Effects of Articular Cartilage Constituents on Phosphotungstic Acid Enhanced Micro-Computed Tomography.

Contrast-enhanced micro-computed tomography (CEµCT) with phosphotungstic acid (PTA) has shown potential for detecting collagen distribution of articular cartilage. However, the selectivity of the PTA staining to articular cartilage constituents remains to be elucidated. The aim of this study was to investigate the dependence of PTA for the collagen content in bovine articular cartilage. Adjacent bovine articular cartilage samples were treated with chondroitinase ABC and collagenase to degrade the proteoglycan and the collagen constituents in articular cartilage, respectively. Enzymatically degraded samples were compared to the untreated samples using CEµCT and reference methods, such as Fourier-transform infrared imaging. Decrease in the X-ray attenuation of PTA in articular cartilage and collagen content was observed in cartilage depth of 0-13% and deeper in tissue after collagen degradation. Increase in the X-ray attenuation of PTA was observed in the cartilage depth of 13-39% after proteoglycan degradation. The X-ray attenuation of PTA-labelled articular cartilage in CEµCT is associated mainly with collagen content but the proteoglycans have a minor effect on the X-ray attenuation of the PTA-labelled articular cartilage. In conclusion, the PTA labeling provides a feasible CEµCT method for 3D characterization of articular cartilage.

Hyperosmolaric contrast agents in cartilage tomography may expose cartilage to overload-induced cell death.

In clinical arthrographic examination, strong hypertonic contrast agents are injected directly into the joint space. This may reduce the stiffness of articular cartilage, which is further hypothesized to lead to overload-induced cell death. We investigated the cell death in articular cartilage while the tissue was compressed in situ in physiological saline solution and in full strength hypertonic X-ray contrast agent Hexabrix(TM). Samples were prepared from bovine patellae and stored in Dulbecco's Modified Eagle's Medium overnight. Further, impact tests with or without creep were conducted for the samples with contact stresses and creep times changing from 1 MPa to 10 MPa and from 0 min to 15 min, respectively. Finally, depth-dependent cell viability was assessed with a confocal microscope. In order to characterize changes in the biomechanical properties of cartilage as a result of the use of Hexabrix™, stress-relaxation tests were conducted for the samples immersed in Hexabrix™ and phosphate buffered saline (PBS). Both dynamic and equilibrium modulus of the samples immersed in Hexabrix™ were significantly (p<0.05) lower than those of the samples immersed in PBS. Cartilage samples immersed in physiological saline solution showed load-induced cell death primarily in the superficial and middle zones. However, under high 8-10 MPa contact stresses, the samples immersed in full strength Hexabrix™ showed significantly (p<0.05) higher number of dead cells than the samples compressed in physiological saline, especially in the deep zone of cartilage. In conclusion, excessive loading stresses followed by tissue creep might increase the risk for chondrocyte death in articular cartilage when immersed in hypertonic X-ray contrast agent, especially in the deep zone of cartilage.

Formalin fixation affects equilibrium partitioning of an ionic contrast agent-microcomputed tomography (EPIC-µCT) imaging of osteochondral samples.

OBJECTIVE: Equilibrium Partitioning of an Ionic Contrast agent with microcomputed tomography (EPIC-µCT) is a non-invasive technique to quantify and visualize the three-dimensional distribution of glycosaminoglycans (GAGs) in fresh cartilage tissue. However, it is unclear whether this technique is applicable to already fixed tissues. Therefore, this study aimed at investigating whether formalin fixation of bovine cartilage affects X-ray attenuation, and thus the interpretation of EPIC-µCT data. DESIGN: Osteochondral samples (n=24) were incubated with ioxaglate, an ionic contrast agent, for 22h prior to µCT scanning. The samples were scanned in both formalin-fixed and fresh conditions. GAG content was measured using a biochemical assay and normalized to wet weight, dry weight, and water content to determine potential reasons for differences in X-ray attenuation. RESULTS: The expected zonal distribution of contrast agent/GAGs was observed for both fixed and fresh cartilage specimens. However, despite no significant differences in GAG concentrations or physical properties between fixed and fresh samples, the average attenuation levels of formalin-fixed cartilage were 14.3% lower than in fresh samples. CONCLUSIONS: EPIC-µCT is useful for three-dimensional visualization of GAGs in formalin-fixed cartilage. However, a significant reduction in X-ray attenuation for fixed (compared to fresh) cartilage must be taken into account and adjusted for accordingly when quantifying GAG concentrations using EPIC-µCT.

Diffusion and near-equilibrium distribution of MRI and CT contrast agents in articular cartilage.

Charged contrast agents have been used both in vitro and in vivo for estimation of the fixed charge density (FCD) in articular cartilage. In the present study, the effects of molecular size and charge on the diffusion and equilibrium distribution of several magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were investigated. Full thickness cartilage disks (Ø = 4.0 mm, n = 64) were prepared from fresh bovine patellae. Contrast agent (gadopentetate: Magnevist((R)), gadodiamide: Omniscan, ioxaglate: Hexabrix or sodium iodide: NaI) diffusion was allowed either through the articular surface or through the deep cartilage. CT imaging of the samples was conducted before contrast agent administration and after 1, 5, 9, 16, 25 and 29 h (and with three samples after 2, 3, 4 and 5 days) diffusion using a clinical peripheral quantitative computed tomography (pQCT) instrument. With all contrast agents, the diffusion through the deep cartilage was slower when compared to the diffusion through the articular surface. With ioxaglate, gadopentetate and gadodiamide it took over 29 h for diffusion to reach the near-equilibrium state. The slow diffusion of the contrast agents raise concerns regarding the validity of techniques for FCD estimation, as these contrast agents may not reach the equilibrium state that is assumed. However, since cartilage composition, i.e. deep versus superficial, had a significant effect on diffusion, imaging of the nonequilibrium diffusion process might enable more accurate assessment of cartilage integrity.

Comparative rheology of low- and iso-osmolarity contrast agents at different temperatures.

BACKGROUND: Several contrast media (CM) are used for diagnostic angiography and coronary percutaneous interventions. Catheter miniaturization allows performance of most diagnostic studies using 4-5 F catheters and interventions using 5-6 F catheters. As a result of catheter lumen downsizing and viscosity of CM, the operators are sometimes required to forcefully inject to produce adequate images. METHODS AND RESULTS: The aim of the study is to perform a comparative rheology analysis between three different commonly used CM: iso-osmolar, nonionic iodixanol, Visipaque, (GE Healthcare); low-osmolar, nonionic ioversol, Optiray; and low-osmolar, ionic ioxaglate, Hexabrix, (Tyco Healthcare, US). The viscosity was experimentally assessed for temperature varying from 14 to 40 degrees C. To reproduce clinical use, an experimental set-up was used and the pressure developed to inject CM was evaluated at different temperatures and compared between the three CM. All three agents demonstrated a nonlinear inverse relationship between temperature and viscosity. At 14 degrees C iodixanol showed a twofold increase in viscosity compared with ioversol and ioxaglate. At 40 degrees C, the difference was reduced to 27%. At room temperature (20 degrees C), the difference in pressure needed to inject CM was 10% between iodixanol and ioxaglate and 6% between iodixanol and ioversol. As the temperatures increased, the differences in pressure became less important, becoming negligible (1%) at 37 degrees C. CONCLUSION: The viscosity of the iso-osmolar nonionic contrast agent iodixanol showed a stronger dependence on temperature compared with ioversol and ioxaglate. The impact of differences in viscosity and pressure to inject between CM were minimized at 37 degrees C. This emphasizes the importance of temperature control when using current low-osmolar CM and iso-osmolar CM with smaller sized catheters.

Cardiac events after low osmolar ionic or isosmolar nonionic contrast media utilization in the current era of coronary angioplasty.

OBJECTIVES: Our study aimed to compare the isosmolar nonionic dimer iodixanol and the low osmolar ionic agent ioxaglate in the current era of percutaneous coronary intervention (PCI), using clopidogrel, enoxaparine, direct stenting, and drug eluting stent. BACKGROUND: Previous studies have suggested an association between thrombus-related events and type of contrast media. METHODS: Our prospective single-center study included 498 consecutive patients who were assigned to receive either iodixanol (n = 231) or ioxaglate (n = 267). The primary endpoint was the cumulative rate of in-hospital major adverse clinical events (MACE). A secondary endpoint was the rate of angiographic or procedural complications. RESULTS: Clinical and angiographic baseline characteristics and procedural data were similar in the 2 groups. A peak anti-Xa > 0.5 IU/ml was obtained in 97% in both groups. Glycoprotein IIb/IIIa inhibitors were used in 42% of patients. Coronary stenting was performed in 91% of patients, with direct stenting in 70%, and drug-eluting stent in 28% of patients. In-hospital MACE was more frequent in patients receiving iodixanol compared with those receiving ioxaglate (4.8% vs. 0.3%, P < 0.005). This difference was mainly related to the appearance of a large thrombus during PCI (6% with iodixanol vs. 0.3% with ioxaglate, P < 0.0001). In multivariate analysis, independent predictors of in-hospital MACE were use of iodixanol (P < 0.01), the higher number of stent used (P < 0.008), bifurcation/ostial lesion (P < 0.01), and balloon dilation before stenting (p < 0.001). CONCLUSIONS: In our study reflecting the current era of PCI, thrombus-related events are more frequent with the isosmolar nonionic dimer iodixanol than with the low osmolar ionic agent ioxaglate.

Role of osmolality of contrast media in the development of post-ERCP pancreatitis: a metanalysis.

The role of osmolality of contrast media (CM) in the development of post-ERCP pancreatitis (PEP) is debated. We therefore performed a metanalysis to determine whether osmolality affects the incidence of PEP. A literature search of English-language studies was performed using computerized databases and manual searching of abstracts and article bibliographies. Randomized controlled trials comparing the incidence of PEP associated with high- and low-osmolality contrast media (HOCM, LOCM) were considered. The outcome assessed was clinical pancreatitis as evidenced by both elevation of pancreatic enzymes and pain. Data were analyzed using logistic regression with terms for study and osmolality. Fisher's exact test was done to compare PEP rates. Homogeneity between studies was indicated by the nonsignificance of the study effect in the logistic regression model. Logistic regression also indicated no difference in PEP rates between LOCM and HOCM (P = 0.399). Comparison of PEP rates in both groups using Fisher's exact test did not indicate a difference in any individual study (all P values > 0.05). Due to the large variation of study sample sizes, we repeated the analysis by creating three study groups. The effect of osmolality was invariant to how the data were combined. The results of this metanalysis indicate that there is no significant difference between HOCM and LOCM with respect to clinical PEP.

Comparative tolerability of contrast media used for coronary interventions.

Radiographic contrast media (CM) are necessary to provide x-ray absorption of the bloodstream; all other observed effects need to be regarded as adverse. Four types of CM are currently used in diagnostic and interventional cardiology: ionic high-osmolar CM (HOCM), either ionic or non-ionic low-osmolar CM (LOCM), and non-ionic iso-osmolar CM (IOCM). Focusing on the potential cardiovascular effects caused by the CM, there is a clear difference between HOCM and the LOCM or IOCM. HOCM have a poorer profile due to a higher incidence of hypotension and electrophysiological effects. To prevent contrast-induced nephropathy, HOCM should be avoided and patients should receive the minimal dose of LOCM or IOCM with intravenous hydration before and after the procedure. Clinical hyperthyroidism has been detected after CM use, but the condition appears, ultimately, to be self-limited and to occur mainly in elderly patients. When assessing the need for a CM in terms of improved patient safety, preventing serious complications should be the major factor determining the choice. CM should not be selected on the basis of minor adverse effects since these are, ultimately, of low clinical relevance. Thrombotic events, in contrast, carry a high clinical relevance and we consider that these should be the main issue governing current choice. Ionic LOCM appear to have better profile than other CM with respect to interaction with platelet function and coagulation. In relation to thrombotic events in randomised clinical studies, ionic CM have been associated, mainly, with favourable and some neutral results compared with non-ionic agents. Only one trial indicated a more pronounced antithrombotic effect of the non-ionic IOCM relative to the ionic LOCM. The antithrombotic advantages of ionic over non-ionic LOCM are, in part, balanced by a greater frequency of minor adverse effects such as nausea, vomiting or cutaneous rashes. A matter of concern is the delayed adverse effects observed with non-ionic IOCM. However, severe and life-threatening reactions are exceptional and there are probably no significant differences between IOCM and LOCM whether ionic or non-ionic. However, in patients with known allergies, non-ionic CM are to be recommended. On the basis of the available pre-clinical and clinical data, the ionic LOCM or the non-ionic IOCM are the agents to be recommended in percutaneous coronary interventions because of their antithrombotic advantages over non-ionic LOCM.

Permeability of iodinated and MR contrast media through two types of hemodialysis membrane.

The clearance of three iodinated contrast media (CM) and three MR-CM through two kinds of hemodialysis (HD) membranes were investigated in vitro. All three MR-CM are not only injected intravenously and mainly secreted through the kidney, but also now commercially available. Each of the six CM showed significantly higher clearance with one kind of HD membrane, with a larger pore size, than that with the other. There were also large differences in clearance between the three iodinated CM with both kinds of HD membranes, but not between the three MR-CM with either kind of membrane. Thus, in order that iodinated CM be removed from the body as soon as possible in HD patients, it is important to consider the choice not only among the iodinated CM, but also between the type of HD membrane that is used. Concerning MR-CM, only the choice of HD membrane is important.

Effect of ultrasound on the release of micro-encapsulated drugs.

Although ultrasound is used extensively in medical therapies and diagnostics, it has been recognized only recently as a method for external controlled diversity of drugs. In this paper, firstly, a literature review on drug delivery and the combination with ultrasound is given. Then an experiment is described on measuring the release of a model drug (hexabrix) under ultrasound irradiation, from a polymer carrier.

Nonfatal adverse reactions to iodinated contrast media: spontaneous reporting to the U.S. Food and Drug Administration, 1978-1994.

PURPOSE: To identify any changes in the frequency of serious, nonfatal adverse drug events (ADEs) reported to the U.S. Food and Drug Administration in 1978-1994 since the introduction of low-osmolality contrast media (LOCM). MATERIALS AND METHODS: Reports of ADEs submitted were reviewed for use of iodinated contrast media. RESULTS: The estimated 170 million contrast medium-enhanced radiologic studies performed in 1978-1994 produced 22,785 reports of mild or moderate ADEs, 2,639 reports of serious but nonfatal ADEs, and 920 reports of death. The most common ADEs (urticaria, dyspnea, vomiting, pruritus, facial edema, and hypotension) ranked similarly for ionic and nonionic contrast media. High-osmolality contrast media were associated with 512 serious, nonfatal ADEs reported in 1978-1986; 1,068 were reported in 1987-1994. Nonionic LOCM were associated with 17 serious, nonfatal ADEs reported in 1978-1986; 609 were reported in 1987-1994. Intrathecal injection of nonionic contrast media was associated with 235 reported serious, nonfatal ADEs; intrathecal ionic [corrected] contrast media were associated with 14 such reported ADEs. CONCLUSION: Reports of serious, nonfatal ADEs are uncommon relative to the use of contrast media. The authors observed no decrease in the number of ADEs reported since the introduction of LOCM but did not consider marketing trends or secular reporting trends.

Reports on contrast media reactions: analysis of data from reports to the U.S. Food and Drug Administration.

PURPOSE: To compare U.S. Food and Drug Administration (FDA) and manufacturer data about patient reactions to ionic and nonionic, low- and high-osmolar contrast media from 1990 through 1994. MATERIALS AND METHODS: Reactions to all available high-osmolar and four low-osmolar contrast media (ioxaglate, iohexol, iopamidol, and ioversol) were compared. Ioxaglate is composed of charged particles, and data are reported separately. Reactions were also compared with data from 1980 to 1984, when only high-osmolar contrast media were available. RESULTS: With high-osmolar contrast media compared with the three noncharged low-osmolar media, the incidence (per million examinations) was highest for all reported reactions (193.8 vs 44.4), severe reactions (37.4 vs 10.5), and deaths (3.9 vs 2.1). With high-osmolar media compared with ioxaglate, respectively, the incidence of total reactions was higher (193.8 vs 142.5), of severe reactions was almost the same (37.4 vs 33.6), and of death was lower (3.9 vs 6.4). The incidence of severe reactions to total reactions was higher with nonionic media (23.7%) and ioxaglate (23.6%) than with ionic media (19.3%). The incidence of death to severe reactions was 19.7% with nonionic media, 19.0% with ioxaglate, and 10.4% with high-osmolar media. The incidence of renal failure (as a percentage of total reports) was approximately 3.6 times higher with all low-osmolar contrast media (2.3%) than with high-osmolar media (0.6%), usually in patients with pathologic cardiac conditions. CONCLUSION: All of these factors merit consideration in the evaluation of the utility of a given contrast medium.

Electrolyte addition to nonionic contrast media. Cardiac effects during experimental coronary arteriography.

Although the incidence of serious adverse effects is low during clinical coronary arteriography, life-threatening cardiovascular complications occasionally occur. Ventricular fibrillation (VF) is most often seen during contrast media (CM) injection through a wedged catheter. A simulated wedged catheter model in dogs has therefore been developed. Further, patients with heart failure are at greater risk for CM-related side effects during coronary arteriography. Thus, an acute ischemic heart failure model has been used. The present thesis was designed to investigate the cardiac electrophysiologic and hemodynamic effects of CM during selective coronary arteriography in normal and failing hearts, and in particular the role of electrolyte addition to nonionic CM. The risk of spontaneously induced VF and the arrhythmogenic mechanisms were studied when using iso-osmolal and low-osmolal CM having different contents of electrolytes, and after pretreatment with antiarrhythmic drugs. Further, effects of adding electrolytes to nonionic CM during single and fast repeated injections in normal and failing hearts were studied. Also possible effects of oxygenating CM were studied. CM injection in a wedged catheter situation had a high risk for VF. Probably, VF was due to induced regional electrophysiologic changes in ventricular activation and repolarization. Pretreatment with antiarrhythmic drugs did not prevent VF. However, addition of low concentrations of electrolytes to nonionic CM reduced the risk for VF in a wedged catheter situation. The results indicate that side-effects of CM during coronary arteriography are related mainly to the passive washout of cardiac electrolytes. Electrolyte shifts during coronary arteriography may change the myocardial Na/Ca balance and cellular calcium control. The nonionic, iso-osmolal CM iodixanol, with a balanced content of sodium and calcium and the low-osmolal, nonionic CM iohexol, also with a balanced content of electrolytes, had about the same low risk for inducing VF and presented a much lower risk for inducing VF than did iohexol and ioxaglate in a wedged catheter situation. Single injection of iohexol with a balanced eletrolyte addition induced only minimal electro-physiologic changes and was well tolerated hemodynamically. Repeated intracoronary CM injections during ischemic heart failure were associated with similar additive electrophysiologic and hemodynamic changes as when using iohexol without electrolyte supplement. Oxygenated and nonoxygenated CM presented the same risk for inducing VF. Only minor electrophysiologic and hemodynamic differences could be detected during wedged catheter injection. In conclusion, addition of key electrolytes to nonionic CM can reduce the risk of cardiac complications during coronary arteriography. Oxygenation of CM does not seem to significantly further reduce the risk.

Biochemical characterization of x-ray contrast media.

RATIONALE AND OBJECTIVES: Eleven ionic and nonionic contrast media were compared in parallel regarding their effects on various biochemical parameters in vitro. Partition coefficient, protein binding, release of histamine, hemolysis inhibition and complement activation were determined as well as inhibition of various enzymes. Additionally, incompatibilities between contrast media and intravascular drugs that often are coadministered were determined. METHODS: Partition coefficients were determined in the system n-butanol/water by spectrophotometry. Protein binding was measured by equilibrium dialysis. Histamine release from rat peritoneal mast cells was measured by radioassay. Hemolysis inhibition and complement activation was determined in beagle dog serum using antibody-coated sheep erythrocytes. The inhibition of enzyme systems was measured photometrically. Incompatibility with coadministered drugs was registered by appearance of precipitations. RESULTS: Hydrophilicity as determined by partition coefficients was highest for iotrolan and lowest for iotetrol. Protein binding ranged from practically zero for most substances to 14% for ioxaglate. Histamine release was highest for diatrizoate (77% at 100 mg I/mL) and lowest for iodixanol (1%). Complement activation at 100 mg I/mL ranged from 0% (diatrizoate, iopamidol) to 77% (iopentol). The inhibition of the enzyme systems urokinase, streptokinase, collagenase, tissue plasminogen activator, and lysozyme was lowest for the nonionic dimers. CONCLUSIONS: All compounds influenced the parameters tested. However, the degree of interaction was different. Although there was no significant correlation between hydrophilicity (partition coefficient) or osmolality and the tested parameters, nonionic dimers seemed to be superior to nonionic monomers. The reason might lie in reduced chemotoxicity of this class of contrast media.

Detection of air emboli in radiographic contrast media by microwave radiometry.

To evaluate the efficacy of a microwave radiometry system in detecting in-line air emboli in radiographic contrast media, air emboli ranging in volume from 0.1 to 0.005 ml were introduced into ionic (ioxaglate) and nonionic (iohexol) contrast media at 22 or 37 degrees pumped at flow rates of 16.7, 180 or 300 ml/min through polyvinlychloride tubing with an inner diameter of 0.100 inches (2.54 mm) over which was fitted a radiometer antenna connected to a Microwave Medical System F+ radiometer and a computerized data acquisition system. A total of 400 determinations were run, with 10 replicate determinations for each unique set of experimental conditions. The success of air emboli detection was not significantly related to contrast media (p = 0.73) or contrast temperature (p = 0.68). Embolus volume (p < 0.0001) and pump speed (p < 0.0001) were significant factors affecting system performance. The system could reliably detect small (0.005 ml) emboli in both ionic and nonionic low-osmolar contrast media.

Nonionic contrast agents produce thrombotic effect by inducing adhesion of leukocytes on human endothelium.

The expression of P-selectin was more upregulated following the exposure to nonionic low osmolar contrast agents than to ionic contrast agents. Exposure to nonionic contrast agents led to a marked adhesion of leukocytes to endothelial cells. Thrombomodulin activity of endothelial cells was decreased, and plasminogen activator inhibitor-1 (PAI-1) and tumor necrosis factor (TNF) alpha in the supernatant were increased when leukocyte adhesion occurred after exposure to nonionic contrast agents. Results suggest that the adhesion of leukocytes to the endothelium increases procoagulant activity.

Vasoconstriction of isolated arteries induced by angiographic contrast media. A comparison of ionic and non-ionic contrast media iso-osmolar with plasma.

Angiographic contrast media (CM) may cause both vasodilatation and vasoconstriction, effects that can only be partly be explained by the media's hyperosmolality. The present study describes a CM-induced vasoconstriction of isolated rabbit coronary arteries that depends on chemotoxicity and ion content of the CM. Rings of arteries were mounted in tissue baths and the constrictions induced by different CM were measured. Iotrolan and iodixanol (non-ionic dimers) caused the most powerful constrictions followed by iohexol (non-ionic monomer) and mannitol. Ioxaglate (ionic dimer) and diatrizoate (ionic monomer) caused no or weak constrictions. By comparing these findings with previous studies, it is concluded that non-ionic media cause vasoconstriction due to depolarization of the smooth muscle cells, an effect that for iohexol can be counteracted by addition of 30 mM NaCl. The ionic media seem to cause hyperpolarization of the cells. This difference between non-ionic and ionic CM might be one of the reasons for the lower tendency of non-ionic CM to cause vasodilatation clinically.

Platelet degranulation induced by some contrast media is independent of their nonionic vs ionic nature.

We confirm that the phenomenon of platelet degranulation exists for both iohexol and diatrizoate, as reported earlier. In contrast to previous conclusions, however, we have determined that the degranulation is independent of the nonionic vs. ionic nature of the media per se, since degranulation was neither seen with nonionic iodixanol nor ionic ioxaglate. The degranulation, further, does not significantly augment platelet function, as measured by flowing whole blood platelet aggregometry.

Laser angioplasty: enough to make your blood boil!

Some of the effects on blood and contrast agents of a laser angioplasty device of the "hot tip" variety have been studied. This device liberates iodine from contrast agents both in the form of soluble free iodide and in the form of solid elemental iodine debris. Some of the solid iodine does not adhere to the probe but remains free and, in vivo, would be available to embolize distal vessels. The liberation of iodine occurs more readily with dimeric agents than with monomeric contrast agents regardless of whether they are ionic or non-ionic. Blood and blood/contrast agent mixtures exhibit local boiling in the vicinity of the hot tip laser probe. Blood so treated exhibits markedly accelerated clotting as indicated by measurements of whole blood clotting times. Untreated blood to which aliquots of blood treated as described above are added also exhibits accelerated clotting. The laser tip, operating in blood/iodine mixtures, becomes coated with a friable black/brown deposit which analysis reveals to be a mixture of carbon and iodine. Again, some of this particulate debris fails to adhere to the probe and is available as free embolic material. The possible practical clinical implications of these observations are discussed.