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PubMed2004

Sonographic depiction of microvessel perfusion: principles and potential.

OBJECTIVE: To provide an overview of the technical aspects and potential clinical applications of microvessel perfusion as depicted by microbubble-enhanced sonography. METHODS: Sonographic depiction of microvessel perfusion was obtained by microbubble-enhanced sonography. This technique was used for imaging in vivo murine tumors and was correlated with magnetic resonance and fluorodeoxyglucose autoradiography. Sonographic estimation of microvessel perfusion used parameters derived from time-activity curves. RESULTS: Preliminary data indicate that accurate and reproducible quantification of microvessel perfusion is possible with the use of microbubble-enhanced sonography. CONCLUSIONS: Microbubble-enhanced sonography can depict microvessel perfusion. This technique has several potential clinical applications, including assessment of tumor blood flow and changes that occur with treatment.

Animals↗

PubMed2004

[Application of dynamic bubble trap in coronary artery bypass with cardiopulmonary bypass: an initial study].

OBJECTIVE: To investigate the effectiveness of dynamic bubble trap (DBT) on air microbubble elimination from both the cardiopulmonary bypass (CPB) circuit and middle cerebral arteries, and evaluate its possible impact on blood cells and coagulatory function. METHODS: Twenty patients undergoing coronary artery bypass graft (CABG), 12 males and 8 females, with similar perioperative data were assigned randomly to DBT group and control group. Each CABG was finished with identical circuit sets except the integration of a DBT between the arterial filtrator and the aortic cannula in the DBT group. Air microbubbles were detected before and after the integration of DBT with ultrasonographic detector and microembolism signals (MES) in middle cerebral arteries were counted by transcranial Doppler (TCD). Plasma free hemoglobin (PFH), lactate dehydrogenase (LDH), fibrinogen, platelet count, coagulation factor II and anti-thrombin III (ATIII) were also assayed respectively before the operation, at the termination of CPB, and 6 hours after the operation. RESULTS: In the DBT group the microbubbles of different size could be expelled significantly with the clearance rates between 68% - 74% (10 - 120 microm bubbles), 79% - 81% (20 - 120 microm bubbles), and 88% - 96% (40 - 120 microm bubbles). During the total CPB phase, the mean number of MES reached 197 +/- 137 in the control group and 158 +/- 178 in the DBT group, without a significant difference between these 2 groups. The PFH and LDH levels raised while the platelet count, fibrinogen level, and coagulation factor II and AT III activities decreased sharply after CPB in these 2 groups, however without significant differences in these parameters between the two groups. CONCLUSION: DBT integration into the CPB circuit enhances neither blood cell damage nor coagulation disturbance. DBT effectively eliminates air microbubbles in arterial conduit; however, its microembolus elimination function is prone to die down during the total period of CPB.

Cardiopulmonary Bypass↗

PubMed2006

Reduction of gaseous microembolism during aortic valve replacement using a dynamic bubble trap.

Serious postoperative psycho-neurological dysfunction is at least partially attributed to the occurrence of gaseous microbubbles in the arterial line of extracorporeal circulation (ECC). Therefore, we investigated in a prospective randomized double blind study whether the usage of dynamic bubble trap (DBT) will reduce microbubble load of patients undergoing aortic valve replacement. Patients (n = 41) were divided into group I (GI, n = 22) with DBT introduced into the arterial line of ECC and group II (GII, n = 19) with placebo-DBT instead. Doppler ultrasonography was used for detection of microbubbles before and after DBT, and for detection of high intensity transient signals (HITS) within the middle cerebral artery. The recording time during ECC was divided into period 1 (P1, until aortic clamp removal) and period 2 (P2, clamp removal until the end of ECC). A significant reduction of microbubble load was found in GI only (p < 0.0001 for ECC; p < 0.0001 for P1; p < 0.0025 for P2). A significant difference in number of HITS between the groups was observed in P1 only (p < 0.002 left middle cerebral artery, p < 0.005 right middle cerebral artery), since in P2 the trapped air in left chamber can go to the supraaortal vessels without passing ECC. In conclusion the use of DBT cannot substitute careful venting after aortic declamping. Nevertheless, reduction of HITS in the cross-clamped period of ECC justifies the use of DBT in patients undergoing open chamber surgery.

Aorta↗

PubMed2001

MR perfusion imaging using encapsulated laser-polarized 3He.

In this work, the use of a new carrier agent for intravascular laser-polarized 3He imaging is reported. Lipid-based helium microbubbles were investigated. Their average diameter of 3 microm, which is smaller than that of the capillaries, makes it possible to conduct in vivo studies. The NMR relaxation parameters T1, T2, and T2* of a microbubble suspension were measured as 90 s, 300 ms, and 4.5 ms, respectively, and in vivo images of encapsulated 3He with signal-to-noise ratios (SNRs) larger than 30 were acquired. Dynamic cardiac images and vascular images of encapsulated 3He were obtained in rats using intravenous injections of microbubble suspensions. Excellent preservation of 3He polarization through the lung capillaries and heart cavities was observed. The first images of 3He microbubble distributions in the lungs were obtained. Additionally, the potential of this technique for lung perfusion assessment was validated through an experimental embolism model with the visualization of perfusion defects.

Animals↗

PubMed1992

Hepatic cavitation. A marker of transient hepatocellular injury during biliary lithotripsy.

Sonographically visible microbubbles attributable to cavitation effects have been observed in bile (within the gallbladder), in hepatic vessels, and within the liver of patients undergoing biliary lithotripsy. Cavitation effects are believed to contribute to stone fragmentation and possibly tissue injury during lithotripsy. To study the latter, the relationship between intraparenchymal hepatic cavitation and serum transaminase activity and clinical follow-up was analyzed in 81 patients undergoing 164 lithotripsy treatments. Seventy-one treatments (43%) resulted in sonographically evident microbubbles in the liver parenchyma during lithotripsy. A temporary, yet statistically significant (P < 0.01) rise in SGOT and SGPT was observed within 2 hr of completion of lithotripsy compared to those patients without hepatic microbubbles. All but one patient had a return to pretreatment baseline levels of SGOT and SGPT by two weeks after lithotripsy. In this patient, persistent elevation of transaminases was attributed to the delayed passage of fragments and not to any sequelae from hepatic cavitation effects. Ultrasound immediately after, two weeks after, and 3-12 months after lithotripsy showed no hepatic structural abnormalities. Ursodiol administration at the time of treatment did not predispose to hepatic cavitation or elevation of transaminase. Detection of hepatic microbubbles during lithotripsy is a marker of hepatocellular injury. Their correlation with transaminase elevation refutes the contention that transaminasemia results solely from fragment passage after lithotripsy. Although not associated with recognizable structural damage or long-term sequelae, cavitation effects and transaminasemia reiterate that shockwaves are not entirely benign as they traverse parenchymal organs.

Alanine Transaminase↗

PubMed1995

Sonicated X-ray contrast agents for quantitative myocardial contrast echocardiography--a critical approach.

Contrast echocardiography with sonicated radiographic contrast agents has been used for the qualitative and quantitative determination of myocardial blood flow. One major problem has been the size of the microbubbles since only bubbles smaller than 8 microns are expected to pass the capillary bed and larger bubbles may obstruct the capillaries and, thus, alter myocardial blood flow. These techniques have been used for several years, but their reliability has not yet been assessed accurately. Five different methods for the production of sonicated radiographic contrast agents (methods 1-3 from the literature, and 4 and 5 from our laboratory; M1-5) were evaluated for their use in quantitative contrast echocardiography. The sonication of non-ionic X-ray contrast media was performed with a standard titanium probe (20 kHz) for methods 1-4, with variation in the sonication time and the number of sonication jets used for each method. In M5, we used bubbles that were produced by the insufflation of oxygen in the X-ray contrast agent; large (> 8 microns) bubbles were destroyed by sonication at 380 kHz (resonance method). Mean bubble size was determined by computerized videomicroscopy. The effect of bubble size on the backscatter of the ultrasonic signal was calculated for each method. Mean bubble size (+/- 1 SD) ranged between 11.5 +/- 4 microns and 16.1 +/- 14 microns for M1-M5. The best values, i.e., the smallest bubbles, were found with M4 (prepressurized contrast medium). Assuming capillary passage for bubbles smaller than 8 microns, only 14%-48% of the bubbles were smaller than 8 microns (M1-M5). The best results with regard to bubble size (< or = 8 microns) were observed with M5 (48% < or = 8 microns). In regard to the influence of bubble size on the backscatter of the ultrasonic signal, 56%-98.5% of the signal was produced by bubbles larger than 15 microns (M1-5) but the best results were obtained with M4. It is concluded that capillary-passage of sonicated microbubbles (< or = 8 microns) can be expected in only 14%-48% of the bubbles for the five different sonication techniques. More than 50% of all microbubbles produced by these techniques are larger than the expected 8 microns. These large bubbles are responsible for the backscatter of the ultrasonic signal in the vast majority of cases. Thus, the sonication of radiographic contrast agents appears to be inappropriate for the production of uniformly small microbubbles and, thus, this method is not suitable for quantitative measurements of coronary blood flow.

Contrast Media↗

PubMed1995

The mechanism and clinical implication of improved left ventricular videointensity following intravenous injection of multi-fold dilutions of albumin with dextrose.

The left ventricular ultrasound videointensity of an intravenous injection of sonicated albumin is improved if the agent is diluted with dextrose prior to sonication. The objective of this study was to determine the mechanism for improved left ventricular ultrasound contrast with intravenous sonicated multi-fold dilutions of albumin with dextrose compared to sonicated albumin alone. Epicardial short axis images of the left ventricle were obtained in 11 mongrel dogs and incremental one part sonicated dilutions (up to 10-fold) of albumin with 5 or 50% dextrose were given intravenously to determine which dilution and dextrose concentration produced optimal left ventricular videointensity. Microbubble size and concentration of these dilutions were measured. The one to seven-fold sonicated dilutions resulted in a slight, but significantly larger microbubble size when compared to sonicated albumin alone (SA), but no difference in concentration. All dilutions produced significantly higher end-diastolic peak videointensity (PVI) in the left ventricle than SA (range 160-569% of SA PVI; p < 0.001) with the three to five-fold dilution producing maximal PVI. Five percent dextrose dilutions produced the same videointensity as 50% dilutions. End-systolic videointensity of both 5 and 50% dextrose dilutions were also over 250% higher than SA (p < 0.001). This resulted in good or excellent end-systolic endocardial border definition in the majority of injections. Therefore, the mechanism for improved left ventricular chamber opacification with multifold sonicated dilutions of albumin with dextrose appears to be due to a small increase in microbubble size and not increased viscosity or microbubble concentration.

Albumins↗

PubMed2001

Quantification of blood flow.

Traditionally, Doppler ultrasound has been used to estimate blood flow as the mean velocity multiplied by the vessel area, but this is subject to significant errors and may be difficult to perform accurately. Microbubbles, developed as contrast agents for ultrasound, were initially envisaged as useful for increasing the intensity of echoes and thus rescuing Doppler studies that were technical failures because of attenuated signals or very slow flow. However, they can act as tracers and, by analogy with isotope techniques, can be used to measure blood flow with transit-time methods which exploit both arterial and venous time-intensity data. An acceptable compromise is to acquire both a tissue intensity curve and one from the feeding artery. The transit of microbubbles across an organ or tissue can be used to estimate haemodynamic alterations, e.g. the arterialisation of the supply to the liver in malignancies and cirrhosis and the delayed arterio-venous transit in the transplant kidney during rejection. The fragility of microbubbles can be turned to advantage by being exploited to create a negative bolus by exposing a tissue slice to a high power beam. The rate of refilling of this slice by circulating microbubbles can then be followed with a low-intensity monitoring beam and the resulting rising exponential curve analysed to extract indices of both the reperfusion rate (the slope) and the fractional vascular volume (the asymptote). The product of these is a measure of true tissue perfusion.

Blood Flow Velocity↗

PubMed1987

Analysis of replicating DNA molecules from embryos of the sea urchin, Hemicentrotus pulcherrimus, by electron microscopy.

DNA was extracted from embryos of the sea urchin, Hemicentrotus pulcherrimus, at the S phase and examined by electron microscopy. We detected replication microbubbles with a mean size of 404 bases, in addition to replication macrobubbles of more than 1.0 kilobase (kb) in length. Seventy-five percent of the center-to-center distances of the microbubbles were 0.6-1.8 kb with a mean of 1.2 kb. Forty-five percent of the microbubbles were arranged as clusters of four or five microbubbles. These results suggest that at least 34% of the initiation sites for DNA replication are present on a DNA molecule in clusters in which the sites are arranged at 1.2-kb intervals.

Animals↗

PubMed1995

Acoustic generation of intra-arterial contrast boluses.

Microbubbles generated by ultrasonic cavitation in vivo might be useable as flow indicators in some situations instead of injectable contrast agents. Knowledge of those vascular microbubble-generating ultrasonic fields which produce from negligible up to significant damage will help improve guidelines for more effective, safer diagnostic and therapeutic ultrasound. Microbubble boluses have been generated by a 1.8-MHz, focused sound field in the in vivo canine abdominal aorta. Spatial peak acoustic intensities of 19,000 W cm-2 generated microbubble boluses when exposure was longer than 12 ms, whereas intensities greater than 4300 W cm-2 generated a bolus when exposure was for 250 ms. The onset time of these boluses (less than one cardiac cycle) is unachievable with intravenous contrast injection. With optimized waveforms and focusing, acoustic bolus generation may prove to be an effective, minimally invasive method for fast performance of certain selective angiography.

Acoustics↗

PubMed2005

Diagnosis of NASH using delayed parenchymal imaging of contrast ultrasound.

BACKGROUND AND AIMS: Non alcoholic steatohepatitis (NASH) is one of the representative liver diseases in the developed countries. Diagnosis of NASH is dependent on histological findings from liver biopsy. Usefulness of contrast ultrasound with Levovist for diagnosis of NASH is described. METHODS AND MATERIALS: Clinical study: Ultrasound contrast agent, Levovist of 2.5g was injected intravenously. The liver was scanned at 5, 10, 15, 20, 30, 40, and 50min after Levovist injection in different planes using a contrast specific ultrasound mode. Changes in microbubble accumulation in the liver were evaluated. The signal intensity from regions of interest (ROI) on the contrast images was measured and accumulation and decrescence of microbubbles were estimated using the time intensity curves (TICs). The image data and TICs were evaluated by blind reviewers. Fifteen patients with NASH, 8 with alcoholic steatohepatitis (ASH), 45 with non alcoholic fatty liver (NAFL), 10 with chronic hepatitis C (CHC) and 10 healthy volunteers were studied. Animal study: Methionine-choline-deficient diet (MCDD) fed rats were used for NASH model. Correlation between microbubble accumulation and morphological and functional changes of sinusoidal endothelium and macrophage was evaluated. RESULTS: The maximum intensity of contrast ultrasound was decreased and time course decrescence was more rapid in NASH than the other groups. These changes were correlated to the degree of centrilobular and pericellular fibrosis but not to steatosis in histological study. Disturbance of microbubble accumulation was correlated with sinusoidal function rather than morphological changes such as fibrosis and parenchymatitis in the animal studies. CONCLUSIONS: The Levovist contrast study enables differential diagnosis between NASH and other diseases that provoke steatosis and fibrosis.

Journal Article↗

PubMed2006

Young Adult Myocardial Infarction and Ischemic Stroke: the role of paradoxical embolism and thrombophilia (The YAMIS Study).

OBJECTIVES: We aimed to investigate the frequency of venous-to-arterial circulation shunts (v-aCS), usually caused by patent foramen ovale (PFO), and thrombophilia in young adults suffering myocardial infarction (MI) and ischemic stroke (IS) and matched healthy control subjects. BACKGROUND: The cause of MI and IS in young adults is often uncertain, and paradoxical embolism might be more frequent than previously thought. METHODS: Young adults (ages 16 to 39 years) surviving MI (n = 101) and IS (n = 101) between 1993 and 1998 were matched by age and gender to 202 control subjects from the same general practitioner practices. The v-aCS were detected by transcranial Doppler after intravenous microbubble ultrasound contrast; "significant" v-aCS (> or =15 microbubble emboli) correlated with PFO on transesophageal echocardiography. A "major" v-aCS was >50 microbubbles spontaneously or >10 microbubbles spontaneously with >80 after provocation. Venous blood was taken for a thrombophilia screen. RESULTS: Myocardial infarction, more frequent in men, was associated with the usual cardiovascular risk factors. More women suffered IS, which was associated only with migraine and hypertension. Neither "significant" nor "major" v-aCS were associated with MI. "Major" v-aCS was found in 24 (25%) IS cases compared with 12 (12%) control subjects (odds ratio 2.80, 95% confidence interval 1.21 to 6.84; p = 0.016). Thrombophilia was not significantly associated with either MI or IS. CONCLUSIONS: Only "major" v-aCS were associated with stroke in young adults. Closure of smaller v-aCS might not be justified.

Adolescent↗

PubMed2002

Human cerebral perfusion analysis with ultrasound contrast agent constant infusion: a pilot study on healthy volunteers.

With ultrasound (US) contrast agent (UCA) continuous infusion providing a steady state, mean tissue microbubble velocity can be assessed by analyzing the reappearance rate after microbubble destruction with US energy (refill kinetics). In this study, we investigated this new approach for the assessment of human cerebral perfusion. A total of 12 healthy volunteers were investigated transtemporally with increasing pulsing intervals (250, 500, 750, 1000, 1250, 1500, 2000, 3000 and 4000 ms) and two UCA infusion rates (0.5 and 1.0 mL/min of Optison). Intensity vs. pulsing interval curves were analyzed using an exponential curve fit and parameters of the curve (plateau echo enhancement, A, representing the microbubble concentration within the interrogated tissue; rate constant, beta, which is related to blood flow and their product, F = Abeta) were compared. For 20/20 investigations being available for further analysis, it was possible to generate a typical exponential intensity vs. pulsing interval curve from the ipsilateral thalamus. The plateau echo enhancement A showed a significant (p = 0.02), and the beta as well as the F values displayed a nonsignificant (p = 0.06, both), increase with infusion rate. The qualitative analysis of beta and F parameter images displayed the most homogeneous visualisation of perfusion in the ipsilateral thalamus and main territory of the middle cerebral artery. In conclusion, it is possible to display the UCA refill kinetics in human cerebral microcirculation after microbubble destruction by transcranial US. Grey-scale harmonic imaging allows a quantitative approach to cerebral perfusion with a large interindividual variation of the parameters.

Adult↗

PubMed2002

On the design of a capillary flow phantom for the evaluation of ultrasound contrast agents at very low flow velocities.

Recently, a new imaging technology has become available that allows the evaluation of tissue perfusion using echo-contrast agents in real-time imaging: power pulse inversion imaging (PPI). Although numerous in vitro phantoms have been designed for different imaging modalities in ultrasound (US), there is a need for a phantom that mimics microcirculation and allows, in particular, the assessment of contrast replenishment kinetics following US-induced destruction of microbubbles using the new method. We, therefore, designed a new capillary flow phantom that takes the requirements of the new US imaging techniques and the physical properties of microbubbles into account and serves flow velocities in the range of microcirculation (1 to 10 mm/s). PPI studies were performed in the newly designed phantom. The contrast agent used was AF0150. We studied homogeneity of contrast distribution within the capillary phantom, constancy of contrast infusion, the dose-effect relationship and, finally, the feasibility of flow assessment using the method of contrast replenishment following US-induced microbubble destruction in a flow velocity range of 2.1 to 9.45 mm/s. Analysis of the replenishment kinetics was performed using the mathematical model f(t) = A(1 - e(-beta t)), with A representing the blood volume and beta the microbubble velocity. The new capillary phantom allowed homogeneous contrast opacification within the perfused capillaries independently of the flow. Constancy of signal intensity was achieved over a time period of almost 2 h, indicating constant contrast delivery. A strong linear correlation between the PPI signal and the contrast dose was found (r = 0.998). Analysis of the replenishment parameters revealed a strong linear relationship between parameter beta and flow (r = 0.994) as well as A * beta and flow (r = 0.984) in the observed flow range. The newly designed perfusion phantom for the evaluation of echo-contrast replenishment kinetics fulfills, at very low flow velocities, important prerequisites such as constancy of contrast delivery, homogeneity of contrast signals, linear dose-effect relation and minimal attenuation. Thus, the new phantom allows standardized analysis of contrast replenishment kinetics using real-time perfusion imaging techniques at flow velocities comparable to those of the microcirculation.

Blood Flow Velocity↗

PubMed2002

The disappearance of ultrasound contrast bubbles: observations of bubble dissolution and cavitation nucleation.

The destruction process of biSphere and Optison ultrasound (US) contrast microbubbles were studied at 1.1 MHz. High-amplitude tone bursts caused shell disruption and/or fragmentation of the microbubbles, leading to dissolution of the freed gas. The bubble destruction and subsequent dissolution process was imaged with a high pulse-repetition frequency (PRF) 10-cycle, 5-MHz bistatic transducer configuration. Three types of dissolution profiles were measured: In one case, biSphere microbubbles showed evidence of dissolution through resonance, during which a temporary increase in the scattering amplitude was observed. In another case, both biSphere and Optison microbubbles showed evidence of fragmentation, during which the scattering amplitude decreased rapidly. Finally, in some cases, we observed the impulsive growth and subsequent rapid decay of signals that appear to be due to cavitation nucleation. Simulations of bubble dissolution curves show good agreement with experiments.

Albumins↗

PubMed2003

Nonlinear behaviors of contrast agents relevant to diagnostic and therapeutic applications.

The nonlinear properties of an encapsulated microbubble of a contrast agent were studied theoretically and experimentally. A modified nonlinear differential equation (Herring equation) was used to describe the radial oscillation of the microbubble and solved numerically. It was found that the nonlinear resonance frequency, at which the peak radial oscillation amplitude occurs, was a decreasing function of the acoustic amplitude of a driving ultrasonic pulse. Optical images of the contrast agent microbubbles under various ultrasonic exposure conditions: 1. sham exposure; 2. 2-MHz spatial peak acoustic pressure = 200 kPa, I(SATA) = 260 mW/cm(2), duty cycle = 7.5%, repetition period = 0.0266 ms; 3. 0.5-MHz spatial peak acoustic pressure = 200 kPa, I(SATA) = 130 mW/cm(2), duty cycle = 7.5%, repetition period = 0.1067 ms; have also shown that the lower-frequency ultrasound (US) excitation (0.5 MHz) is more effective in disruption of the microbubbles due to acoustic inertial cavitation than the higher frequency US (2 MHz).

Algorithms↗

PubMed2002

The usefulness of a 10% air-10% blood-80% saline mixture for contrast echocardiography: Doppler measurement of pulmonary artery systolic pressure.

OBJECTIVES: We assessed an air-blood-saline mixture for Doppler measurement of pulmonary artery systolic pressure (PASP) and the mechanism of enhancement of the Doppler signal by this mixture. BACKGROUND: Underestimation of PASP by Doppler echocardiography occurs with inadequate continuous wave (CW) signals of tricuspid regurgitation (TR). METHODS: We assessed in vitro the diameter and concentration of microbubbles of agitated air-saline mixture, air-blood-saline mixture and 10% air-10% plasma-80% saline mixture immediately, 5, 10 and 20 s after agitation. In 20 patients, PASP was estimated by Swan-Ganz catheter and CW Doppler of TR: 1) without contrast injection; 2) with intravenous injection of 10% air-90% saline; and 3) 10% blood-10% air-80% saline mixture. RESULTS: Compared to air-saline, addition of blood or plasma to the air-saline solution significantly increased the concentration of microbubbles (p < 0.001). The air-blood-saline (26.7 +/- 7.2 microm) and air-plasma-saline mixture (25.3 +/- 7.4 microm) had smaller microbubbles than air-saline mixture (31.6 +/- 8.2 microm) (p < 0.001). The correlation between Doppler- and catheter-measured PASP at baseline (r = 0.64) improved with agitated air-saline (r = 0.86). With the air-blood-saline mixture, the correlation further improved (r = 0.92) and the best limits of agreement were obtained. CONCLUSIONS: The combination of the patient's own blood is a method of making a sterile solution of numerous small microbubbles for injection into the right-sided cardiac chambers. Clinically, the air-blood-saline mixture is easily prepared at bedside and is superior to the air-saline mixture in assessing PASP in patients with inadequate CW Doppler signals.

Blood Pressure↗

PubMedDate not supplied

Pitfalls in quantitative contrast echocardiography: the steps to quantitation of perfusion.

Current methods used clinically to assess myocardial perfusion are invasive and expensive. As the technology of ultrasound imaging improves, CE may provide a relatively inexpensive, noninvasive means of quantitating myocardial perfusion. Issues regarding stability of microbubble contrast agents must be studied more closely under physiologic conditions. As such, encapsulated microbubbles may provide more stability under physiologic pressures than free gas microbubbles. Introducing high concentrations of contrast, either by hyperconcentrating the contrast agent or by increasing the injection rate, may provide greater stability under physiologic conditions. Further, before quantitative statement of tissue perfusion can be made, the relationship between tracer concentration and system response must be established. Further, a "linear" postprocessing ultrasound setting does not eliminate this requirement as data must still undergo nonlinear transformation during log compression and time-gain compensation. Additionally, issues regarding "electronic thresholding" must be explored more extensively in vivo. Commercial ultrasound scanners, in their present form, may not offer adequate sensitivity for absolute quantitative studies. Further development of modified ultrasound systems may provide sufficient sensitivity for quantitative perfusion imaging. CE offers a potentially powerful tool in the clinical management of patients with ischemic heart disease. Conventional coronary angiography provides information on the size of a lesion, but accompanying tissue perfusion distal to the lesion cannot be determined. Doppler ultrasonography determines velocity of blood flow in large vessels but does not offer the potential to quantitate tissue perfusion. Clearly, CE has a place in the future of diagnostic imaging. The recent work of Ito et al. demonstrated the qualitative potential of CE in the identification of "areas at risk" in patients who had undergone thrombolysis or percutaneous transluminal coronary angioplasty after an acute myocardial infarction. With further improvement in the ultrasound imaging techniques and microbubble stability, CE may offer an inexpensive, noninvasive means of assessing myocardial perfusion.

Albumins↗