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Renal cortical ischemia in rabbits revealed by contrast-enhanced power Doppler sonography.

OBJECTIVE: Our goals were to describe and quantify redistribution of renal cortical blood flow during systemic hypotension in rabbits using contrast-enhanced power Doppler sonography and to explore the feasibility of creating real-time regional blood flow maps of the kidney. MATERIALS AND METHODS: Mild, moderate, and severe systemic hypotension (70%, 50%, and 40% of baseline measurements, respectively) were induced by controlled exsanguination in nine anesthetized rabbits. Sagittal power Doppler sonograms of the kidney were obtained during and after i.v. injection of 0.2 ml per kilogram of body weight of an experimental microbubble-based contrast agent. Doppler sonograms were analyzed for anatomic distribution of contrast agent and changes in mean pixel intensity over time. Cortical time-intensity curves were drawn and the area under the curve was compared with regional renal blood flow as measured by radiolabeled microspheres using linear regression in eight of the nine rabbits during graded hypotension. RESULTS: Graded hypotension resulted in increasing thickness of the nonperfused peripheral cortex (p < .001 by analysis of variance) with preservation of deeper cortical flow on enhanced Doppler sonograms. Other changes included decreased peak enhancement ratios and area under the curve values (p < .0001) and increased time to peak enhancement for cortex (p < .01). We found a strong correlation between cortical area under the curve and regional renal blood flow (r = .86, p < .0001). These changes were not shown without contrast enhancement. CONCLUSION: Peripheral cortical perfusion is disproportionately affected during systemic hypotension. Contrast-enhanced power Doppler sonography shows potential for depicting changes in regional renal blood flow in real time and without radiation.

Animals↗

Contrast-enhanced sonography of vesicoureterorenal reflux in children: preliminary results.

OBJECTIVE: The aim of our study was to evaluate contrast-enhanced sonography as an alternative to radiographic voiding cystourethrography in the detection of vesicoureteral reflux. SUBJECTS AND METHODS: A total of 46 children, ranging in age from 3 weeks to 14 years (median: 4 years, 6 months) with 92 ureterorenal units were investigated for reflux using radiographic voiding cystourethrography and contrast-enhanced sonography in one session. After sonography of the urinary tract, the bladder was filled with saline solution via a catheter. Later, a contrast-enhancing agent was instilled and sonography was repeated. Documentation was done using S-VHS video and a laser camera. Reflux was diagnosed when microbubbles were observed in the ureter or in the renal pelvis. In addition, conventional voiding cystourethrography was performed. Patients without micturition during either sonography or radiographic examination were excluded (eight ureterorenal units). RESULTS: The findings obtained by contrast-enhanced sonography and voiding cystourethrography were concordant in 78 ureterorenal units (92.9%). No reflux was detected in 67 units (79.8%) by either method. With voiding cystourethrography as the standard of reference, the sensitivity of contrast-enhanced sonography was 91.7%; the specificity, 93.1%; and the accuracy, 92.9%. The positive predictive value was 68.8%, and the negative predictive value was 98.5%. CONCLUSION: Contrast-enhanced sonography is highly sensitive for the detection of vesicoureteral reflux. Therefore, it may reduce the number of radiographic investigations.

Child, Preschool↗

Tumor vascularity of breast lesions: potentials and limits of contrast-enhanced Doppler sonography.

OBJECTIVE: We investigated improving the evaluation of benignity in breast lesions using Doppler sonography with galactose palmitic acid-coated microbubbles. SUBJECTS AND METHODS: In 77 patients with 84 breast tumors scheduled for surgical tumor removal, color-coded duplex sonography was performed before and after administration of Levovist. Of the 77 patients, 25 with 28 lesions had been treated for prior breast carcinoma. The parameters investigated were the following: degree of enhancement, number of tumor vessels, time to maximum enhancement, and the pattern of vascular morphology and course. RESULTS: Findings in malignant tumors (n = 53) showed a greater number of vessels and a faster stronger enhancement after Levovist administration, whereas a definite partial overlap with results from benign tumors (n = 31) was found. The best distinction was produced by vascular morphology and course, with a sensitivity of 90% and a specificity of 81 %. In 23 of the 25 patients who previously underwent surgery, a clear distinction was possible between a postoperative scar (n = 11) and a tumor recurrence (n = 17). CONCLUSION: Although administration of the contrast agent clearly improved evaluation of benign features on Doppler sonography, absolute certainty cannot be achieved. The feasibility of making an otherwise difficult distinction between a scar and tumor recurrence on sonography and mammography appears to be promising, but further studies are necessary.

Breast Neoplasms↗

Radiofrequency thermal ablation of hepatocellular carcinoma: using contrast-enhanced harmonic power doppler sonography to assess treatment outcome.

OBJECTIVE: We evaluated the accuracy of contrast-enhanced harmonic power Doppler sonography in assessing the outcome of radiofrequency thermal ablation of hepatocellular carcinoma. SUBJECTS AND METHODS: Fifty patients with 65 hepatocellular carcinoma nodules (1-5 cm in diameter; mean diameter, 2.5 cm) were studied using unenhanced and contrast-enhanced harmonic power Doppler sonography before and after IV administration of a microbubble contrast agent. The examinations were repeated after treatment of the tumors with radiofrequency ablation. Findings of the Doppler studies were compared with those of dual-phase helical CT, which were used as points of reference for assessing treatment outcome. RESULTS: Before radiofrequency treatment, intratumoral blood flow was revealed by unenhanced power Doppler sonography in 48 (74%) of 65 hepatocellular carcinoma nodules. After injection of the contrast agent, intratumoral enhancement was observed in 61 (94%) of 65 hepatocellular carcinomas (p < 0.01). After radiofrequency treatment, all 51 (84%) of the 61 hepatocellular carcinomas found to be necrotic on helical CT scans failed to show enhancement on power Doppler sonograms. In nine of the 10 lesions that showed a residual viable tumor on helical CT scans, persistent intratumoral enhancement-matching the enhancing areas on helical CT images-was revealed by power Doppler sonography. These nine hepatocellular carcinomas were subjected to repeated radiofrequency thermal ablation with the guidance of contrast-enhanced power Doppler sonography. Complete necrosis was seen after the second treatment session in six of the nine lesions. CONCLUSION: Contrast-enhanced harmonic power Doppler sonography is an accurate technique for assessing the outcome of radiofrequency thermal ablation of hepatocellular carcinoma and may be useful in guiding additional treatment in patients with incomplete response to initial efforts.

Aged↗

Impact of the continuous infusion of Levovist on color Doppler sonography in portal hypertension.

OBJECTIVE: This study was undertaken to investigate to what extent continuous infusion of a galactose-based microbubble contrast agent (Levovist) allows evaluation of the portal vascular system in patients with portal hypertension and for whom baseline unenhanced color Doppler sonography was nondiagnostic. SUBJECTS AND METHODS: We performed color Doppler sonography at baseline and during IV Levovist infusion (4 g, 300 mg/min). First, we measured the duration of portal vein visualization during Levovist infusion in 15 patients in whom unenhanced color Doppler sonography failed to show the portal confluence from a subcostal view. This duration of improved portal conspicuity was termed "diagnostic window." We then compared in 30 patients enhanced color Doppler sonographic findings with conventional imaging methods, including portography (n = 14), helical CT (n = 4), or gadolinium-enhanced MR angiography (n = 12), and we recorded the investigator's confidence in the color Doppler sonographic result before and after Levovist infusion. RESULTS: The diagnostic window achieved by the Levovist infusion was 13.6 +/- 0.9 min. At baseline, color Doppler sonography was nondiagnostic in 19 patients. The diagnostic confidence level was low in all the remaining 11 patients. During Levovist infusion, color Doppler sonography remained nondiagnostic only in two of 30 patients. The confidence level was low in five patients and high in 23 patients. In 26 of these 28 patients, echo-enhanced color Doppler sonographic findings were confirmed by reference methods. CONCLUSION: The continuous infusion of Levovist achieved a sufficient echo enhancement from the portal vascular bed and allowed a valid diagnostic color Doppler sonographic examination in portal hypertensive patients for whom color Doppler sonography would otherwise be nondiagnostic.

Adult↗

Radiofrequency ablation of hepatocellular carcinoma: therapeutic response using contrast-enhanced coded phase-inversion harmonic sonography.

OBJECTIVE: This study was performed to evaluate the usefulness of contrast-enhanced coded phase-inversion harmonic sonography in assessing the therapeutic response of percutaneous radiofrequency ablation in patients with hepatocellular carcinoma. SUBJECTS AND METHODS: Sixty-seven patients with a total of 107 examinations on 91 hepatocellular carcinoma nodules underwent coded harmonic angio, a technique of coded phase-inversion harmonic sonography, using the IV microbubble contrast agent Levovist before and after percutaneous radiofrequency ablation. The intratumoral blood vessels and tumor parenchymal stain were detected in the early arterial phase and the late vascular phase, respectively. The results of contrast-enhanced imaging with coded harmonic angio were compared with those of three-phase dynamic CT. RESULTS: Before treatment, all examined 107 hepatocellular carcinoma nodules were found to be hypervascular on contrast-enhanced imaging with coded harmonic angio. After radiofrequency ablation, contrast-enhanced coded harmonic angio detected persistent signal enhancement in 41 examined nodules (38.3%), whereas this technique showed no intratumoral enhancement in the remaining 66 (61.7%) examined nodules. Compared with dynamic CT, the sensitivity, specificity, and diagnostic accuracy of contrast-enhanced coded harmonic angio were 95.3%, 100%, and 98.1%, respectively. With contrast-enhanced coded harmonic angio, we found that it was difficult to identify the safety margin that can be detected on dynamic CT. CONCLUSION: Contrast-enhanced imaging with coded harmonic angio may provide an alternative approach that has high diagnostic agreement with dynamic CT in assessing the therapeutic effect of radiofrequency ablation in hypervascular hepatocellular carcinomas, in spite of having limitations in identifying the safety margin.

Aged↗

Characterization of focal liver lesions in real time using harmonic imaging with high mechanical index and contrast agent levovist.

OBJECTIVE: The aim of this study was to characterize focal hepatic lesions using agent detection imaging and Levovist. MATERIALS AND METHODS: Sixty-five patients (21 male and 44 female; age range, 8-82 years; mean +/- standard deviation, 58.1 +/- 14.5 years) were independently evaluated by two observers in a blinded manner using stored sonographic images. Seventy-five lesions were found: 15 hepatocellular carcinomas, nine focal nodular hyperplasias, two adenomas, 21 hemangiomas, 23 metastases, and five regenerative nodules. Nine patients were excluded (six because of technical failures, three with unproven diagnoses). New high-mechanical-index software was used to reveal power harmonic responses from contrast microbubble destruction. After a venous bolus injection of 4 g of Levovist at a strength of 400 mg/mL, delayed imaging was used to study lesion enhancement in the arterial, portal, and parenchymal phases. Two comparisons were made. The first was between the B-mode image and the first contrast-enhanced image after the flash. The second was between color Doppler sonograms and real-time contrast-enhanced perfusion images. RESULTS: Contrast-enhanced images after the flash and real-time contrast-enhanced images revealed more information for the characterization of the lesion than did gray-scale and color Doppler images (p < 0.0001, Wilcoxon's signed rank test). Different types of lesions showed statistically significant differences in enhancement during each of the three vascular phases (p < 0.005, Kruskal-Wallis test). Lesions with lower contrast enhancement were metastases and regenerating nodules. Good agreement was present between the two observers; differences were not statistically significant (p > 0.05). CONCLUSION: Agent detection imaging with Levovist increased diagnostic confidence in the characterization of focal hepatic lesions as compared with standard sonography.

Adolescent↗

Oral glucosamine for 6 weeks at standard doses does not cause or worsen insulin resistance or endothelial dysfunction in lean or obese subjects.

Glucosamine is a popular nutritional supplement used to treat osteoarthritis. Intravenous administration of glucosamine causes insulin resistance and endothelial dysfunction. However, rigorous clinical studies evaluating the safety of oral glucosamine with respect to metabolic and cardiovascular pathophysiology are lacking. Therefore, we conducted a randomized, placebo-controlled, double-blind, crossover trial of oral glucosamine at standard doses (500 mg p.o. t.i.d.) in lean (n = 20) and obese (n = 20) subjects. Glucosamine or placebo treatment for 6 weeks was followed by a 1-week washout and crossover to the other arm. At baseline, and after each treatment period, insulin sensitivity was assessed by hyperinsulinemic-isoglycemic glucose clamp (SI(Clamp)) and endothelial function evaluated by brachial artery blood flow (BAF; Doppler ultrasound) and forearm skeletal muscle microvascular recruitment (ultrasound with microbubble contrast) before and during steady-state hyperinsulinemia. Plasma glucosamine pharmacokinetics after oral dosing were determined in each subject using a high-performance liquid chromatography method. As expected, at baseline, obese subjects had insulin resistance and endothelial dysfunction when compared with lean subjects (SI(Clamp) [median {25th-75th percentile}] = 4.3 [2.9-5.3] vs. 7.3 [5.7-11.3], P < 0.0001; insulin-stimulated changes in BAF [% over basal] = 12 [-6 to 84] vs. 39 [2-108], P < 0.04). When compared with placebo, glucosamine did not cause insulin resistance or endothelial dysfunction in lean subjects or significantly worsen these findings in obese subjects. The half-life of plasma glucosamine after oral dosing was approximately 150 min, with no significant changes in steady-state glucosamine levels detectable after 6 weeks of therapy. We conclude that oral glucosamine at standard doses for 6 weeks does not cause or significantly worsen insulin resistance or endothelial dysfunction in lean or obese subjects.

Administration, Oral↗

Evaluation of quantified contrast-enhanced color and power Doppler ultrasonography for the assessment of vascularity and perfusion of naturally occurring tumors in dogs.

OBJECTIVE: To investigate subjective and computerized methods of evaluation of color Doppler (CD) and power Doppler (PD) ultrasonographic images (obtained before and after administration of contrast medium) for quantitative assessment of vascularity and perfusion of various naturally occurring tumors in dogs. SAMPLE POPULATION: 34 tumors in 34 dogs. PROCEDURE: Tumors in dogs were examined via CD and PD ultrasonography before and after i.v. injection of a microbubble contrast agent (pre- and postcontrast examinations, respectively). Images were digitized for subjective assessment of vessel density and vascular pattern and computer-aided assessment of parameters of vascularity (fractional area [FA]) and perfusion (color-weighted FA [CWFA] and mean color-weighted FA [CWFA] and mean color level). RESULTS: With both analysis methods, more vessels were identified in precontrast PD ultrasonographic images than in precontrast CD ultrasonographic images. Moreover, compared with values for precontrast PD ultrasonography, FA, CWFA, and mean color level were higher for postcontrast PD ultrasonography. In postcontrast images, there was a significant association between vessel densities determined through subjective and computerized assessments. Although sample size was small, vascularity of squamous cell carcinomas was significantly greater than that of other tumor types. Ten of the 19 softer than issue that sarcomas had low vessel density with minor contrast enhancement. With increasing gross tumor volume, FA and CWFA decreased for all Doppler ultrasonographic methods. CONCLUSIONS AND CLINICAL RELEVANCE: Higher values of the ultrasonographic parameters representing vascularity and perfusion of tumors in dogs were determined via PD ultrasonography after administration of contrast medium than via PD or CD ultrasonography without administration of contrast medium.

Animals↗

Real-time contrast-enhanced specific ultrasound in staging and follow-up of splenic lymphomas.

From January 2003 to April 2005 we studied 25 lymphoma patients (10 with HD, 4 with low-grade NHL, 6 with high-grade NHL and 5 with chronic lymphatic leukaemia; 14 men, 11 women, age range 28-79 years). After a baseline US study we rapidly injected 4.8 mL of the second-generation microbubble contrast agent SonoVue (Bracco, Italy). Contrast enhanced studies were carried out with the contrast-specific software named Contrast Tuned Imaging (Esaote, Italy) using a continuous, harmonic acquisition and a low acoustic pressure. The CS-US findings were correlated with results of standard tools, including CT, MRI, US follow up. CS-US revealed correctly 47 out of the 52 lesions identified by CT scan, in the absence of false positive findings (sensitivity = 90%; Specificity = 100%, in comparison to CT scan). Complete concordance in evaluating the lesion extension of the CS-US in respect to CT was 88%, while underestimate occurred in 9% and overestimate in 3% of cases. On the contrary, basic sonography defined correctly the dimensional alteration in 52% of the cases, underestimated in 35% and overestimated in 13%, thus showing significantly lower accuracy (chi-square = 30.0, p < 0.001). In our experience, CS-US was superior to conventional sonography even from a qualitative point of view.

Adult↗

Gas bubble detection in fluid lines by means of pulsed Doppler ultrasound.

A pulsed Doppler instrument running at 1.5 MHz resonance frequency was used for detection of microbubbles within a recirculating fluid line. Glass beads of nominal 200 microns were injected to get a statistical calibration level of the set-up. This is achieved by identifying the peak intensity of the bubble size histogram which reflected the microsphere size.

Gases↗

Detection of hepatic VX2 tumors in rabbits: comparison of conventional US and phase-inversion harmonic US during the liver-specific late phase of contrast enhancement.

OBJECTIVE: To compare phase-inversion sonography during the liver-specific phase of contrast enhancement using a microbubble contrast agent with conventional B-mode sonography for the detection of VX2 liver tumors. MATERIALS AND METHODS: Twenty-three rabbits, 18 of which had VX2 liver tumor implants, received a bolus injection of 0.6 g of Levovist (200 mg/ml). During the liver-specific phase of this agent, they were evaluated using both conventional sonography and contrast-enhanced phase-inversion harmonic imaging (CEPIHI). Following sacrifice of the animals, pathologic analysis was performed and the reference standard thus obtained. The conspicuity, size and number of the tumors before and after contrast administration, as determined by a sonographer, were compared between the two modes and with the pathologic findings. RESULTS: CE-PIHI demonstrated marked hepatic parenchymal enhancement in all rabbits. For VX2 tumors detected at both conventional US and CE- PIHI, conspicuity was improved by contrast-enhanced PIHI. On examination of gross specimens, 52 VX2 tumors were identified. Conventional US correctly detected 18 of the 52 (34.6%), while PIHI detected 35 (67.3%) (p < 0.05). In particular, conventional US detected only three (8.3%) of the 36 tumors less than 10 mm in diameter, but CE-PIHI detected 19 such tumors (52.8%) (p < 0.05). CONCLUSION: Compared to conventional sonography, PIHI performed during the liver-specific phase after intravenous injection of Levovist is markedly better at detecting VX2 liver tumors.

Animals↗

Focal hepatic lesions: evaluation with contrast-enhanced gray-scale harmonic US.

OBJECTIVE: To determine the findings of various focal hepatic lesions at contrast-enhanced gray-scale ultrasound (US) using a coded harmonic angio (CHA) technique and emphasizing lesion characterization. MATERIALS AND METHODS: The study involved 95 patients with 105 focal hepatic lesions, namely 51 hepatocellular carcinomas (HCCs), 22 metastases, 22 hemangiomas, four cases of focal nodular hyperplasia (FNH), and six nontumorous nodules. After the injection of a microbubble contrast agent (SH U 508A), gray-scale harmonic US studies using a CHA technique were performed with a combination of continuous scanning to assess the intratumoral vasculature (vascular imaging) and interval-delay scanning to determine the sequential enhancement pattern (acoustic emission imaging). Each imaging pattern was categorized and analyzed. RESULTS: At vascular imaging, 69% of HCCs (35/51) showed irregular branching vessels, while in 91% of metastases (20/22) a peripherally stippled pattern was observed. Intratumoral vessels were absent in 95% of hemangiomas (21/22) and all nontumorous lesions (6/6), while in 75% of FNHs (3/4) a spoke-wheel pattern was evident. At acoustic emission imaging, 71% of HCCs (36/51) showed heterogeneous enhancement and 86% (19/22) of metastases showed rim- or flame-like peripheral enhancement during the early phase, with washout occurring in all HCCs and metastases (100%, 73/73) during the late phase. In hemangiomas, enhancement was either peripheral and nodular (19/22, 86%) or persistent and homogeneous (3/22, 14%), and 75% of FNHs (3/4) became isoechoic during the late phase. CONCLUSION: At contrast-enhanced gray-scale US using a CHA technique, a period of continuous scanning depicted the intratumoral vasculature, and interval-delay scanning demonstrated the sequential enhancement pattern. The characteristic findings of various focal hepatic lesions were thus determined.

Carcinoma, Hepatocellular↗

Grey scale enhancement of rabbit liver and kidney by intravenous injection of a new lipid-coated ultrasound contrast agent.

AIM: To assess the grey scale enhancement of a new lipid-coated ultrasound contrast agent in solid abdominal organs as liver and kidney. METHODS: Size distribution and concentration of the lipid-coated contrast microbubbles were analyzed by a Coulter counter. Two-dimensional (2D) second harmonic imaging of the hepatic parenchyma, the inferior vena cava and the right kidney of the rabbits were acquired before and after contrast agent injection. Images were further quantified by histogram in Adobe Photoshop 6.0. Time-intensity curves of hepatic parenchyma, inferior vena cava and renal cortex were generated from the original grey scale. RESULTS: The 2D images of hepatic parenchyma and cortex of the kidney were greatly enhanced after injection and the peak time could last more than 50 min. CONCLUSION: This new lipid ultrasound contrast agent could significantly enhance the grey scale imaging of the hepatic parenchyma and the renal cortex for more than 50 min.

Animals↗

Renal perfusion imaging using contrast-enhanced phase-inversion ultrasound.

AIMS: We evaluated different techniques of contrast-enhanced phase-inversion ultrasound to visualize renal perfusion in native kidneys and kidney transplants. MATERIALS AND METHODS: Contrast-enhanced phase inversion ultrasound with different levels of mechanical index and frame rate was performed in 20 kidneys of 13 healthy volunteers. In addition, five dysfunctioning kidneys of patients with chronic renal failure, five functionally intact kidney transplants, three kidney transplants with compensated renal failure, and two kidney transplants with acute rejection were studied. Analysis using a software algorithm for time-resolved perfusion imaging was compared to single-image analysis performed by three independent radiologists. RESULTS: Optimal depiction of renal perfusion was achieved only by using a mechanical index, which was high enough to destroy the microbubbles of the contrast agent (burst imaging) combined with a low frame rate (0.5 images/second). Renal cortex and medulla showed a homogeneous enhancement in kidneys of healthy volunteers and functionally intact renal transplants. Dysfunctioning kidneys of patients with chronic renal failure as well as kidney transplants with compensated renal failure or acute rejection showed a significantly reduced level of enhancement. Computer-assisted time-resolved perfusion analysis was not superior to single-image analysis. CONCLUSION: Renal perfusion patterns of normal and abnormal tissue can be visualized using contrast-enhanced phase-inversion ultrasound imaging.

Adult↗

Determination of ejection fraction from contrast echocardiography using videodensitometry in an in vitro model.

To examine whether ejection fraction can be estimated by videodensitometric analysis of contrast washout from a chamber, a model was constructed consisting of a 60-ml syringe and a modified Harvard respirator. Ejection fraction could be adjusted mechanically. Echocardiographic images were recorded on videotape and analyzed on an offline computerized analysis system. To calibrate the relationship between target concentration and videodensity on our sector scanner-videodensity analysis system, we used a phantom with constant attenuation and eight cones with known, varying relative scatterer concentration. The time-gain-compensation curve was kept constant on the ultrasound instrument and videodensity was measured from videotapes by an offline computer system. In the image of each cone, a 10 X 70 pixel operator-designated region of interest was chosen, and mean videodensity/pixel (256 level gray scale) was calculated. A logarithmic relation was found between scatterer concentration and videodensity. This excellent log relationship existed at all three gain levels studied: at 40% of maximum gain, r = .96; at 50% gain, r = .99; and at 60% gain, r = .99 (all p less than .001). Boluses of .5 ml sonicated Hypaque were then injected into the chamber and the contrast washout was recorded at ejection fractions of 20, 30, 40, 50, 60, and 70%. Bolus delivery and complete contrast mixing was attained except at ejection fraction 20%. Using the first two to four stroke videodensity decay the ejection fraction was calculated by estimating microbubble concentration decline using the logarithmic regression equation between videodensity and scatter concentration obtained during calibration.(ABSTRACT TRUNCATED AT 250 WORDS)

Densitometry↗

On the application of ultrasonic contrast agents for blood flowmetry and assessment of cardiac perfusion.

The stability, size, and ultrasonic properties of several ultrasonic microbubble contrast agents such as Albunex, SHU-454, 1% hydrogen peroxide, and sonicated solutions such as 70% and 50% dextrose, 70% sorbitol, 5% albumin, Renografin-76, and others were evaluated. Albunex was the only tested agent that was sufficiently stable over an extended period of time for in vitro ultrasonic characterization. The attenuation and backscatter coefficients of Albunex at 5 and 7.5 MHz were found to be linearly proportional to microsphere concentration at low concentrations (less than 0.01% for attenuation and less than 0.002% for backscatter). Also, Albunex was found to be more echogenic than soft tissues at 5 MHz even after being diluted to 0.0003% of the original concentration. Next, the feasibility of using this acoustic information for contrast blood flowmetry was investigated. In vitro flow estimates in a mock flow loop were made using only the ultrasonic properties of the contrast agent. Bolus injections of Albunex and indicator-dilution curves inferred from ultrasonic measurements were used to estimate calibrated flow rate ranging from 400 to 5000 mL/min. The flow estimates from attenuation measurements showed a good correlation with those from an independent method (r = 0.97), but the results from backscatter studies did not correlate well. These results demonstrate that attenuation measurement may be a feasible alternative for in vivo blood flow measurement in conjunction with the indicator dilution principle or estimation of tissue perfusion such as myocardial perfusion using a time-activity approach.

Albumins↗

Galactose-based intravenous sonographic contrast agent: experimental studies.

A galactose-based sonographic contrast agent, which produces stable microbubbles capable of traversing the cardiopulmonary circulation, was used to enhance Doppler signals in blood vessels of varying size after intravenous injection. A series of experiments using dogs, rabbits, and woodchucks was conducted to establish the ability of the agent to enhance the reflectivity of normal tissue, tumor tissue, and blood. Although no enhancement was perceptible in tissue on the sonogram, significant enhancement of color and spectral Doppler signals was demonstrated in a variety of vessels. These included the aorta, vena cava, and portal vein as well as such small vessels as those of the retina of the eye, renal cortex, liver parenchyma, and gallbladder wall. Both spectral and color Doppler enhancement was shown in naturally occurring woodchuck hepatomas. Peak Doppler signal enhancement after bolus injection was approximately 10 dB with a dose of 0.01 ml/kg. Recirculation of the agent provided enhancement after intravenous bolus injection for more than 3 min. With a steady intravenous infusion of 0.2 ml/min/kg, Doppler signal enhancement of about 14 dB was maintained continuously for more than 5 min. The results of these animal experiments, in particular in small vessels and with recirculation after intravenous injection, suggest excellent potential for future clinical applications.

Angiography↗