning with SPECT/CT. Plaque phenotype was classified as pathological intimal thickening, fibrous cap atheroma or fibrocalcific using histology sections based on distinct morphological characteristics. Plaque segments were subsequently immuno-stained with LFA-1 and SST2 and quantified in terms of positive area fraction and compared against the corresponding SPECT images. RESULTS: Focal uptake of co-localising dual-radiotracers identified the heterogeneous distribution of inflamed regions in the plaques which co-localised with positive immuno-stained regions of LFA-1 and SST2. [111In]In-Danbirt and [99mTc]Tc-Demotate 2 uptake demonstrated a significant positive correlation (r = 0.651; p = 0.001). Fibrous cap atheroma plaque phenotype correlated with the highest [111In]In-Danbirt and [99mTc]Tc-Demotate 2 uptake compared with fibrocalcific plaques and pathological intimal thickening phenotypes, in line with the immunohistological analyses. CONCLUSION: A dual-isotope acquisition protocol permits the imaging of multiple leukocyte subsets and the pro-inflammatory macrophages simultaneously in atherosclerotic plaque tissue. [111In]In-Danbirt may have added value for assessing the total inflammation levels in atherosclerotic plaques in addition to classifying plaque phenotype.

Nuclear Imaging of Post-infarction Inflammation in Ischemic Cardiac Diseases - New Radiotracers for Potential Clinical Applications.

Acute myocardial infarction is one of the leading causes of death in the western world. Despite major improvements in myocardial reperfusion with sophisticated percutaneous coronary intervention technologies and new antithrombotic agents, there is still no effective therapy for preventing post- infarction myocardial injury and remodeling. Death of cardiomyocytes following ischemia results in "danger signals" that elicit an inflammatory reaction to remove cell debris and form scar tissue. Optimal healing of the damaged myocardial tissue requires a coordinated cellular response for sufficient wound healing and scar formation. However, if this inflammatory reaction is overactive or incompletely resolved, adverse left ventricular remodeling and heart failure may occur. Treatment aimed at the modulation of the post-MI inflammatory response has been widely pursued and investigated. Although improved infarct healing was shown in many experimental preclinical studies, to date, clinical trials using anti-inflammatory treatment strategies have been far less successful. Clearly, a need exists for predicting and selecting patients at risk and selecting the most appropriate therapy for individual patients. To this end, imaging of the post-MI response has been a topic of significant interest. In this review, we first discuss the clinical complications resulting from myocardial inflammation following AMI and the need for non-invasive imaging techniques using radiolabeled tracers. We then discuss the inflammatory reaction cascade following acute myocardial infarction, the inflammatory reaction cascade following acute myocardial infarction focusing on inflammatory cell types involved herein, and potential imaging targets for identifying these cells during the inflammatory process. In addition, we discuss specific characteristics and limitations of various preclinical animal models for ischemic heart disease since they are crucial in the development and evaluation of the imaging techniques. Finally, we discuss the need for non-invasive imaging approaches using radiolabeled tracers.

Autoradiographical assessment of inflammation-targeting radioligands for atherosclerosis imaging: potential for plaque phenotype identification.

PURPOSE: Many radioligands have been developed for the visualization of atherosclerosis by targeting inflammation. However, interpretation of in vivo signals is often limited to plaque identification. We evaluated binding of some promising radioligands in an in vitro approach in atherosclerotic plaques with different phenotypes. METHODS: Tissue sections of carotid endarterectomy tissue were characterized as early plaque, fibro-calcific plaque, or phenotypically vulnerable plaque. In vitro binding assays for the radioligands [111In]In-DOTATATE; [111In]In-DOTA-JR11; [67Ga]Ga-Pentixafor; [111In]In-DANBIRT; and [111In]In-EC0800 were conducted, the expression of the radioligand targets was assessed via immunohistochemistry. Radioligand binding and expression of radioligand targets was investigated and compared. RESULTS: In sections characterized as vulnerable plaque, binding was highest for [111In]In-EC0800; followed by [111In]In-DANBIRT; [67Ga]Ga-Pentixafor; [111In]In-DOTA-JR11; and [111In]In-DOTATATE (0.064 ± 0.036; 0.052 ± 0.029; 0.011 ± 0.003; 0.0066 ± 0.0021; 0.00064 ± 0.00014 %Added activity/mm2, respectively). Binding of [111In]In-DANBIRT and [111In]In-EC0800 was highest across plaque phenotypes, binding of [111In]In-DOTA-JR11 and [67Ga]Ga-Pentixafor differed most between plaque phenotypes. Binding of [111In]In-DOTATATE was the lowest across plaque phenotypes. The areas positive for cells expressing the radioligand's target differed between plaque phenotypes for all targets, with lowest percentage area of expression in early plaque sections and highest in phenotypically vulnerable plaque sections. CONCLUSIONS: Radioligands targeting inflammatory cell markers showed different levels of binding in atherosclerotic plaques and among plaque phenotypes. Different radioligands might be used for plaque detection and discerning early from vulnerable plaque. [111In]In-EC0800 and [111In]In-DANBIRT appear most suitable for plaque detection, while [67Ga]Ga-Pentixafor and [111In]In-DOTA-JR11 might be best suited for differentiation between plaque phenotypes.

Side-by-side viewing of anatomically aligned left ventricular segments in three-dimensional stress echocardiography.

BACKGROUND: Dobutamine stress echocardiography (DSE) suffers from high interobserver and inter-institution variability in the diagnosis of myocardial ischemia. Therefore, we developed a three-dimensional (3D) analysis tool that makes it possible to anatomically align 3D rest and stress data systematically, to generate optimal, nonforeshortened standard anatomical cross sections and to analyse the images synchronized and side-by-side. AIM OF THE STUDY: To investigate whether this 3D analysis tool could improve interobserver agreement on myocardial ischemia during 3D DSE. METHODS: The study comprised 34 consecutive patients with stable chest pain who underwent both noncontrast and contrast 3D DSE. Two observers scored segmental wall motion using a conventional analysis and the novel analysis with the new 3D tool. RESULTS: The two observers agreed on the presence or absence of myocardial ischemia in 81 of 102 coronary territories (agreement 79%, kappa (kappa) 0.28) during noncontrast 3D imaging and 92 of 102 coronary territories (agreement 90%, kappa 0.65) during contrast-enhanced 3D imaging. With the new 3D analysis software these numbers improved to 98 of 102 coronary territories (agreement 96%, kappa 0.69) during noncontrast 3D imaging and 98 of 102 coronary territories (agreement 96%, kappa 0.82) during contrast-enhanced 3D imaging. CONCLUSION: The use of a 3D DSE analysis tool improves interobserver agreement for myocardial ischemia both for noncontrast and contrast images.

Contrast-enhanced three-dimensional dobutamine stress echocardiography: between Scylla and Charybdis?

AIMS: Real-time three-dimensional echocardiography (RT3DE) allows quick volumetric scanning of the left ventricle (LV). We evaluated the diagnostic accuracy of contrast-enhanced stress RT3DE for the detection of coronary artery disease (CAD) in comparison with coronary arteriography as the reference technique. METHODS AND RESULTS: Forty-five consecutive patients (age 59 +/- 10, 31 males) referred for coronary angiography were examined by contrast-enhanced RT3DE. Wall motion analysis was performed off-line by dedicated software. New or worsening wall motion abnormalities were detected in 17 of 28 patients with significant CAD (sensitivity 61%), and in two of 17 patients without significant CAD (specificity 88%). The sensitivity for detection of single-vessel CAD was 8/15 patients (53%), for two-vessel CAD 4/6 (67%), and for three-vessel CAD 5/7 (71%). In 35 patients, comparison with conventional RT3DE was available. The image quality index at rest improved from 2.5 +/- 1.2 to 3.2 +/- 1.0 (P < 0.001) with contrast and at peak stress from 2.3 +/- 1.2 to 3.1 +/- 1.0 (P < 0.001). Interobserver agreement on the diagnosis of myocardial ischaemia improved from 26 of 35 studies (74%, kappa = 0.44) with conventional stress RT3DE to 30 of 35 studies (86%, kappa = 0.69) with contrast-enhanced stress RT3DE. Sensitivity increased from 50 to 55% and specificity from 69 to 85% with contrast-enhanced stress RT3DE in this subset of patients. CONCLUSION: Despite some important practical and theoretical benefits, contrast-enhanced stress RT3DE currently has only moderate diagnostic sensitivity due to several technical limitations as temporal and spatial resolution.

Dobutamine stress echocardiography for the detection of coronary artery disease in women.

Dobutamine stress echocardiography (DSE) has good diagnostic accuracy for the diagnosis of coronary artery disease (CAD). However, in most published diagnostic studies, patients are predominantly men. In women, diagnostic accuracy may be lower because of a lower prevalence and extent of CAD, a higher incidence of dobutamine stress-induced hypotension (resulting in less stress or even nondiagnostic test results), smaller left ventricular chamber size, and the beneficial effects of estrogens on the induction of myocardial ischemia. To determine the diagnostic accuracy of DSE in women, 14 diagnostic studies published through 2006 were identified through a Medline search. For a total of 901 patients, the weighted mean sensitivity and specificity were 72% and 88%, respectively. In 7 studies directly comparing results in women and men, conflicting results were reported. However, pooled data showed nearly identical values for sensitivity and specificity in women and men. Additionally, in 6 studies directly comparing DSE results in women with those of stress nuclear scintigraphy, DSE was as sensitive and more specific to detect CAD (90% vs 70%, p <0.0001). The excellent specificity of DSE in women was also confirmed by excellent normalcy rates, ranging from 92% to 100% in women, with a <5% pretest probability of CAD. In conclusion, despite some theoretical limitations, DSE has reasonable sensitivity and excellent specificity for the detection of CAD in women. Considering the diagnostic problems of exercise electrocardiography and nuclear scintigraphy in women, stress echocardiography may be the stress modality of choice in women because of its superior diagnostic specificity.

Usefulness of ultrasound contrast agent to improve image quality during real-time three-dimensional stress echocardiography.

Dobutamine stress echocardiography is an accepted tool for the diagnosis of coronary artery disease. Some investigators have claimed that 3-dimensional imaging improves the diagnostic accuracy of dobutamine stress echocardiography. The purpose of the present investigation was to examine the role of contrast echocardiography in the improvement of segmental quality and interobserver agreement during stress real-time 3-dimensional echocardiography (RT3DE). The study comprised 36 consecutive patients with stable chest pain referred for routine stress testing. Three-dimensional images were acquired with an RT3DE system with an X4 matrix-array transducer. All available reconstructed 2-dimensional segments were graded as optimal, good, moderate, or poor. Wall motion was scored as normal, mild hypokinesia, severe hypokinesia, akinesia, or dyskinesia. At peak stress, 466 of the 612 segments (76%) could be analyzed during conventional RT3DE. With contrast-enhanced RT3DE, the number of available segments increased to 553 (90%). The image quality index during conventional RT3DE was 2.2, whereas with contrast-enhanced RT3DE, it was 3.1. With conventional RT3DE, 2 independent observers agreed on the diagnosis of myocardial ischemia in 85 of 108 coronary territories (79%, kappa = 0.26). With contrast-enhanced RT3DE, agreement increased to 95 of 108 coronary territories (88%, kappa = 0.59). Study agreement on myocardial ischemia was present in 26 of 36 studies (72%, kappa = 0.43) with conventional RT3DE and in 32 of 36 studies (89%, kappa = 0.77) with contrast-enhanced RT3DE. In conclusion, during stress RT3DE, contrast-enhanced imaging significantly decreases the number of poorly visualized myocardial segments and improves interobserver agreement for the diagnosis of myocardial ischemia.

Comparison of contrast agent-enhanced versus non-contrast agent-enhanced real-time three-dimensional echocardiography for analysis of left ventricular systolic function.

Ultrasound contrast has shown to improve endocardial border definition. The purpose of this study was to evaluate the value of contrast agent-enhanced versus non-contrast agent-enhanced real-time 3-dimensional echocardiography (RT3DE) for the assessment of left ventricular (LV) volumes and ejection fraction. Thirty-nine unselected patients underwent RT3DE with and without SonoVue contrast agent enhancement and magnetic resonance imaging (MRI) on the same day. An image quality index was calculated by grading all 16 individual LV segments on a scale of 0 to 4: 0, not visible; 1, poor; 2, moderate; 3, good; and 4, excellent. The 3-dimensional data sets were analyzed offline using dedicated TomTec analysis software. By manual tracing, LV end-systolic volume, LV end-diastolic volume, and LV ejection fraction were calculated. After contrast agent enhancement, mean image quality index improved from 2.4 +/- 1.0 to 3.0 +/- 0.9 (p <0.001). Contrast agent-enhanced RT3DE measurements showed better correlation with MRI (LV end-diastolic volume, r = 0.97 vs 0.86; LV end-systolic volume, r = 0.96 vs 0.94; LV ejection fraction, r = 0.94 vs 0.81). The limits of agreement (Bland-Altman analysis) showed a similar bias for RT3DE images with and without contrast agent but with smaller limits of agreement for contrast agent-enhanced RT3DE. Also, inter- and intraobserver variabilities decreased. In a subgroup, patients with poor to moderate image quality showed an improvement in agreement after administration of contrast agent (+/-24.4% to +/-12.7%) to the same level as patients with moderate to good image quality without contrast agent (+/-10.4%). In conclusion, contrast agent-enhanced RT3DE is more accurate in assessment of LV function as evidenced by better correlation and narrower limits of agreement compared with MRI, as well as lower intra- and interobserver variabilities.

213Bi-[DOTA0, Tyr3]octreotide peptide receptor radionuclide therapy of pancreatic tumors in a preclinical animal model.

PURPOSE: The somatostatin analogue [DOTA0, Tyr3]octreotide (DOTATOC) has previously been labeled with low linear energy transfer (LET) beta-emitters, such as 177Lu or 90Y, for tumor therapy. In this study, DOTATOC labeled with the high-LET alpha-emitter, 213Bi, was evaluated. EXPERIMENTAL DESIGN: The radiolabeling, stability, biodistribution, toxicity, safety, and therapeutic efficacy of 213Bi-DOTATOC (specific activity 7.4 MBq/microg) were investigated. Biodistribution studies to determine somatostatin receptor specificity were done in Lewis rats at 1 and 3 hours postinjection. Histopathology of various organs was used to evaluated toxicity and safety. Therapeutic efficacy of 4 to 22 MBq 213Bi-DOTATOC was determined in a rat pancreatic carcinoma model. RESULTS: Radiolabeling of the 213Bi-DOTATOC was achieved with radiochemical purity >95% and an incorporation yield > or = 99.9%. Biodistribution data showed specific binding to somatostatin receptor-expressing tissues. Administration of free 213Bi, compared with 213Bi-DOTATOC, resulted in higher radioactivity accumulation at 3 hours postinjection in the kidneys [34.47 +/- 1.40% injected dose/g (ID/g) tissue versus 11.15 +/- 0.46%, P < 0.0001] and bone marrow (0.31 +/- 0.01% ID/g versus 0.06 +/- 0.02%, P < 0.0324). A significant decrease in tumor growth rate was observed in rats treated with >11 MBq of 213Bi-DOTATOC 10 days postinjection compared with controls (P < 0.025). Treatment with >20 MBq of 213Bi-DOTATOC showed significantly greater tumor reduction when compared with animals receiving <11 MBq (P < 0.02). CONCLUSIONS: 213Bi-DOTATOC showed dose-related antitumor effects with minimal treatment-related organ toxicity. No acute or chronic hematologic toxicities were observed. Mild, acute nephrotoxicity was observed without evidence of chronic toxicity. 213Bi-DOTATOC is a promising therapeutic radiopharmaceutical for further evaluation.

Three-dimensional echocardiographic analysis of left ventricular function during hemodialysis.

BACKGROUND: The effects of hemodialysis (HD) on left ventricular (LV) function have been studied by various echocardiographic techniques (M-mode, 2D echocardiography). These studies are hampered by a low accuracy of measurements because of geometric assumptions regarding LV shape. Three-dimensional echocardiography (3DE) overcomes this limitation. METHODS: We tested the feasibility of 3DE assessment of LV function during HD. Conventional biplane Simpson rule (BSR) and single plane area length method (SPM) for LV function analysis were used as a reference. RESULTS: 12 HD patients were studied and in 10 (83%) a total of 80 3D datasets were acquired. In 3 patients, one dataset (4%) was of insufficient quality and excluded from analysis. Correlation between SPM, BSR and 3DE for calculation of end-diastolic (EDV, r = 0.89 and r = 0.92, respectively), end-systolic volume (ESV, r = 0.92 and r = 0.93, respectively) and for ejection fraction (EF, r = 0.90 and r = 0.88, respectively) was moderate. Limits-of-agreement results for EDV and ESV were poor with confidence intervals larger than 30 ml. Both 2DE methods underestimated end-diastolic and end-systolic volume, while overestimating ejection fraction. CONCLUSION: 3DE is feasible for image acquisition during HD, which opens the possibility for accurate and reproducible measurement of LV function during HD. This may improve the assessment of the acute effect of HD on LV performance, and guide therapeutic strategies aimed at preventing intradialytic hypotension.

[Real-time 3-dimensional echocardiography: can there be one more dimension?]. / Real-time 3-dimenziós echokardiográfia--lehet egy dimenzióval több?

There is an essential importance of non-invasive imaging methods for evaluation of cardiac patients. Theoretically, the heart can be examined exactly, if due to its nature assessed in three dimensions (3D) concerning the heart cycle. In recent studies it has been confirmed that the second-generation real-time three-dimensional echocardiography offers optimal opportunity for three-dimensional evaluation of cardiac structures. Real-time three-dimensional echocardiography is a valuable tool for exact evaluation of ventricular and atrial volumes and ventricular masses. Valves and congenital abnormalities can be analysed 'en-face' with this new methodology. The usefulness of this method with stress protocols has been confirmed. The aim of the present review is to demonstrate advantages of this new promising method showing recent technological limitations as well.

Seven-year follow-up after dobutamine stress echocardiography: impact of gender on prognosis.

OBJECTIVES: The aim of this study was to investigate the effects of gender on long-term prognosis of patients undergoing dobutamine stress echocardiography (DSE). BACKGROUND: Gender differences in the predictors of outcome among patients with known or suspected coronary artery disease undergoing DSE have not been adequately studied. METHODS: We studied 2,276 men and 1,105 women with known or suspected coronary artery disease who underwent DSE. Follow-up events were cardiac death and nonfatal myocardial infarction (MI). RESULTS: Dobutamine stress echocardiography was normal in 687 men (30%) and 483 women (44%) (p <0.0001). Ischemia on DSE was present in 1,194 men (52%) and 416 women (38%) (p <0.001). During a mean follow-up of 7 +/- 3.4 years, there were 894 (26%) deaths (442 attributed to cardiac causes) and 145 (4%) nonfatal MIs. The annual cardiac event rate was 2.5% in men and 1.2% in women with normal DSE. Independent predictors of cardiac events in patients with normal DSE using a Cox proportional hazards regression analysis were male gender (hazard ratio [HR]: 1.7 [range 1.1 to 2.8]), age (HR: 1.02 [range 1.01 to 1.04]), history of heart failure (HR: 3.4 [range 1.5 to 7.9]), previous MI (HR: 1.7 [range 1.1 to 2.8]), and diabetes (HR: 2.4 [range 1.3 to 4.5]). Independent predictors of cardiac events in patients with an abnormal DSE were age (HR: 1.03 [range 1.02 to 1.04]), history of heart failure (HR: 1.7 [range 1.3 to 2.1]), diabetes (HR: 1.4 [range 1.1 to 1.8]), heart rate at rest (HR: 2.8 [range 1.4 to 5.8]), wall motion abnormalities at rest (HR: 1.06 [range 1.04 to 1.09]), and ischemia on DSE (HR: 1.04 [range 1.02 to 1.07]). Myocardial ischemia was an independent predictor of cardiac events in both men and women. CONCLUSIONS: Dobutamine stress echocardiography provides independent prognostic information in both men and women. In patients with normal DSE, gender is independently associated with cardiac events. The outcome of patients with abnormal DSE is not related to gender, after adjusting for stress echocardiographic abnormalities.

Comparison of real-time three-dimensional echocardiography to magnetic resonance imaging for assessment of left ventricular mass.

This is the first study to assess the feasibility and accuracy of real-time 3-dimensional echocardiography (RT-3DE) for the measurements of left ventricular (LV) mass in patients with congenital heart disease (CHD) compared with magnetic resonance imaging (MRI). Twenty patients (60% men) with CHD were evaluated by MRI and RT-3DE on the same day. Their mean age was 29 +/- 8 years (range 19 to 49). RT-3DE was performed with a Philips Sonos 7500 echocardiographic system and LV mass analyses with the assistance of TomTec software. The results for LV mass obtained by manual tracing were compared with Signa 1.5-T MRI data. The acquisition of RT-3DE data sets was feasible in all 20 patients. Nine patients (45%) had good, 5 patients (25%) moderate, and 6 patients (30%) poor image quality of the 3-dimensional data set. The time of 3-dimensional data acquisition was 4 +/- 2 minutes. Off-line image processing and tracing required approximately 11 +/- 3 minutes. A very good correlation was observed between RT-3DE data with sufficient image quality and MRI (r = 0.98, y = 0.96x + 4.1, SEE 9.8 g), with a mean difference of 2.0 +/- 20 g. Interobserver agreement was excellent (r = 0.99, y = 0.97x + 3.81), with a mean difference of -1 +/- 11 g. In conclusion, the assessment of LV mass from RT-3DE data is feasible in patients with CHD. The mass of an abnormally shaped left ventricle can be determined with high accuracy and low interobserver variability in patients with good or moderate echocardiographic image quality.

Harmonic 3-D echocardiography with a fast-rotating ultrasound transducer.

Although the advantages of three-dimensional (3-D) echocardiography have been acknowledged, its application for routine diagnosis is still very limited. This is mainly due to the relatively long acquisition time. Only recently has this problem been addressed with the introduction of new real-time 3-D echo systems. This paper describes the design, characteristics, and capabilities of an alternative concept for rapid 3-D echocardiographic recordings. The presented fast-rotating ultrasound (FRU)-transducer is based on a 64-element phased array that rotates with a maximum speed of 8 Hz (480 rpm). The large bandwidth of the FRU-transducer makes it highly suitable for tissue and contrast harmonic imaging. The transducer presents itself as a conventional phased-array transducer; therefore, it is easily implemented on existing 2-D echo systems, without additional interfacing. The capabilities of the FRU-transducer are illustrated with in-vitro volume measurements, harmonic imaging in combination with a contrast agent, and a preliminary clinical study.

Usefulness of contrast echocardiography for diagnosis of left ventricular noncompaction.

Many imaging modalities have been evaluated for the diagnosis of left ventricular noncompaction (LVNC). Echocardiography with color Doppler flow imaging is currently the diagnostic modality of choice. In this study, the usefulness of contrast echocardiography to diagnose LVNC was examined, and the diagnostic criteria were evaluated.

Comparison of all-cause mortality in women with known or suspected coronary artery disease referred for dobutamine stress echocardiography with normal versus abnormal test results.

The presence of myocardial ischemia during dobutamine stress echocardiography is independently associated with an increased risk of all-cause mortality in women after adjustment for clinical data. This association is observed in patients who have proved coronary artery disease and in patients who have no history of coronary artery disease.

Long-term prediction of mortality in elderly persons by dobutamine stress echocardiography.

BACKGROUND: Dobutamine stress echocardiography (DSE) was shown to provide incremental prognostic information. However, its role in the prediction of mortality in elderly persons is not well defined. We assessed the value of DSE in the prediction of mortality and hard cardiac events during long-term follow-up in patients older than 65 years. METHODS: We studied 1434 patients >65 years old (mean age 72 +/- 3 years) who underwent DSE for evaluation of coronary artery disease. Ischemia was defined as new or worsening wall motion abnormalities. Follow-up events were total mortality and hard cardiac events (cardiac mortality and nonfatal myocardial infarction). Multivariable Cox regression analysis was used to identify the independent predictors of follow-up events. RESULTS: Ischemia was detected in 675 patients (47%). Five hundred six patients (35%) had a normal study, and 253 (18%) had fixed wall motion abnormalities. During a mean follow-up of 6.5 years, 532 (37%) deaths occurred, of which 249 (17%) were due to cardiac causes. A nonfatal myocardial infarction occurred in 45 patients (3%). Independent predictors of all-cause mortality in a multivariate analysis model were age (hazard ratio [HR] 1.06; 95% confidence interval [CI], 1.05-1.08), male sex (HR 1.5; 95% CI, 1.2-1.8), hypertension (HR 1.2; 95% CI, 1.1-1.4), smoking (HR 1.3; 95% CI, 1.1-1.6), diabetes (HR 1.4; 95% CI, 1.1-1.8), rest wall motion abnormalities (HR 1.07; 95% CI, 1.06-1.09), and ischemia (HR 1.3; 95% CI, 1.1-1.6). Independent predictors of hard cardiac events were age (HR 1.07; 95% CI, 1.05-1.09), male sex (HR 1.3; 95% CI, 1.1-1.7), smoking (HR 1.3; 95% CI, 1.1-1.6), diabetes (HR 1.6; 95% CI, 1.2-2.2), rest wall motion abnormalities (HR 1.13; 95% CI, 1.12-1.16), and ischemia (HR 2.1; 95% CI, 1.5-2.8). CONCLUSION: DSE provides independent prognostic information to predict all-cause mortality and hard cardiac events in elderly patients.

Left ventricular volume estimation in cardiac three-dimensional ultrasound: a semiautomatic border detection approach.

RATIONALE AND OBJECTIVES: We propose a semiautomatic endocardial border detection method for three-dimensional (3D) time series of cardiac ultrasound (US) data based on pattern matching and dynamic programming, operating on two-dimensional (2D) slices of the 3D plus time data, for the estimation of full cycle left ventricular volume, with minimal user interaction. MATERIALS AND METHODS: The presented method is generally applicable to 3D US data and evaluated on data acquired with the Fast Rotating Ultrasound (FRU-) Transducer, developed by Erasmus Medical Center (Rotterdam, the Netherlands), a conventional phased-array transducer, rotating at very high speed around its image axis. The detection is based on endocardial edge pattern matching using dynamic programming, which is constrained by a 3D plus time shape model. It is applied to an automatically selected subset of 2D images of the original data set, for typically 10 equidistant rotation angles and 16 cardiac phases (160 images). Initialization requires the drawing of four contours per patient manually. We evaluated this method on 14 patients against MRI end-diastole and end-systole volumes. Initialization requires the drawing of four contours per patient manually. We evaluated this method on 14 patients against MRI end-diastolic (ED) and end-systolic (ES) volumes. RESULTS: The semiautomatic border detection approach shows good correlations with MRI ED/ES volumes (r = 0.938) and low interobserver variability (y = 1.005x - 16.7, r = 0.943) over full-cycle volume estimations. It shows a high consistency in tracking the user-defined initial borders over space and time. CONCLUSIONS: We show that the ease of the acquisition using the FRU-transducer and the semiautomatic endocardial border detection method together can provide a way to quickly estimate the left ventricular volume over the full cardiac cycle using little user interaction.