Aging does not change the compressive stiffness of mandibular condylar cartilage in horses.

OBJECTIVE: Aging can cause an increase in the stiffness of hyaline cartilage as a consequence of increased protein crosslinks. By induction of crosslinking, a reduction in the diffusion of solutions into the hyaline cartilage has been observed. However, there is a lack of knowledge about the effects of aging on the biophysical and biochemical properties of the temporomandibular joint (TMJ) cartilage. Hence, the aim of this study was to examine the biophysical properties (thickness, stiffness, and diffusion) of the TMJ condylar cartilage of horses of different ages and their correlation with biochemical parameters. MATERIALS AND METHODS: We measured the compressive stiffness of the condyles, after which the diffusion of two contrast agents into cartilage was measured using Contrast Enhanced Computed Tomography technique. Furthermore, the content of water, collagen, GAG, and pentosidine was analyzed. RESULTS: Contrary to our expectations, the stiffness of the cartilage did not change with age (modulus remained around 0.7 MPa). The diffusion of the negatively charged contrast agent (Hexabrix) also did not alter. However, the diffusion of the uncharged contrast agent (Visipaque) decreased with aging. The flux was negatively correlated with the amount of collagen and crosslink level which increased with aging. Pentosidine, collagen, and GAG were positively correlated with age whereas thickness and water content showed negative correlations. CONCLUSION: Our data demonstrated that aging was not necessarily reflected in the biophysical properties of TMJ condylar cartilage. The combination of the changes happening due to aging resulted in different diffusive properties, depending on the nature of the solution.

Contrast-enhanced CT with a high-affinity cationic contrast agent for imaging ex vivo bovine, intact ex vivo rabbit, and in vivo rabbit cartilage.

PURPOSE: To quantify the affinity of a cationic computed tomography (CT) contrast agent (CA(4+)) and that of an anionic contrast agent (ioxaglate) to glycosaminoglycans (GAGs) in ex vivo cartilage tissue explants and to characterize the in vivo diffusion kinetics of CA(4+) and ioxaglate in a rabbit model. MATERIALS AND METHODS: All in vivo procedures were approved by the institutional animal care and use committee. The affinities of ioxaglate and CA(4+) to GAGs in cartilage (six bovine osteochondral plugs) were quantified by means of a modified binding assay using micro-CT after plug equilibration in serial dilutions of each agent. The contrast agents were administered intraarticularly to the knee joints of five New Zealand white rabbits to determine the in vivo diffusion kinetics and cartilage tissue imaging capabilities. Kinetics of diffusion into the femoral groove cartilage and relative contrast agent uptake into bovine plugs were characterized by means of nonlinear mixed-effects models. Diffusion time constants (τ) were compared by using a Student t test. RESULTS: The uptake of CA(4+) in cartilage was consistently over 100% of the reservoir concentration, whereas it was only 59% for ioxaglate. In vivo, the contrast material-enhanced cartilage reached a steady CT attenuation for both CA(4+) and ioxaglate, with τ values of 13.8 and 6.5 minutes, respectively (P = .04). The cartilage was easily distinguishable from the surrounding tissues for CA(4+) (12 mg of iodine per milliliter); comparatively, the anionic contrast agent provided less favorable imaging results, even when a higher concentration was used (80 mg of iodine per milliliter). CONCLUSION: The affinity of the cationic contrast agent CA(4+) to GAGs enables high-quality imaging and segmentation of ex vivo bovine and rabbit cartilage, as well as in vivo rabbit cartilage. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112246/-/DC1.

The effect of iodinated contrast agent properties on renal kinetics and oxygenation.

OBJECTIVE: We analyzed renal kinetics and renal oxygenation in rats after administration of several classes and formulations of contrast agents (CAs) with a focus on the influence of osmolality and substance-specific properties. MATERIALS AND METHODS: We investigated the renal kinetics of a nonionic, dimeric CA (iodixanol) formulated in 3 different osmolalities (hypo-osmolar, iso-osmolar, low-osmolar) and compared it to nonionic, low-osmolar (iopromide), and ionic, low-osmolar CAs (ioxaglate) using computed tomography for a period of 24 hours. The CAs were administered intravenously at a dosage of 4 g iodine/kg body weight. The average exposure was calculated, and urine viscosities were compared before the injection and during the time intervals of 0 to 60 minutes and 60 to 120 minutes after the injection. Renal oxygenation levels of the renal cortex and medulla were estimated using blood-oxygen-level-dependent magnetic resonance imaging. We used histologic methods to systematically analyze the gravity of vacuole formation based on the physicochemical and substance-specific properties of each CA. RESULTS: Iso-osmolar and hypo-osmolar iodixanol and, to a lesser extent, iodixanol/mannitol accumulated rapidly in the kidneys during the first 5 minutes of the injection and remained higher 2, 4, 6, and 24 hours after the injection compared with iopromide and ioxaglate, which showed fast iodine excretion. Similarly, lower renal blood oxygen levels were estimated for all iodixanol formulations as compared with ioxaglate and iopromide. The incidence of vacuole formation was high for all iodixanol formulations and for ioxaglate (6 of 6 rats) and low for iopromide (1 of 6 rats). Moderate severity of vacuoles was determined for the iodixanol solutions; minimal severity, for ioxaglate and iopromide. CONCLUSIONS: We identified a superior profile for the low-osmolar CAs compared with the iso-osmolar CAs regarding rapid excretion, short-term renal exposure, and renal oxygenation.

Retention of iodinated contrast material within renal cysts in a patient with autosomal dominant polycystic kidney disease.

Hyperdense renal cysts, a common condition in autosomal dominant polycystic kidney disease, may be induced by haemorrhage into the cysts. However, hyperdense renal cysts resulting from retention of contrast material after intravenous injection is extremely uncommon because the intravenous administration of contrast material does not induce an increase in the attenuation of renal cysts. We report a case of retention of iodinated contrast material within renal cysts in a patient with autosomal dominant polycystic kidney disease.

Contrast-enhanced CT of articular cartilage: experimental study for quantification of glycosaminoglycan content in articular cartilage.

PURPOSE: To investigate the diagnostic potential of delayed contrast material-enhanced computed tomography (CT) of articular cartilage in quantification of glycosaminoglycan (GAG) concentration in normal and degenerated articular cartilage ex vivo by using a clinical CT scanner. MATERIALS AND METHODS: This study was exempted by the institutional and animal review boards, and informed consent was not required. Forty intact porcine patellae were extracted and assigned to either a control (n = 20) or a trypsin-treated group (ie, GAG-depleted group) (n = 20). Ten patellae in each group were immersed in anionic contrast agent (ioxaglate, 40%) and the other ten in neutral contrast agent (iopromide, 35%) for 2 hours. To determine the contrast agent concentration within cartilage, samples were scanned with a clinical CT scanner immediately after the immersion time, and the x-ray attenuation of cartilage was measured. CT images were compared with safranin O-stained histologic sections, and actual GAG contents were determined with a dimethylmethylene blue assay. RESULTS: Ioxaglate was taken up by GAG-depleted cartilage to a greater extent than by normal cartilage (P = .01). In contrast, the penetration of iopromide was not significantly different between GAG-depleted and normal cartilage (P = .1). The loss of GAGs in trypsin-treated cartilage was confirmed microscopically by using safranin O-stained sections, and a dimethylmethylene blue assay also confirmed that GAG content was markedly decreased in trypsin-treated cartilage (P = .003). CONCLUSION: This study showed that contrast-enhanced CT images of articular cartilage could reflect the GAG content within the cartilage by allowing measurement of the concentration of anionic iodine-based contrast agent accumulated in the cartilage.

Quantitative assessment of articular cartilage morphology via EPIC-microCT.

OBJECTIVE: The objective of the present study was to validate the ability of Equilibrium Partitioning of an Ionic Contrast agent via microcomputed tomography (EPIC-microCT) to nondestructively assess cartilage morphology in the rat model. DESIGN: An appropriate contrast agent (Hexabrix) concentration and incubation time for equilibration were determined for reproducible segmentation of femoral articular cartilage from contrast-enhanced microCT scans. Reproducibility was evaluated by triplicate scans of six femora, and the measured articular cartilage thickness was independently compared to thickness determined from needle probe testing and histology. The validated technique was then applied to quantify age-related differences in articular cartilage morphology between 4, 8, and 16-week-old (n=5 each) male Wistar rats. RESULTS: A 40% Hexabrix/60% phosphate buffered saline (PBS) solution with 30 min incubation was optimal for segmenting cartilage from the underlying bone tissue and other soft tissues in the rat model. High reproducibility was indicated by the low coefficient of variation (1.7-2.5%) in cartilage volume, thickness and surface area. EPIC-microCT evaluation of thickness showed a strong linear relationship and good agreement with both needle probing (r(2)=0.95, slope=0.81, P<0.01, mean difference 11+/-22 microm, n=43) and histology (r(2)=0.99, slope=0.97, P<0.01, mean difference 12+/-10 microm, n=30). Cartilage volume and thickness significantly decreased with age while surface area significantly increased. CONCLUSION: EPIC-microCT imaging has the ability to nondestructively evaluate three-dimensional articular cartilage morphology with high precision and accuracy in a small animal model.

pQCT study on diffusion and equilibrium distribution of iodinated anionic contrast agent in human articular cartilage--associations to matrix composition and integrity.

OBJECTIVE: X-ray imaging of articular cartilage using anionic contrast agents has been introduced for quantification of tissue glycosaminoglycan (GAG) concentration. In this in vitro study we investigated diffusion and equilibrium distribution of an anionic contrast agent in human articular cartilage and related the results to tissue composition and integrity. METHODS: Osteochondral cylinders (d=4.0mm, n=24) were prepared from femoral medial condyles (FMCs, cartilage thickness 2.13+/-0.54 mm, mean+/-standard deviation [SD]), and tibial medial plateaus ([TMPs]1.99+/-0.38 mm) of human cadaver knees. Samples were immersed for 24h at room temperature in 21 mM concentration of anionic contrast agent Hexabrix. The X-ray absorption maps and profiles were measured before immersion, and after every 2h of immersion using clinical peripheral quantitative computed tomography (pQCT). RESULTS: An increase in X-ray attenuation along cartilage depth, indicating a characteristic density profile increasing from superficial to deep tissue, could be seen in pQCT images acquired without contrast agent. The complete diffusion of the contrast agent into cartilage took more than 12h. However, the uronic acid concentration correlated with the contrast agent concentration in femoral cartilage (r=-0.76, n=12, P=0.004) as early as after 2h of immersion, and the linear correlation was virtually unchanged during the remaining 22 h. Similarly, the histological tissue integrity (Mankin score) correlated positively with the contrast agent concentration in tibial cartilage (r=+0.75, P=0.005) after 2h of immersion. The X-ray absorption profiles before immersion, i.e., without the contrast agent, and after 24h of immersion were significantly correlated (r=-0.76+/-0.34, mean+/-SD). CONCLUSIONS: Although the complete contrast agent diffusion into human articular cartilage in vitro took more than 12h, significant apparent correlations were revealed between the spatial proteoglycan (PG) and contrast agent distributions already after 2h of immersion. At the stage of incomplete penetration, however, the spatial contrast agent concentration distribution cannot directly reflect the true PG distribution as the Donnan equilibrium has not been reached. However, in degenerated cartilage the diffusion rate increases. Obviously, this can lead to the reported correlation between the bulk PG content and the bulk contrast agent concentration already at the early stages of diffusion.

A randomized trial of saline hydration to prevent contrast nephropathy in chronic renal failure patients.

BACKGROUND: Contrast nephropathy (CN) is a common cause of renal dysfunction that may be prevented by saline hydration and by drugs such as theophylline or furosemide. Whether oral saline hydration is as efficient as intravenous saline hydration is unknown. The preventive efficacy of theophylline and furosemide for CN remains controversial. The purpose of the current study was to evaluate the efficacy of oral saline hydration and of intravenous saline hydration plus theophylline or furosemide for the prevention of CN. METHODS: We prospectively studied 312 patients with chronic renal failure (serum creatinine 201+/-81 micromol/l, Cockcroft clearance 37+/-12 ml/min/1.73 m(2)), who were undergoing various radiological procedures with a non-ionic, low osmolality contrast agent. Patients were randomly assigned to four arms. In arm A, patients received 1 g/10 kg of body weight/day of sodium chloride per os for 2 days before the procedure. In arm B, patients received 0.9% saline intravenously at a rate of 15 ml/kg for 6 h before the procedure. In arm C, patients received the same saline hydration as in arm B plus 5 mg/kg theophylline per os in one dose 1 h before the procedure. In arm D, patients received the same saline hydration as in arm B plus 3 mg/kg of furosemide intravenously just after the procedure. RESULTS: Patients were well-matched with no significant differences at baseline in any measured parameters. Acute renal failure, defined as an increase in serum creatinine of 44 micromol/l (0.5 mg/dl), occurred in 27 out of 312 patients (8.7%). There was no significant difference between the rate of renal failure in the different arms of the study: five out of 76 (6.6%) in arm A, four out of 77 (5.2%) in arm B, six out of 80 (7.5%) in arm C and 12 out of 79 (15.2%) in arm D. No patient had fluid overload or a significant increase in blood pressure in the 2 days following the radiological procedure. The independent predictors of CN were diabetes mellitus, high baseline serum creatinine and high systolic blood pressure. CONCLUSIONS: Oral saline hydration was as efficient as intravenous saline hydration for the prevention of CN in patients with stage 3 renal diseases. Furosemide and theophylline were not protective.

Elimination of low-osmolality contrast media by hemodialysis.

PURPOSE: To compare the dialyzability and safety of 2 types of low-osmolality contrast media administered to end-stage renal failure patients maintained on regular hemodialysis. MATERIAL AND METHODS: Of 44 CT examinations, iohexol was used in 22 and ioxaglate in the other 22. Adverse reactions and hemodynamic changes were recorded. Thirty minutes after the beginning of CT investigation, hemodialysis was commenced. Elimination rate and clearance of the contrast media were measured as indices of their dialyzability. RESULTS: After 4 hours of hemodialysis, 78.4+/-6.5% of iohexol and 72.4+/-6.0% ioxaglate were eliminated. Clearance of iohexol was higher than that of ioxaglate at all sampling times. No severe hemodynamic change nor adverse reaction were observed. Minor reactions were more frequently observed in the ioxaglate group. CONCLUSION: Iohexol, a nonionic monomeric contrast medium, is more advantageous for hemodialysis patients than ioxaglate, an ionic dimeric contrast medium.

Renal cortical retention of contrast medium after angiography as assessed by delayed CT: a multivariate analysis.

Renal cortical retention (RCR) of contrast medium discovered by delayed X-ray examination is sometimes reported in patients with problems in the urinary system. However, we frequently found RCR even in patients with normal renal function. Therefore, we examined the incidence and factors involved in RCR by delayed computed tomography (CT) 12-24 hours after angiography in 168 patients. RCR was found in 80 of 168 cases (48%). Ioxaglate (60%) and iohexol (60%) showed higher incidences of RCR than diatrizoate (37%) and iopamidol (37%). Multivariate logistic regression analysis was performed to determine the predisposing factors of RCR. Dose of administered contrast medium by body weight (p = 0.004), age (p = 0.009), sex (p = 0.013), type of contrast medium (p = 0.003), serum albumin (p = 0.011), and serum creatinine (p = 0.002) were identified as significant and independent predisposing factors of RCR. We suggest that RCR is not a rare phenomenon if delayed CT is carried out.

[Hepato-biliary excretion of water-soluble iodinated contrast medium shortly after abdominal angiography].

Thirty-nine patients underwent CT examination 15 to 30 min after abdominal angiography with ioxaglate. Gallbladder opacification was observed in 15 patients in the absence of clinical evidence of renal impairment. Among them, 14 patients revealed liver cirrhosis or chronic hepatitis, and one patient showed severe fatty liver on CT. The amount of contrast medium used varied from 70 ml to 310 ml (mean 180 ml). There was no significant relationship between visualization of the gallbladder and the total dose of ioxaglate or presence of liver dysfunction, which indicated that gallbladder opacification was not a rare phenomenon on CT shortly after abdominal angiography with a normal dose of ioxaglate. Gallbladder opacification on CT examination shortly after abdominal angiography shows that the hepatobiliary tract is important in the excretion of ioxaglate.

Low osmolality contrast media and metabolic changes in the myocardium during free and reduced coronary flow in the dog.

The authors assessed whether intracoronary injection of low osmolality contrast media induces metabolic and electrocardiographic changes consistent with myocardial ischemia in anesthetized dogs. Ioxaglate and iohexol were injected into the left main coronary artery (eight dogs) and into a carotid-coronary artery shunt (eight dogs), during free coronary flow and during 50% flow reduction. Blood samples were obtained simultaneously from a femoral artery and from a small cardiac vein draining the contrast perfused area. Contrast media had no immediate or late effects on lactate balance during free or reduced flow. Early depression of the ST segment in epicardial ECG did not reflect ischemia. The authors conclude that the two low-osmolality contrast media, iohexol and ioxaglate, did not induce ischemic changes in the myocardium.

Pharmacokinetics of three contrast media in experimental pancreatography.

Diatrizoate, iohexol and ioxaglate were compared in experimental pancreatography in piglets. Outflow of contrast medium (CM) through the pancreatic papilla was permitted (n = 14) or impaired (n = 17) during examination. The CM concentrations were measured in portal and systemic plasma and in lymph to study the absorption of CM. Absorption of diatrizoate and iohexol was similar in both types of experiment, but radiographically, diatrizoate escaped significantly earlier from the pancreatic duct when outflow was permitted (p less than 0.01), suggesting that the CM was absorbed mainly during injection. Ioxaglate concentrations rose more slowly in systemic plasma and lymph, and fell more slowly in the portal plasma than those of diatrizoate and iohexol, which suggests that ioxaglate was absorbed over a longer period. When outflow was impaired, ioxaglate concentrations remained on a lower level, indicating less penetration in the pancreatic parenchyma. CM absorption varied markedly within each group, suggesting that variations in intraductal pressure and flow are more important in absorption than the type of CM used.

Does dilution of contrast media affect contrast enhancement? An experimental study in rats.

The effect of contrast media (CM) dilution on contrast enhancement was studied using CM representing four structurally different molecular types at osmolalities ranging from 135 to 1340 mosm/kg. Diatrizoate (ionic monomer), iopamidol (nonionic monomer), ioxaglate (ionic dimer), and iodecol (nonionic dimer) were each given at a dose of 500 mgI/kg and at concentrations of both 300 and 150 mgI/mL. Contrast media concentrations were measured using iodine 125I. Tissue blood volumes were determined using human serum albumin labeled with 131I. For each of the four CM at each of the two concentrations and after each of five time intervals following injection (0, 15, 40, 120, and 300 seconds), five rats were killed (total = 200 rats). Blood and 14 other tissues were studied. Dilution of the CM did not lead to any lower iodine tissue concentrations, iodine distribution volumes, plasma volumes, or hematocrit. The authors conclude that lowering CM osmolality by dilution with water should improve tolerance without affecting CT contrast enhancement.

Pharmacokinetics and renal accumulation of three iodinated contrast agents. A comparative study of Telebrix, Hexabrix and Omnipaque in the rabbit.

Male and female New Zealand rabbits were given a single bolus injection of 5 ml/kg of Telebrix, Hexabrix or Omnipaque intravenously. Animals were sacrificed 2, 8 and 24 h after the injection. One group of animals received a continuous i.v. infusion of contrast medium at a constant rate of 2.5 ml/kg/h for 4 h. Animals from this group were killed 30 min after the end of the infusion. Product clearance from plasma was studied in the animals given the i.v. bolus of contrast material and sacrified at 24 h postinjection. Plasma and tissue concentrations of contrast material were determined by high-performance liquid chromatography. Plasma elimination half-lives were identical in males and females and for all three products (approximately 45 min). The same held true for the volume of distribution which comprised between 20 and 26% of body weight. At 2 h postinjection, renal cortical concentrations of contrast medium were 8 to 10 times higher than plasma concentrations. For all three contrast agents, concentrations found in the renal cortex were higher than those in the medulla or the papilla at all observation times. As compared with the evolution of plasma concentrations over time, renal accumulation of the products was found to be persistent. The ionic or non-ionic nature of the tested products and their hydrophilic properties seem to play an essential role in the renal accumulation pattern.

[Comparative pharmacokinetics and renal accumulation of the iodized contrast media: ioxitalamic acid, ioxaglic acid and iohexol in the rabbit]. / Pharmacocinétique et accumulation rénale comparatives de trois produits de contraste iodés: l'acide ioxitalamique, l'acide ioxaglique et l'iohexol chez le lapin.

Male and female rabbits were given a I.V. bolus injection of a single 5 ml/kg dose of either ioxitalamic acid, ioxaglic acid or iohexol. Animals were killed 2 hours, 8 hours and 24 hours after the injection. One group of animals received a continuous I.V. infusion of contrast agent at a constant rate of 2.5 ml/kg/hour of four hours. Animals were killed 30 minutes after the end of the infusion. Plasma and tissue concentrations of contrast agents were assayed using an HPLC method. A pharmacokinetic study was performed after the I.V. bolus injection. This study shows that: 1) Plasma elimination half-lives were identical in males and in females as well as for all three products. This half life is about 45 minutes. The distribution volume was identical in male and females as well as for all three products and was comprised between 20% and 26% of body weight. 2) For all three contrast agents, the renal cortical concentrations are higher than in the medulla or the papilla at all the observation times. The renal cortical accumulation of contrast agents is persistent in comparison to plasma concentrations. 3) Ionic and lipophilic properties of contrast agents seem to play an important role on the renal accumulation pattern.