Katsufumi Mizushige

Leukocyte-Targeted Myocardial Contrast Echocardiography Can Assess the Degree of Acute Allograft Rejection in a Rat Cardiac Transplantation Model

Background—Repetitive endomyocardial biopsies are necessary to monitor the effects of immunosuppressants after cardiac transplantation. Contrast ultrasound with microbubble targeting of leukocytes detects acute leukocyte infiltration. We examined whether leukocyte-targeted myocardial contrast echocardiography (MCE) could provide for the quantitative assessment of acute cardiac rejection. Methods and Results—Hearts from Brown Norway rats or Lewis rats were transplanted into other Brown Norway rats. Isografts and groups of allografts either untreated or treated with cyclosporin A (CsA) at a low dose (3 mg · kg−1 · d−1) or high dose (10 mg · kg−1 · d−1) from 3 days before transplantation were compared at posttransplantation day 3. Echocardiography-derived left ventricular wall thickening was comparable among the 4 groups. Myocardial blood flow assessed with MCE, relating pulsing intervals with signal intensity (SI), was slightly decreased only in untreated allografts. However, myocardial SI (in gray levels) obtained after a 10-minute period allowing microbubble–leukocyte interactions after contrast injection exhibited a clear gradient in these groups (12±2 in untreated allografts, 9±5 in allografts treated with low-dose CsA, 6±3 in allografts treated with high-dose CsA, and 2±1 in isografts, P <0.001). The pattern of difference in SI among the groups agreed well with that in ED-1–positive cell (macrophage) count (25±7, 12±4, 5±3, and 1±0 cells per high-power field, respectively, P <0.001), which correlated with CD3-positive cell (T lymphocyte) count (33±5, 22±5, 9±4, and 1±0 cells per high-power field, respectively, P <0.001). Conclusions—Leukocyte-targeted MCE can noninvasively assess the degree of rejection in transplanted hearts by directly revealing the magnitude of intramyocardial infiltration of macrophages and T lymphocytes.

Assessment of right ventricular perfusion after right coronary artery occlusion by myocardial contrast echocardiography

OBJECTIVESnThe purpose of this study was to examine the ability of myocardial contrast echocardiography (MCE) to assess right ventricular (RV) perfusion.nnnBACKGROUNDnAlthough MCE can readily assess left ventricular perfusion abnormalities, there are no data regarding the ability to assess RV perfusion abnormalities.nnnMETHODSnThe right coronary artery (RCA) was occluded in 10 open-chest dogs. Myocardial contrast echocardiography was performed with 0.27 g/min Levovist infusion by harmonic power Doppler with electrocardiographically gated intermittent triggered imaging at pulsing intervals ranging from 1:1 to 1:20 at baseline and 90 min after RCA occlusion. Video-intensity of the RV wall was plotted against pulsing intervals and was fitted to an exponential function: y = A(1-exp(-bt)), where A is the plateau video-intensity and b is the rate of video-intensity rise. Myocardial contrast echocardiography and microsphere-derived myocardial blood flow (MBF) measurements were performed at baseline and 90 min after RCA occlusion.nnnRESULTSnBecause the severity of RV perfusion abnormalities assessed by MBF varied during RCA occlusion, diverse grades of patchy opacification defects were observed by MCE. The RV wall thickness decreased, and the RV dimension increased, after RCA occlusion in each dog. The correlation of occlusion to baseline MBF ratios in the RV wall was closer to the ratio of b (r = 0.897, p = 0.0004) than A (r = 0.767, p = 0.0097) and was the closest to the ratio of Axb (r = 0.935, p < 0.0001).nnnCONCLUSIONSnThe RCA occlusion is manifested by RV wall thinning and dilation as well as by perfusion abnormalities consisting of patchy opacification defects by MCE. Myocardial contrast echocardiography-derived refilling parameters can be applied to assess RV perfusion abnormalities produced by RCA occlusion.

Quantitative assessment of coronary stenosis by harmonic power Doppler with a simple pulsing sequence and vasodilator stress in patients.

OBJECTIVESnWe examined whether myocardial contrast echocardiography (MCE) with harmonic power Doppler (HPD) employing a simple ultrasound pulsing sequence enables estimation of the severity of coronary artery stenosis in patients.nnnBACKGROUNDnContrast intensity (CI) during MCE with intravenous microbubble infusion is dependent on the myocardial blood flow velocity (MBFV) and pulsing interval (PI).nnnMETHODSnBased on an in vitro experiment, we devised the MBFV index calculated as the reciprocal of the magnitude of CI decay produced by abrupt PI shortening during intermittent imaging. In 68 coronary artery territories from 49 patients, myocardial HPD images were acquired during intravenous infusion of Levovist, while the long PI with 1:10 electrocardiographic gating was shortened to 1:1, both at baseline and during adenosine triphosphate infusion. The MBFV index in each coronary territory and MBFV reserve as the ratio between hyperemia and baseline were compared with the severity of corresponding coronary artery stenosis assessed by quantitative coronary angiography (QCA) or by pressure guide wire as the fractional flow reserve (FFR).nnnRESULTSnBoth the MCE-derived MBFV index during hyperemia and MBFV reserve exhibited significant negative correlations with the QCA-derived stenosis severity (r = -0.56 and r = -0.64, respectively). The MBFV reserve positively correlated with FFR (r = 0.89). By combining the cutoff values of the MBFV index during hyperemia and MBFV reserve, > or =75% of stenoses defined by QCA were determined, with a sensitivity of 77.3%, specificity of 93.4%, and accuracy of 88.3%.nnnCONCLUSIONSnShortening of PI during intravenous MCE with intermittent HPD imaging under vasodilator stress enables assessment of coronary artery stenoses in patients.

Potential pitfalls of visualization of myocardial perfusion by myocardial contrast echocardiography with harmonic gray scale B-mode and power Doppler imaging

Objective: The present study compared the regional variation of myocardial signal intensity in visualizing myocardial perfusion by myocardial contrast echocardiography (MCE) between harmonic gray scale and power Doppler imaging. Methods: MCE was performed in 12 patients by electrocardiographic (ECG)-gated intermittent triggered MCE with harmonic gray scale and power Doppler imaging following slow intravenous injection of 0.5 ml contrast agent (Optison®). The interval between the ECG triggers (pulsing interval) was increased from every heart beat (1:1) to every 2 (1:2), 4 (1:4), and 8 (1:8) cardiac cycles to allow incremental microbubble (contrast agent) replenishment. The MCE images were recorded when attenuation produced by the left ventricular cavity was minimal. The background-subtracted videointensity was measured in 7 segments in an apical 4-chamber view: 3 (apical, mid, and basal) septal segments, 3 (apical, mid, and basal) lateral segments, and 1 apex segment (apical cap). Results: The background-subtracted videointensity for each segment was greater with the power Doppler than the gray scale imaging (p < 0.01). With the gray scale imaging, the background-subtracted videointensity in the basal septal segment demonstrated a negative value at all pulsing intervals, and the value (−9 ± 13) was significantly lower than that (22 ± 20) in the apical lateral segment at a pulsing interval of 1:8 (p < 0.01). With power Doppler imaging, the background-subtracted videointensity was high even in the basal septal segment (112 ± 33), and no significant difference was observed among each segment. Conclusions: The findings indicate that quantitative assessment of myocardial perfusion based upon background-subtracted videointensity may be difficult in the far field with harmonic gray scale imaging although the attenuation is not apparent by visual analysis. Harmonic power Doppler is more sensitive for detecting basilar perfusion in the far field compared with harmonic gray scale imaging.

Contrast transesophageal echocardiography in diagnosing congenital enlargement of the right atrium: A case report

Congenital malformation of the right atrium or the coronary sinus is rare, and cases are clas sified into 1 of the following 4 categories: (1) congenital enlargement of right atrium, (2) single diverticulum, (3) multiple diverticula of the right atrium, and (4) diverticulum of the coronary sinus. This report presents a 63-year-old man with cardiomegaly and no chest symptoms. A chest radiograph revealed an enlarged cardiac silhouette with a prominent right heart border. Although a transesophageal echocardiography revealed marked enlargement of the right atrium, neither further anomaly nor massive regurgitation was observed. The systolic pulmonary artery pressure derived from the peak velocity of mild tricuspid regurgitation was 38 mm Hg. Secondary enlargement of the right atrium due to atrial septal defect or pulmonary venous connection anomaly was deemed negligible by use of transesophageal contrast echocardiography, and primary enlargement of the right atrium was confirmed. Trans esophageal echocardiography using ultrasound contrast was determined to be feasible for diagnosing congenital malformation of the right atrium.

Effect of microbubble fragility on transit rate measurement by contrast echography

We sought to propose a simplified method to measure flow velocity based on ultrasonic microbubble destruction, and investigated the effect of microbubble shell fragility on such measurement. Acoustic density (AD) from the second harmonic short axis image of flow was obtained at variable velocities (2 to 73 mm/s) in an in vitro model during long (1000 ms) and short (33 ms) interval ultrasound (US) pulsing, allowing complete and partial microbubble replenishment between pulses, respectively. Microbubbles with shell elastic modulus of 0.4 MPa and 16 MPa were tested. By shortening pulsing interval, AD diminished gradually, rather than abruptly, to a plateau level for both microbubbles. The extent of AD decay was greater for the fragile than the strong microbubbles. A linear relationship existed between the magnitude of AD decay and flow velocity only in the higher and lower velocity range for the fragile and the strong microbubbles, respectively. Thus, difference in contrast intensities during long and short pulsing intervals, respectively, allowing complete and partial replenishment may provide for velocity measurement, in which choice of optimal microbubble fragility for the range of velocity to measure may increase the accuracy.

Spatial distribution of right ventricular perfusion abnormalities following acute right coronary artery occlusion: a study by myocardial contrast echocardiography and blue dye staining.

AbstractObjective: Although echocardiography is used for diagnosing right ventricular (RV) infarction produced by right coronary artery (RCA) nocclusion, there has been no data on the spatial distribution of RV perfusion abnormalities following acute RCA occlusion. We examined this distribution by myocardial contrast echocardiography (MCE) and blue dye staining in canine models. Methods: The RCA was occluded in 10 open-chest dogs. MCE was performed with 0.27 g/min Levovist infusion by harmonic power Doppler with electrocardiogram gated intermittent triggered imaging at baseline and at 90 min after RCA occlusion. The opacification defects were assessed at the basal, middle, and apical levels of the RV free wall by short-axis view. The extent of the risk area of the occluded RCA, expressed as a percentage of the RV free wall, was measured at each level by injecting blue dye at the end of the experiments. In 10 other dogs, the left anterior descending coronary artery (LAD) was occluded by ligating the proximal portion of the LAD to examine the territory of the LAD on the same levels of the RV free wall by injecting blue dye. Results: Although patchy opacification defects accompanying RV dilation were observed at the basal and middle levels during RCA occlusion, no apical defects were observed in any dogs by MCE. The risk area of the occluded RCA, as delineated by blue dye, was larger in the basal than apical level of the RV free wall in all 10 dogs (basal: 79 ± 9%; middle: 48 ± 14%; apical: 3 ± 6%, pxa0<xa00.0001). The risk area of the occluded LAD (basal: 17 ± 7%; middle: 12 ± 6%; apical: 6 ± 6%) was smaller than the risk area of the occluded RCA nat the basal and middle levels of the RV free wall (pxa0<xa00.0001), and no significant difference was observed at the apical level. Conclusions: RV perfusion abnormalities produced by RCA occlusion are larger in the basal than apical level of the RV free wall. This finding elucidates the spatial distribution of the territory of the RCA on the RV free wall, and may help in identifying and assessing RV ischemia by echocardiography in humans. Moreover, the data in the current study indicate that RV infarction may be produced by occlusion of the coronary arteries except RCA, because the territory of the LAD on the RV free wall is clearly delineated.

Difference of optimal dose of contrast agent between gray-scale and power Doppler imaging in assessing graded coronary stenosis by myocardial contrast echocardiography.

Rationale and Objectives:In myocardial contrast echocardiography (MCE), power Doppler imaging is more sensitive to contrast agent (microbubble) than gray-scale B-mode imaging; however, no data exist regarding the optimal contrast dose in power Doppler imaging. This study examined the optimal dose of contrast agent for power Doppler in assessing coronary stenosis. Methods:Three grades of coronary stenosis were produced in 6 open-chest dogs. MCE was performed with gray-scale and power Doppler during continuous infusion of 0.2 mL/min FS-069. Thereafter, MCE was repeated with power Doppler during continuous infusion of 0.1 mL/min FS-069. Results:Although the videointensity in the stenosed bed with power Doppler (214 ± 14) was greater than gray scale (35 ± 17) during 0.2 mL/min FS-069 infusion (P < 0.0001), power Doppler failed to identify milder coronary stenoses because videointensity in stenosed bed was quickly saturated with contrast agent. The videointensity in the stenosed bed with power Doppler (127 ± 49) during 0.1 mL/min FS-069 infusion was greater than gray scale (35 ± 17) during 0.2 mL/min FS-069 infusion (P < 0.0001), and all levels of stenosis were identified with power Doppler, even though the dose of contrast agent was half of that of gray scale imaging. The correlation between videointensity and myocardial blood flow was better in the case of power Doppler at 0.1 mL/min FS-069 infusion (r = 0.77, P < 0.0001) than in the case of gray scale imaging at 0.2 mL/min FS-069 infusion (r = 0.66, P < 0.01). Conclusions:These data support the need for a lower dose of contrast agent for power Doppler than for gray scale to detect milder coronary stenosis and avoid saturation of imaging fields.

A comparison of video and digital data in the assessment of myocardial perfusion abnormalities by myocardial contrast echocardiography.

Objective: The objective of the present study was to compare the digital and video data of myocardial contrast echocardiography (MCE) to assess altered myocardial blood flow produced by graded coronary stenoses. Methods: Three grades of left anterior descending (LAD) coronary artery stenosis and occlusion were created in eight open-chest canine models. MCE was performed with BR1 infusion by harmonic power Doppler with ECG gated intermittent triggered imaging at pulsing intervals ranging from 1:1 to 1:10. For images that were recorded simultaneously on both a videotape (video data) and an optical disk (digital data), myocardial signal intensity in the LAD region was plotted vs. pulsing intervals and was fitted to an exponential function:y=A(1 − e−bt), where A is the peak plateau signal intensity, and b is the rate of signal intensity rise for quantification of myocardial blood flow. Results: Both values for A and b progressively decreased with a greater level of stenosis. The correlation of A with myocardial blood flow (determined by use of fluorescent microspheres) was weak with digital data (r= 0.38, p= 0.037), and was insignificant with video data (r= 0.16, p= 0.38). The correlation of b with microsphere-derived myocardial blood flow was better than that of A with both video and digital data, and was similar between the two kinds of data (video:r= 0.69, p < 0.0001; digital:r= 0.68, p < 0.0001). Conclusions: Video and digital MCE data are equivalent in their ability to quantify altered myocardial blood flow produced by graded coronary stenoses.