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.

Use of perfluorooctylbromide (PFOB) to detect liver abscesses with computed tomography. Safety and efficacy.

Although perfluorooctylbromide (PFOB) is known to stimulate macrophages, particulates given intravenously (IV) can inhibit the body's response to infection by blocking the reticuloendothelial system. Since PFOB enhances abscesses on computed tomography (CT), the authors evaluated its safety and efficacy by assessing the mortality and abscess volume in 104 rabbits with intrahepatic abscesses given either PFOB or lactated Ringer's (LR), and by comparing its efficacy to that of 76% meglumine sodium diatrizoate (MSD76). Abscesses were produced by injecting a virulent strain of E. coli into the liver. Two days later, five of the rabbits had died. Of the remaining rabbits, 50 were given 5 g/kg PFOB IV, and 49 were given an equal volume of LR. All rabbits had a CT scan at four and at ten days after infusion. They were killed before the second CT scan. Thirty seconds before being killed, 28 rabbits given LR were given a bolus of 2 ml/kg MSD76 IV. Following CT, rabbits were frozen, sliced, and photographed. Abscess volumes were calculated by digitizing the photographs of the anatomic sections and the CT images. MSD76 enhanced the liver by 105 Hounsfield units (HU) more than the liquefied abscess center. The abscess wall enhanced to the same degree as liver, resulting in nonvisualization of three of six abscesses less than 3 mm in size, and a 30% underestimation of true abscess volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Potential role of PFOB enhanced sonography of the kidney. I. Detection of renal function and acute tubular necrosis.

Perfluorooctylbromide (PFOB) enhances the echogenicity of perfused tissues on sonography. Since PFOB is not filtered and is limited to the intravascular space, the particles are concentrated in the vasa rectae as they travel across the osmotic gradient. Because sonography has been unable to detect renal function, we aimed to determine whether sonography when aided by PFOB could detect and distinguish the normal from the abnormal osmotic gradient. The sonographer, unaware of rabbit assignment, imaged both kidneys in 17 rabbits before and 24 hours after the temporary occlusion of one of the renal arteries and then again after the infusion of up to 5 ml/kg of PFOB (N = 10) or saline (N = 7). Two normal rabbits were imaged before and after PFOB infusion and then again after i.v. furosemide. Without PFOB, the normal and impaired kidneys were indistinguishable. The echogenicity of the medulla which was darker than cortex in normal kidneys became brighter than cortex after PFOB (increased by 117% +/- 10%; P less than 0.01). PFOB, which was visible in the renal medulla on real-time sonography, produced an echogenic gradient that increased in brightness towards the papillary tip. Because the medulla of kidneys with ATN mildly increased in brightness after PFOB (increased by 40% +/- 7.8%; P less than 0.01), and because the echogenic gradient produced by PFOB was reversed (decreased in brightness towards the papillary tip), ATN kidneys were distinguished from normal kidneys in all 10 rabbits after 2.5 ml/kg PFOB. Medullary echogenicity produced by PFOB in normal kidneys was lost after furosemide.(ABSTRACT TRUNCATED AT 250 WORDS)

IV injection of air-filled human albumin microspheres to enhance arterial Doppler signal: a preliminary study in rabbits.

When air-filled human albumin microspheres are injected IV, they have been shown to traverse the pulmonary circulation and markedly influence the echogenicity of the left atrium and ventricle. We studied the possibility that the microspheres can be used to enhance the Doppler signal from systemic arteries and the portal vein. Doppler sonography of the aorta, renal artery, intrarenal branch, and portal vein was performed after the IV injection of saline or microspheres in doses of 1.0, 0.5, 0.3, and 0.1 ml in four rabbits. With appropriate blinding of the observers, subjective estimates of enhancement of the Doppler signal were made in each case. All injections of saline had no detectable effect. All four doses of microspheres enhanced the Doppler signal in the aorta in all rabbits. Signals from the renal artery enhanced in all rabbits after injections of 0.3 ml or greater, but in only two rabbits after 0.1 ml. Although the 1.0-ml dose enhanced the Doppler signal from the intrarenal arterial branch in all rabbits, the 0.5- and 0.3-ml doses enhanced signals in two and the 0.1-ml dose in one. The effect was typical for bolus IV injections. The mean time from injection to onset of enhancement was 5 sec and the effect lasted for 12 sec. Portal venous signals were evaluated in three rabbits. Ten injections were made, four at 1.0 ml and two at each of the lesser doses. Portal vein signals enhanced after all four injections of 1.0 ml of microspheres but after only one of the six injections of lower doses. Our results show that the IV injection of air-filled human albumin microspheres enhances the Doppler signal from systemic arteries and the portal vein and that the microspheres have the potential to serve as a contrast agent for Doppler sonography in humans.

Hemodynamic effects of intravenous lecithin-based perfluorocarbon emulsions in dogs.

We evaluated and compared the acute hemodynamic effects of perfluorooctylbromide-100% (PFOB), a fluorocarbon emulsified in lecithin without pluronic-F68 (F68), to those of a standard iodinated contrast agent, renografin-76% (R76), and Fluosol-DA 20% (Fluosol), a fluorocarbon emulsified in part by F68. Five open chest dogs were instrumented to evaluate hemodynamic changes after iv injection of PFOB (1 ml.1 g/kg) and R76 (1 ml.0.37 g of iodine/kg). Fluosol (1 ml.0.2 g/kg) was given to two of the five dogs at the end of their study. Fluosol caused transient hemodynamic collapse in both dogs. R76 caused the known transient effect of hypotension (-15.4 +/- 3.3%) followed by hypertension (6.5 +/- 2.7%) and an increase in aortic flow (29.3 +/- 3.9% at 30 sec). PFOB caused minimal, clinically insignificant decrease in aortic flow (4 +/- 1% at 10 sec).