Mechanically Tunable Hollow Silica Ultrathin Nanoshells for Ultrasound Contrast Agents.

Perfluoropentane (PFP) gas filled biodegradable iron-doped silica nanoshells have been demonstrated as long-lived ultrasound contrast agents. Nanoshells are synthesized by a sol-gel process with tetramethyl orthosilicate (TMOS) and iron ethoxide. Substituting a fraction of the TMOS with R-substituted trialkoxysilanes produces ultrathin nanoshells with varying shell thicknesses and morphologies composed of fused nanoflakes. The ultrathin nanoshells had continuous ultrasound Doppler imaging lifetimes exceeding 3 hours, were twice as bright using contrast specific imaging, and had decreased pressure thresholds compared to control nanoshells synthesized with just TMOS. Transmission electron microscopy (TEM) showed that the R-group substituted trialkoxysilanes could reduce the mechanically critical nanoshell layer to 1.4 nm. These ultrathin nanoshells have the mechanical behavior of weakly linked nanoflakes but the chemical stability of silica. The synthesis can be adapted for general fabrication of three-dimensional nanostructures composed of nanoflakes, which have thicknesses from 1.4-3.8 nm and diameters from 2-23 nm.

Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver--update 2012: a WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS.

Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.

Optimization of iron oxide nanoparticle detection using ultrashort echo time pulse sequences: comparison of T1, T2*, and synergistic T1- T2* contrast mechanisms.

Iron oxide nanoparticles (IONPs) are used in various MRI applications as negative contrast agents. A major challenge is to distinguish regions of signal void due to IONPs from those due to low signal tissues or susceptibility artifacts. To overcome this limitation, several positive contrast strategies have been proposed. Relying on IONP T(1) shortening effects to generate positive contrast is a particularly appealing strategy because it should provide additional specificity when associated with the usual negative contrast from effective transverse relaxation time (T(2)*) effects. In this article, ultrashort echo time imaging is shown to be a powerful technique which can take full advantage of both contrast mechanisms. Methods of comparing T(1) and T(2)* contrast efficiency are described and general rules that allow optimizing IONP detection sensitivity are derived. Contrary to conventional wisdom, optimizing T(1) contrast is often a good strategy for imaging IONPs. Under certain conditions, subtraction of a later echo signal from the ultrashort echo time signal not only improves IONP specificity by providing long T(2)* background suppression but also increases detection sensitivity, as it enables a synergistic combination of usually antagonist T(1) and T(2)* contrasts. In vitro experiments support our theory, and a molecular imaging application is demonstrated using tumor-targeted IONPs in vivo.

Real-time cerebral angiography: sensitivity of a new contrast-specific ultrasound technique.

BACKGROUND AND PURPOSE: To test a new contrast-specific sonography imaging method that offers visualization of the intracranial vasculature in a manner similar to that seen on angiography. MATERIALS AND METHODS: Thirty patients (35 sonography studies total) were included in the study after they provided written informed consent. The patients were scanned through the temporal bone window from both sides after intravenous injection of an ultrasound contrast agent (UCA; perflexane lipid microspheres [Imagent]). The goal was to visualize the intracranial arteries, including the middle (M1-M3), anterior (A1 and A2), and posterior (P1-P3) cerebral arteries, using an axial scanning plane. The studies were performed using a contrast-specific imaging mode, based on a phase inversion technique (transcranial ultrasound angiography [tUSA]). For sensitivity, the results were compared with x-ray angiography as the "gold standard." For interobserver reliability, 24 of 35 sonography studies were evaluated by 2 physicians with little training in transcranial sonography and by a seasoned sonographer. RESULTS: The sensitivity of tUSA ranged between 0.778 (95% confidence interval [CI] of 0.577-0.914) and 0.963 (95% CI of 0.810-0.999). The sensitivities were similar among physicians with little training in transcranial sonography and the seasoned sonographer, indicating high inter-rater reliability. Overall, tUSA provided high anatomic resolution and vascular delineation even of small vessels in the millimeter range. At peak intensity, no UCA-related artifacts were observed. CONCLUSION: tUSA provides images of the intracranial arteries similar to those obtained at angiography with high anatomic resolution, reasonable sensitivity, and interobserver reliability.

Novel method for the formation of monodisperse superheated perfluorocarbon nanodroplets as activatable ultrasound contrast agents.

Microbubble (MB) contrast agents have positively impacted the clinical ultrasound (US) community worldwide. Their use in molecular US imaging applications has been hindered by their limited distribution to the vascular space. Acoustic droplet vaporization (ADV) of nanoscale superheated perfluorocarbon nanodroplets (NDs) demonstrates potential as an extravascular contrast agent that could facilitate US-based molecular theranostic applications. However these agents are metastable and difficult to manufacture with high yields. Here, we report a new formulation technique that yields reliable, narrowly dispersed sub-300 nm decafluorobutane (DFB) or octafluoropropane (OFP)-filled phospholipid-coated NDs that are stable at body temperature, using small volume microfluidization. Final droplet concentration was high for DFB and lower for OFP (>1012vs. >1010 NDs per mL). Superheated ND stability was quantified using tunable resistive pulse sensing (TRPS) and dynamic light scattering (DLS). DFB NDs were stable for at least 2 hours at body temperature (37 °C) without spontaneous vaporization. These NDs are activatable in vitro when exposed to diagnostic US pressures delivered by a clinical system to become visible microbubbles. The DFB NDs were suficiently stable to allow their processing into functionalized NDs with anti-epithelial cell adhesion molecule (EpCAM) antibodies to target EpCAM positive cells.

In vivo prostate cancer detection and grading using restriction spectrum imaging-MRI.

BACKGROUND: Magnetic resonance imaging (MRI) is emerging as a robust, noninvasive method for detecting and characterizing prostate cancer (PCa), but limitations remain in its ability to distinguish cancerous from non-cancerous tissue. We evaluated the performance of a novel MRI technique, restriction spectrum imaging (RSI-MRI), to quantitatively detect and grade PCa compared with current standard-of-care MRI. METHODS: In a retrospective evaluation of 33 patients with biopsy-proven PCa who underwent RSI-MRI and standard MRI before radical prostatectomy, receiver-operating characteristic (ROC) curves were performed for RSI-MRI and each quantitative MRI term, with area under the ROC curve (AUC) used to compare each term's ability to differentiate between PCa and normal prostate. Spearman rank-order correlations were performed to assess each term's ability to predict PCa grade in the radical prostatectomy specimens. RESULTS: RSI-MRI demonstrated superior differentiation of PCa from normal tissue, with AUC of 0.94 and 0.85 for RSI-MRI and conventional diffusion MRI, respectively (P=0.04). RSI-MRI also demonstrated superior performance in predicting PCa aggressiveness, with Spearman rank-order correlation coefficients of 0.53 (P=0.002) and -0.42 (P=0.01) for RSI-MRI and conventional diffusion MRI, respectively, with tumor grade. CONCLUSIONS: RSI-MRI significantly improves upon current noninvasive PCa imaging and may potentially enhance its diagnosis and characterization.

Myocardial infarct size determined by computed transmission tomography in canine infarcts of various ages and in the presence of coronary reperfusion.

Thirty-one dogs underwent in vivo scanning with computed transmission tomography; 15 dogs were studied within 7 days (mean 4) after coronary occlusion, 10 dogs 21 to 25 days (mean 28) after occlusion and 6 dogs 4 days after coronary reperfusion of a 2 to 3 hour coronary ligation. Ungated scans (1 cm in depth) of the left ventricle were obtained from apex to base to determine infarct size. In all animals with documented (postmortem) infarction (n = 26), contrast medium caused delayed enhancement of the entire infarct or the periphery of the infarct. Infarct size was calculated from scans showing contrast enhancement of the infarct. Infarct size was also determined from the postmortem heart using histochemical morphometry (nitroblue tetrazolium) and then compared with infarct size derived from tomography using the outer margin of the contrast-enhanced periphery of the infarct as the border of the infarct. Infarct size calculated by the tomographic technique (excluding the animals without an infarct) correlated well with infarct size determined at autopsy (r = 0.90, p less than 0.001). The tomographic estimate (18.2 +/- 11.3 g) of infarct size was similar to autopsy values (18.6 +/- 11.8 g, p = NS). Thus, ungated computed transmission tomographic imaging of the heart can reliably estimate infarct size in a variety of potential clinical circumstances, particularly when the area of rim enhancement of the infarct is included within the presumed infarct region.

Novel technique for characterizing prostate cancer utilizing MRI restriction spectrum imaging: proof of principle and initial clinical experience with extraprostatic extension.

BACKGROUND: Standard magnetic resonance imaging (MRI) of the prostate lacks sensitivity in the diagnosis and staging of prostate cancer (PCa). To improve the operating characteristics of prostate MRI in the detection and characterization of PCa, we developed a novel, enhanced MRI diffusion technique using restriction spectrum imaging (RSI-MRI). METHODS: We compared the efficacy of our novel RSI-MRI technique with standard MRI for detecting extraprostatic extension (EPE) among 28 PCa patients who underwent MRI and RSI-MRI prior to radical prostatectomy, 10 with histologically proven pT3 disease. RSI cellularity maps isolating the restricted isotropic water fraction were reconstructed based on all b-values and then standardized across the sample with z-score maps. Distortion correction of the RSI maps was performed using the alternating phase-encode technique. RESULTS: 27 patients were evaluated, excluding one patient where distortion could not be performed. Preoperative standard MRI correctly identified extraprostatic the extension in two of the nine pT3 (22%) patients, whereas RSI-MRI identified EPE in eight of nine (89%) patients. RSI-MRI correctly identified pT2 disease in the remaining 18 patients. CONCLUSIONS: In this proof of principle study, we conclude that our novel RSI-MRI technology is feasible and shows promise for substantially improving PCa imaging. Further translational studies of prostate RSI-MRI in the diagnosis and staging of PCa are indicated.

A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran.

UNLABELLED: We report the synthesis and preliminary biologic testing of a synthetic macromolecule, (99m)Tc-diethylenetriaminepentaacetic acid (DTPA)--mannosyl-dextran, for sentinel node detection. METHODS: Synthesis started with a 2-step process that attaches a high density of amino-terminated leashes to a dextran backbone. Allyl-bromide was reacted with pharmaceutical-grade dextran to yield allyl-dextran. After diafiltration with water, filtration, and lyophilization, the product was reacted with aminoethanethiol and ammonium persulfate. The resulting amino-conjugated dextran was dialyzed, filtered, and lyophilized. The mixed anhydride method was used to attach DTPA; after dialysis, filtration, and lyophilization, 2-imino-2-methoxyethyl-1-D-mannose was used to attach the receptor substrate. The molecular diameter was measured by dynamic light scattering. Amino, mannose, and DTPA densities were measured by trinitrobenzene sulfonate assay, sulfuric acid/phenol assay, and inductively coupled plasma spectroscopy of gadolinium-DTPA-mannosyl-dextran, respectively. Receptor affinity was measured by Scatchard assay of rabbit liver. Axillary, popliteal, and iliac lymph nodes and each injection site were assayed for radioactivity at 1 and 3 h after injection of approximately 3.7 MBq (0.050 mL) (99m)Tc-DTPA-mannosyl-dextran (0.22 nmol) or filtered (99m)Tc-sulfur colloid into the foot pads. Four animals were studied at each time point. RESULTS: DTPA-mannosyl-dextran had a molecular weight of 35,800 g/mol and a molecular diameter of 7.1 nm. The final amine, mannose, and DTPA densities were 23, 55, and 8 mol per dextran. Labeling yields were in excess of 98% and stable for 6 h. Specific activities of 74 x 10(6) GBq/mol were achieved. The equilibrium dissociation constant for binding to the mannose-terminated glycoprotein receptor was 0.12 +/- 0.07 nmol/L. The popliteal extraction at both 1 h and 3 h was significantly (P < 0.05) higher for (99m)Tc-DTPA-mannosyl-dextran (90.1% +/- 10.7% and 97.7% +/- 2.0%, respectively) than for filtered (99m)Tc-sulfur colloid (78.8 +/- 6.5 and 67.4% +/- 26.8%, respectively). (99m)Tc-DTPA-mannosyl-dextran exhibited significantly faster injection site clearance than did filtered (99m)Tc-sulfur colloid. The (99m)Tc-DTPA-mannosyl-dextran percentage injected dose (%ID) for the front and rear paws was 52.6 +/- 10.5 and 52.3 +/- 8.0 at 1 h and 45.7 +/- 8.5 and 43.6 +/- 8.2 at 3 h after administration. The filtered (99m)Tc-sulfur colloid %ID for the front and rear paws was 70.4 +/- 11.0 and 66.3 +/- 15.1 at 1 h and 55.5 +/- 7.8 and 66.9 +/- 8.5 at 3 h. Lymph node accumulation of each agent at either 1 or 3 h was not significantly different. CONCLUSION: (99m)Tc-DTPA-mannosyl-dextran is a receptor-based sentinel node radiotracer that exhibits the desired properties of rapid injection site clearance and low distal node accumulation. This molecule is the first member of a new class of diagnostic agents based on a macromolecular backbone with a high density of sites for the attachment of substrates and imaging reporters.

In vitro magnetic relaxation times of the ischemic and reperfused rabbit kidney: concise communication.

To assess the effects of renal ischemia and reperfusion on in vitro magnetic relaxation times (T1 = magnetization recovery, T2 = spin echo), we evaluated the spectroscopic characteristics of the renal cortex from 25 rabbits. Eight served as controls (Group 1), nine had one renal pedicle ligated for 1 hr (Group 2), and eight (Group 3) were occluded for 1 hr and reperfused for 30 min. For intra-animal comparison purposes, % H2O content, T1 (msec), and T2 (msec) of the ischemic (reperfused) kidney were normalized to the values from the normal kidney within the same animal. Renal ischemia consistently increased water content, which was exaggerated by reperfusion. In association with ischemia, T1 fell, and with reperfusion T1 lengthened. T2 increased with ischemia and declined from the peak ischemic effects with reperfusion.

Ultrasonic enhancement of myocardial infarction with perfluorocarbon compounds in dogs.

Fluosol-DA 20% (Fluosol) and perfluoroctylbromide (PFOB), 2 types of perfluorocarbon emulsions (PFCs), were evaluated as sound contrast agents in imaging acute myocardial infarction (MI) in dogs. Operative ligation of a coronary artery was performed in 9 dogs. PFC was administered 2 days after occlusion. One dog received Fluosol, 10 ml/kg body weight, 2 dogs received 20 ml/kg, and 2 received 25 ml/kg; 2 dogs received PFOB, 20 ml/kg, and 2 dogs received 25 ml/kg. Just before and 2 days after PFC administration, real-time, 2-dimensional ultrasound examination of the heart was performed in the short-axis view from apex to base. No enhancement was seen at the 10-ml/kg dose, but significant mild echogenic enhancement of all MIs occurred after 20 ml/kg. Moderate to marked enhancement was noted after 25 ml/kg. The enhancement was either diffuse throughout the MI or localized to the rim. Initial studies suggest that the mechanism of enhancement is related, at least in part, to the accumulation of PFC-filled macrophages within the MI.

In vivo assessment by computed tomography of the natural progression of infarct size, left ventricular muscle mass and function after acute myocardial infarction in the dog.

Quantification of myocardial infarct (MI) size is of prognostic importance in patients with acute ischemic damage. Evaluation of the efficacy of interventions for salvage of ischemic myocardium depends on the accurate estimation of the ischemic area and a knowledge of the natural progression of the infarct. Computerized transmission tomography (CTT) is a reliable in vivo technique for estimating infarct size. We serially studied 8 dogs over approximately 1 month after occlusion of the left anterior descending coronary artery using both ungated and prospectively electrocardiogram-gated CTT. Scans were obtained 20 minutes after occlusion and then several more times until the dogs were killed. Using the ungated CTT scans, infarct size increased from 0 to 4 days (+ 65 +/- 20%, mean +/- standard error of the mean, p less than 0.05), then progressively decreased. The initial perfusion defect overestimated the eventual MI size at 1 month by 33 +/- 15% (p less than 0.05). The MI size at necropsy correlated well (r = 0.98, p less than 0.001) with CTT MI size determined just before sacrifice. Non-infarcted left ventricular (LV) muscle mass increased significantly (27 +/- 7% greater at 1 month compared with day 0, p less than 0.01) over time, presumably representing compensatory LV hypertrophy. The LV muscle mass at necropsy correlated well (r = 0.94, p less than 0.001) with CTT LV muscle mass just before sacrifice.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrasound contrast agents. State of the art.

In the development of sonographic contrast agents it is clear that the material properties of the contrast have a profound effect on the resulting effectiveness of the product requiring careful manipulations of its properties. The important parameters are particle size, imaging frequency, density, compressibility, particle behavior (surface tension, internal pressure, bubble-like qualities), and equally important biodistribution characteristics and tolerance. Particulate agents appear to be the most likely materials, and gas filled particles are by far the most effective reflectors. However, the gas-based agents reported to date appear to have a short blood half-life. The fluorocarbon emulsions and the solid particles with entrapped air appear to be the most promising agents for abdominal imaging.

1982 Memorial Award Paper. Detection of regional myocardial dysfunction during ischemia with computerized tomography: documentation and physiologic basis.

Cross-sectional imaging techniques have the potential for measuring left ventricular (LV) wall thickness (WTh) dynamics. This proposition was assessed in a canine experimental model, using prospectively gated computed tomography (CT) scans before and after occlusion of a coronary artery. Gated CT scans detected loss of wall thickening in the LV anterior segment immediately after occlusion of the left anterior descending coronary artery in two dogs. After demonstrating the feasibility of using gated CT scans to demonstrate ischemic functional abnormalities by monitoring wall thickness changes, we assessed the relationship between regional wall thickening dynamics and coronary blood flow in eight anesthetized dogs. Graded circumflex (Cx) coronary artery stenosis (CAS) was produced while sonomicrometer crystals continuously recorded LV WTh and extent of wall thickening (EWTh) in the anterior descending and the Cx distributions. The first significant change in EWTh in the ischemic segment occurred at 33% decrease in CBF (P less than .05) which corresponded to an 80% CAS. At 33% decrease in CBF, there was a concomitant increase in EWTh in the normal segment. In conclusion, we have demonstrated the feasibility of using gated CT to detect myocardial ischemia by monitoring WTh dynamics. Physiologic studies document a close relationship between regional wall thickening dynamics and coronary blood flow and should provide a basis for interpretation of dynamic cross-sectional images of the left ventricle in ischemic heart disease.

Potential role of PFOB in diagnostic imaging.

Perfluorochemicals (PFCs) are versatile compounds with a variety of applications in industry and in medicine. Their medical applications are in oxygen transport and diagnostic imaging. These agents are the only ultrasound contrast agents capable of altering tissue echogenicity. The bromine atom in perfluoroocytlbromide (PFOB) makes this agent the only PFC visible by computed tomography. PFOB contains many fluorine atoms and no hydrogen, so it can be used for fluorine MR imaging or as a signal void for hydrogen imaging. All of these applications are presently in clinical trials in the United States and Europe. PFOB is an exciting new contrast agent because of its low or insignificant toxicity, its universality across all imaging modalities, and its potential impact upon diagnostic applications.

Enhancement of the echogenicity of flowing blood by the contrast agent perflubron.

RATIONALE AND OBJECTIVES: Perflubron, or perfluorooctylbromide, is an effective ultrasound and computed tomography contrast agent in a lecithin emulsion form. The authors studied acoustical properties of perflubron emulsion in static human and flowing porcine blood for concentrations from 0% to 30% weight per volume. METHODS: Propagation velocity (c), the intensity attenuation coefficient (mu), density (rho), and particle size were measured directly. Because the backscatter of flowing blood is dependent on shear rate, relative echogenicity was measured as a function of perflubron concentration in whole porcine blood, in a laminar flow system, at shear rates of 16.0 to 68.5 sec-1 for realtime sector scanner images obtained at 7.5 MHz. RESULTS: Neat perflubron is a colorless liquid with density of 1.93 g.mL-1 and velocity of 630 m.sec-1. The following values were obtained at 4.7 MHz in static human blood (hematocrit 44%) at expected human in vivo blood concentrations of 3.1% perflubron versus pure human blood: rho = 1.11 versus 1.05 g.mL-1, c = 1,480 versus 1,576 m.sec-1, mu = 1.00 versus 0.36 dB.cm-1. The mean echogenicity of whole porcine blood increased substantially with perflubron concentration and was inversely proportional to blood shear rate. CONCLUSION: Adding 3.1% concentration of perflubron increased image echogenicity at all shear rates studied, ranging from 70% at 68.5 sec-1 (16.3 cm.sec-1) up to 180% at 16.0 sec-1 (3.8 cm.sec-1). Perflubron enhancement of blood is marked and demonstrates shear rate dependence like that of whole blood.

AUR Memorial Award 1990. The physiologic basis of the radiodense renal medulla after the administration of blood pool contrast agent PFOB.

The hypothesis that the greater CT enhancement of the renal medulla relative to cortex after the administration of perfluorooctylbromide (PFOB) was due to the renal medullary osmotic gradient was tested in eight dogs infused with 10 g/kg PFOB. Urine osmolarity and CT attenuation of the cortex and medulla of each kidney under the full effect of antidiuretic hormone were measured before and after 40 mg of furosemide given intravenously, which is known to destroy the renal osmotic gradient. In an attempt to measure the fractional blood volume of the cortex and medulla, which could account for the observed difference on CT, 10 mCi of 99mTc-labeled erythrocytes were given and cortical and papillary tip tissue samples harvested within 1 minute of the animals' death. Cortical blood volume was eight times that of the medulla (21.6 +/- 5.1% vs 2.7 +/- 0.5%, P less than 0.01) and was not significantly affected by furosemide. Furosemide markedly decreased urine osmolarity (1473 +/- 176 mOsm to 454 +/- 45 mOsm, P less than 0.01), had a minor effect on cortical attenuation (decreased from 90.4 +/- 8.2 to 85.1 +/- 8.1 HU, P less than 0.01), and a marked effect on medullary attenuation (decreased from 140.9 +/- 12.4 to 85.9 +/- 8.9 HU, P less than 0.01) which resulted in total loss of corticomedullary contrast (decreased from 20.0 +/- 3.1% to 0.1 +/- 2.2%, P less than 0.01). Thus, the observed greater CT attenuation of the medulla than cortex following the administration of PFOB, a blood pool agent, is due to the osmotic gradient across the medulla which increases the concentration of the agent in the vasa rectae.

In vivo estimation of perfluorooctylbromide concentration in tissues.

Currently, the only available method to measure perfluorooctylbromide (PFOB) in tissues requires its extraction with a solvent followed by gas chromatography. Not only is this method invasive, but it cannot be validated because the amount of unextracted PFOB is unknown. Using a cylindrical CT phantom with eight wells in the wall filled with bromine (Br) standards, an in vivo method to measure PFOB tissue concentration was developed. Neutron activation analysis (NAA) was used to calibrate and validate the phantom since NAA allows the quantification of Br by making Br radioactive without the need for extraction. Once NAA was validated for PFOB, the phantom was calibrated using 80 rats and tested using 20 rats relative NAA. The phantom produced linear correlation between CT number and known PFOB concentrations with r = 0.998. After its calibration with NAA, the CT method produced a linear correlation between tissue PFOB concentration determined by CT and NAA near the line of identity with an r = 0.984, thus allowing the determination of PFOB tissue content in vivo noninvasively.

Comparison of different perfluorocarbons as ultrasound contrast agents.

RATIONALE AND OBJECTIVES: The sonographic properties of Fluosol 20% (F20), which was recently approved for clinical use as an oxygen carrier for coronary angioplasty, were compared to those of perflubron emulsion, which is still in clinical testing. METHODS: Contrast agents were evaluated in 21 normal rabbits divided into three groups of seven rabbits each. All rabbits received 2.7 g/kg of perfluorocarbon (PFC). One group received 2.7 ml/kg of an experimental formulation of perflubron emulsion AF0102, which contains 1 g of PFC in 1 ml of emulsion (P100), the other received 13.5 ml/kg of F20 (1 ml has 0.2 g of PFC), and the third received 13.5 ml/kg of P100 diluted to a 20% concentration (P20). All rabbits were scanned by a blinded sonographer before, during, and immediately after infusion, and then again at 30 minutes and 48 hours. Doppler enhancement, echogenicity of inferior vena cava lumen, echogenic enhancement of perfused tissues, and reticuloendothelial organs were assessed. RESULTS: P100 and P20 had nearly identical sonographic properties at all points. During their vascular phase they enhanced Doppler signal, filled the lumen of the IVC and hepatic veins with flowing echogenic reflectors, and enhanced perfused tissues. F20 had no detectable sonographic effect during its vascular phase. All three emulsions enhanced the liver relative to kidney to a similar degree at 48 hours. CONCLUSIONS: Because RE enhancement was similar for F20, P100, and P20, and because P100 and P20 had similar properties during the vascular phase, the lack of vascular effect of F20 could not be due to the different PFCs used in these agents, or due to the difference in the dilution or volume. The most likely cause for the observed sonographic behavior of F20 and P100 is the difference in emulsion formulation.

Perfluoroctylbromide. Acute hemodynamic effects, in pigs, of intravenous administration compared with the standard ionic contrast media.

Perfluoroctylbromide (PFOB) is a relatively new noniodinated contrast media that, after intravenous administration, produces prolonged opacification of the blood pool and subsequently selectively enhances the liver and spleen on computed tomography. There has been concern regarding the hemodynamic effect of this agent but little actual knowledge exists in this regard. Accordingly, the acute transient hemodynamic effects of PFOB emulsion were evaluated in five pigs and compared with the standard ionic contrast agent meglumine sodium diatrizoate (Renografin-76). Left ventricular (LV) pressure, internal diameter, and wall thickness were monitored during the alternate intravenous administration of 930 mg/ml PFOB and 370 mg/ml R-76 at a rate of 20 mls/second for a total volume of 1 ml/kg body weight. Renografin-76 caused a significant decrease in LV pressure and dp/dt (rate of change of LV pressure), and an increase in LV end-systolic diameter and a decrease in LV end-diastolic wall thickness. PFOB caused no change in LV pressure and dimensions. Thus, rapid intravenous administration of PFOB does not induce significant acute alterations in left ventricular pressure, dp/dt, dimension, or wall thickness.