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PubMed1998

Can cerebrovascular microemboli induce cognitive impairment in patients with prosthetic heart valves?

Doppler ultrasonography can be used to detect the presence of emboli in the cerebral arterial circulation. Emboli can be produced by different sources and can be of different nature: solid elements as thrombi, platelet aggregates or atheromatous material, or gaseous when they are produced during the decompression phase of diving or during extracorporeal circulation (ECC) procedures. A more recent source of emboli has been found in the mechanical prostheic heart valves (MHV). The emboli generated by MHV are likely of gaseous nature and are found in the middle cerebral artery blood flow at a variable rate, where they are detected by transcranial Doppler sonography. The mechanism of production of these microbubbles may be related to the rapid leaflet motion especially at closure when very high local pressure gradients appear, which may be able to provoke a release of the disolved blood gas. Solid element emboli constitute a major cause of cerebrovascular disease and particularly stroke. Conversely, gaseous emboli coming from ECC or MHV are considered as clinically silent. Nevertheless, cognitive alterations have been reported after ECC. As the MHV carriers are chronically submitted to embolic events, it can be assumed that cognitive impairments may occur also in these patients. A preliminary study was designed to inpatients attention and memory in patients with normally functioning MHV and microemboli, with biological prosthesis and in normal subjects. In the two groups of patients, episodic memory was significantly altered relatively to the control group. In the MHV carriers group, a significant decrease in working memory performance was observed relatively to the two other groups. These results confirm a long term effect of the microembolization occuring during ECC and point out the effect of the chronic exposition to microemboli.

Bioprosthesis↗

PubMed1998

Investigation of peripheral arterial disease--the expanding role of echo-enhanced color flow doppler and duplex sonography.

Contrast angiography is widely regarded as the gold standard investigation in peripheral artery disease (PAD). It produces images that are diagnostically valuable, but is limited by its inability to image the vessel walls or the dynamics of blood flow in the lumen. Color duplex sonography is increasingly used in PAD to replace or pre-empt angiography. It is a simple non-invasive technique that gives information about both structural and dynamic anomalies in the peripheral arteries, with an accuracy close to that of angiography. Certain situations are difficult to visualize using this technique. Arteries that are deep-lying, calcified, obscured by fat or bowel gas, or that contain low-velocity blood flow, will generate sub-optimal scans due to inadequate returning signal strength. This can be corrected by the use of microbubble echo-enhancing agents, which increase the strength of the returning signal, generating a clear image from which a diagnosis can be made. Results of multicenter studies of echo-enhanced color duplex sonography in PAD are reviewed and the impact of the technique on the diagnostic work-up of PAD is assessed.

Algorithms↗

PubMed1998

Portohepatic vascular pathology and liver disease: diagnosis and monitoring.

A number of diseases alter the normal pathophysiology of the portohepatic vascular system. The impact of these changes depends on the severity of the disease and the involvement of the entrahepatic vasculature. Cirrhosis of the liver is not a vascular disease but the effects on the liver architecture result in severe disease often accompanied by hepatic vascular changes. Alcohol abuse and viral infections are the most common causes of cirrhosis. Portal hypertension (PHT) is one of the most frequently seen sequelae of liver cirrhosis. It results in the formation of porto-systemic collateral channels which may lead to varices and hemorrhage. Primary liver cancer is also strongly associated with liver cirrhosis. Hepatocellular carcinoma (HCC) is the most common liver cancer seen in patients with cirrhosis. There are four types of HCC based on its growth patterns: infiltrative, expansive, mixed and diffuse. Raised plasma levels of alpha-fetoprotein are a characteristic of HCC. However, this marker is unreliable in patients with smaller tumors. Ultrasound is an inexpensive, non-invasive and safe diagnostic technique used to detect portal vein changes in PHT and to identify HCC lesions in the liver. Grey scale ultrasound reveals the portal vein changes and the portal-systemic collaterals which typify PHT. The technique is most useful for diagnosis or confirmation of moderate to severe disease. HCC nodules have characteristic ultrasound patterns which help in differential diagnosis. Doppler ultrasound provides functional as well as anatomical information about blood flow in the liver and is especially useful in detecting HCC and the abnormal blood vessel architecture which surrounds a tumor. However, despite their usefulness, both imaging techniques have limitations which may be improved by the use of echo-enhancing agents. Levovist(R) is a galactose-based microbubble echo-enhancing agent which has an excellent safety profile and utility in enhancing ultrasound images of the liver. It markedly improves diagnostic confidence and reduces the percentage of non-diagnostic ultrasound scans in patients with abnormal liver pathologies. The use of echo-enhanced ultrasound to diagnose liver disease may obviate the need for more expensive and invasive diagnostic procedures.

Blood Flow Velocity↗

PubMed2002

Functional ultrasound methods in oncological imaging.

The real time nature of ultrasound and functional methods such as Doppler ultrasound mean that ultrasound can claim to have always been a functional imaging method, but recent developments in quantitation, dramatic improvement in Doppler performance and now microbubbles have created many exciting new applications. These include methods for assessing the neovascularity of tumours, for following the effects of therapy and for predicting the likelihood of development of metastatic disease at the staging of primary tumours.

Contrast Media↗

PubMed2002

Patent foramen ovale: a cause of significant post-coronary artery bypass grafting morbidity.

We describe two patients who underwent coronary artery bypass grafting complicated by postoperative hypoxemia due to a patent foramen ovale with right-to-left shunting. We discuss different hypotheses to explain the shunt: decreased right ventricular compliance, right atrial geometric changes due to septal distension or ischemia, exceeding filling pressure and localised haemorragic pericardial tamponade and low atrial pressure when correcting aortic stenosis. We emphasize the close interplay of pericardectomy and the four cardiac chambers including the distortion of the heart axis. The contrast echo produced by microbubbles of air is the safest and the most accurate procedure to detect the shunt. The two patients progressed positively with an extracorporeal circulation of short duration and without complications linked to the intervention. We conclude that postoperative unexplained hypoxemia must always exclude diagnosis of right-to-left shunting due to a patent foramen ovale (PFO).

Aged↗

PubMed1997

Systematic surgical closure of patent foramen ovale in selected patients with cerebrovascular events due to paradoxical embolism. Early results of a preliminary study.

OBJECTIVE: To define therapeutic strategy for management of patients with ischemic stroke due to a high probability of paradoxical embolism through a Patent Foramen Ovale (PFO). METHODS: Since 1988 all consecutive patients with cerebrovascular events and PFO from the Stroke Registry of our population-based primary-care center are prospectively studied and followed. Since 1992, among 118 patients with cryptogenic embolic brain infarct or transient ischemic attack (TIA) and PFO, 32 consecutive patients younger than 60 years who presented at least two of the following criteria were admitted for surgery: history of Valsalva strain before stroke (11); multiple clinical events (13); multiple infarcts on brain Magnetic Resonance Imaging (MRI) (15); atrial septal aneurysm (ASA) (16); large right-to-left shunt (> 50 microbubbles) (12). RESULTS: Operative time 135' +/- 33'. CPB time 34' +/- 14'. Aortic crossclamping time 16' +/- 6'. Post-operative bleeding 485 +/- 170 ml. No homologous blood transfusion required. No neurological, cardiac or renal complications. All patients were followed-up corresponding to a cumulative time of 601 patient-months. This revealed no recurrent vascular events nor silent new brain lesions on brain MRI. Systematic simultaneous contrast Trans Esophageal Echocardiography (TEE)-Trans Cranial Doppler showed a small residual interatrial shunt in two patients. CONCLUSION: Surgical closure of a patent foramen ovale can be accomplished with very low morbidity and reduce efficiently the risk of stroke recurrence. It seems to be the option of choice in selected patients with a higher (> 1.5%/year) risk of stroke recurrence.

Adult↗

PubMed2000

Relative ultrasonographic echogenicity of standard, dimpled, and polymeric-coated needles.

PURPOSE: To use quantitative ultrasonographic measurements to compare the effect of a polymeric coating designed to increase needle echogenicity to commercially available needles. MATERIALS AND METHODS: Commercially available standard smooth and dimpled echogenic tip 21-gauge needles established reference levels of echogenicity in gelatin-based and turkey breast phantoms. Examples of both types of needles were coated with a thin polymeric film that utilizes entrapped microbubbles of air on its surface to increase echogenicity. Samples of each type in both coated and noncoated versions were placed in phantoms in matched positions and imaged with clinical ultrasound machines. Similar numbers of each category were evaluated at various angles of insonation for a total of 109 images. Similar numbers of each category were imaged at 5-minute intervals for up to 38 minutes for a total of 226 images. Images were recorded, digitized, and evaluated for relative echo strength in arbitrary echogenic brightness units. RESULTS: Coating increased peak echogenicity over the entire needle to a level that closely approximates the peak echogenicity of dimpled needle tips (means: dimpled = 834, coated smooth = 803, coated dimpled = 823; P = .54). Smooth is lower than this group at 468 (P = .0001). Representative area echogenicity increased with coating or dimpling (smooth = 377 vs coated smooth = 778, coated dimpled = 690, dimpled = 775; P = .0001). Coating increased peak values 74% and area values 95% compared to smooth. Decreased angles of insonation moderately reduced echogenicity on coated smooth, coated dimpled, and dimpled, while it decreased to below good visibility threshold on standard smooth needles. The echogenicity of the coated needles fades in saline with time (1%/min). CONCLUSION: Objective measurements show that this coating significantly increases echogenicity of entire needles to match that obtained with a dimpled tip.

Animals↗

PubMed2003

Transcatheter closure of residual atrial septal defect after cardiac transplantation.

A 55-year-old male patient experienced 2 acute neurologic events 3 weeks after orthotopic cardiac transplantation. Transesophageal echocardiography demonstrated a patent foramen ovale in the native portion of the interatrial septum with bidirectional shunting by Doppler and microbubble contrast. The defect was closed successfully with a CardioSeal transcatheter septal closure device. This case demonstrates the advantages of the percutaneous approach for closure of residual defects in the post-operative patient.

Cardiac Catheterization↗

PubMed2001

Contrast-enhanced B-mode US angiography in the assessment of experimental in vivo and in vitro atherosclerotic disease.

RATIONALE AND OBJECTIVES: This study was performed to (a) test the hypothesis that filling the arterial lumen with echoes at B-mode ultrasound (US) enables the assessment of wall and luminal abnormalities and (b) compare contrast material-enhanced B-mode US with color and power Doppler US angiography. MATERIALS AND METHODS: Atherosclerotic lesions were created in 14 rabbit aortas and imaged with color Doppler and B-mode US before and after the intravenous administration of 0.3 mL of AF0150, a US contrast agent. In addition, four replicas of diseased human carotid arteries were immersed in a tissue-mimicking phantom and imaged with B-mode and color and power Doppler US before and after the administration of 1 mL of AF0150 per liter of porcine blood. Radiopaque plastic casts of the rabbit aortas and contact radiographs of the plastic replicas served as standards. RESULTS: Although color and power Doppler US allowed immediate localization of the lumen, precise estimation of stenoses and reliable visualization of surface irregularities were not possible. After AF0150 administration, angiogram-like images of the lumen were created with B-mode US, allowing rapid assessment of the entire vessel lumen and wall. Consequently, luminal stenoses were more accurately measured than with unenhanced B-mode US (r2 = 0.94, P < .0001 vs r2 = 0.21, P = .25) or Doppler (r2 = 0.42, P < .03). In addition, plaques and ulcerations were visible only with contrast-enhanced B-mode US. CONCLUSION: Microbubbles fill the arterial lumen with echoes at B-mode US, creating an angiogram-like image. The ability to visualize the inner and outer surfaces of the vascular wall improved the evaluation of luminal and wall abnormalities.

Animals↗

PubMed2003

Evaluation of liver parenchymal blood flow with contrast-enhanced US: preliminary results in healthy and cirrhotic patients.

RATIONALE AND OBJECTIVES: To determine whether changes in hepatic parenchymal blood flow in cirrhotic patients can be evaluated with contrast-enhanced ultrasound (US) after Levovist administration. MATERIALS AND METHODS: Ten normal volunteers, 16 Child A and 16 Child C cirrhotic patients were evaluated with contrast-enhanced US. Frames obtained at progressively increasing pulse intervals of 2, 4, 7, and 10 seconds in the same scan plane during infusion of Levovist (300 mg/mL, 150 mL/h) have been digitally recorded. Pulse intervals versus signal intensity (PI-SI) plots were fitted to a straight line whose slope is proportional to the speed of blood in the liver parenchyma. Enhancement differences in late phase have been evaluated measuring the SI after 7 minutes from the beginning of the infusion. RESULTS: The slope of the PI-SI plot of the Child A cirrhotic patients was significantly lower than the slope of the normal controls (P < 0.05); conversely, no significant differences were found between the slope of the patients with Child C cirrhosis and that of the normal controls. In comparison with the normal subjects, the average SI at late phase decreased significantly both in patients with Child A (P < 0.05) and Child C (P < 0.001) cirrhosis. CONCLUSION: Microbubble contrast agents could provide a noninvasive tool to detect and monitor hemodynamic changes that occur in the cirrhotic liver. Changes in the hepatospecific properties at late phase have also been demonstrated.

Aged↗

PubMed2003

US characterization of focal hepatic lesions with intermittent high-acoustic-power mode and contrast material.

RATIONALE AND OBJECTIVES: This study was performed to determine whether ultrasound (US) performed with SonoVue, a contrast agent that contains microbubbles filled with sulfur hexafluoride vapor, depicts differential patterns of contrast enhancement in focal hepatic lesions. MATERIALS AND METHODS: Forty focal hepatic lesions (15 hepatocellular carcinomas [HCCs], 10 metastases, 11 hemangiomas, and four focal nodular hyperplasias) in 39 patients were evaluated by means of US, color Doppler US, and contrast-enhanced US performed by using intermittent high-acoustic-power mode. Contrast-enhanced helical computed tomography (11 patients) and US-guided fine needle aspiration (28 patients) were used as reference procedures. Contrast enhancement patterns were defined by means of both subjective and objective analysis, and baseline and contrast-enhanced US scans were reviewed offline. RESULTS: Thirteen of 15 HCCs, eight of 10 metastases, and all four hemangiomas with an atypical pattern at baseline US were correctly characterized after SonoVue injection. Two of 15 HCCs and two of 10 metastases remained indeterminate, with no characteristic baseline or contrast-enhanced patterns identified. Baseline US was essential in characterizing all hemangiomas with a typical pattern (n = 7), and color Doppler US with spectral analysis of tumoral vessels was essential in characterizing focal nodular hyperplasia. The percentage of diagnostic agreement with reference procedures was significantly increased (P < .001) for contrast-enhanced US compared with baseline US. CONCLUSION: Characteristic patterns of US contrast enhancement with SonoVue help in characterizing and differentiating focal hepatic lesions.

Carcinoma, Hepatocellular↗

PubMed1997

Radiofrequency tissue ablation with a cooled needle in vitro: ultrasonography, dose response, and lesion temperature.

RATIONALE AND OBJECTIVES: Radiofrequency (RF) tissue ablation with a cooled needle electrode (probe) can produce large lesions. By using this technique on ex vivo calf livers, the authors evaluated the role of ultrasound (US), dose response, and temperature course with time. METHODS: RF ablation was produced with a 14-gauge probe with a 2-cm exposed tip. The lesions were examined with US and macroscopically after various treatment durations. Tissue temperature was measured with thermosensors inserted 1, 2, and 3 cm from the probe. RESULTS: Before treatment the tip of the probe was easy to visualize with US, but treatment microbubbles obscured the lesion and probe. After treatment, the lesions appeared hypoechoic. Lesion size was underestimated based on US findings. Lesion size was logarithmically correlated to treatment duration. Lesion temperature increased at an increased rate with higher wattage applied and with decreased distance from the probe. CONCLUSION: US is useful for probe placement before treatment and might be of value after treatment. Lesion size increases reproducibility with treatment duration.

Animals↗

PubMed1997

Use of intravenous contrast material in transcranial sonography.

RATIONALE AND OBJECTIVES: The appearance of the intracranial vasculature was compared on power and color Doppler ultrasound (US) scans obtained with and without a microbubble contrast agent. MATERIALS AND METHODS: Nine patients (three men, six women) aged 42-70 years (mean age, 53 years) participated in the study. Seven patients underwent both color Doppler US and power Doppler US before and after intravenous administration of contrast agent, and two underwent only color Doppler US. All patients had previously undergone cerebral angiography. RESULTS: Before contrast material was administered, power Doppler US was more sensitive than color Doppler US in the detection of intracranial vessels (P < .05); neither technique depicted the entire circle of Willis in eight of nine patients. Postcontrast power Doppler US depicted more vascular segments than postcontrast color Doppler US (P < .01) or precontrast power Doppler US (P < .01). Use of intravenous contrast material enabled the entire circle of Willis to be evaluated from a single temporal bone acoustic window with both power Doppler US and color Doppler US in all patients. Contrast-enhanced power Doppler US depicted vessels not shown by enhanced color Doppler US. CONCLUSION: Contrast-enhanced power Doppler US depicted more vessels, better demonstrated specific vascular segments, and provided better vascular definition of the intracranial vasculature than contrast-enhanced color Doppler US or unenhanced power Doppler US.

Adult↗

PubMed2001

Detection of tumor parenchymal blood flow in hepatic tumors: value of second harmonic imaging with a galactose-based contrast agent.

Purpose. To evaluate the detectability of tumor vascularity in hepatic tumors by second harmonic imaging with the administration of a microbubble contrast agent, Levovist. Materials and methods: Twenty-four patients with hepatic tumors (21 hepatocellular carcinoma, one focal nodular hyperplasia and two liver metastasis) were studied using Aloka SSD 5500 with the administration of Levovist. Intermittent harmonic gray-scale imaging (HGSI) and intermittent harmonic power Doppler imaging (HPDI) were performed on every tumor and the detectability of the two harmonic imaging modes were compared with that of dynamic CT. Results: Tumor vessels and tumor parenchymal blood flow were obtained in hypervascular tumors in the early arterial phase, and metastasis presented peripheral enhancement. When dynamic CT was taken as a gold standard, the sensitivity, specificity and accuracy of detecting tumor vascularity for intermittent HGSI were 55.6, 100 and 66.7%, and for intermittent HPDI were 83.3, 100 and 87.5%, respectively. The difference of detectability between the two modes was statistically significant (P<0.05). Depth of the lesion from the abdominal wall was a major factor affecting the detectability of tumor vascularity. Conclusion: With the administration of Levovist, intermittent HPDI was more sensitive than intermittent HGSI to demonstrate tumor vessels and tumor blood flow. Second harmonic imaging with Levovist would be a promising valuable means for investigating specific vascular features in hepatic tumors.

Journal Article↗

PubMed2003

Evaluation of hemodynamics in esophageal varices. Value of endoscopic color Doppler ultrasonography with a galactose-based contrast agent.

Endoscopic color Doppler ultrasonography (ECDUS) is a useful modality for obtaining color flow images of esophageal varices. Levovist is a microbubble echo-enhancing agent, which improves Doppler ultrasound examination. In this paper, we compared vessel images detected with pre-contrast with those detected by enhanced ECDUS using Levovist in 62 patients with esophageal varices. Color flow images of esophageal varices and paraesophageal veins by pre-contrast ECDUS were obtained in 62 (100%) of the 62 patients. Vessel images of perforating veins were obtained in 48 (77.4%) of the 62 patients with pre-contrast ECDUS. The perforating veins were classified into three types according to the flow direction. Type 1 showed in-flow from the paraesophageal veins to the esophageal varices, Type 2 showed out-flow from the esophageal varices to the paraesophageal veins, and Type 3 was a mixed type showing both in-flow and out-flow. After Levovist contrast, color flow images detected with pre-contrast ECDUS were improved in all patients. Color flow images of perforating veins were obtained in 60 (96.8%) of the 62 patients by enhanced ECDUS using Levovist. Pre-contrast-diagnosed Type 2 patterns had been re-diagnosed as Type 3 in five patients, and three cases with Type 1 had been relabeled as Type 3 pattern using Levovist. The use of Levovist contrast can improve the diagnostic quality of ECDUS examinations of esophageal variceal patients, yielding a much clearer picture of the hemodynamics.

Journal Article↗

PubMed2004

Clinical application of quantitative analysis in real-time MCE.

The introduction of stable microbubble contrast agents and technological advances have recently made it feasible to perform quantitative measurements of microvascular damage by myocardial contrast echocardiography (MCE). Qontrast is a new software system far such measurements. It includes physiological filters, global rescale, regional rescale, automatic myocardial tracking, manual ECG trigger and parametric imaging. Qontrast was tested on 5 pigs given sulphur hexafluoride bubbles (I ml/min) and fluorescent microspheres (reference) after the induction of 50% and 100% stenosis of left anterior descending coronary artery. The image sequences were repeated four times using different ultrasound (US) equipment. A close correlation was found between the ratio risk area/control area by microspheres and the equivalent ratio risk area/control area (Sl x beta) by MCE, being approximately 0.9 far any contrast modality tested. Parametric MCE and SPELT were compared in 12 patients with recent myocardial infarction, including 119 segments. Agreement amounted to 83% (kappa: 0.53 far peak SI and 0.55 far SI x beta). The sensitivity and specificity of peak SI far detecting abnormal segmental tracer uptake were 67% and 88%; the values far Sl x beta were 70% and 87%. Parametric MCE is a promising imaging technique far the assessment of myocardial perfusion in patients with suspected or known coronary artery disease.

Animals↗

PubMed2005

Rapidly prototyped three-dimensional nanofluidic channel networks in glass substrates.

Microfluidic and nanofluidic technologies have long sought a fast, reliable method to overcome the creative limitations of planar fabrication methods, the resolution limits of lithography, and the materials limitations for fast prototyping. In the present work, we demonstrate direct 3D machining of submicrometer diameter, subsurface fluidic channels in glass, via optical breakdown near critical intensity, using a femtosecond pulsed laser. No postexposure etching or bonding is required; the channel network (or almost any arbitrary-shaped cavity below the surface) is produced directly from "art-to-part". The key to this approach is to use very low energy, highly focused, pulses in the presence of liquid. Microbubbles that result from laser energy deposition gently expand and extrude machining debris from the channels. These bubbles are in a highly damped, low Reynolds number regime, implying that surface spalling due to bubble collapse is unimportant. We demonstrate rapid prototyping of three-dimensional "jumpers", mixers, and other key components of complex 3D microscale analysis systems in glass substrates.

Glass↗

PubMedDate not supplied

Tailoring of physical and chemical properties of macro- and microhydrogels based on telechelic PVA.

Poly(vinyl alcohol), PVA, is amenable to several structural modifications because of the presence of the hydroxyl moiety in the backbone. The chemical versatility of this polymer can be used for the obtainment of new wall-to-wall pH-responsive PVA chemical hydrogels and for the preparation of air-filled microspheres, for example, microbubbles. Here, we report on the characterization of the physical and chemical properties of these novel networks that can be potentially used in different biomedical applications as controlled drug delivery and as ultrasonic contrast agent.

Hydrogels↗