Comparing deposition characteristics of various embolic particles using an in vitro prostate microvasculature model.

PURPOSE: To compare spatial distributions of radiopaque glass (RG) microspheres, trisacryl gelatin (TAG) microspheres, and polyvinyl alcohol (PVA) foam particles within a planar in vitro microvascular model of the hyperplastic hemiprostate. MATERIALS AND METHODS: A microvascular model simulating hyperplastic hemiprostate was perfused with a water-glycerin mixture. A microcatheter was positioned distal to the model's prostatic artery origin and embolic particles (RG: 50 µm, 100 µm, and 150 µm; TAG: 100-300 µm and 300-500 µm; and PVA: 90-180 µm and 180-300 µm) were administered using a syringe pump. Microscopic imaging and subsequent semantic segmentation were performed to quantify particle distributions within the models. Distal penetrations were quantified statistically via modal analysis of the particle distributions. RESULTS: Maximum distal penetration was observed for RG 50, followed by RG 100 and then TAG 100-300 and RG 150. TAG 300-500, PVA 90-180, and PVA 180-300 particles exhibited the lowest distal penetrations. The distal penetration metrics between groups were significantly different (p < 0.05) except between TAG 100-300 and RG 150 and between PVA 90-180 and PVA 180-300. CONCLUSIONS: Comparing the spatial distributions of embolic particles in an in vitro microvascular model simulating the hyperplastic hemiprostate revealed that noncompressible particles and those with narrower size calibrations and smaller relative diameters exhibited higher degrees of distal packing. The embolization front was less distinct for particles with wider size calibrations, which resulted in smaller, more distal emboli along with larger, more proximal emboli. PVA and TAG 300-500 particles both exhibited relatively low overall distal penetration.

Imageable Radioembolization Microspheres for Treatment of Unresectable Hepatocellular Carcinoma: Interim Results from a First-in-Human Trial.

PURPOSE: To Describe 6-Month safety, efficacy and multimodal imageability after imageable glass Yttrium-90 radioembolization for unresectable Hepatocellular Carcinoma (HCC) in a First-in Human Trial METHODS: Eye90 microspheres® (Eye90), an FDA Breakthrough Designated Device, are glass radiopaque Y-90 microspheres visible on CT and SPECT/CT. Six subjects with unresectable HCC underwent selective (≤ 2 segments) Eye90 treatment in a prospective open-label pilot trial. Key inclusion criteria included liver only HCC, ECOG ≤ 1, total lesion length ≤ 9 cm and Child-Pugh A. Prospective partition dosimetry was utilized. Safety, biochemistry, toxicity, adverse events (AE), multimodal imageability on CT and SPECT/CT and 3 and 6-month MRI local modified RECIST (mRECIST) response was evaluated. RESULTS: 6 subjects with HCC (7 lesions) were treated with Eye90 and followed to 180 days. Administration success was 100%. Eye90 CT radiopacity distribution correlated with SPECT/CT. Target lesion complete response was observed in 3 of 6 subjects (50%) and partial response in 2 (33.3%). Two subjects could not be assessed at 180 days. At 180 days, target lesion complete response was maintained in 3 subjects (50%) and partial response in 1 (16.7%). All subjects reported AEs, and 5 reported AEs related to treatment. There were no treatment related serious AEs. CONCLUSIONS: Eye90 was safe and effective in six subjects with unresectable HCC up to 6 months. Eye90 was imageable via CT and SPECT/CT with correlation between CT radiopacity and SPECT/CT radioactivity distribution. Eye90 provided previously unavailable CT based tumor targeting information.

90Y Contamination in the Interventional Radiology Suite: VARSKIN Estimation of Skin and Eye Injury and Review of Mitigation Strategies.

Our objective was to demonstrate, through computer simulations, radiation exposure levels from a 90Y contamination event during radioembolization procedures to calculate the radiation doses from various contamination scenarios. We also provide reasonable safety protocols to prevent contamination and minimize radiation exposure during decontamination. Methods: Simulations were performed using the computer code VARSKIN+, version 1.0, to determine the amount of radiation exposure resulting from different contamination scenarios. Results: The annual radiation dose limit to the skin and the lens of the eye was exceeded within 23 s of exposure to a 44-MBq droplet. Double layers of surgical gloves and level 3 gowns provided some attenuation of radiation from 90Y contamination by reducing the dose rate by 39% and 44%, respectively. Two layers of surgical gloves offered the best ratio of radiation protection without compromising dexterity. Conclusion: This study demonstrated that radiation exposures during 90Y spills or contamination events can be considerable. Interventional radiology and nuclear medicine personnel must be mindful of the risks, follow strategies to prevent spills, and be familiar with recommended decontamination procedures for spills in the interventional radiology suite.

Clinical consensus statement: Establishing the roles of locoregional and systemic therapies for the treatment of intermediate-stage hepatocellular carcinoma in Canada.

BACKGROUND: Hepatocellular carcinoma (HCC) a leading cause of cancer mortality worldwide and approximately one-third of patients present with intermediate-stage disease. The treatment landscape of intermediate-stage HCC is rapidly evolving due to developments in local, locoregional and systemic therapies. Treatment recommendations focused on this heterogenous disease stage and that take into account the Canadian reality are lacking. To address this gap, a pan-Canadian group of experts in hepatology, transplant, surgery, radiation therapy, nuclear medicine, interventional radiology, and medical oncology came together to develop consensus recommendations on management of intermediate-stage HCC relevant to the Canadian context. METHODS: A modified Delphi framework was used to develop consensus statements with strengths of recommendation and supporting levels of evidence graded using the AHA/ACC classification system. Tentative consensus statements were drafted based on a systematic search and expert input in a series of iterative feedback cycles and were then circulated via online survey to assess the level of agreement. RESULTS & CONCLUSION: The pre-defined ratification threshold of 80 % agreement was reached for all statements in the areas of multidisciplinary treatment (n = 4), intra-arterial therapy (n = 14), biologics (n = 5), radiation therapy (n = 3), surgical resection and transplantation (n = 7), and percutaneous ablative therapy (n = 4). These generally reflected an expansion in treatment options due to developments in previously established or emergent techniques, introduction of new and more active therapies and increased therapeutic flexibility. These developments have allowed for greater treatment tailoring and personalization as well as a paradigm shift toward strategies with curative intent in a wider range of disease settings.

Comparison of Bolus Versus Dual-Syringe Administration Systems on Glass Yttrium-90 Microsphere Deposition in an In Vitro Microvascular Hepatic Tumor Model.

PURPOSE: To utilize an in vitro microvascular hepatic tumor model to compare the deposition characteristics of glass yttrium-90 microspheres using the dual-syringe (DS) and traditional bolus administration methods. MATERIALS AND METHODS: The microvascular tumor model represented a 3.5-cm tumor in a 1,400-cm3 liver with a total hepatic flow of 160 mL/min and was dynamically perfused. A microcatheter was placed in a 2-mm artery feeding the tumor model and 2 additional nontarget arteries. Glass microspheres with a diameter of 20-30 µm were administered using 2 methods: (a) DS delivery at a concentration of 50 mg/mL in either a single, continuous 2-mL infusion or two 1-mL infusions and (b) bolus delivery (BD) of 100 mg of microspheres in a single 3-mL infusion. RESULTS: Overall, the degree of on-target deposition of the microspheres was 85% ± 11%, with no significant differences between the administration methods. Although the distal penetration into the tumor arterioles was approximately 15 mm (from the second microvascular bifurcation of the tumor model) for all the cases, the distal peak particle counts were significantly higher for the DS delivery case (approximately 5 × 105 microspheres achieving distal deposition vs 2 × 105 for the BD case). This resulted in significantly higher deposition uniformity within the tumor model (90% for the DS delivery case vs 80% for the BD case, α = 0.05). CONCLUSIONS: The use of this new in vitro microvascular hepatic tumor model demonstrated that the administration method can affect the deposition of yttrium-90 microspheres within a tumor, with greater distal deposition and more uniform tumor coverage when the microspheres are delivered at consistent concentrations using a DS delivery device. The BD administration method was associated with less favorable deposition characteristics of the microspheres.

Interventional Radiology in Canada: Current Challenges and Future Directions.

OBJECTIVE: We aim to define the practice of interventional radiology (IR) in Canada, barriers that have been faced by interventional radiologists, and ways in which the Canadian Interventional Radiology Association (CIRA) have attempted to address these issues. CONCLUSION: IR has faced significant challenges in the Canadian setting. Recognizing the need to address these challenges, leaders in the field of IR in Canada founded the CIRA to serve as our national voice and lobby group.

Clinical IR in Canada: The Evolution of a Revolution.

PURPOSE: To investigate the current status and evolution of both the interventional radiologist's role as a clinician and the practice of interventional radiology (IR) over the past decade in Canada. MATERIALS AND METHODS: In 2015, an online survey was e-mailed to 210 interventional radiologists, including all Canadian active members of the Canadian Interventional Radiology Association (CIRA) and nonmembers who attended CIRA's annual meeting. Comparisons were made between interventional radiologists in academic versus community practice. The results of the 2015 survey were compared with CIRA's national surveys from 2005 and 2010. RESULTS: A total of 102 interventional radiologists responded (response rate 49%). Significantly more academic versus community interventional radiologists performed chemoembolization, transjugular intrahepatic portosystemic shunt, aortic interventions, and arteriovenous malformation embolization (P < .05). Ninety percent of respondents were involved in longitudinal patient care, which had increased by 42% compared with 2005; 46% of interventional radiologists had overnight admitting privileges, compared with 39% in 2010 and 29% in 2005. Eighty-six percent of interventional radiologists accepted direct referrals from family physicians, and 83% directly referred patients to other consultants. Sixty-three percent participated in multidisciplinary tumor board. The main challenges facing interventional radiologists included a lack of infrastructure, inadequate remuneration for IR procedures, and inadequate funding for IR equipment. Significantly more community versus academic interventional radiologists perceived work volume as an important issue facing the specialty in 2015 (60% vs 34%; P = .02). CONCLUSIONS: Over the past decade, many Canadian interventional radiologists have embraced the interventional radiologist-clinician role. However, a lack of infrastructure and funding continue to impede more widespread adoption of clinical IR practice.

Advances in Degradable Embolic Microspheres: A State of the Art Review.

Considerable efforts have been placed on the development of degradable microspheres for use in transarterial embolization indications. Using the guidance of the U.S. Food and Drug Administration (FDA) special controls document for the preclinical evaluation of vascular embolization devices, this review consolidates all relevant data pertaining to novel degradable microsphere technologies for bland embolization into a single reference. This review emphasizes intended use, chemical composition, degradative mechanisms, and pre-clinical safety, efficacy, and performance, while summarizing the key advantages and disadvantages for each degradable technology that is currently under development for transarterial embolization. This review is intended to provide an inclusive reference for clinicians that may facilitate an understanding of clinical and technical concepts related to this field of interventional radiology. For materials scientists, this review highlights innovative devices and current evaluation methodologies (i.e., preclinical models), and is designed to be instructive in the development of innovative/new technologies and evaluation methodologies.

Composition-property relationships for radiopaque composite materials: pre-loaded drug-eluting beads for transarterial chemoembolization.

The purpose of this study was to synthesize and optimize intrinsically radiopaque composite embolic microspheres for sustained release of doxorubicin in drug-eluting bead transarterial chemoembolization. Using a design of experiments approach, 12 radiopaque composites composed of polylactic-co-glycolic acid and a radiopaque glass (ORP5) were screened over a range of compositions and examined for radiopacity (computed tomography) and density. In vitro cell viability was determined using an extract assay derived from each composition against the human hepatocellular carcinoma cell line, HepG2. Mathematical models based on a D-Optimal response surface methodology were used to determine the preferred radiopaque composite. The resulting radiopaque composite was validated and subsequently loaded with doxorubicin between 0 and 1.4% (wt% of polylactic-co-glycolic acid) to yield radiopaque composite drug-eluting beads. Thereafter, the radiopaque composite drug-eluting beads were subjected to an elution study (up to 168 h) to determine doxorubicin release profiles (UV-Vis spectroscopy) and in vitro cell viability. Radiopaque composites evaluated for screening purposes had densities between 1.28 and 1.67 g.cm(-3), radiopacity ranged between 211 and 1450HU and cell viabilities between 91 and 106% were observed. The optimized radiopaque composite comprised 23 wt% polylactic-co-glycolic acid and 60 wt% ORP5 with a corresponding density of 1.63 ± 0.001 g.cm(-3), radiopacity at 1930 ± 44HU and cell viability of 89 ± 7.6%. Radiopaque composite drug-eluting beads provided sustained doxorubicin release over 168 h. In conclusion, the mathematical models allowed for the identification and synthesis of a unique radiopaque composite. The optimized radiopaque composite had similar density and cell viability to commercially available embolic microspheres. It was possible to preload doxorubicin into radiopaque composite drug-eluting beads, such that sustained release was possible under simulated physiological conditions.

Mixture designs to assess composition-structure-property relationships in SiO2-CaO-ZnO-La2O3-TiO2-MgO-SrO-Na2O glasses: potential materials for embolization.

Embolization with micron-sized particulates is widely applied to treat uterine fibroids. The objective of this work was to develop mixture designs to predict materials composition-structure-property relationships for the SiO2-CaO-ZnO-La2O3-TiO2-MgO-SrO-Na2O glass system and compare its fundamental materials properties (density and cytocompatibility), against a state-of-the-art embolic agent (contour polyvinyl alcohol) to assess the potential of these materials for embolization therapies. The glass structures were evaluated using ²9Si MAS NMR to identify chemical shift and line width; the particulate densities were determined using helium pycnometry and the cell viabilities were assessed via MTT assay. ²9Si MAS NMR results indicated peak maxima for each glass in the range of -82.3 ppm to -89.9 ppm; associated with Q² to Q³ units in silicate glasses. All experimental embolic compositions showed enhanced in vitro compatibility in comparison to Contour PVA with the exceptions of ORP9 and ORP11 (containing no TiO2). In this study, optimal compositions for cell viability were obtained for the following compositional ranges: 0.095-0.188 mole fraction ZnO; 0.068-0.159 mole fraction La2O3; 0.545-0.562 mole fraction SiO2 and 0.042-0.050 mole fraction TiO2. To ensure ease of producibility in obtaining good melts, a maximum loading of 0.068 mole fraction La2O3 is required. This is confirmed by the desirability approach, for which the only experimental composition (ORP5) of the materials evaluated was presented as an optimum composition; combining high cell viability with ease of production (0.188 mole fraction ZnO; 0.068 mole fraction La2O3; 0.562 mole fraction SiO2 and 0.042 mole fraction TiO2).

Preliminary investigation of the dissolution behavior, cytocompatibility, effects of fibrinogen conformation and platelet adhesion for radiopaque embolic particles.

Experimental embolic particles based on a novel zinc-silicate glass system have been biologically evaluated for potential consideration in transcatheter arterial embolization procedures. In addition to controlling the cytotoxicity and haemocompatibility for such embolic particles, its glass structure may mediate specific responses via dissolution in the physiological environment. In a 120 h in-vitro dissolution study, ion release levels for silicon (Si4+), sodium (Na+), calcium (Ca2+), zinc (Zn2+), titanium (Ti4+), lanthanum (La3+), strontium (Sr2+), and magnesium (Mg2+), were found to range from 0.04 to 5.41 ppm, 0.27-2.28 ppm, 2.32-8.47 ppm, 0.16-0.20 ppm, 0.12-2.15 ppm, 0.16-0.49 ppm and 0.01-0.12 ppm, respectively for the series of glass compositions evaluated. Initial release of Zn2+ (1.93-10.40 ppm) was only evident after 120 h. All compositions showed levels of cell viabilities ranging from 61.31 ± 4.33% to 153.7 ± 1.25% at 25%-100% serial extract dilutions. The conformational state of fibrinogen, known to induce thrombi, indicated that no changes were induced with respect of the materials dissolution by-products. Furthermore, the best-in-class experimental composition showed equivalency to contour PVA in terms of inducing platelet adhesion. The data generated here provides requisite evidence to continue to in-vivo pre-clinical evaluation using the best-in-class experimental composition evaluated.

Endovascular exclusion of a splenic artery aneurysm using a pipeline embolization device.

The Pipeline Embolization Device (ev3 Endovascular Inc, Plymouth, Minnesota) is a new endovascular device designed to exclude suitable intracranial aneurysms. A 56-year-old woman presented with a symptomatic 4.1-cm splenic artery aneurysm (SAA) that was successfully managed with a two-staged treatment plan involving selective segmental splenic artery embolization and subsequent deployment of a Pipeline Embolization Device across the aneurysm neck to exclude the aneurysm and maintain splenic perfusion.

Survey of radiologists' knowledge regarding the management of severe contrast material-induced allergic reactions.

PURPOSE: To evaluate radiologists' knowledge of the appropriate management of severe contrast material-induced allergic reactions by means of a telephone survey. MATERIALS AND METHODS: Institutional research ethics board approval was obtained. Following verbal consent, a telephone survey of radiologists working in Canada's 13 English-speaking and 13 U.S. university-affiliated radiology departments was performed. Participants were selected by using a multistage sampling scheme and simple random sampling within departments. Given a severe contrast material-induced allergic reaction case scenario, radiologists were first asked their initial medication of choice, then questioned specifically on the use of epinephrine. The Canadian and U.S. cohorts were compared by using the chi(2) and Fisher exact tests, as appropriate, and proportions and 95% confidence intervals (CIs) were computed. RESULTS: A total of 253 (81%) of 311 radiologists from a 30% target population were surveyed. Ninety-one percent (231 of 253; 95% CI: 88%, 94%) of radiologists chose epinephrine as the most important initial medication. No radiologist gave the ideal response, but 41% (94 of 231; 95% CI: 35%, 47%) provided an acceptable administration route, concentration, and dose; 17% (n = 39; 95% CI: 12%, 22%) of radiologists provided an overdose. Only 11% (27 of 253; 95% CI: 7%, 15%) of radiologists knew what concentration of epinephrine was available in their drug kit and/or crash cart and what equipment would be required to administer it to a patient. CONCLUSION: Radiologists' knowledge of epinephrine for the management of severe contrast material-induced allergic reactions is deficient.

Is routine micropuncture access necessary for percutaneous nephrostomy? A randomized trial.

OBJECTIVE: To compare the micropuncture technique and the conventional large-bore needle approach for renal access. METHODS: From July 1999 to July 2000, patients referred to interventional radiology for emergent or elective percutaneous nephrostomy with normal coagulation profiles were considered for the study. Nephrostomy procedures were performed using a micropuncture system or large-bore needle for collecting system access; 24 nephrostomy procedures were randomized to each group using permuted blocks and opaque sealed envelopes. Gross hematuria, quantitative urine red blood cell counts, pain scores and procedural success were compared between the 2 groups. RESULTS: There was a small difference in the incidence of gross hematuria between the large-bore needle and micropuncture groups (12 [50%] v. 8 [33%] patients), but this difference was not statistically significant. Quantitative urine red blood cell counts obtained immediately after and 24 hours after nephrostomy placement showed no significant differences. Significantly fewer needle passes were required for access in the large-bore needle group than the micropuncture group (1.7 v. 2.8, p = 0.01), and mean procedure duration was 7 minutes longer in the micropuncture group, although this difference was not significant. No differences in pain scores or procedure success were seen. CONCLUSION: Percutaneous nephrostomy performed with a micropuncture system in patients with normal coagulation profiles does not significantly decrease organ bleeding or pain. More needle passes and manipulations are required, which may increase procedure duration. The additional costs of routine micropuncture access for percutaneous nephrostomy are not supported by this study.