Quantitative evaluation of non-ischemic dilated cardiomyopathy by late iodine enhancement using rapid kV switching dual-energy computed tomography: A feasibility study.

OBJECTIVES: The aim of this study was to evaluate the feasibility of myocardial iodine density and extracellular volume fraction (ECV) from delayed iodine density images using dual-energy computed tomography (DECT) for differentiation between non-ischemic dilated cardiomyopathy (NIDCM) patients and normal subjects. METHODS: Forty-six subjects were imaged, including 35 normal subjects and 11 patients with NIDCM. All subjects underwent myocardial delayed enhancement (MDE) imaging on rapid-kVp switching DECT. Global and segmental iodine density and ECV were calculated from MDE images. Histogram analysis was also performed. Receiver-operator characteristic (ROC) analysis was used to determine the cut-off value and diagnostic performances in differentiating NIDCM patients from normal subjects. RESULTS: Global iodine density and ECV were significantly higher in NIDCM compared with normal controls (iodine: 14.19 ±â€¯3.90 vs. 10.69 ±â€¯1.88 in 100 µg/cm3, p = 0.015; ECV: 31.35 ±â€¯2.53% vs. 26.62 ±â€¯2.69%, p < 0.001). In histogram analyses, kurtosis was higher in NIDCM than in controls (0.47 ±â€¯0.46 vs. 1.26 ±â€¯0.88, p < 0.001). On segmental analysis, ECV showed higher values in NIDCM than in controls for all segments. ECV could differentiate between normal myocardium and NIDCM with 91.0% sensitivity and 86.0% specificity at a cut-off of 28.82% (area under the curve of ROC, 0.906). Iodine density could differentiate between normal myocardium and NIDCM with 91% sensitivity and 60% specificity at a cut-off of 11.18 (area under the curve of ROC, 0.812). CONCLUSIONS: Iodine density and ECV values from DECT may provide indices offering high diagnostic accuracy for discriminating between NIDCM and normal myocardium.

Can dual-energy CT replace perfusion CT for the functional evaluation of advanced hepatocellular carcinoma?

OBJECTIVES: To determine the degree of relationship between iodine concentrations derived from dual-energy CT (DECT) and perfusion CT parameters in patients with advanced HCC under treatment. METHODS: In this single-centre IRB approved study, 16 patients with advanced HCC treated with sorafenib or radioembolization who underwent concurrent dynamic perfusion CT and multiphase DECT using a single source, fast kV switching DECT scanner were included. Written informed consent was obtained for all patients. HCC late-arterial and portal iodine concentrations, blood flow (BF)-related and blood volume (BV)-related perfusion parameters maps were calculated. Mixed-effects models of the relationship between iodine concentrations and perfusion parameters were computed. An adjusted p value (Bonferroni method) < 0.05 was considered significant. RESULTS: Mean HCC late-arterial and portal iodine concentrations were 22.7±12.7 mg/mL and 18.7±8.3 mg/mL, respectively. Late-arterial iodine concentration was significantly related to BV (mixed-effects model F statistic (F)=28.52, p<0.0001), arterial BF (aBF, F=17.62, p<0.0001), hepatic perfusion index (F=28.24, p<0.0001), positive enhancement integral (PEI, F=66.75, p<0.0001) and mean slope of increase (F=32.96, p<0.0001), while portal-venous iodine concentration was mainly related to BV (F=29.68, p<0.0001) and PEI (F=66.75, p<0.0001). CONCLUSIONS: In advanced HCC lesions, DECT-derived late-arterial iodine concentration is strongly related to both aBF and BV, while portal iodine concentration mainly reflects BV, offering DECT the ability to evaluate both morphological and perfusion changes. KEY POINTS: • Late-arterial iodine concentration is highly related to arterial BF and BV. • Portal iodine concentration mainly reflects tumour blood volume. • Dual-energy CT offers significantly decreased radiation dose compared with perfusion CT.

Biodegradation of phenol, salicylic acid, benzenesulfonic acid, and iomeprol by Pseudomonas fluorescens in the capillary fringe.

Mass transfer and biological transformation phenomena in the capillary fringe were studied using phenol, salicylic acid, benzenesulfonic acid, and the iodinated X-ray contrast agent iomeprol as model organic compounds and the microorganism strain Pseudomonas fluorescens. Three experimental approaches were used: Batch experiments (uniform water saturation and transport by diffusion), in static columns (with a gradient of water saturation and advective transport in the capillaries) and in a flow-through cell (with a gradient of water saturation and transport by horizontal and vertical flow: 2-dimension flow-through microcosm). The reactors employed for the experiments were filled with quartz sand of defined particle size distribution (dp=200...600 µm, porosity ε=0.42). Batch experiments showed that phenol and salicylic acid have a high, whereas benzenesulfonic acid and iomeprol have a quite low potential for biodegradation under aerobic conditions and in a matrix nearly close to water saturation. Batch experiments under anoxic conditions with nitrate as electron acceptor revealed that the biodegradation of the model compounds was lower than under aerobic conditions. Nevertheless, the experiments showed that the moisture content was also responsible for an optimized transport in the liquid phase of a porous medium. Biodegradation in the capillary fringe was found to be influenced by both the moisture content and availability of the dissolved substrate, as seen in static column experiments. The gas-liquid mass transfer of oxygen also played an important role for the biological activity. In static column experiments under aerobic conditions, the highest biodegradation was found in the capillary fringe (e.g. ßt/ß0 (phenol)=0 after t=6 d) relative to the zone below the water table and unsaturated zone. The highest biodegradation occurred in the flow-through cell experiment where the height of the capillary fringe was largest.

Reactive transport of iomeprol during stream-groundwater interactions.

The transport and biochemical transformations of the iodinated X-ray contrast medium (ICM) iomeprol were studied at the stream/groundwater interface. During a one-month field experiment piezometric pressure heads, temperatures, and concentrations of redox-sensitive species, iomeprol and 15 of its transformation products (TPs) were collected in stream- and groundwater. The data set was analyzed and transformation processes and rates identified by comparing conservative and reactive transport simulations. ICM and TP transformations were simulated as a cometabolic process during organic carbon degradation. Using iomeprol/TPs ratios as calibration constrain mitigated the uncertainties associated with the high variability of the ICM wastewater discharge into the investigated stream. The study provides evidence that biodegradation of ICM occurs at the field-scale also for predominantly denitrifying conditions. Under these anaerobically dominated field conditions shortest simulated half-life (21 days) was in the same range as previously reported laboratory-determined half-lives for aerobic conditions.

In vitro design and characterization of the nonviral gene delivery vector iopamidol, protamine, ethiodized oil reagent.

PURPOSE: To demonstrate cellular selectivity toward hepatoma cells and compare the efficiency of gene delivery of a novel nonviral vector of iopamidol, protamine, and ethiodized oil reagents (VIPER). MATERIALS AND METHODS: Rat hepatocellular carcinoma (HCC) cells were transfected in triplicate under varying conditions by using firefly luciferase as a reporter gene. Conditions included variations of a protamine:DNA (P:D) complex (20:1, 50:1, 100:1, 200:1 mass ratios), iopamidol (0%, 10%, 33%), and ethiodized oil (0%, 1%, 2%, 4%, 8%, and 16%). The conditions affording efficient gene transfer and ease of translation to in vivo studies were selected for cell line comparison (HCC cells vs hepatocytes). Adenoviral transduction was compared with nonviral vector transfection. RESULTS: At low concentrations, ethiodized oil increased transfection efficiency regardless of P:D mass ratio. However, high concentrations resulted in significant attenuation. Unexpectedly, the addition of iopamidol to P:D complexes markedly improved transfection efficiency. When using an optimal P:D, iopamidol, and ethiodized oil solution, DNA transfection of normal liver and tumor cells showed significant selectivity for tumor cells. In the context of hepatoma cells, transfection efficiency with the nonviral vector was better than 10(4) pfu adenovirus. CONCLUSIONS: The development and characterization of the VIPER system provides a possible alternative to viral gene therapy of HCC.

Viscosity of iodinated contrast agents during renal excretion.

OBJECTIVE: Modern iodinated non-ionic contrast agents (CAs) can be classified based on their molecular structure into monomeric and dimeric CAs and have at comparable iodine concentrations a different viscosity and osmolality. During their renal excretion, CAs are concentrated in the renal tubuli which might enhance the viscosity difference between monomeric and dimeric CAs. The viscosity of a CA might have an underestimated importance for renal safety, as suggested by recent publications. In this study, we investigated the viscosities of CAs at the concentrations expected to be present in renal tubules. This concentration process was simulated in vitro using dialysis. Furthermore, we investigated urine viscosity and urine flow in rodents after administration of several non-ionic monomeric and dimeric CAs. MATERIALS AND METHODS: To estimate the viscosity of the CAs in vivo, we performed an in vitro dialysis of monomeric and dimeric CAs at various physiological osmolalities of the renal tubulus (290, 400, 500, 700 and 1000 mOsm/kg H2O). Following the dialysis, the iodine concentrations and the viscosities of the CAs were determined. Furthermore, to investigate the concentration process in vivo, we measured the urine viscosity and the urine flow in Han Wister rats after the administration of Iopromide, Iohexol, Ioversol, Iomeprol, Iodixanol, and Iosimenol at comparable iodine concentrations. As a control, saline was injected at the same volume. RESULTS: In vitro dialysis of the dimeric CA increased the iodine concentration and strongly increased the viscosity at all tested osmolalities. In contrast, for the monomeric agents an increase in concentration and viscosity was observed only at 700 as well 1000 mOsm/kg H2O but to a lesser extent. In summary, dialysis strongly enhanced the viscosity differences between the non-ionic monomeric and dimeric CAs. The administration of dimeric CAs leads to a strong increase in urine viscosity; this was not observed for the monomeric CAs. In contrast, a significantly higher urine flow was measured after the administration of the monomeric CAs as compared to the dimeric CAs. CONCLUSION: We demonstrated that the viscosity differences between monomeric and dimeric CAs are strongly enhanced due to a concentration process of the CAs upon increasing osmolalities, a process which is likely to take place in a similar manner in the tubular system. This result suggests that the viscosity of the dimeric agents increases dramatically in vivo and gives a plausible explanation for measured enhancement of urine viscosity upon dimeric CA administration. On the other hand, the higher osmolality of the monomeric agents causes an osmodiuresis, indicated by a higher urine flow, which leads to a faster elimination of the CAs from the kidney.

Multistep approach for the structural identification of biotransformation products of iodinated X-ray contrast media by liquid chromatography/hybrid triple quadrupole linear ion trap mass spectrometry and (1)H and (13)C nuclear magnetic resonance.

This study investigated the application of a hybrid triple quadrupole linear ion trap mass spectrometer (Qq-LIT-MS) in combination with NMR to elucidate the chemical structures of 27 biotransformation products (TPs) of the nonionic iodinated X-ray contrast media (ICM), iohexol, iomeprol, and iopamidol, formed in contact with soil. The combination of MS(2) and MS(3) spectra with Qq-LIT-MS was essential to determine the MS fragmentation pathways crucial for structural elucidation. (1)H and (13)C NMR analyses were needed to confirm the chemical structures of TPs proposed by MS fragmentation. Biotransformation occurred exclusively at the side chains of the iodinated X-ray contrast media, while the iodinated benzene ring remained unaltered. Several of the newly identified TPs of the ICM were found in surface water, groundwater, and even drinking water. Concentrations as high as 1450 +/- 110 ng/L (iomeprol TP629) were detected in groundwater that is influenced by wastewater infiltration, and as high as 289 +/- 41 ng/L (iomeprol TP643) in drinking water.

Photocatalytic degradation of carbamazepine, clofibric acid and iomeprol with P25 and Hombikat UV100 in the presence of natural organic matter (NOM) and other organic water constituents.

The photocatalytic degradation of natural organic matter (NOM) and organic substance mixtures under simulated solar UV light has been investigated with suspended TiO(2). It could be shown by size-exclusion chromatography that photocatalysis of NOM led to a reduction of the average hydrodynamic radii and presumably of the nominal molecular weight, too. The decrease of the UV/Vis absorption of NOM was faster than the NOM mineralization. This study also focuses on the different abilities of photocatalytic materials (P25 and Hombikat UV100) to decrease persistent substances influenced by the presence of NOM and mixtures of pharmaceuticals or diagnostic agents. In general, the presence of NOM and other organic substances retarded the photocatalysis of a specific persistent substance by the combination of radiation attenuation, competition for active sites and surface deactivation of the catalyst by adsorption. The results of this work prove that photocatalysis is a promising technology to reduce persistent substances like NOM, carbamazepine, clofibric acid, iomeprol and iopromide even if they are present in a complex matrix.

Pharmacokinetics and tissue distribution of iomeprol in animals.

The pharmacokinetics of iomeprol, a new triiodinated nonionic radiographic contrast agent, has been studied in rats, rabbits and dogs. Following intravenous administration, iomeprol did not bind measurably to plasma proteins and was rapidly excreted in unchanged form, mostly through the kidneys. The compound was rapidly distributed to the plasma and thence to the extracellular spaces. Iomeprol did not accumulate in specific organs or tissues except for those involved in its elimination, i.e. the kidneys and the liver. However, 24 h after administration, less than 1% of the injected dose remained in the tissues. The overall profile was very similar to the published profiles of other radiographic contrast agents used in uroangiography.

Neurotoxicity of nonionic low-osmolar contrast media. A receptor binding study.

RATIONALE AND OBJECTIVES: The use of the newest nonionic, water-soluble, low-osmolar radiographic contrast media (CM) is still associated with occasional adverse reactions affecting the neural tissues. Because these CM display lipophilic potential in their interactions with biological membranes when diffusing within the brain parenchyma, they could affect neurotransmitter binding to the receptors. Two representative nonionic CM, iopamidol and iohexol, were studied to assess whether CM-related neurotoxicity derived from their interactions with specific receptors on neural membranes. METHODS: Binding assays were carried out in vitro on crude total membrane or crude synaptic membrane preparations from selected brain areas (cortex, striatum, hippocampus, cerebellum). The concentrations of CM and reference drugs that reduce specific binding of each ligand by 50% of its maximum value (IC50) were determined using radioligands to the receptors of the most common neurotransmitters in the central nervous system, including excitatory amino acids. RESULTS: Neither iopamidol nor iohexol inhibited the (3H) ligand binding to any kind of receptor up to very high concentrations (100 microM). CONCLUSIONS: The nonionic, low-osmolar CM did not influence the normal functions of neural membranes in our model. This suggests that occasional neurotoxic effects do not occur as a consequence of specific action on brain receptors. These CM may have an indirect, postmembrane site of action.

Hemodialysis and iopamidol clearance after subclavian venography.

RATIONALE AND OBJECTIVES: The dialyzability of iopamidol is unknown and was investigated in patients undergoing long-term hemodialysis for chronic renal failure. METHODS: Ten patients received 30 ml Niopam 300 (Bracco SpA, Milan, Italy) (identical to 18372 mg iopamidol) intravenously into a forearm vein to investigate for occult subclavian stenosis. RESULTS: The elimination half-life of iopamidol before hemodialysis was 69.6 hours and during 4 hours of hemodialysis was 3.5 hours. A single 4-hour hemodialysis cleared 55.7% (95% Ci 51-5-59.8) of the administered dose, while second and third dialyses cleared 25.3% (95% Ci 21.4-29.1) and 10.1% (95% Ci 7.7-12.6) of the administered dose, respectively. Two patients with significant residual urine excretion excreted more than 10% of the administered dose in the urine. For anuric patients, extrarenal clearance provided total body clearance of up to 0.266 L/hr. CONCLUSIONS: Hemodialysis is a rapid and efficient means of clearing iopamidol provided it is performed soon after the contrast study.

[A formulation of iopamidol for the radiologic examination of the gastrointestinal tract. Preclinical studies]. / Formulazione di iopamidolo per l'esame radiologico del tratto gastro-intestinale. Studi preclinici.

Animal studies were carried out using an oral solution of a low osmolality non ionic contrast medium iopamidol, developed for gastrointestinal examinations. The new formulation was evaluated for image quality in studies of the upper and lower gastrointestinal tract. Margins of safety were defined by subjecting the compound to a number of toxicological and pharmacological experiments. The experiments were designed to reveal qualitative and quantitative differences between the formulation of iopamidol and Gastrografin, a conventional ionic contrast medium. The results indicate that the formulation of iopamidol is safer than a conventional hypertonic water soluble contrast medium and diagnostically superior in the gastrointestinal tract examinations.

Penetration of the brain by nonionic water soluble tri- and hexaiodinated contrast media. Experimental autoradiographic study of two contrast media: Iotrol and Iopamidol labelled with iodine 125.

After suboccipital injection of Iotrol and Iopamidol labelled with iodine 125 in rabbits, we measured residual radioactivity in the whole brain and optical density on autoradiographs of brain sections obtained 2, 8 and 24 h after injection. Residual radioactivity is higher with Iotrol than with Iopamidol after 8 h and 24 h. At densitometry, while the penetration of the cortex is the same with both media at 2 h (although subcortical passage of Iotrol is greater), by 8 h the concentration of Iopamidol is twice that of Iotrol, and at 24 h it is three times as high. A similar pattern was seen in the subcortical region. These densitometric findings are in agreement with previous electrophysiological studies, in which changes were less severe and more transient with Iotrol than with Iohexol. There is nevertheless an apparent lack of agreement between the studies of radioactivity and the electrical findings. The lower neurotoxicity of Iotrol may be explained by: a longer half-life in the subarachnoid space; its larger molecules, which inhibit diffusion in the extracellular fluid, and its more hydrophilic nature, which reduces intracellular penetration.

Physicochemical properties and degree of protein binding of iopentol.

Osmolality, viscosity, partition coefficients and degree of protein binding of iopentol are presented. The properties of iopentol are compared with those of iohexol and iopamidol.

Pharmacokinetics of lopamidol after intrathecal administration in humans.

The kinetics of iopamidol, a new nonionic radiocontrast agent, were evaluated in 10 patients undergoing lumbar myelography. The doses of iopamidol administered intrathecally were 11 and 15 ml of a 200-mg iodine per ml solution in one and nine patients, respectively. Radiographs were made within 30 to 40 min and CTs were taken at about 1, 6, and 23 hr after iopamidol administration. The diagnostic quality and usefulness of the conventional and CT myelograms were considered excellent. In the lumbosacral subarachnoid space, the densitometry CT readings were maximal at 1 hr, whereas in the cervical subarachnoid space, peak CT values were reached at 6 hr. Plasma and urine samples were taken at frequent intervals up to 48 hr after the contrast agent was administered. Peak plasma levels of iopamidol were observed at 2.9 hr and were no longer detectable at 48 hr. The 48-hr urinary recovery for all patients averaged 66 +/- 8% of the dose. In all but one patient, iopamidol was cleared almost completely from the CSF within 24 hr. Side effects after iopamidol administration were transient and minor, and were not related to the CT readings or its systemic clearance.

Rate of clearance of intrathecal iopamidol in the dog.

The incidence of post-myelographic side-effects has been significantly reduced since the advent of the new generation of water-soluble, non-ionic, contrast media (CM). One of these CM, iopamidol, has recently been released for clinical intrathecal use in Australia. Clinical evaluations have shown iopamidol to give excellent diagnostic results. However, many adverse side-effects have been cited in the literature. Reactions to iopamidol following myelography are thought to be due to the lack of a physiologic barrier between the extracellular fluid of the brain parenchyma and the CSF, thereby allowing CM to penetrate the brain parenchyma tissue, following subarachnoid injection. This study investigates the rate of clearance of intrathecal iopamidol from the brain in dogs by performing coronal CT scans at intervals over a 48 h, post-injection period. Analysis of similar regions of interest (ROI) for each time period indicate that iopamidol can be detected in canine brains for at least 48 h following intrathecal injection (P less than 0.05). Furthermore, the disappearance of iopamidol from the brain parenchyma is approximately logarithmic in form, with a half-life of approximately 22 h.