Gas emulsions as ultrasound contrast agents. Preliminary results in rabbits and dogs.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
R F Mattrey
Publications and source records attributed to R F Mattrey.
Perflubron as an oral contrast agent for MR imaging: results of a phase III clinical trial.
PURPOSE: To assess perflubron for magnetic resonance (MR) imaging in the abdomen and pelvis in a multicenter trial. MATERIALS AND METHODS: MR images were obtained in 127 subjects before and after ingestion of perflubron with T1-, proton-density-, and T2-weighted sequences at 0.38, 1.0, or 1.5 T. Postcontrast images were compared with baseline images, and percentage of additional bowel darkened, distinction of bowel from adjacent tissue, and change in image artifact were graded. RESULTS: Perflubron increased the bowel darkening in over 92% of subjects with all sequences and field strengths. It improved definition of the left lobe of the liver and body and tail of the pancreas in 67%, 29%, and 42% of subjects, respectively, and of the uterus and bladder in 80% and 76%. Abnormal tissue was more conspicuous in 69% of subjects. Highest scores were achieved when the upper abdomen was imaged 5-30 minutes and the pelvis 10-40 minutes after ingestion. No image artifacts or side effects were attributed to perflubron. CONCLUSION: Perflubron is safe, and its efficacy was unaffected by pulse sequences, magnetic field strength, or time delay.
Abdomen↗
Perfluorocarbon-enhanced sonography: value in detecting acute venous thrombosis in rabbits.
OBJECTIVE: We have previously shown that perfluorocarbon emulsions administered i.v. act as contrast material during sonography by creating moving echoes in veins. Accordingly, we performed a study on rabbits designed to establish the value of perfluorocarbon-enhanced sonography in detecting acute venous thrombi. MATERIALS AND METHODS: Constriction of the inferior vena cava (IVC) just above the renal veins was established surgically in 15 rabbits. Thrombus was induced in the IVC in 10 of these; the other five served as controls. Gray-scale and color Doppler sonography were performed before and after the i.v. infusion of 3 ml/kg of perflubron emulsion (formulation AF0102, Alliance Pharmaceutical, San Diego, CA). Sonograms were evaluated for the presence and extent of thrombus. Three additional rabbits with percutaneously induced IVC thrombosis were studied before and after the i.v. administration of 0.2 ml of a preparation of microbubbles of perfluorocarbon gas (formulation PRD002, Alliance Pharmaceutical). In these animals thrombi were confirmed at autopsy. RESULTS: Unenhanced sonograms allowed detection of thrombi in the IVC in nine of the 10 animals with surgically induced thrombus but were inaccurate in determining clot extent. Filling the lumen of the IVC with moving echoes created by administration of perflubron emulsion allowed more complete delineation of the size and extent of thrombus and permitted detection of residual venous flow not observed on unenhanced scans. The perfluorocarbon gas microbubbles provided similar benefits. CONCLUSION: Our results show that i.v. administration of perflubron emulsion or perfluorocarbon gas microbubbles improves imaging of veins on sonography and may aid in the assessment of thrombi.
Acute Disease↗
The potential role of perfluorochemicals (PFCs) in diagnostic imaging.
Although perfluorochemicals (PFCs) are known for their ability to carry oxygen, they are the most versatile and only universal contrast agents with important applications using x-ray, ultrasound, or magnetic resonance (MR). The characteristics that make them unique diagnostic agents are lack of hydrogen atoms, immiscibility with water, low surface tension, compressibility, and long intravascular persistence when emulsified and given i.v. When made radiopaque, they are visible with x-ray computed tomography (CT) and standard radiography. Because the neat liquid is inert it can be ingested, instilled in the lung, or introduced into any hollow organ to image the lumen without untoward effects. The long intravascular persistence allows the imaging of blood vessels and vascularized tissues. Small or deep vessels become visible on Color Doppler Imaging and angiographic images of any vascular tree including the coronaries can be rendered from the serial CT images. As PFCs accumulate within RE cells, specific liver and spleen enhancement is achieved allowing the detection of small tumors within these organs. When injected interstitially, the particles find their way to the draining lymphnodes providing detail of the internal architecture to detect the presence or absence of tumor involvement on both CT and sonography. Using 19F MR, tissue perfusion and tissue pO2 measurements can be achieved. As can be seen, the applications of PFC in diagnosis are vast, unique, and important. These new capabilities will carry radiological tools to new horizons.
Diagnostic Imaging↗
Monitoring of pO2 by spin-spin relaxation rate 1/T2 of 19F in a rabbit abscess model.
The purpose of this study was to confirm the relationship of T1 and T2 relaxation rate vs. pO2 in vivo of 19F MR signal measured from intracellular perflubron. Our work to date has demonstrated that 1/T2 is more sensitive to pO2 than 1/T1 in the in vitro environment. The advantage of 1/T2 vs. 1/T1 is the speed of measurement and sensitivity. Seven alternating T1 and T2 measurements were obtained during a continuous acquisition using the TTISS pulse sequence. An abscess model was used for the in vivo experiments where rabbits were infused with 5ml/kg Oxygent HT 10 days prior to scanning. The abscess model was used because it has been shown that perflubron accumulates in macrophages located in the abscess wall. This technique thus provided signal from the intracellular milieu. The results of this study proved that pO2 monitoring by measuring T2 of 19F is feasible and can be used in-lieu of the T1 measurement. Given that the T2 measurement is much more rapid than the T1 measurement and that T2 changes are more sensitive than T1 changes with alterations in pO2, T2 should prove to be practical and useful for monitoring transient rapid changes in pO2.
Abscess↗
Reducing magnetic susceptibility differences using liquid fluorocarbon pads (Sat Pad): results with spectral presaturation of fat.
Explore the source record for details and available documents.
Adipose Tissue↗
Efficacy of Imagent BP at 1.5ml/kg in a rabbit liver tumor model.
We have shown using a Vx2 rabbit model that 3 and 5ml/kg of perflubron emulsion were highly effective in imaging liver tumors. The results from preliminary clinical trials suggested that should the infusion rate be increased, a 1.5ml/kg may be efficacious. This study determined whether 1.5ml/kg given as a bolus IV would be efficacious to image liver tumors using a Vx2 rabbit model. Vx2 tumors were implanted in 5 NZW rabbits, CT of the liver was performed during held expiration at 80kV and 800mAS, before and shortly after 1.5ml/kg Imagent BP (ImBP), again at 30 minutes and 3 days. Regions of interest (ROIs) were drawn over the CT image of the spleen, liver, inferior vena cava, and tumor, CT# obtained and average enhancement of each tissue calculated at each time point. 4 animals had tumors .5cm or greater. Precontrast, tumors were faintly seen on CT. Blood was brighter than liver shortly after infusion and isointense with liver at 30 minutes. Tumors did not enhance following contrast. Except for the liver and spleen, all tissues returned to baseline on the 3rd day. Therefore a clinical trial to determine the efficacy of 1.5ml/kg ImBP to image the liver is warranted.
Animals↗
The use of Imagent BP as a blood pool contrast agent to visualize and quantitate liver tumor burden.
The accurate quantitation of liver tumor burden and visualization of lesions in three dimensions (3D) can assist in treatment planning and can allow monitoring of therapy. Previous attempts have used CT and standard contrast media. Because the iodinated agents rapidly diffuse into tumors, usually effacing, and at time enhancing tumor edges, they decrease accuracy and make image segmentation difficult. CT portography suffers from flow related artifacts and does not allow the distinction of tumors from hemangiomas. Blood pool contrast is ideal in this setting since it enhances liver, liver vessels and hemangiomas, but not tumors, 'physiologically' splitting the image into normal and abnormal tissues. This ongoing study assesses the feasibility of this technique to visualize tumor and presents a scheme to automatically quantitate tumor volume. It utilized a rabbit VX2 liver tumor model and CT scanning shortly after the infusion of 3 ml/kg perflubron emulsion. Cut sections of the frozen carcass served as gross pathologic correlation. Images were imported onto a Sparc workstation, 3D reformatted and tumor and liver volume calculated. Histograms of pixel intensity clearly separated tumors from liver and liver from surrounding structures allowing the easy demarcation of tumor and liver margins.
Animals↗
Polyarteritis nodosa presenting as acute orchitis: a case report and review of the literature.
We report a case of polyarteritis nodosa initially presenting as acute orchitis and review 4 similar reports in the literature. Of the cases 2 were diagnosed preoperatively. In 2 cases in which immunological markers were measured abnormal values were obtained. All 5 cases required biopsy for diagnosis.
Acute Disease↗
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.
Animals↗
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.
Blood Flow Velocity↗
Perfluorooctylbromide as a contrast agent for CT and sonography: preliminary clinical results.
OBJECTIVE: Perflubron emulsion is a bromine-based particulate contrast agent that is taken up selectively by the liver and spleen after IV injection. It does not leave the vascular space and also persists in the blood for a longer period than iodinated contrast agents do. We performed a preliminary study to determine the value of the IV perflubron emulsion as a contrast material for CT and sonography. SUBJECTS AND METHODS: To determine the safety and dose response of perflubron emulsion as an IV contrast agent for CT and sonography, 18 cancer patients, 14 of whom had hepatic metastases, were given 0.5-3.0 ml/kg of the emulsion. Sonography and CT of the liver and spleen were performed before and immediately after infusion and then again at 24 hr. RESULTS: A persistent increase in the density of blood, liver, and spleen was observed, where maximal enhancements of 55, 39, and 317 H, respectively, were achieved. Tumor conspicuity increased as metastases enhanced minimally (7 H or less). Peak enhancement of the liver and spleen was delayed to 24 hr with higher doses of perflubron; however, the immediate postinfusion scan allowed the distinction of vessels from hepatic lesions. Sonographically, an increase in tumor echogenicity relative to liver was observed in nine of the 14 subjects, allowing the detection of additional metastases in two. Splenic echogenicity in the near field increased relative to kidney; however, attenuation increased markedly at the time of peak concentration, limiting beam penetration. Similar but milder changes were observed in the liver. Adverse effects occurred in 14 of the subjects; these included lower back pain in six, delayed fever in eight, and malaise in three. CONCLUSION: Perflubron emulsion produced prolonged enhancement of blood, liver, and spleen and increased the conspicuity of liver metastases. However, the side effects encountered could limit its use to a selected population of patients.
Adult↗
Tubular ectasia of the testicle: sonographic and MR imaging appearance.
OBJECTIVE: Ectasia of the seminiferous tubules at the level of the mediastinum is a recently recognized benign condition of the testicles. Although it may have typical sonographic features, the condition can at times be difficult to distinguish from tumors on the basis of sonography. We describe the sonographic and MR appearance of this condition in seven men in whom we were able to distinguish tubular ectasia from tumors of the testicles on the basis of the imaging findings. MATERIALS AND METHODS: Ectasia of the seminiferous tubules was histologically proved in a man who had an intratesticular mass seen on sonograms and MR images. We analyzed the sonographic and MR imaging features in this man and in six others who had similar imaging findings but did not have biopsy proof of tubular ectasia. RESULTS: The first patient was a man with bilateral findings who had a unilateral orchiectomy that revealed ectasia of the seminiferous tubules. Spermatocelectomy was performed in another man whose testis was normal on surgical inspection and on subsequent follow-up. Imaging findings have remained unchanged in one man with 3-year imaging follow-up and in three men with clinical follow-up of 8-22 months. One patient was lost to follow-up. At presentation, most of the men were more than 55 years old. All had a scrotal mass typical of a spermatocele on physical examination, with normal testes when the testes could be palpated. The spermatocele was larger than 4 cm in six of 11 involved epididymides. On imaging, in five of the seven patients, the intratesticular process was bilateral, involved the mediastinum testis, began at the periphery adjacent to the spermatocele, and extended for a variable distance within the testis. On sonograms, the lesion was hypoechoic with coarse internal echoes. MR imaging of six of the seven patients showed characteristic findings and allowed the identification of two additional testicles with tubular ectasia that were missed sonographically. Lesions had a homogeneous signal similar to that of the coexisting spermatocele with all pulse sequences. They were hypointense relative to the testis on T1- and proton density-weighted images and, unlike tumors, were not visible on T2-weighted images. CONCLUSION: Our experience suggests that ectasia of the seminiferous tubules can be distinguished from testicular tumor on the basis of characteristic clinical, sonographic, and MR imaging findings. Thus, orchiectomy is unnecessary to establish the diagnosis and to rule out tumor.
Diagnosis, Differential↗
Value of brominated fluorocarbons for the radiographic diagnosis of small-bowel obstruction: comparison with other contrast agents in rats.
OBJECTIVE: The disadvantages of water-soluble gastrointestinal contrast agents include high osmolality, contrast dilution, and severe toxicity if aspirated. Perfluorocarbons are nontoxic in the lung and peritoneal cavity. Because perfluorocarbons are immiscible with water, they have no osmotic effect and cannot be diluted. Because these properties offer theoretical advantages over traditional gastrointestinal contrast agents, we compared two perfluorocarbons with barium and ionic and nonionic iodinated contrast material in a rat model of small-bowel obstruction. MATERIALS AND METHODS: Twelve groups of six rats each had ligation of the terminal ileum (obstruction model) or of the terminal ileum and mesenteric artery (obstruction with ischemia model). Each rat received 3 ml of barium, meglumine sodium diatrizoate, iohexol, neat perfluorooctyl bromide, neat perfluorohexyl bromide, or saline (control animals). Contrast media were given at the recommended concentrations, and their progression was evaluated on serial radiographs by an observer who was not aware of the model or the contrast medium given. When one contrast material reached the point of obstruction, all rats in the group were sacrificed and a final radiograph was obtained. Three radiologists, who were not aware of the contrast medium given, on two separate occasions independently reviewed the radiographs and ranked the contrast agents for their relative radiopacity, mucosal definition, speed of transit, gastric retention, and bowel distension. RESULTS: When data from both models were combined, perfluorocarbons were judged on the final image to be the most radiodense, to provide the sharpest mucosal detail, to have the least gastric retention, and to have faster progression than barium. Whereas meglumine sodium diatrizoate and iohexol reached the point of obstruction more rapidly than the perfluorocarbons and barium, they had the greatest gastric retention, caused the most bowel distension, and were the least radiopaque. CONCLUSION: Our results show that the radiopaque perfluorocarbons are suitable as gastrointestinal contrast agents and have favorable radiographic characteristics in this animal model. When these results are combined with the low-toxicity profile of perflubron, clinical evaluation of this agent for the radiographic assessment of bowel obstruction is warranted.
Absorption↗
Hypertrophic pyloric stenosis: volumetric measurement of nasogastric aspirate to determine the imaging modality.
Explore the source record for details and available documents.
False Negative Reactions↗
The use of Imagent BP in diagnostic imaging research and 19F magnetic resonance for PO2 measurements.
Imagent BP (90% w/v perflubron emulsion) is radiopaque and serves as an X-ray contrast medium. Quantitative X-ray Computed Tomography, provides the means to non-invasively estimate tissue perflubron concentration providing three unique capabilities: 1) The use of the same animal for biodistribution and elimination analysis; 2) The precise geographic distribution of the agent to more accurately quantitate localized accumulations; and 3) The ability to gather physiologic data by monitoring the time dependent distribution of perflubron. It is known that the T1(-1) of 19F of perfluorochemicals is linearly related to the dissolved oxygen which allows the quantitation of PO2 in-vivo. We showed using perflubron in phanta that not only was T1(-1) linearly related to PO2 but also T2(-1) and both were insensitive to perflubron concentration. Since flow interferes with signal, the first in-vivo experiments have focused on stationary perflubron located within phagocytes. T1(-1) measured from this environment suggested a PO2 of 15-25 Torr. T1(-1) increased by nearly 50% when the FIO2 was increased from 20 to 100% reflecting an increase in intracellular PO2 on the order of 25 Torr.
Animals↗
A prospective, randomized comparison of computed tomography with conventional diagnostic methods in the evaluation of penetrating injuries to the back and flank.
We prospectively compared computed tomography with conventional diagnostic methods in the evaluation of penetrating injuries to the back and flank in 85 patients. Immediate laparotomy was performed in 24 patients because of physical findings, and these patients were not randomized. Nine unnecessary operations were performed in this group, and these nine patients had significantly higher hospital costs than patients in either randomized group. In the randomized patients, there were only three true-positive and three false-positive findings. Both computed tomographic evaluation (31 patients) and conventional evaluation (30 patients) were highly accurate and specific for injuries that required operation. Evaluation with computed tomography required a longer time to make a hospital disposition but required fewer diagnostic tests. Computed tomography can be useful in the assessment of penetrating injuries to the back and flank.
Abdominal Injuries↗
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)
Animals↗