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Determination of blood flow velocity and transit time in cerebral arteriovenous malformation using microdroplet angiography.

Advancement in imaging and biomedical technology has improved the use of catheter-based transarterial embolization (occlusive therapy) of cerebral arteriovenous malformations (AVMs). Among a variety of embolic agents, liquid adhesives (acrylates) have proven to be more successful in permanent obliteration of AVMs. The use of liquid adhesives requires the experience and skill of the operator. However, acquiring accurate information on blood flow and transit times through the AVM prior to embolization can optimize the treatment. In addition, knowledge of the polymerization time and behavior of the acrylate enables a complete and safe occlusion of the arteriovenous transition within the AVM nidus. Standard commercially available iodine-based contrast agents seem to be insufficient to determine AVM transit times from angiograms. For a more accurate assessment of AVM transit times, the use of a nonsoluble contrast agent (Ethiodol) and a high-speed digital subtraction angiography (DSA) is suggested. Small amounts (<20 microl) of Ethiodol were infused to create microdroplets and traced using DSA at 15 fps. Transit time, defined as the time interval required for a droplet to reach the venous part of the AVM after being flushed from the tip of the catheter, could be accurately calculated. Postprocessing was used to calculate trajectories and velocities of microdroplets.

Angiography, Digital Subtraction↗

First-pass entry of nonionic contrast agent into the myocardial extravascular space. Effects on radiographic estimates of transit time and blood volume.

BACKGROUND: Almost all x-ray-based techniques intended to assess regional myocardial perfusion from myocardial concentration-time curves following the administration of soluble contrast agents assume that these agents behave as intravascular indicators and can therefore provide measurements of intravascular transit time and intramyocardial blood volume. METHODS AND RESULTS: We tested this assumption by comparing a conventional nonionic contrast agent (ioversol) to a particulate emulsion (ethiodol) that remained in the vascular space in closed-chest dogs during pharmacological vasodilation. Using fast computed tomography (CT), pairs of myocardial CT intensity-time curves were obtained following sequential bolus aortic administration of the two contrast agents. The emulsion (particle size less than 3 microns) was almost completely washed out of the myocardial region of interest within a few seconds, as would be anticipated for a vascular indicator. At the onset of recirculation, CT intensity for ethiodol fell to 5 +/- 1% (SEM) of peak values in normally perfused areas and to 10 +/- 4% of peak values in an area in which flow had been reduced by 50% by a chronically implanted coronary artery occluder (p = NS). In comparison, the diffusible nonionic contrast agent ioversol showed substantial intramyocardial retention at the onset of recirculation. At the time of recirculation, CT intensities for ioversol averaged 36 +/- 2% of peak values in normally perfused nonstenotic areas and 54 +/- 4% of peak values in stenotic areas (p less than 0.01). Using residue function analysis for a diffusible indicator, first-pass extractions of the conventional nonionic agent averaged 33 +/- 2% in normally perfused areas and 50 +/- 3% in stenotic areas (p less than 0.01). Because of the significant first-pass myocardial retention of ioversol, both mean myocardial appearance time and intramyocardial blood volume were consistently overestimated. CONCLUSIONS: Soluble radiographic contrast agents, like other small molecules, enter the interstitial space to a degree, which is important because it affects estimates of myocardial perfusion based on transit time and intramyocardial blood volume. Indicator dilution models intended to quantify myocardial perfusion with conventional radiographic contrast agents need to account for this extravascular exchange.

Animals↗

[Intra-arterial injection of an oily antineoplastic agent in hepatic cancer].

A lymphographic agent, Ethiodol, injected via the hepatic artery was found to remain selectively in the tumor vessels of hepatoma for a long time in our clinic. Taking advantage of this selective continuous peripheral embolization, a lipophilic high molecular anticancer agent, SMANCS (Copolymer of styrene maleic acid conjugated to Neocarzinostatin) dissolved in Ethiodol was administered via the celiac axis or the hepatic artery with Seldinger's method. Anticancer effect was examined by histological findings of specimens removed using hepatic resection (13 cases) and autopsy (1 case) in 14 patients receiving this treatment. Anticancer effect of this treatment became clear through histological findings. In the patients administered SMANCS more than 0.26 mg per 1 cm2 of maximum cut-surface area, complete or widespread necrosis of the tumor occurred, whereas non-cancerous liver tissue remained unaffected.

Adult↗

Intravasation during hysterosalpingography using oil-base contrast media.

The use of oil-base contrast media for hysterosalpingography provides detailed imaging and the added information of a delayed film. Intravasation with possible embolization of oily media is often cited as a morbid complication. There are reports of significant morbidity associated with the use of high-viscosity oil media such as Lipiodol. Ethiodol has a significantly lower viscosity than Lipiodol. The incidence of intravasation can be reduced by proper timing of the study and avoidance of excessive pressures during instillation. With fluoroscopy, the early manifestations of intravasation can be detected, allowing the operator to limit the volume of embolized medium. We report 13 cases of intravasation (6 with embolization) with no morbidity during hysterosalpingography performed with Ethiodol. These data suggest that embolization of low-viscosity oil contrast media in low volumes is a relatively benign process. The text of this paper contains data on the clinical histories and courses of the 13 cases cited.

Blood Vessels↗

Hysterosalpingography contrast media and chromotubation dye inhibit peritoneal lymphocyte and macrophage function in vitro: a potential mechanism for fertility enhancement.

OBJECTIVE: To determine the effects of hysterosalpingography (HSG) contrast media (CM) and chromotubation dye on peritoneal lymphocyte proliferation and macrophage phagocytosis in vitro. DESIGN: Peritoneal fluid (PF) lymphocytes and macrophages were isolated from 40 subfertile women undergoing diagnostic laparoscopy and 12 fertile women having laparoscopic tubal ligation. Dilutions of renografin, ethiodol, methylene blue, and indigo carmine were added to peritoneal lymphocyte and macrophage cultures. Tissue culture media alone served as control. Lymphocyte proliferation was assessed by hemocytometer counts and 3H-thymidine incorporation. Macrophage function was determined by phagocytosis of fluorescent microspheres. RESULTS: Peritoneal lymphocyte proliferation and macrophage phagocytosis were significantly inhibited by renografin, ethiodol, methylene blue, and indigo carmine in a dose-dependent manner. CONCLUSION: Inhibition of PF immune cell function by HSG CM and chromotubation dye may provide a potential mechanism for fertility enhancement after these diagnostic procedures.

Cell Survival↗

Intraarterial infusion of 5-fluoro-2-deoxyuridine-C8 dissolved in a lymphographic agent in malignant liver tumors. A preliminary report.

The drug 5-fluoro-2-deoxyuridine-C8 (FUdR-C8), one of the lipophilic prodrugs of FUdR, was dissolved in an oily lymphographic agent (Lipiodol Ultra Fluid, Andre Gelbe Laboratory, Paris, France; Ethiodol, Savage Laboratories, Melville, NY) and used for the intraarterial treatment of malignant liver tumors. From August 1985 to June 1988, 33 patients with hepatocellular carcinoma and 13 patients with metastatic liver tumors were treated with this agent at the Kumamoto University Hospital and its affiliated hospitals. The response rate (complete remission [CR] and partial remission [PR]) was 27.6% for hepatocellular carcinomas and 46.1% for metastatic liver tumors. The cumulative 1-year survival rate was 55.1% for hepatocellular carcinomas and 70.0% for metastatic liver tumors. More than a 50% decrease in the tumor marker level was observed in ten of 21 patients with hepatocellular carcinoma and in two of eight patients with metastatic liver tumors. The side effects, which were transient and controlled with conservative treatment, included fever, abdominal pain, nausea, vomiting, and acute gastritis.

Adult↗

Three-dimensional canine renovascular structure and circulation visualized in situ with the dynamic spatial reconstructor.

The dynamic spatial reconstructor--a unique, high speed, volume-scanning, X-ray computed tomographic imaging system--was utilized to examine canine renovascular anatomy and renal circulation in situ. In each of the four kidneys examined in this study initial scans were done during bolus injections of angiographic contrast material into the renal artery. A subsequent scan was then performed following an injection of methyl-methacrylate-based casting compound that had been contrast enhanced with ethiodol. After the scans, each kidney was removed, and its parenchyma was digested in potassium hydroxide to expose the vascular cast. Comparison of casts with their reconstructed images and with images obtained during injection of contrast material showed that interlobar arteries and occasionally arcuate arteries could be clearly detected. Although discrete vessels less than 1 mm in diameter could not be resolved, dynamic changes in parenchymal distribution of density during passage of contrast material allowed interpretation of flow through the multiple capillary beds of the kidney. Such analysis indicated that maximal density was in the outer-middle zone of the cortex throughout the duration of the scan. Analysis of artery-to-vein transit time showed arrival of contrast material in the renal vein as soon as 3 sec, and continuation for longer than 8 sec, after the renal artery bolus. In conclusion, renal circulation in the dog can be discretely visualized with the dynamic spatial reconstructor up to the level of the arcuate arteries; however, capillary flow as a whole can be followed through the cortex, and the results suggest the presence of both rapid and slow components of peritubular circulation.

Animals↗

Colonoscopic indirect lymphangiography in a canine model.

Colorectal malignancies metastasize most frequently to mesenteric lymph nodes. Preoperative staging of these nodes by current modalities is problematic. This study evaluates the feasibility of indirect mesenteric lymphangiography as a colonoscopic technique in a canine model. Ten mongrel dogs underwent endoscopic submucosal injection of Ethiodol at various sites in the transverse, descending, and rectosigmoid areas. Serial abdominal roentgenograms were obtained up to 2 weeks postinjection. In seven of the animals, demonstration of mesenteric nodal uptake corresponding to the area(s) of injection was radiographically documented. In the remaining animals (early in the series) nodal opacification was inadequate. This lack of nodal uptake appeared to be due to nonsubmucosal contrast injection. No complications were noted. Colonoscopic indirect lymphangiography appears to be a safe and potentially useful modality in the evaluation of mesocolonic lymph nodes. Further studies to refine this technique and investigate its potential to preoperatively delineate abnormal nodal architecture are warranted.

Animals↗

Influence of nutritional state on the disposal of orally and intramuscularly administered iodized oil to iodine repleted older children and adult women.

Iodinated oil (Ethiodol, 1 or 2 ml) was administered po or by im administration to adult women and older children in rural highland Ecuador who were either well nourished or malnourished to determine the effect of nutritional status on the disposal rate of iodine. These subjects resides in a region previously severely deficient in iodine, but this had been corrected in these subjects by prior administration of iodinated oil or by use of iodized salt or both. Malnutrition as determined by the conventional standards of height for age was associated with a significantly shortened retention time of the administered iodine, whether given po or im. The half life of retention was approximately half in the malourished of that in the well nourished. If these findings can be extrapolated to chronically iodine deficient subjects, then malnourished populations in need of iodine supplementation should either receive higher dosages than those conventionally employed or more frequent dosage.

Adolescent↗

In utero hematopoietic stem cell transplantation with haploidentical donor adult bone marrow in a canine model.

OBJECTIVE: Chimerism can be achieved in a canine model of in utero bone marrow transplantation with > or =1 x 10(8) CD34(+) haploidentical donor cells per kilogram without graft-versus-host disease. STUDY DESIGN: In utero bone marrow transplantation was performed by ultrasound-guided intraperitoneal infusion in 30- to 41-day-old canines with CD34(+) selected cells from paternal bone marrow at doses of 1.3 x 10(8) to 2.5 x 10(10) CD34(+) cells/kg. A method for marking control littermates was developed with intraperitoneal ethiodol. Postnatal studies included histologic, fluorescent in situ hybridization canine Y probe, and polymerase chain reaction-based chimerism analyses. RESULTS: Term survival was 86% to 100% for transplantations > or =34 days versus 14% and 43% at 30 and 31 days. Microchimerism (<1%) was demonstrated in tissues from 4 informative litters that included thymus, liver, skin, spleen, and intestine. Neither gestational age nor donor CD34 cell dosage altered the level of engraftment in these experiments. There was no evidence of graft-versus-host disease. CONCLUSION: In utero bone marrow transplantation in a canine model achieves microchimerism with high CD34(+) cell doses.

Animals↗

Computed tomography of hepatic oil embolism following lymphangiography.

Computed tomographic (CT) findings in two cases of hepatic oil embolism following lymphangiography are described. Both patients had lymphatic obstruction and opacification of the liver due to collateral flow of lymphangiographic contrast. Computed tomography of the liver showed a distinctive branching pattern due to the intrahepatic ethiodol.

Adult↗

Prostatography.

The direct intraprostatic injection of ethiodol was done in 10 cases to visualize the prostate gland. Immediately after the injection the contrast material was distributed uniformly throughout the prostatic lobe, opacifying it with a fine reticular pattern (prostatogram). The size, shape and intravesical projection of the prostate could be studied accurately in all patients and the findings were confirmed at operation. All patients tolerated the procedure well without any local or systemic complications. Direct intraprostatic injection of the contrast material did not alter the gross nor the microscopic anatomy of the gland. Prostatography is a safe adjuvant radiologic procedure to obtain a 3-dimensional image of prostatic hypertrophy. This information would be useful in the proper planning of operative or radiation treatment of prostatic diseases. It also might be helpful in delineating the deep-seated suspicious prostatic nodules that are inaccessible for clinical examination.

Aged↗

Prostatic lymphography.

Direct intraprostatic injection of ethiodol was done in 12 patients with benign prostatic hypertrophy to visualize lymphatic drainage of the prostate gland. In all 12 patients lymphatics of the prostate could be visualized well. The findings of our study indicate that the prostate mainly drains through 3 sets of lymphatics: 1) the main and important set of lymphatics starts from the superolateral angle of the prostate and courses along the lateral pelvic wall to drain into the internal iliac lymph nodes, 2) some lymphatics drain into the lymph nodes in the presacral area and 3) in 45% of the patients lymphatics from the apex of the prostate travel along the course of the internal pudendal vessels to the internal iliac lymph nodes. From the internal iliac lymph nodes the drainage is to the common iliac lymph nodes and, finally, to the lumbar lymph nodes. Each lateral lobe of the prostate drains mainly into the ipsilateral group of lymph nodes with little crossover of lymphatics to the opposite side. All patients tolerated the procedure well and there were no complication during or after the procedure. We believe that this procedure is a safe, simple and direct method to visualize lymphatic drainage of the human prostate gland.

Ethiodized Oil↗

Serum pancreastatin levels predict response to hepatic artery chemoembolization and somatostatin analogue therapy in metastatic neuroendocrine tumors.

INTRODUCTION: Neuroendocrine tumors often metastasize to the liver and present with disabling hormonal symptoms. Hepatic artery chemoembolization (HACE) combined with somatostatin therapy, pre-embolization, peri-embolization and post-embolization, at doses to control symptoms, is an aggressive approach that can relieve hormonal symptoms with minimal morbidity and mortality. METHODS: Chemoembolization was performed using 30 mg of adriamycin, 50 mg of mitomycin, 12 ml of hexabrix, 10 ml of ethiodol, and 360-500-microm particles. Pancreastatin, a split product of chromogranin A, was measured pre-HACE and post-HACE in all patients. RESULTS: Forty-three chemoebolization procedures were performed in 34 symptomatic patients from December 1995 to August 1999. Seventeen patients had intestinal primaries (50%), seven had pancreatic primaries (20%), five had bronchial primaries (15%), and five had unknown primaries (15%). Systemic pancreastatin levels were improved or stable in 31 patients (78%). Symptoms were improved in these 31 patients (78%). Systemic serotonin levels were improved or stable in 24 patients (60%). Radiographic improvement or stability was seen in 18 patients (45%). Procedural related morbidity included pain, fevers, nausea, vomiting, and transient elevations of liver function studies in 75-100% of patients. There was one procedural related mortality (2%). Less than 20% improvement in pancreastatin levels from baseline was associated with death in five of five patients (100%). This was not observed with serotonin levels. CONCLUSION: Measurement of serum pancreastatin levels is an easy and useful method to predict success in patients who undergo HACE plus somatostatin therapy for metastatic neuroendocrine tumors to the liver. This therapeutic approach is effective in relieving symptoms in 78% of patients, with minimal major morbidity or mortality.

Adult↗

Determinants of postembolization syndrome after hepatic chemoembolization.

PURPOSE: Postembolization syndrome (PES) occurs in the majority of patients undergoing hepatic chemoembolization, and is the major reason for hospitalization after the procedure. The ability to identify which groups of patients are at increased or decreased risk of PES would be useful to better counsel patients, to minimize toxicity, and to plan inpatient versus outpatient therapy. MATERIALS AND METHODS: Seventy hepatic chemoembolization procedures were performed in 29 patients using cytotoxic drugs mixed with Ethiodol and polyvinyl alcohol. The following procedural variables were retrospectively assessed and evaluated for association with PES and length of postprocedural hospitalization: gallbladder embolization, lobe embolized, percentage liver volume embolized, percentage embolized volume occupied by tumor, previous embolization of the same territory, and dose of chemoembolic emulsion. Logistic regression was used to quantify the relative effect of each procedural variable. RESULTS: Gallbladder embolization and dose administered were associated with an increased risk of PES and an extended hospitalization, with odds ratios of 2.8 and 3.0, and 3.0 and 4.6, respectively. Previous embolization was associated with a decreased risk of both PES and extended hospitalization, with odds ratios of 0.5 and 0.4, respectively. There was a statistical trend toward significance for gallbladder embolization (P = .06), dose administered (P = .07), and previous embolization (P = .14). CONCLUSION: Clinically relevant predictors of the severity of PES and length of postprocedural hospitalization may exist. Avoiding embolization of the gallbladder reduces the risk of PES. Re-embolization of previously treated vessels is associated with decreased toxicity and may assist in selecting patients for treatment on an outpatient basis, especially when a reduced dose is required.

Antineoplastic Combined Chemotherapy Protocols↗

Treatment of hepatocellular carcinoma with sub-selective transcatheter arterial oily chemoinfusion.

Transarterial therapy for primary liver cancer is gaining more acceptance. The technique of transarterial treatment of such cancers is, however, quite varied. To determine the value of our approach, we analyzed our experience with transarterial oily chemoinfusion (TOCI) of primary liver cancer over a 4.9-year period. Since 1997, over 300 such procedures have been performed at our institution. We report the results of the first 253 procedures, which were performed using a subsegmental technique with a mixture of doxorubicin, cisplatin, ethiodol, with selective Gelfoam embolization. Actuarial survival rates at 1, 2, and 3 years were calculated with Kaplan-Meier and multivariate analysis was performed by Cox regression. The median overall survival was 28.6 +/- 4.5 months following diagnosis. By univariate analysis, TNM clinical stage I or II, Karnofsky score above 80%, absence of extrahepatic disease, absence of vascular invasion, unifocal disease, pretreatment alpha-fetoprotein levels less than 500 ng/ml, hypervascularity of lesions, and lesion size less than 5 cm were all strong predictors of favorable patient survival at 1, 2, and 3 years (75%, 60%, and 50% respectively). Based on our experience, TOCI with selective embolization has similar survival benefit as the traditional chemoembolization but is associated with fewer complications.

Adult↗

[A new contrast medium emulsion for lymphography (author's transl)].

A new contrast medium for lymphography has been developed. It is suitable for direct, such as bi-pedal, lymphangiography, and has certain advantages compared with the commercially available contrast medium Ethiodol, such as absence of a lipogranulomatous reaction and less extensive oil emboli in the lungs. It is also possible to use the substance for indirect, retrosternal lymphography. The substance is indirect, retrosternal lymphography. The substance is an emulsion of triglycerides of iodinated poppy seed oil. The method of preparation of the emulsion is described.

Animals↗

2-Octyl-cyanoacrylate (Dermabond), a new glue for variceal injection therapy: results of a preliminary animal study.

BACKGROUND: Endotherapy of bleeding gastric varices is problematic. The aim of this descriptive study in an animal model was to compare 2-octyl-cyanoacrylate (Dermabond), a Food and Drug Administration-approved agent for superficial wound closure, to N-butyl-2-cyanoacrylate (Histoacryl), an agent available outside of the United States for the endoscopic treatment of bleeding gastric varices. METHODS: Eight New Zealand white rabbits were randomly assigned to either the study agent Dermabond or the control agent, Histoacryl. Both active agents were equally mixed with ethiodized poppy seed oil (Ethiodol) and injected into the auricular vein. The animals were euthanized at various time intervals after injection. A 2 cm strip of tissue on either side of the injection site along with the adjacent perivascular tissues were resected for histologic evaluation. RESULTS: The use of 0.5 mL of Dermabond effectively induced vascular occlusion compared with 0.2 mL of Histoacryl. The histologic changes acutely and at 1 week were similar with each mixture. CONCLUSION: Dermabond may be useful in the treatment of gastric variceal bleeding, but further studies are necessary to determine dose response rates in animals and humans.

Animals↗