Perfluoroctylbromide contrast enhancement of malignant neoplasms: preliminary observations

Fluorocarbons have been used for years as propellants in aerosol sprays. Because of their ability to transport oxygen, perfluorocarbon compounds have been more recently used in artificial fluid respiration. Monobrominated perfluorocarbon compounds are radiopaque and have low enough vapor pressures to be tolerated in biologic systems. Microemulsions of these compounds have been detected in mouse and rat neoplasms and appear to be located within macrophages. In this study of the potential usefulness of these compounds for radiographic contrast enhancement, rabbits with V2 carcinoma thigh implants received either a high-dose (10--12 ml/kg) or a low-dose (2 ml/kg) emulsion of perfluoroctylbromide intravenously. Dense contrast enhancement of some of the V2 carcinomas was demonstrated by both computed tomography and conventional radiography. Four of the five rabbits in the high-dose group died within 9 days but all six rabbits in the low-dose group survived beyond 9 days. Death in the high-dose group was associated with pulmonary consolidation and anesthesia although some animals had extensive V2 metastases. These compounds have some interesting potential applications in imaging, pending further study of their toxicity.     

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.     

Evidence for spleen-specific uptake of a microbubble contrast agent: a quantitative study in healthy volunteers

PURPOSE: To evaluate the pharmacokinetics of the microbubble contrast agent BR1. MATERIALS AND METHODS: Twenty healthy volunteers were injected via arm vein with a 1.2-mL bolus of BR1. Ultrasonographic images of liver and right kidney and of spleen and left kidney were obtained intermittently for 5 minutes with low-mechanical-index software (to minimize microbubble destruction) that shows stationary microbubbles in green. Percentage total uptake was calculated as the number of green pixels in the region of interest for each organ over time, divided by the total pixels. Relative uptake, the ratio of total uptake in liver to that in right kidney and of total uptake in spleen to that in left kidney, and differential uptake, the difference in total uptake between liver and right kidney and between spleen and left kidney, were calculated. Total uptake for each organ was plotted against time, and the gradient of a best-fit straight line was calculated. Wilcoxon signed rank test was used to compare mean uptake values in each subject. Mann-Whitney U test was used for comparisons in sex and age. RESULTS: Total uptake declined over 5 minutes in left and right kidney and in liver (from 88% +/- 10% [1 minute] to 67% +/- 14% [5 minutes]), but not in spleen (range, 90%-99%). Mean relative uptake +/- 1 SD for spleen increased from 2.3 +/- 0.7 (1 minute) to 3.7 +/- 2.3 (5 minutes) (P =.005) but for liver was constant: 2.1 +/- 0.9 (1 minute) and 2.3 +/- 0.4 (5 minutes) (P =.06). Mean differential uptake +/- 1 SD for spleen increased from 51.3% +/- 14.9% (1 minute) to 65.0% +/- 9.1% (5 minutes) (P =.002). Significant difference was seen over time in total uptake gradients between spleen and left kidney (P =.014) but not between liver and right kidney or right and left kidney. No difference was seen between men and women or with age. CONCLUSION: BR1 produces spleen-specific enhancement that is longer (5 minutes) than the blood pool phase.     

Perfluoroctylbromide as a contrast agent for computed tomographic imaging of septic and aseptic arthritis

Perfluoroctylbromide (PFOB), a perfluorocarbon macrophage-labeling contrast agent, was applied to computed tomographic imaging of septic and aseptic arthritis models in rabbits. Marked enhancement of induced pyarthrosis was observed in both the knee and the sacroiliac joint. Moderate enhancement was noted in tetracycline-induced synovitis of the knee. Sterile synovitis of the sacroiliac joint and simple knee joint effusion showed no enhancement. These results suggest that PFOB is a useful contrast medium for the diagnosis of and distinction between septic and sterile arthritis.     

Nano/microparticles and ultrasound contrast agents

Microbubbles have been used for many years now in clinical practice as contrast agents in ultrasound imaging. Recently, their therapeutic applications have also attracted more attention. However, the short circulation time (minutes) and relatively large size (two to ten micrometers) of currently used commercial microbubbles do not allow effective extravasation into tumor tissue, preventing efficient tumor targeting. Fortunately, more multifunctional and theranostic nanoparticles with some special advantages over the traditional microbubbles have been widely investigated and explored for biomedical applications. The way to synthesize an ideal ultrasound contrast agent based on nanoparticles in order to achieve an expected effect on contrast imaging is a key technique. Currently a number of nanomaterials, including liposomes, polymers, micelles, dendrimers, emulsions, quantum dots, solid nanoparticles etc., have already been applied to pre or clinical trials. Multifunctional and theranostic nanoparticles with some special advantages, such as the tumor-targeted (passive or active), multi-mode contrast agents (magnetic resonance imaging, ultrasonography or fluorescence), carrier or enhancer of drug delivery, and combined chemo or thermal therapy etc., are rapidly gaining popularity and have shown a promising application in the field of cancer treatment. In this mini review, the trends and the advances of multifunctional and theranostic nanoparticles are briefly discussed.     

CT of the liver: a survey of prevailing methods for administration of contrast material

The members of the Society of Body Computed Tomography were surveyed to determine the most frequently used method of administering contrast material in CT studies of the liver. The respondents represented CT departments performing liver examinations in 22 institutions. No department relied solely on noncontrast scans. In 12 (54%) of 22 institutions, only contrast-enhanced scans were performed. The preferred dose for enhancement was 150 ml of 60% contrast material. Eight (36%) of the 22 respondents obtained images during the administration of a bolus of contrast material, whereas nine (41%) obtained images during the administration of a sustained drip infusion given after a loading bolus. Follow-up in 1987 revealed that two departments had switched to obtaining images during the administration of a bolus. The availability of CT power injectors and refinements in the rapid-scanning capabilities of CT scanners have increased the popularity of obtaining images of the liver during the administration of a bolus of contrast material. Despite this, in many departments, contrast material is still administered via drip infusion in CT studies of the liver.     

Advertising of contrast material: a developing problem

Problems exist when indications for the use of new contrast agents and new indications for the use of conventional contrast agents are considered in relation to advertisements. Ultimately, the consumer pays the cost of expensive FDA testing, often to prove what is already obvious. Other medically indicated uses of a contrast agent may remain unapproved because there is no financial incentive to seek approval, and needed modifications in already approved advertisements may not be sought for the same reason. A cooperative effort among manufacturers, radiologists, and the FDA is needed to improve the process.     

超声造影在肝脏疾病中的应用进展

随着一代代新型超声对比剂的相继问世和造影成像技术的不断发展 ,超声造影成像已成为超声医学界关注的热点 ,其在肝脏疾病诊断、鉴别诊断与肝肿瘤非手术治疗疗效监测中的应用不但广泛 ,而且具有独到的优点和重要的临床价值。本文综合文献资料 ,对超声对比剂与成像技术加以概括 ,并将超声造影在肝脏疾病中的临床应用现状与进展进行综述。     

Magnetite albumin microspheres: a new MR contrast material

A superparamagnetic MR contrast agent was synthesized by incorporating 150-250-A particles of magnetite (Fe3O4, Fe2O3) in 1-5 microns human serum albumin microspheres. Magnetite albumin microspheres (MAM) target almost exclusively to the reticuloendothelial system after IV administration, are stable in vitro and in vivo, and possess a long shelf life. The agent has a large magnetic susceptibility effect that selectively reduces T2 with little effect on T1. Biodistribution studies that use a dose of 20 mg MAM/kg show prompt clearance from the blood pool with marked decrease in T2 for rat liver (40%) and spleen (45%) with a small decrease in liver (5%) and spleen (10%) T1 values. Pulmonary T1 and T2 decrease transiently over the first 24 hr, while no significant changes were observed in other tissues. Imaging of a rabbit VX2 tumor model resulted in a 200% increase in the contrast ratio of VX2 tumor to normal liver on T2-weighted and mixed T1-/T2-weighted pulse sequences after administration of contrast agent. The extreme potency, excellent targeting, and apparent lack of toxicity of this agent suggest that MAM probably will have a clinical application in detecting focal hepatic and splenic lesions.     

Hepatic transit time of ultrasound contrast in biopsy characterized liver disease

PURPOSE: To study the hepatic transit time of an ultrasound contrast agent in patients with liver disease, and to evaluate the mechanism(s) of the well-established shorter cubital vein to hepatic vein transit time in cirrhosis. MATERIAL AND METHODS: Thirty-four patients scheduled for Menghini liver biopsy were studied by ultrasound after injection of 2.5 g Levovist (Schering, Berlin, Germany) into an arm vein. The time from injection until the first appearance of contrast echoes in the hepatic artery and hepatic veins was registered. Hepatic transit time was the difference between the two. RESULTS: Biopsy showed cirrhosis in 9 patients, other diffuse hepatic pathology in 23 patients, and normal liver in 2 patients. Mean hepatic vein arrival time was earlier in cirrhosis than in other liver disease (19.4 s versus 26.0 s; P = 0.013), and hepatic transit time was shorter (6.6 s versus 11.6 s; P = 0.024). A hepatic transit time <10 s was found in all patients with cirrhosis, but also in 10 of 23 patients with other liver pathology. CONCLUSION: Hepatic transit time measurement could not be used to distinguish between cirrhosis and other hepatic pathology, but a transit time = 10 s excluded cirrhosis. The earlier hepatic vein arrival time in cirrhosis is apparently mainly caused by intrahepatic shunting rather than by early arrival of contrast to the liver.     

Additional value of contrast enhanced intraoperative ultrasound for colorectal liver metastases

BACKGROUND: Substantial recurrence rates following partial liver resection for colorectal liver metastases (CRM) imply that small metastases remain undetected using intraoperative ultrasound (IOUS). The aim of this study was to evaluate the additional value of contrast enhanced IOUS (CE-IOUS) when compared to preoperative contrast enhanced computed tomography (CE-CT) and IOUS in liver surgery for CRM. METHODS: After obtaining informed consent, 39 consecutive patients with CRM were included prospectively for evaluation. The study population consisted of 26 male and 13 female patients with a median (range) age of 62 (49-83) years. A lesion-per-lesion analysis was performed with histopathological examination as the reference standard after resection and follow-up for unresected lesions. The added value of CE-IOUS in correctly diagnosing malignant lesions was statistically evaluated, using receiver operating characteristic curves. RESULTS: A total of 234 lesions were identified, 137 of which were malignant, according to the reference standard. The addition of CE-IOUS did not improve the diagnostic accuracy when compared to the combination of CE-CT and IOUS (P=0.617). In one of two patients with newly detected lesions on CE-IOUS the extent of resection changed. CONCLUSIONS: The addition of CE-IOUS to preoperative CE-CT and IOUS does not improve the ability to characterize already detected lesions. In a small number of patients it appears to facilitate the detection of new metastatic lesions with implications on surgical strategy.     

Role of contrast enhanced ultrasound in characterization of focal liver lesions

Aim

The purpose of the study was to describe the enhancement patterns of focal liver lesions (FLLs) on contrast enhanced sonography (CEUS), assessing the potential of this technique for characterizing the lesions and to compare its diagnostic accuracy with conventional baseline sonography including color Doppler.

Materials and methods

Between August 2009 and July 2010, 50 patients with FLLs underwent gray scale sonography, color Doppler and CEUS. The enhancement patterns of these FLL’s were analyzed throughout the arterial phase, the portal venous phase and the extended portal venous phase (the late parenchymal phase). The final diagnosis was established on the basis of histopathologic examination or CT/MRI imaging.

Results

Out of these 50 FLLs, 33 were malignant (4 hepatocellular carcinoma and 29 metastasis) and 17 were benign (5 hemangioma, 5 abscess, 2 cyst and 1 each of FNH, focal fat sparing area, focal fatty infiltration, adenoma and benign/granulomatous lesion). The enhancement patterns after injecting microbubble contrast agent allowed characterization of FLLs. The malignant lesions showed intratumoral and/or peritumoral vascularity during the arterial phase and perfusion defect during the late parenchymal phase. Contrast enhanced sonography improved sensitivity in detecting malignancy (CEUS vs. baseline sonography, 100% vs. 81.8%).

Conclusion

CEUS improves detection and characterization of FLLs. It should be used as problem solving tool in cases where conventional gray scale and color Doppler sonography are non-diagnostic.     

Wideband harmonic imaging: a novel contrast ultrasound imaging technique

A novel ultrasonic imaging method, wideband harmonic imaging, for nonlinear imaging of microbubble contrast agents is evaluated. In wideband harmonic mode, two pulses of alternate phase are send out. The image is then processed from the sum of both pulses, resulting in an image of nonlinear scatterers such as microbubbles. A prototype ultrasound system, Siemens Elegra, was evaluated with in vitro investigations and animal trials, using conventional, harmonic and wideband harmonic settings with the galactose based ultrasound contrast agent Levovist. Wideband harmonic imaging offers superior sensitivity for ultrasound contrast agents compared to conventional imaging and harmonic imaging. At low transmit power settings (MI 0. 1-0.5) the nonlinear response is already sufficient to generate a image of the blood pool distribution of Levovist in the rabbit kidney including the microvasculature, with clear delineation of vessels and perfused parenchyma. At high transmit amplitudes, nonlinear tissue response reduced the apparent image contrast between contrast agent and tissue. The results suggest that wideband harmonic imaging is currently the most sensitive contrast imaging technique, maintaining highest spatial resolution. This may add to image quality and offer new clinical potential for the use of ultrasound contrast agents such as Levovist.