Incompatibility of water-soluble contrast media and intravascular pharmacologic agents. An in vitro study.

In vitro incompatibilities between nine water-soluble contrast media and 21 intravascular pharmacologic agents were investigated using naked-eye observation and a centrifuge. Most of the previously reported incompatibilities were verified, and a few new incompatibilities were discovered: phentolamine mesylate with diatrizoate sodium, diatrizoate meglumine, ioxaglate, and iothalamate; diatrizoate meglumine with diazepam and meperidine hydrochloride; and diatrizoate sodium with meperidine hydrochloride. There were no incompatibilities when the pharmacologic agents investigated were mixed with ioxithalamate, iopromide, iopamidol, and iohexol.     

Myocardial infarction: assessment with an intravascular MR contrast medium. Work in progress

The effect of a new intravascular magnetic resonance (MR) contrast medium (gadolinium diethylenetriaminepentaacetic acid [DTPA] polylysine) was evaluated in acute, subacute, and chronic myocardial infarctions in rats. Signal intensity (SI) was measured before and after intravenous administration of Gd-DTPA polylysine. Before administration of contrast material, chronic infarctions had lower SI than normal myocardium. With Gd-DTPA polylysine, three zones were identified in acute and subacute stages of myocardial infarction, but in the chronic stage, images demonstrated two zones. In acute and subacute infarctions, Gd-DTPA polylysine produced greater enhancement (over 60 minutes) in the peri-infarction zone than in the normal or infarcted myocardium. In chronic infarctions, Gd-DTPA polylysine had no discernible effect on the SI of the central infarction zone. Overall, it caused no significant hemodynamic effects. MR imaging with Gd-DTPA polylysine produced differential tissue enhancement in myocardial infarctions, which varied according to the age of the infarction.     

Early detection of extravasation of radiographic contrast medium. Work in progress.

Microwave radiometry is a passive and noninvasive technique that allows quick detection of subcutaneous temperature changes. The feasibility of this technique for differentiating normal intravenous infusions of radiographic contrast medium from extravasations of contrast medium was tested in anesthetized dogs. Room-temperature and heated ionic and nonionic contrast media were administered at flow rates ranging from 0.2 to 9.9 mL/sec by means of a power injector. On the basis of these experiments, an algorithm to adjust for extravasation detection thresholds as a function of injection flow rates was developed. With this algorithm, results showed a false-positive rate of 0% at all infusion rates and false-negative rates of 2%, 2%, and 4% at pump speeds of 0.2, 1.0, and 9.9 mL/sec, respectively. The times of these extravasation "alarms" corresponded to maximum extravasated volumes, respectively, of 4, 6.5, and 8 mL. Microwave radiometry has clinical potential for early detection of extravasation of contrast medium administered with power injectors.     

Pharmacokinetics of intravascular contrast agents in computerized tomography (author's transl)]

The pharmacokinetic behaviour of intravascular renal and biliary contrast agents is being evaluated with help of CT-densitometry. Contrast enhancement is best with high-dose bolus injection and rapid sequence CT-scanning of at least 4 cuts per minute.     

CAD in CT colonography without and with oral contrast agents: progress and challenges.

Computed tomographic colonography (CTC), also known as virtual colonoscopy, is an emerging alternative technique for screening of colon cancers. CTC uses CT to provide a series of cross-sectional images of the colon for detection of polyps and masses. Fecal tagging is a means of labeling of residual feces by an oral contrast agent for improving the accuracy in the detection of polyps. Computer-aided diagnosis (CAD) for CTC automatically determines the locations of suspicious polyps and masses in CTC and presents them to radiologists, typically as a second opinion. Despite its relatively short history, CAD has become one of the mainstream techniques that could make CTC prime time for screening of colorectal cancer. Rapid technical developments have advanced CAD substantially during the last several years, and a fundamental scheme for the detection of polyps has been established, in which sophisticated 3D image processing, analysis, and display techniques play a pivotal role. The latest CAD systems indicate a clinically acceptable high sensitivity and a low false-positive rate, and observer studies have demonstrated the benefits of these systems in improving radiologists' detection performance. Some technical and clinical challenges, however, remain unresolved before CAD can become a truly useful tool for clinical practice. Also, new challenges are facing CAD as the methods for bowel preparation and image acquisition, such as tagging of fecal residue with oral contrast agents, and interpretation of CTC images evolve. This article reviews the current status and future challenges in CAD for CTC without and with fecal tagging.     

Gadolinium-DTPA liposomes as a potential MRI contrast agent. Work in progress

To evaluate the use of liposomes containing Gadolinium-DTPA (Gd-DTPA) as potential intravascular contrast agents, we synthesized and tested Gd-DTPA liposomes. A freeze-thaw extrusion process was used to synthesize neutral unilamellar vesicles. Using this technique, we prepared 0.4 micron vesicles with encapsulation efficiency as high as 39% for Gd-DTPA. In vitro dialysis showed that essentially 100% of the Gd-DTPA was retained with the liposomes after 72 hours of dialysis. MR imaging of in vitro samples showed concentration-dependent increase in signal intensity with Gd-DTPA liposomes. Imaging of rats after intravenous injection of Gd-DTPA liposomes showed sustained intravascular contrast enhancement of vascular structures and liver greater than free Gd-DTPA. There was no evidence of acute toxicity in rats during the imaging experiments or on follow-up of two months. Paramagnetic liposomes may be useful to enhance the vasculature, liver, and spleen.     

Quantification of intravascular and extravascular contributions to BOLD effects induced by alteration in oxygenation or intravascular contrast agents

A simple model is presented that allows quantitative separation of the contributions of signals from water in blood and extravascular parenchyma due to changes in blood oxygenation, induced either by brain activation or by alteration of inspired oxygen. The separation is based on the progressive attenuation of the signals in the vasculature of different levels when bipolar field gradient pulses are applied. Diffusion-weighted spin-echo echo-planar imaging sequences were used to measure signal changes under various conditions in both animals and human volunteers. Normoxic-hyperoxic episodes were induced in rats before and after injection of a superparamagnetic iron oxide contrast agent. Signal changes produced by visual stimulation were measured in human volunteers, and in volunteers subject to alternating normoxic-hyperoxic episodes, and with administration of Gd-DTPA. Analysis of the results with our simple model suggests that the apparent diffusion coefficient increases and R2 ( = 1/T₂) decreases upon brain activation, with a large component from extravascular water related to the decrease in the blood de-oxyhemoglobin concentration. Furthermore, this study suggests that apparent diffusion coefficient of the extravascular component alone may provide localization of neuronal activation.     

Comparison of liver perfusion parameters studied with conventional extravascular and experimental intravascular CT contrast agents

RATIONALE AND OBJECTIVES: To compare liver perfusion parameters obtained by using an extravascular contrast agent and a blood-pool agent. MATERIALS AND METHODS: Fifteen rabbits were imaged with a continuous 40-second single-slice computed tomography acquisition after a bolus injection of contrast agent (physiologic bolus duration 4-5 seconds, extravascular iohexol, n = 7; experimental nanoparticulated blood-pool agent WIN8883, n = 8). Time-density curves were generated for the aorta, portal vein, and liver. From the curves, arterial, portal, and total blood flows and hepatic perfusion index (HPI, arterial-to-total perfusion ratio) were determined by using two commonly applied fundamentally different analyzing methods: the single-compartment model and the peak gradient (PG) method. Also, the gamma variate fitting method was used. RESULTS: By using the single-compartment model, the obtained HPI and total blood flow were 0.14 +/- 0.04 and 2.29 +/- 0.40 (mL/min/mL(tissue)) for WIN8883, and 0.15 +/- 0.06 (P = .54) and 4.60 +/- 1.14 (mL/min/mL(tissue)) (P = .0002) for iohexol, respectively. With the PG, HPI and total blood flow were 0.15 +/- 0.08 and 1.27 +/- 0.24 (mL/min/mL(tissue)) for WIN8883, and 0.20 +/- 0.06 (P = .12) and 2.11 +/- 0.25 (mL/min/mL(tissue)) (P = .00002) for iohexol, respectively. With the blood pool agent, similar contrast enhancement to the conventional agent was achieved with about 36% reduced dosage of iodine per body weight (mg I/kg). CONCLUSIONS: HPI was found to be quite insensitive to different contrast agent types and analyzing methods. However, the arterial, portal and total liver blood flow values strongly depend on contrast agent type and modeling method.     

MR对比剂的临床应用及研究进展

尽管MR具有多序列、多参数、多方位成像以及较高的软组织分辨力，但在实际工作中发现某些病变与正常组织的T1甚至T2弛豫时间无明显差别。另外，有些病变虽有明显的异常信号，但诊断与鉴别诊断仍较困难，还有些病变较小，平扫不易显示。在这些情况下，我们需要应用MR对比剂来帮助解决。     

Ytterbium-DTPA. A potential intravascular contrast agent

Ytterbium-DTPA was evaluated as a potential intravascular contrast agent. Ytterbium-DTPA was synthesized from ytterbium oxide and diethylene triamine penta-acetic acid (DTPA). CT scans of increasing concentrations of ytterbium and iodine showed that at 125 kVp, ytterbium was denser than an equal concentration of iodine. The LD50 of intravenous ytterbium-DTPA was 10 mM/kg (1.73 g ytterbium/kg) in rats. In enhanced CT scans and pulmonary angiography in dogs, ytterbium was visibly denser than iodine, and CT Hounsfield units showed greater enhancement of the aorta and inferior vena cava with ytterbium. The animals showed no sign of acute or delayed toxicity. Ytterbium-DTPA deserves further evaluation as a contrast agent for high kVp techniques.     

Micro-MR angiography of normal and intratumoral vessels in mice using dedicated intravascular MR contrast agents with high generation of polyamidoamine dendrimer core: reference to pharmacokinetic properties of dendrimer-based MR contrast agents.

Pharmacokinetic characteristics of intravascular macromolecular magnetic resonance imaging (MRI) contrast agents with polyamidoamine dendrimer cores smaller than generation-7 were previously studied in the literature. To evaluate the effects of greater hepatic uptake on the pharmacokinetics of the larger generation dendrimers, the MRI contrast agents GxD-(1B4M-Gd)(2(x+2)) were synthesized with generation-7, -8, and -9 polyamidoamine dendrimers and 2-(p-isothiocyanatobenzyl)-6-methyl-diethylenetriaminepentaacetic acid (1B4M). Their pharmacokinetic characteristics in mice were compared with that of G6D-(1B4M-Gd)(256). In biodistribution and dynamic micro-MRI studies, significantly less renal accumulation of G7D-(1B4M-Gd)(512), G8D-(1B4M-Gd)(1024), and G9D-(1B4M-Gd)(2048) was shown compared to G6D-(1B4M-Gd)(256) (P < 0.01). There was a significantly greater accumulation of G8D-(1B4M-Gd)(1024) and G9D-(1B4M-Gd)(2048) in the liver compared to G6D-(1B4M-Gd)(256) and G7D-(1B4M-Gd)(512) (P < 0.01). The highest blood retention of all dendrimer-based MRI contrast agents was exhibited by G7D-(1B4M-Gd)(512) (P < 0.01). The normal and intratumoral fine vessels of approximately 100 microm diameter were visualized in normal or tumor-bearing mice by high resolution three-dimensional-micro-MR angiographs with G7D-(1B4M-Gd)(512) and G8D-(1B4M-Gd)(1024) with good vessel-to-soft tissue contrast. In summary, increased accumulation in the liver with concomitant decreased uptake in the kidney was caused by increased molecular sizes of the dendrimer-based MRI contrast agents.     

Optimizing lesion contrast without using contrast agents.

The essence of optimizing lesion detection is increasing the signal-to-noise (S/N) for the lesion while decreasing the S/N of the background. Maneuvers which improve one aspect of lesion detection may have a deleterious effect on another. For example, thinner slices decrease partial volume averaging (important for detection of small lesions) but also decrease S/N. Attempts to increase S/N by lowering the bandwidth may increase the TE, decreasing the degree of T1-weighting. Fast spin echo (FSE) generally offers the best T2-weighting for detection of long T2 lesions. However, lesions with short T2s (due to magnetic susceptibility effects) are better detected with gradient echo techniques. Strategies which decrease background S/N include those based on chemical shift differences (ie, spectroscopic techniques like FatSat) and those based on differences in T1 (ie, inversion recovery [IR] techniques like STIR and FLAIR).     

Modification of embolic-PVA particles with MR contrast agents.

We report the synthesis and characterization of polyvinyl alcohol (PVA) embolic particles modified with a clinically approved magnetic resonance (MR) contrast agent. PVA particles are used during transcatheter arterial embolization (TAE) procedures and this minimally invasive technique is a widely employed treatment for inoperable tumors. The PVA particles are injected into tumor vessels and prevent blood flow which results in tumor attenuation. An accurate assessment of the endpoint of embolization is critical to successful TAE procedures. Recent reports suggest that 20% of endpoint determination of TAE procedures by angiographic techniques are erroneous. Real time, in vivo imaging of the embolic particles would overcome this limitation. The contrast-modified PVA particles described here show an 80% decrease in T(1) relaxation times compared to unmodified particles. Images of particles in capillary tubes of similar size to catheters used in TAE procedures are clearly visible by MRI.     

Catalog of intravascular contrast media

The ionic intravascular contrast media formulations now commercially available are presented, along with those new formulations, nonionic and ionic, that have a significant reduced osmolality compared with those previously available.     

Work in progress: reduction of calcium activity by radiopaque contrast media

An in vitro examination of the effects of radiopaque contrast media anions, cations, additives, and ionic strength on ionic calcium level using ion-specific electrodes was made. The calcium-binding additives sodium citrate and sodium EDTA produced the largest reduction in ionic calcium. At the same iodine concentration the anions diatrizoate, iothalamate, metrizoate, and ioxaglate reduced ionic calcium by essentially the same amount. Sodium compounds reduced ionic calcium more than did meglumine compounds, a difference that is probably related to dissociation. The nonionic compounds iohexol and iopamidol did not reduce ionic calcium significantly. Ionic strength appears to have little direct effect on ionic calcium at and above physiologic levels. All ionic contrast media bind significant amounts of ionic calcium at the high concentrations achieved during selective arteriography. Since the anions are only weak calcium binders supplemental calcium can restore the level of ionic calcium.     

Ventricular opacification after intravascular injections of contrast material.

The cerebral ventricles of two neonates were demonstrated on CT scans and plain radiographs after the intra-arterial injection of contrast material. Leakage of contrast material into the ventricles after intravenous injection probably indicates damage of the blood-brain barrier. Breakdown of this barrier results only from severe and prolonged anoxia because cerebral vessels are much more resistant to anoxia than neuronal tissues. The authors have not observed ventricular opacification in adults.