Perfluoroctylbromide Research Articles

Scalable and modular 8-channel transmit and 8-channel flexible receive coil array for 19 F MRI of large animals.

To introduce an RF coil system consisting of an 8-channel transmit (Tx) and 8-channel receive (Rx) coil arrays for 19 F MRI of large animals. The Tx efficiency and homogeneity of the 8-element loop coil array (loop size: 6× 15 cm2 ) were simulated for two different pig models rendered from MR images. An 8-channel Rx coil array consisting of a flexible 6-channel posterior and a 2-channel planar anterior array was designed to fit on the abdomen of an average-sized pig in supine position. Measurements were performed in a grid phantom and ex vivo on a pig model with perfluoroctylbromide (PFOB)-filled tubes inserted in the thorax. Measured and simulated Tx efficiency and homogeneity for the 8-channel and 5-channel arrays were in good agreement: 1.87 ± 0.22μT/√kW versus 1.96 ± 0.29μT/√kW, and 2.29 ± 0.39μT/√kW versus 2.41 ± 0.37μT/√kW. An isolation of 38 ± 8dB is achieved between the 19 F Tx and Rx elements, and over 30dB between the 1 H and 19 F elements. The PFOB-filled vials could be clearly identified within the cadaver abdomen with an SNR of 275 ± 51 for a 3D gradient-echo sequence with 2-mm isotropic resolution and 12 averages, acquired in 9:52 min:s. Performance of the Tx array was robust against phase and amplitude mismatches at the input ports. A modular and scalable Tx array offers improved Tx efficiency in 19 F MRI of large animals with various sizes. Although conventional birdcage coils have superior Tx efficiency within the target region of interest, scalability of the Tx array to animal size is a major benefit. The described 19 F coil provides homogeneous excitation and high sensitivity detection in large pig models.

Echogenicity enhancement by end-fluorinated polylactide perfluorohexane nanocapsules: Towards ultrasound-activable nanosystems.

We have synthesized novel fluorinated polyesters and formulated them into nanocapsules of perfluorohexane as ultrasound contrast agents. This nanosystem has been thoroughly characterized by several techniques and we show that fluorination of the biodegradable polymer favors the encapsulation of perfluorohexane without producing further reduction of cell viability. Contrary to nanocapsules of perfluoroctyl bromide formulated with the fluorinated polymers [32], the presence of the fluorinated moieties leads to an increase of echogenicity that is dependent of the length of the fluorinated moiety. Morevover, the ability of nanocapsules to explode when submitted to focused ultrasound also depends on the length of the fluorinated chain. These results pave the way to theranostic perfluorohexane nanocapsules co-encapsulating a drug for precision delivery using focused ultrasound.

新造影剤、Perfluoroctyl Bromide の気管支ならびに肺胞造影に関する基礎的および臨床的研究

新造影剤、Perfluoroctyl Bromide の気管支ならびに肺胞造影に関する基礎的および臨床的研究

Blood substitutes: where do we stand today?

Blood substitutes: where do we stand today?

Perfluorocarbons in the Twenty-First Century: Clinical Applications as Transfusion Alternatives

The risks of allogeneic transfusion are well known to physicians and have prompted a search for alternatives. Perfluorocarbons were introduced into clinical trials in the early 1980's with the hope that these products would develop into acceptable blood substitutes. Unfortunately, the limited potency, short half-life, and potential toxicity of these early formulations coupled with unrealistic expectations for efficacy prevented the perfluorocarbons from playing a significant role in transfusion medicine. Recent changes in formulation to improve efficacy and eliminate toxicity have stimulated renewed interest in perfluorocarbons as alternatives to allogeneic transfusion. Our recent work has focused on the role of perfluoroctylbromide (PFOB), a second generation perfluorocarbon, as an adjunct to autologous transfusion and acute normovolemic hemodilution (ANH), rather than as a total blood substitute. Initial animal experiments have shown the ability of small doses of PFOB to maintain oxygen delivery without the need for blood transfusion in the setting of hemodilution. Our presentation will focus on subsequent clinical work using PFOB as an alternative to both allogeneic and autologous blood transfusion during ANH. We believe that perfluorocarbons such as PFOB will have a significant role in the future as one of several, additive alternatives to blood transfusion.

Perfluoroctyl bromide as a blood pool contrast agent for computed tomographic angiography

We determined whether perfluoroctyl bromide (perflubron) could be used as a computed tomography (CT) angiographic agent by studying vessel visibility (celiac artery, superior mesenteric artery [SMA], and renal arteries) with spiral CT and three-dimensional (3D) reconstructions. Five rhesus monkeys were examined with a perflubron emulsion (90% [w/v] perfluorochemical; administered intravenously at a dose of 1.5 ml/kg and at a rate of 0.5 ml/sec. Spiral CT was performed immediately and at 5 hr after injection. Three dimensional images of the aorta at the level of the celiac artery, SMA, and renal arteries were reconstructed and blindly rated 0-4 (0 = not seen; 4 = excellent visualization) by two observers. All the vessels had the best ratings immediately after injection: celiac artery, 2.8 +/- 0.42; SMA, 2.7 +/- 0.48; left renal artery, 2.1 +/- 0.99; and right renal artery, 1.2 +/- 1.03. The ratings after the 5-hr delay were as follows: celiac artery, 1.3 +/- 1.34; SMA, 1.5 +/- 1.08; left renal artery, 1.5 +/- 0.97; and right renal artery, 1.2 +/- 0.79. Spiral CT angiography with a perflubron emulsion successfully demonstrated all vessels immediately and at 5 hr after contrast agent infusion. Further refinements of the dose, rate, and reconstruction technique are expected to increase vessel visibility over this wide imaging window.

High-Resolution Computed Tomographic Bronchiolography Using Perfluoroctylbromide (PFOB)

The use of perfluoroctylbromide (PFOB), a liquid ventilatory agent, was evaluated as a computed tomographic contrast agent to visualize small airway anatomy to the level of the centrilobular bronchiole, normally not visible on high-resolution computed tomography (HRCT). A freshly excised neonatal lamb heart-lung preparation was tracheally intubated, suspended in a saline bath, and mechanically ventilated with gas. After obtaining HRCT control images with suspended respiration using continuous positive airway pressure, 30 ml of perfluorocytlbromide was instilled into the trachea and repeat scans were obtained. These images demonstrated PFOB filling and distending the airways to the level of the centrilobular bronchioles and their first order branches. There was only minimal spillage into air spaces, allowing excellent anatomic detail of the bronchiolar structures. A liquid ventilatory agent, PFOB is a superb candidate as a bronchographic contrast agent due to its promotion of gas exchange, low toxicity, low surface tension, radiopacity, and vaporized excretion via the lung. It has great potential to evaluate small airway disease when used in conjunction with HRCT.

Reblurred deconvolution method for chemical shift removal in F-19 (PFOB) MR imaging.

Perfluorocarbons such as perfluoroctylbromide (PFOB) can be used as contrast agents in the vascular system for fluorine-19 magnetic resonance imaging or as synthetic oxygen carriers. F-19 imaging has been proposed for studying the vascular system, capillary flow, tissue perfusion, and tumor oxygenation. A major difficulty is that F-19 compounds often have complex multipeak spectra. These peaks result in chemical shift artifacts, lower signal-to-noise ratios, and blurred images. Each peak also excites a different section when a section-select gradient is applied. Direct inverse filtering is the simplest deconvolution method for correcting such artifacts; however, two major difficulties present themselves: functional singularity and noise amplification at high frequencies. The use of a new reblurred deconvolution (RED) method appears to overcome these problems. Although this method is based on iterative deconvolution in the spatial domain, the computational overhead is negligible. Since the point spread function and object data are already available in the time domain as FID data, RED appears to be useful for eliminating chemical shift artifacts and suppressing noise amplification while restoring the original image without loss of resolution.

Perfluoroctylbromide as a gastrointestinal contrast agent for MR imaging: use with and without glucagon.

The utility of perfluoroctylbromide (PFOB) as a gastrointestinal contrast agent for magnetic resonance (MR) imaging was evaluated with MR examinations performed in 30 subjects (16 healthy volunteers and 14 patients). Transaxial T1-, proton density-, and T2-weighted MR images were acquired in each subject before and after the administration of PFOB. The healthy volunteers each underwent two sets of post-PFOB MR examinations, one before and one after glucagon administration. The degree of bowel marking, clarity of bowel-wall visualization, ability to distinguish bowel from adjacent parenchymal organs, and severity of phase-encoding artifacts were independently analyzed by two reviewers. Oral administration of PFOB significantly (P less than .001) increased the percentage of bowel loops with low signal intensity. Subcutaneous administration of glucagon significantly (P less than .001) increased the clarity of bowel-wall visualization on post-PFOB MR studies. The severity of phase-encoding artifacts did not change substantially after administration of PFOB or glucagon.

Dose Related Biodistribution & Elimination of 100% PFOB Emulsion

Perfluoroctylbromide (PFOB) has been applied successfully as an oxygen carrier and a contrast agent for X-ray, computed tomography, ultrasound and Magnetic Resonance Imaging (MRI). Knowledge of the pharmacokinetics of emulsion particle uptake and elimination is critical for determining proper dose and timing of diagnostic studies. This study was intended to define major organ biodistribution and half-life as well as total body half-life as a function of dose.Determination of biodistribution and major organ half-life was achieved by administering 100% PFOB emulsion intravenously to 180 rats divided into 3 dose groups of 0.3, 0.6 & 1.0 g/kg. Each group was divided into 6 subgroups (n = 10; S male and 5 female). Each subgroup was sacrificed at either 6 or 90 min., 1,2,7, or 28 days post injection. 16 different tissue samples were collected and PFOB concentration determined by iso-octane extraction and gas chromatographic (GC) analysis. Total body half-life was determined by administering PFOB intravenously t...

Specific enhancement of intra-abdominal abscesses with perfluoroctylbromide for CT imaging.

Perfluoroctylbromide (PFOB), a radiopaque reticuloendothelial system contrast media for computed tomography, has been shown to accumulate in macrophages. In the current study PFOB was tested in rabbits as an abscess imaging agent. Two abscesses were induced in each of 24 rabbits, one in the liver and the other in the peritoneal cavity. CT of the rabbit abdomen was performed four days later, two days after the administration of 5 gm/Kg of PFOB to 12 of these rabbits. The average enhancement of the wall of liver abscesses was by 140 Hounsfield units (HU) relative to the enhanced liver and peritoneal abscesses by 135 HU relative to the control group. This enhancement was secondary to the intense accumulation of PFOB filled macrophages in the abscess wall. In those rabbits where the liver abscess ruptured, the edges of the peritoneal collections enhanced by 147 HU. Regions of inflammation prior to liquifaction enhanced considerably. These areas could not be detected in the animals not receiving PFOB. Though the liquified center of liver abscesses could be seen in the absence of PFOB, none of the peritoneal abscesses could be detected in the animals not receiving PFOB. In contradistinction, all peritoneal abscesses enhanced considerably following PFOB allowing their prospective localization. In conclusion, PFOB accumulates in abscess walls and areas of inflammation producing marked CT enhancement of liver and peritoneal abscess collections. This enhancement allowed the differentiation of peritoneal abscess collections from adjacent bowel.

Perfluoroctylbromide as a blood pool contrast agent for liver, spleen, and vascular imaging in computed tomography.

Perfluoroctylbromide (PFOB) in emulsion form was tested as a blood pool imaging agent for computed tomography (CT) in five animals (three dogs and two pigs). Computed tomography of the kidneys, liver, spleen, and mediastinum was performed in the control state and at various time intervals after the end of PFOB infusion. The attenuation coefficient of the vascular space increased by 117 Hounsfield units (HU) (range 105-128 HU), the liver by 54 HU (range 43-70 HU), and the spleen by 77 HU (range 69-86 HU) 30 to 50 min after the end of PFOB infusion, 5 ml/kg. The vascular space enhanced by 25 HU for every g of PFOB/100 ml of blood and remained at almost a constant level for hours after the end of infusion. In conclusion, PFOB emulsion, in addition to hepatosplenic enhancement, produces prolonged and substantial opacification of the vascular space, allowing CT imaging of the heart and vascular structures minutes to hours after the end of infusion.

Ultrasonic enhancement of myocardial infarction with perfluorocarbon compounds in dogs

Fluosol-DA 20%® (Fluosol) and perfluoroctyl-bromide (PFOB), 2 types of perfluorocarbon emulsions (PFCs), were evaluated as sound contrast agents in imaging acute myocardial infarction (Ml) 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 Ml or localized to the rim. Initial studies suggest that the mechanism of enhancement is related, at least in part, to the accumulation of RFC-filled macrophages within the MI.

Perfluoroctylbromide: a liver/spleen-specific and tumor-imaging ultrasound contrast material.

The effect of perfluoroctylbromide (PFOB) on liver and tumor echogenicity was evaluated in rabbits. The echogenicity of the kidney, which is not affected by PFOB, was used as the basis for comparison in the liver studies. For the liver echogenicity study, sonography was performed on four rabbits, two with PFOB and two without PFOB, and four rabbits prior to and following the intravenous administration of 5 ml/kg PFOB. All livers were equal to or less echogenic than kidney in the control animals. All livers became more echogenic than kidney two days after administration of PFOB. The effect of PFOB on tumor echogenicity was evaluated in 18 rabbits with VX2 tumor implanted in the liver. Ultrasound studies of all rabbits were performed by the same physician before and two days after half the rabbits had received PFOB (5 ml/kg intravenously). The reviewers correctly identified all rabbits that received PFOB by visualization of an echogenic rim around the hepatic tumors.

Perfluoroctylbromide: a reticuloendothelial-specific and tumor-imaging agent for computed tomography.

Perfluoroctylbromide (PFOB) was evaluated as a liver/spleen-specific and tumor imaging agent in 30 rabbits implanted with VX2 tumors. Computed tomographic (CT) scanning of all rabbits was performed after sacrifice. Half of the animals were given 5 ml/kg of PFOB emulsion intravenously 48 hours prior to sacrifice. Twenty rabbits were used for anatomic correlation and ten for histologic analysis. PFOB concentration was measured in normal liver and spleen in eight rabbits at two days, in six rabbits at seven days, and in six rabbits at 14 days after PFOB administration (5 ml/kg, intravenously). PFOB increased the CT numbers of the liver by 49 HU and the spleen by 250 HU. More important for diagnostic purposes, PFOB produced dense enhancement of the rim of the tumor. The density of the rim of the tumor was increased by 102 HU as a result of accumulation of PFOB in macrophages at the periphery of the tumor. The half-life of PFOB in the liver and the spleen was approximately five days.

CT determination of renal and hepatic microvascular volumes in experimental acute renal failure.

Alterations in renal blood flow are considered to play an important role in the pathogenesis of acute renal failure. Most techniques designed to assess organ blood flow and microcirculatory disturbances are relatively invasive and cumbersome. This study describes a noninvasive method for the determination of an organ's fractional vascular volume (FVV)-the fraction of an organ occupied by blood vessel lumen. It utilizes computed tomographic (CT) scanning and a contrast agent, perfluoroctylbromide (PFOB), which remains intravascular and is not excreted by the kidney. Acute renal failure (ARF) was induced in rats by intraperitoneal injection of glycerol (5 g/kg). CT scans of kidneys, liver, and heart were performed prior to and following intravenous administration of PFOB. FVV of kidney and liver were calculated prior to induction of ARF and at selected time periods following ARF (20-50 minutes and 60-120 minutes). FVV of the kidney decreased significantly 20-50 minutes following ARF and had returned to control values at 60-120 minutes. Renal histologic abnormalities were more severe at the later time period. Thus, early alterations in blood flow precede pathologic abnormalities in the kidney following glycerol-induced ARF. Determination of an organ's fractional vascular volume is a simple noninvasive technique which provides useful information on the microcirculation during the course of experimental disease.

Failure of iosulamide to enhance hepatic tumors in rats.

Iosulamide, an experimental cholangiographic agent recently being evaluated for hepatic contrast enhancement in computed tomography, has been investigated in the rat for the differential enhancement between the liver and three histologically different experimental tumors (a well differentiated mammary adenocarcinoma, a poorly differentiated colon carcinoma, and a hepatoma). After intravenous injection of iosulamide in dosages of 140 and 280 mg iodine per kg, iodine concentrations were determined in blood, liver and tumors at 1, 5, 10, and 30 minutes, using x-ray energy spectrometry. Compared with the surrounding liver parenchyma, the iodine concentrations were generally higher in the breast carcinoma. With respect to the liver, iodine concentrations varied greatly in the colon carcinoma and hepatoma. The iodine washout from all three tumors was relatively slow. Since the distribution volume of cholangiographic contrast agents includes both vascular and interstitial space, the relatively high and prolonged iosulamide accumulation in tumors can be explained by a relatively large interstitial compartment, which is apparently characteristic of neoplastic lesions. This, together with the modest iodine concentrations found in the liver, suggests that iosulamide is of little use in computed tomography for the differential enhancement of liver and hepatic tumors.

Perfluoroctyl Bromide Emulsions as Radiopaque Media

Brominated perfluorocarbon compounds are a new and unique type of contrast agents. These compounds are biologically inert and chemically stable. Highly concentrated (8:l to 10:l by volume) oil in water emulsions have been found to be stable and non-irritating and useful in bronchography in humans and animals and in angiography in animal studies. The physical properties of these unusual emulsions have been investigated. The emulsiona have non-Newtonian properties, low interfacial tensioas and a broad distribution of particle size.The emulsion, as well as the pure compounds, has been the subject of an IND application with the Food and Drug Administration. The investigations on the use of the emulsion in bronchography and the pure compounds in alveolography md gastroen-terography are on going and are in Phase II of the IND.