Technetium-99m low density lipoproteins: preparation and biodistribution.

The focal uptake by human atherosclerotic lesions of 125I bound to low density lipoproteins (LDL) can be demonstrated by external imaging. However, 125I has poor imaging characteristics. Therefore, we have developed a technique for labeling LDL with technetium. To facilitate analysis, LDL was first labeled with 99mTc, by reduction of TcO4- with dithionite in the presence of the protein. The labeled LDL was stable to electrophoresis, ultracentrifugation, and passage in vivo. This technique was repeated with minor modification with 99mTc to prepare [99mTc] LDL for use as an imaging agent. Its biodistribution in 16 rabbits was similar to that of [125I] LDL and it allowed high resolution external imaging of LDL uptake by tissues, including the injured, healing, arterial wall, and the adrenal cortex.

AUR Memorial Award 1992. Quantification of amino acids in human body fluids by 1H magnetic resonance spectroscopy. A specific test for the identification of abscess.

RATIONALE AND OBJECTIVES: When polymorphonucleocytes are incubated in proteinaceous fluid, they cause extensive protein degradation, which leads to accumulation of free amino acids. The authors tested whether these free amino acids, particularly valine and leucine, also accumulate in human abscess fluids, but not in other body fluids, and thus could be a specific and distinguishing marker for the presence of an abscess. METHODS: Thirty fluids, obtained by percutaneous drainage from 28 patients, were lyophilized and reconstituted in 2H2O before in vitro 1H magnetic resonance (MR) spectroscopy. Concentrations of valine and leucine were determined by comparison of spectra before and after addition of known amounts of valine and leucine. Two chart reviewers, blinded to the spectroscopic results, categorized cases as abscess (n = 14), non-abscess (n = 15), or infection but not abscess (n = 1). RESULTS: The concentration of valine and leucine was significantly higher in the abscess fluids, 2.57 +/- 1.90 mM than in the non-abscess fluids, 0.25 +/- 0.33 mM (P < .001). The one infected fluid which was not an abscess had no amino acids. Using 0.8 mM as the threshold concentration of valine and leucine necessary for the diagnosis of abscess resulted in a sensitivity rate of 86% and a specificity rate of 94%. CONCLUSION: The authors conclude that identification of high concentrations of valine and leucine by 1H MR spectroscopy may be a specific test for the diagnosis of abscess. This technique merits further investigation in vivo.

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.

Gadolinium enhancement of the leptomeninges caused by hydrocephalus: a potential mimic of leptomeningeal metastasis.

A patient had severe hydrocephalus and diffuse leptomeningeal enhancement on MR which mimicked leptomeningeal spread of a primary brain tumor. The leptomeningeal enhancement resolved completely after decompression of the hydrocephalus. Data suggest that the leptomeningeal enhancement is caused by vascular stasis induced by the hydrocephalus.

Neuroimaging findings in rare amebic infections of the central nervous system.

The imaging findings in a case of panamebic meningoencephalitis and in a case of granulomatous amebic encephalitis, two rare infections of the central nervous system caused by amebae, are presented and the world literature is reviewed. The brain CT findings in panamebic meningoencephalitis are nonspecific; our case showed diffuse edema. In the case of granulomatous amebic encephalitis, there was evidence of large arterial occlusions and MR demonstration of spinal cord infarctions.

19F chemical shift imaging technique to measure intracellular pO2 in vivo using perflubron.

RATIONALE AND OBJECTIVES: There is a linear relation between the T1 relaxation rate of fluorine-19 (19F) of perfluorochemicals (PFCs) and the partial pressure of the oxygen (pO2) dissolved in the PFC. A line scan technique was used to overcome the significant chemical shift and low signal-to-noise ratio (SNR) of in vivo 19F magnetic resonance imaging. This study was designed to determine whether the line scan technique could detect the effect of oxygen on 19F T1. In addition, its ability to detect changes in intracellular pO2 when the inspired gas was raised from 20% to 100% O2 also was investigated. METHODS: The T1 relaxation rate of samples of perflubron emulsion diluted from 3.5% to 70% w/v and equilibrated with N2-O2 gas mixtures (pO2 range = 10-450 mm Hg) was measured using the line scan technique. The gas and emulsion pO2 were measured with a blood gas analyzer. The liver T1 relaxation rate was measured in three rabbits given 5 ml/kg perflubron emulsion 4 and 8 days earlier as they breathed room air and then 100% O2. We used a prototype cylindrical coil double-tuned to hydrogen-1 (1H) and 19F and selected a line through the liver. The scanning parameters yielded a voxel size of 20 x 20 x 15.6 mm. Liver and blood samples were obtained postsacrifice for perflubron concentration measurement. RESULTS: A linear relation between the 19F T1 relaxation rate (1/T1) of the 3.5% w/v emulsion and dissolved pO2 was established with a slope of 0.0033 (sec-1/mm Hg) and a correlation coefficient of .991. As the PFC concentration increased by 1,900%, the slope increased by 21.2%. The 1/T1 for the liver was 0.182 +/- 0.004 sec-1 at baseline. It increased to 0.247 +/- 0.022 sec-1 when rabbits breathed 100% O2 (p = .023), which corresponded to an increase in intracellular pO2 of 19.7 mm Hg. The liver-to-blood PFC concentration ratio was 500:1. CONCLUSION: In vitro measurements with the line scan technique replicated the established linear dependence of 1/T1 on pO2. In vivo measurements indicated a 20-mm Hg increase in intracellular pO2 of liver phagocytes when the inspired gas was changed from 20% to 100% O2.

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.