Guidelines from the Japanese Society of Echocardiography: Guidance for the management and maintenance of echocardiography equipment.

Echocardiography plays a pivotal role as an imaging modality in modern cardiology practice. Information derived from echocardiography is definitely helpful for patient care. The Japanese Society of Echocardiography has promoted echocardiography in routine clinical and research use. One of the missions of the Society is to provide information that is useful for high-quality examinations. To ensure this, we believe that equipment in good condition and a comfortable environment are important for both patient and examiner. Here, the Guideline Preparation Committee of the Japanese Society of Echocardiography has established brief guidance for the routine use of echocardiography equipment.

Inhibition of HIF-1alpha by the anticancer drug TAS106 enhances X-ray-induced apoptosis in vitro and in vivo.

In a previous study, we showed that a novel anticancer drug, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (TAS106, ECyd) increased the antitumour efficacy of X-irradiation. However, its effects on hypoxic cells in tumours remain unclarified. Here, we show that TAS106 enhances the induction of apoptosis in X-irradiated human gastric adenocarcinoma MKN45 and MKN28 cells under hypoxia in vitro. At the same time, the accumulation of HIF-1alpha observed under hypoxia was shown to be decreased to the level of normoxia in the presence of 0.1 microM TAS106. To study the function of HIF-1alpha protein in apoptosis of hypoxic cells, we employed an HIF-1alpha reductive approach using its specific antisense oligodeoxynucleotide. The reduction of HIF-1alpha gene expression dramatically enhanced X-ray-induced apoptosis in hypoxic cells. In in vivo experiments in which MKN45 cells were transplanted into severe combined immunodeficient (SCID) mice, TAS106 (0.5 mg kg(-1)) suppressed HIF-1alpha expression and subsequently reduced the area of the hypoxic region in the tumour and enhanced the induction of apoptosis in the hypoxic region when combined with 2 Gy of X-irradiation. These results suggest the possibility that TAS106 acts as a potent radiosensitiser through the inhibition of HIF-1alpha expression and can be a useful agent against radiotherapy-resistant hypoxic cells in solid tumours.

Radiofrequency spectral analysis of attenuated ultrasound signals in experiments with echo contrast microbubbles.

Conventional gray-scale myocardial contrast echocardiography cannot distinguish perfused but attenuated from nonperfused myocardium because both may appear similar at low image intensity. We hypothesized that with radiofrequency spectral analysis of attenuated ultrasound signals, the harmonic-to-fundamental frequency ratio of the peak power spectrum (HFR(P)) could determine the presence of contrast microbubbles. We measured frequency responses of Optison microbubbles at defined degrees of ultrasound signal attenuation with different formulations of silicone (55D, 80A, and 3M); gray-scale intensities of Optison plus water compared with degassed water were analyzed at different attenuation settings (-25, -32, and -44 dB, respectively). HFR(P) values of Optison plus water were significantly higher than reference values of degassed water at each attenuation setting (55D, -14 +/- 2 dB versus -30 +/- 2 dB, P <.001; 80A, -19 +/- 2 dB versus -30 +/- 3 dB, P <.01; 3M, -22 +/- 2 dB versus -30 +/- 3 dB, P <.05), even though conventional videodensitometric analysis could not distinguish them. HFR(P) analysis objectively detects microbubbles in clinically relevant conditions of attenuation.

Doppler echocardiography-derived index of myocardial performance (TEI index): comparison with brain natriuretic peptide levels in various heart disease.

Plasma brain natriuretic peptide (BNP) has diagnostic and prognostic value in heart failure. Cardiac dysfunction varies from systolic or diastolic dysfunction alone to the combination of both. In the present study, Doppler echocardiographic parameters, including the Doppler echocardiography-derived index (TEI index), were compared with plasma BNP levels in 74 patients with various heart diseases. Blood sampling was performed before an echocardiographic examination was conducted. The TEI index was defined as the summation of isovolumic contraction and relaxation time divided by ejection time. In patients with left ventricular (LV) systolic dysfunction (ejection fraction <50%), the TEI index and BNP were increased significantly compared with patients with normal LV systolic function (p<0.05). Patients with a TEI index > or =0.45 showed significantly increased BNP levels compared with patients with a TEI index <0.45, irrespective of LV systolic function (241.4+/-451.2 vs 65.9+/-81.8pg/ml; p<0.05). The TEI index was significantly higher in patients with a BNP > or =73pg/ml than in patients with BNP <73pg/ml (0.57+/-0.24 vs 0.46+/-0.17; p<0.05). Other echocardiographic parameters did not correlate significantly with levels of plasma BNP. Of the echocardiographic parameters, a simple Doppler index (TEI index) that combines systolic and diastolic function can detect LV dysfunction in patients with high levels of plasma BNP in various heart diseases.

Three-dimensional magnetic resonance imaging of lung and liver tumors in mice by use of transversal multislice magnetic resonance images.

PURPOSE: To diagnose lung and liver tumors experimentally induced in mice in three-dimensional magnetic resonance (MR) images constructed by superimposing transversal multislice MR images of thoracic and abdominal regions taken under a high magnetic field of 7.05 tesla (T). METHODS: Lung and liver tumors were induced by administration of urethane to A/J mice and implantation of transplantable colon-26 cells into BALB/c mice, respectively. Two-dimensional (2-D) multislice MR images from the thoracic to abdominal regions were taken under the proton density-weighted conditions. Each organ in the 2-D MR images was pseudocolored, and a three-dimensional (3-D) image was constructed by superimposing them on a UNIX computer, using volume-rendering software. RESULTS: In the normal mouse, each organ in the thoracic and abdominal regions was three-dimensionally imaged and was clearly distinguished from the others. In mice with tumors in the lung or liver, the pathologic changes in the tissue could be visualized in 3-D images. CONCLUSIONS: The MR images three-dimensionally constructed by use of a method combining MR imaging under a high magnetic field of 7.05 T and a computer technique using volume-rendering software was useful for diagnosis of lung and liver tumors experimentally induced in mice.

Vibro-acoustography: quantification of flow with highly-localized low-frequency acoustic force.

The intersection of two ultrasound beams with slightly different frequencies results in generation of a localized radiation force and stimulates emission of audio signals from targeted objects. Vibro-acoustography uses this phenomenon to probe elastic properties of objects. Vibro-acoustography of contrast microbubbles in degassed water produced quantitative flow measurements from analysis of their acoustic emission. We used a dual-beam transducer generating bursts of 40-kHz vibrations. The vibrations resulted from interference of 3.48-MHz and 3.52-MHz confocal beams intersecting at the center of a thin plastic conduit. We tested flows of 13,48, 85, and 120 mL/min of contrast microbubbles at concentrations from 1.2 x 10(5) to 6 x 10(9) bubbles/mL. The amplitude of the acoustic emission was linear with microbubble concentrations up to a value of 3.6 x 10(5) bubbles/mL. A replenishment method for microbubble contrast and flow rate analysis was used with radiation force bursts deployed at 0.05, 0.1, 0.2, (.5, 1, and 2-second pulsing intervals. The relation between the pulsing intervals and the peak amplitude was fitted by an exponential curve and a rate constant calculated for each tested flow rate. The rate constant values were linearly correlated with the tested flows. The vibro-acoustography method provides objective, quantitative, and highly-localized assessment of flow using contrast microbubbles.

Fatal cardiac rupture: a case of subepicardial aneurysm after myocardial infarction.

We report a case in which 2-dimensional echocardiography established the diagnosis of a left ventricular subepicardial aneurysm that was followed by rupture and sudden death before surgery. Two-dimensional echocardiography is of great help in detecting this rare complication after myocardial infarction. Urgent surgical treatment is warranted for this condition.

Beneficial effect of combination therapy with ozagrel and pranlukast in exercise-induced asthma demonstrated by krypton-81 m ventilation scintigraphy--a case report.

INTRODUCTION: We evaluated the effect of combination therapy with thromboxane A2 synthesis inhibitor and leukotriene receptor antagonist in a patient with exercise-induced asthma using krypton-81 m ventilation scintigraphy. CLINICAL PICTURE: In a patient with exercise-induced asthma, we found exercise-induced abnormalities of respiratory function test and ventilation scintigraphy, and increases in plasma concentrations of thromboxane B2 and leukotriene C4 with exercise. TREATMENT: A thromboxane A2 synthesis inhibitor (ozagrel) and a leukotriene receptor antagonist (pranlukast) were prescribed. OUTCOME: After treatment for 2 weeks, abnormalities of respiratory function test and ventilation scintigraphy improved. CONCLUSIONS: The combination therapy with ozagrel and pranlukast might be useful for the relief of symptoms in patients with exercise-induced asthma, and krypton-81 m ventilation scintigraphy could be a useful tool for visible evaluation of treatment.

Clinical significance of perfusion imaging of the left atrial wall and structures in its cavity by contrast echocardiography.

This study examined whether myocardial contrast echocardiography (MCE) can visualize left atrial appendage myocardial perfusion using transesophageal echocardiography (TEE) with intracoronary injection of sonicated albumin. We also evaluated blood flow into normal structures (i.e. muscular trabeculae) and abnormal masses (i.e. fresh thrombi and myxomas) within the left atrium by MCE. TEE images were obtained with a biplane or multiplane 5 MHz transducer in 16 patients without significant coronary artery occlusive disease. Left atrial appendage myocardium was divided into 4 segments in both the transverse and longitudinal planes, and contrast opacification of each segment during MCE was visually evaluated by 2 independent observers. Visual assessment of contrast opacification of prominent muscular trabeculae within the left atrial appendage (6 patients), and of left atrial or left atrial appendage thrombi (4 patients), was also performed. The ratio of background-subtracted peak videointensity from muscular trabeculae or thrombi versus left atrial appendage myocardium was determined as corrected peak videointensity. In 3 patients with myxomas, contrast opacification of the tumor was visually assessed. Ninety-six segments of left atrial appendage myocardium were visually analyzed. Contrast opacification of the left atrial appendage myocardium was identified in 92 of 96 segments (96%, 95% confidence interval 0.90-0.98) by Observer 1 and in 91 of 96 segments (95%, 95% confidence interval 0.88-0.98) by Observer 2. MCE also enhanced the imaging of left atrial appendage muscular trabeculae, but not of left atrial or left atrial appendage thrombi. Corrected peak videointensity from thrombi was significantly lower than that from muscular trabeculae (0.15 +/- 0.11 vs 0.95 +/- 0.18, p < 0.05). All myxomas were distinctly opacified by MCE. Transesophageal MCE with intracoronary injection of sonicated albumin can image left atrial appendage myocardial perfusion. MCE allows the evaluation of blood flow into normal structures and abnormal masses within the left atrium.

MR imaging of hepatic injury in the LEC rat under a high magnetic field (7.05 T).

Visualization of copper-induced hepatitis (CuH) in LEC rats was performed by using an MRI apparatus equipped with a magnet producing a high magnetic field of 7.05 T. When three groups of LEC rats (6-16 [pre-hepatitis], 15-26 [acute hepatitis] and 40-77 [chronic hepatitis] weeks old) were examined by MRI under T2-weighted imaging conditions which are suitable for the diagnosis of human hepatitis, hypointense MR images of the livers were, as a whole, obtained in all groups, suggesting that these conditions were not adequate for imaging of CuH of LEC rats. The shortening of the T1 and T2 relaxation times of livers due to an excess amount of paramagnetic irons under the high magnetic field was responsible for the lowering of MR signal intensities of the livers, especially those of 15 to 26-week old rats showing acute hepatitis. However, theoretical calculation of the MR signal intensities using the T1 and T2 relaxation times of the livers indicated that their imaging might be possible under proton density-weighted conditions even with a high magnetic field. Experimental results showed that hepatic injury was visualized as hyperintense regions in the MR image of the liver in the acute-phase rat.

Differential diagnosis of left ventricular mural thrombi by myocardial contrast echocardiography: a preliminary study.

Two-dimensional echocardiography has become the procedure of choice to diagnose left ventricular mural thrombi. However, small or flat thrombi may be difficult to distinguish from myocardium. The spatial distribution of the ventricular myocardial blood flow can be imaged with myocardial contrast echocardiography (MCE). The authors presumed that the absence of arterial supply to a fresh thrombus may allow MCE to distinguish between thrombus and myocardium. In the 2 cases presented here, MCE was performed with the same technique as that used for the purpose of visualization of myocardial perfusion; as a result, an apical mural thrombus, indistinct from myocardium before MCE, was visualized as a contrast defect during imaging. Conversely, myocardium that mimicked a thrombus was imaged by MCE as a contrast-opacified area. These findings suggest that MCE after reperfusion therapy is useful to distinguish mural thrombi from myocardium.

[Endothelial-derived nitric oxide mediates the peripheral vasodilatory effects of amrinone in humans].

Amrinone, which is used for the treatment of acute congestive heart failure, has vasodilatory and positive inotropic effects through the increment of intracellular cyclic adenosine monophosphate. Recent in vitro investigations have shown that amrinone has an endothelium-dependent vasodilatory effect. The present study examined whether amrinone shows this endothelium-dependent vasodilatory effect in human peripheral vessels. Forearm blood flow during intra-arterial infusion of graded doses (12.5, 25, 50, 100, 200 micrograms/min) of amrinone was measured using plethysmography in 10 healthy subjects without organic vascular disease before and after nitric oxide synthase blocking with NG-monomethyl-L-arginine (L-NMMA, 400 mumol). The graded dose of amrinone produced progressive increases in amrinone plasma concentrations, and a dose over 100 micrograms/min caused amrinone plasma concentrations of more than 1.0 microgram/ml. The increase in forearm blood flow in response to amrinone was significantly depressed after L-NMMA doses of less than 100 micrograms/min, but the increase in forearm blood flow during infusion of higher doses (100, 200 micrograms/min) was not affected by L-NMMA. These results suggest that endothelial-derived nitric oxide may partially contribute to amrinone-induced vasodilation in humans. Thus, the vasodilatory effect of amrinone might be impaired in patients with endothelial dysfunction.

Improved visualization of the left atrial appendage by transthoracic 2-dimensional tissue harmonic compared with fundamental echocardiographic imaging.

We compared fundamental and tissue harmonic transthoracic echocardiographic imaging for the delineation of the left atrial appendage (LAA) in 32 subjects. The LAA images recorded in the parasternal short-axis view were divided into 4 segments and 2 observers independently graded for each segment using a visual scoring system ranging from 0 to 3 (0 = no, 3 = clearly visible over the entire length of the segment). For the 128 segments, the averaged segment scores were significantly increased after switching to harmonic imaging (1.32 +/- 0.69 versus 1.60 +/- 0.81 for fundamental and tissue harmonic imaging, respectively; P <.0005 for observer 1, and 1.38 +/- 0.65 versus 1.61 +/- 0.82, respectively; P <.001 for observer 2). In a patient with LAA thrombus, the image contrast of the thrombus was improved in harmonic compared with fundamental imaging. These data suggest that tissue harmonic imaging significantly improves image quality of the LAA.

Intravascular ultrasound evaluation of plaque distribution at curved coronary segments.

Although the distribution of atherosclerosis at the curved coronary segments has implications for atherogenesis and interventional procedures, few data exist regarding the plaque distribution in these sites. Therefore, we prospectively analyzed the intravascular ultrasound images of 55 coronary sites from 37 patients where the atherosclerotic plaque and pericardium were simultaneously demonstrated by intravascular ultrasound. The pericardial images were defined as a high-intensity linear echo image moving during cardiac cycles outside the vessel wall. By the line that was parallel to the pericardial image, the vessel area was divided into 2 semicircles with the same area, namely myocardial and pericardial sides. In each side, the maximal thickness, area, and percent area of plaque were measured. The plaque thickness and area of the myocardial side were significantly greater (1.5 +/- 0.5 mm, 4.9 +/- 2.1 mm or 66%, mean +/- SD) than those of the pericardial side (1.1 +/- 0.4 mm, 3.5 +/- 2.1 mm2 or 45%, p < 0.01). The maximal plaque thickness was positioned at the point with a mean angle of 139 +/- 37 degrees from the point just facing the pericardial image, indicating that atherosclerosis was eccentrically located on the opposite side of the pericardium in these coronary segments, and suggesting that the side of the pericardial image represents the outer curvature of the coronary artery. These results indicate that the pericardial images can be seen by intravascular ultrasound, facilitating the recognition of the disease distribution in situ. The eccentric plaque located on the inner wall at the curved coronary segments, probably due to uneven local shear stress, may have implications for the interventional procedures for these segments.

Visualization of the topographical structure of the anesthetized mouse brain by MR microimaging.

A nuclear magnetic resonance (NMR) spectrometer equipped with a magnet producing a high and extremely uniform magnetic field (7.05 T) was combined with a strong field gradient coil (3.5 mT/cm) and applied to MR microimaging of the mouse brain to visualize its topographical structure. Since the proton-density-weighted condition (long repetition time (TR) and short echo time (TE); TR/TE = 3,000 ms/10.4 ms) was found to be the most suitable for imaging the mouse brain, mid-sagittal and coronal sections in 1-mm- or 0.3-mm-thick slices were imaged according to the multislice spin echo sequence with 2 or 8 acquisitions, a 2 kHz pulse width and a 256 x 256 data matrix. As expected, the resolution of MR microimaging was comparable to that of the histological sections. The white matter especially, could be distinguished from the gray matter in some regions of the brain. Coronal sections of the brain also showed that the hippocampal CA1-CA3 regions were distinguishable from the other regions. The results suggested that the present MR microimaging technique might be a useful tool for the study of topological anatomy and submicroscopic research using brains of small laboratory animals.

Relationship between progressive microvascular damage and intramyocardial hemorrhage in patients with reperfused anterior myocardial infarction: myocardial contrast echocardiographic study.

BACKGROUND: Recent studies indicated that ischemic microvascular damage may be reversible or progressive after coronary reflow. Intramyocardial hemorrhage is a phenomenon that reflects severe microvascular injury. We examined the relationship between temporal changes in microvascular perfusion patterns detected by myocardial contrast echocardiography (MCE) and intramyocardial hemorrhage detected by magnetic resonance imaging (MRI) in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The study population consisted of 24 patients with anterior AMI. All patients underwent MCE shortly after reflow and in the chronic stage (a mean of 31 days after reflow). Wall motion score (WMS) was determined as the sum of 16 segmental scores (dyskinetic/akinetic=3 to normal=0) at days 1 and 31. Gradient-echo acquisition and gadolinium-DTPA-enhanced spin-echo MRI were performed within 10 days after reflow. In MCE shortly after reflow, 16 patients (67%) showed contrast enhancement and the other 8 patients (33%) showed a sizable contrast defect. In the chronic stage, a persistent contrast defect was observed in 7 of 8 patients with a contrast defect shortly after reflow. Consistent contrast enhancement was observed in 12 of 16 patients (75%) with contrast enhancement shortly after reflow, indicating that a contrast defect newly appeared in 4 patients (25%). Intramyocardial hemorrhage was detected in 9 patients (38%): 5 of 7 patients with a persistent contrast defect and in all 4 patients with a new appearance of a contrast defect during the chronic stage. The patients without hemorrhage showed a significant improvement in WMS compared with patients with hemorrhage at day 31 (5+/-5 versus 19+/-6, P<.0005). CONCLUSIONS: These results suggest that irreversible microvascular damage to the ischemic myocardium may cause intramyocardial hemorrhage after reflow, associated with impaired recovery of left ventricular function. Contrast enhancement within the risk area shortly after reflow does not necessarily indicate long-term microvascular salvage.

Enhanced expression of lipocortin-1 as a new immunosuppressive protein in cancer patients and its influence on reduced in vitro peripheral blood lymphocyte response to mitogens.

To clarify the mechanism of immunosuppression in cancer-bearing hosts, the expression of lipocortin-1 (LC1), a new immunosuppressant, and its effects on the in vitro mitogen responsiveness of peripheral blood mononuclear cells (PBMC) were investigated in cancer patients. Immunohistochemical studies showed LC1 expression in the cytoplasm of inflammatory cells morphologically recognized as a macrophage lineage, infiltrating the tumor interstices of gastric cancer. LC1 protein was detected in the ascitic fluid from gastric cancer patients using Western blot analysis. LC1 expression in PBMC was studied using a fluorescence-activated cell sorter (FACScan), which revealed that the percentage of CD14 and LC1 double positive cells was much greater in cancer patients than in healthy individuals. The proliferative response of PBMC by concanavalin A (ConA) stimulation was significantly suppressed in patients with advanced cancer, while the intact mitogen responsiveness in healthy individuals was inhibited when recombinant LC1 was added to the cultures. A similar inhibitory effect was induced by adding the supernatant of cancerous ascites or spleen cell cultures derived from advanced cancer patients. These inhibitory effects were eliminated, and the suppressed mitogen responsiveness in cancer patients recovered to the control level of healthy individuals when anti-LC1 antibody was added to the cultures. These findings indicate that LC1 is produced and expressed in cancer patients, and deeply involved in the immunosuppressive mechanism of tumor-bearing hosts.

Prediction of outcome of electrical cardioversion by left atrial appendage flow velocities in atrial fibrillation.

We evaluated the usefulness of left atrial appendage (LAA) flow velocity during atrial fibrillation as an objective measure for prediction of the outcome of electrical cardioversion. Left atrial appendage peak velocities were measured by transesophageal echocardiography before cardioversion in 56 patients. Left atrial thrombus was demonstrated in 6 (11%) of these patients. Cardioversion was then performed in the 50 patients who did not have a thrombus and in 1 patient whose left atrial thrombus disappeared after anticoagulant therapy (n = 51). Thirty-eight patients converted to sinus rhythm which remained stable until discharge (initial success group). Of these, long-term (> 6 months) maintenance of sinus rhythm was achieved in 31 patients (82%). Five patients with almost no detectable appendage contractions during atrial fibrillation were classified in the initial failure group. The peak LAA flow velocity was significantly higher in patients with the initial success group compared with the patients in the initial failure group (25.6 +/- 12.0 vs 15.3 +/- 10.7 cm/s, respectively; p < 0.01). Left atrial appendage flow velocity during atrial fibrillation may be useful for identifying candidates for electrical cardioversion.

Magnetic resonance imaging of hepatocellular carcinoma in Long-Evans cinnamon rats under a magnetic field of 7.05 T.

Magnetic resonance (MR) images of livers in 3-, 12- and 29-month-old Long-Evans Cinnamon(LEC) rats (male) were taken under a magnetic field of 7.05 T. MR images of sagittal and transversal sections were obtained in 1-mm-thick slices by T1-weighted and two-dimensional Fourier transformation techniques. The data matrix size was 256 phase-encoded steps. Each image was obtained through four acquisitions. Three-month-old rats gave MR images with low signal intensity over the liver probably due to the shorting of its T1 and T2 relaxation times. However, 12-month-old rats gave hyperintense regions around hepatic veins in right hepatic lobe, which was assigned to hepatocellular carcinoma. In 29-month-old rats, MR images with hyperintensity throughout the hepatic lobe were observed. These MR images, therefore, suggested that hepatocellular carcinoma in LEC rats developed from the restricted regions surrounding hepatic veins. In the present study, T1-weighted MR imaging under a magnetic field of 7.05 T was shown to be applicable to the diagnosis of hepatic cancer in LEC rats.