Reed A. Omary

Quality Improvement Guidelines for Percutaneous Management of the Thrombosed or Dysfunctional Dialysis Access

John E. Aruny, MD, Curtis A. Lewis, MD, John F. Cardella, MD, Patricia E. Cole, PhD, MD, Andrew Davis, MD, Alain T. Drooz, MD, Clement J. Grassi, MD, Richard J. Gray, MD, James W. Husted, MD, Michael Todd Jones, MD, Timothy C. McCowan, MD, Steven G. Meranze, MD, A. Van Moore, MD, Calvin D. Neithamer, MD, Steven B. Oglevie, MD, Reed A. Omary, MD, Nilesh H. Patel, MD, Kenneth S. Rholl, MD, Anne C. Roberts, MD, David Sacks, MD, Orestes Sanchez, MD, Mark I. Silverstein, MD, Harjit Singh, MD, Timothy L. Swan, MD, Richard B. Towbin, MD, Scott O. Trerotola, MD, Curtis W. Bakal, MD, MPH, for the Society of Interventional Radiology Standards of Practice Committee

Quality Improvement Guidelines for Percutaneous Permanent Inferior Vena Cava Filter Placement for the Prevention of Pulmonary Embolism

PULMONARY embolism (PE) continues to be a major cause of morbidity and mortality in the United States. Estimates of the incidence of nonfatal PE range from 400,000 to 630,000 cases per year, and 50,000 to 200,000 fatalities per year are directly attributable to PE (1–4). The current preferred treatment for deep venous thrombosis and PE is anticoagulation therapy. However, as many as 20% of these patients will have recurrent PE (1,5,6). Interruption of the inferior vena cava (IVC) for the prevention of PE was first performed in 1893 with use of surgical ligation (7). Over the years, surgical interruption took many forms (ligation, plication, clipping, or stapling) but IVC thrombosis was a frequent complication after these procedures. Endovascular approaches to IVC interruption became a reality in 1967 after the introduction of the Mobin-Uddin filter (8). Many devices have since been developed for endoluminal caval interruption but, currently, there are six devices commercially available in the United States. These devices are designed for permanent placement. For detailed information regarding each of these filters, the reader is referred to several published reviews (9–12). Selection of a device requires knowledge of the clinical settings in which filters are used, evaluation of the clot trapping efficiency of the device, occlusion rate of the IVC and access vein, risk of filter migration, filter embolization, structural integrity of the device, and ease of placement. Percutaneous caval interruption can be performed as an outpatient or inpatient procedure. However, practically speaking, most filter placements will occur in the inpatient population because of ongoing medical therapy for acute thromboembolic disease or underlying illness. The IVC should be assessed with imaging before placement of a filter, and the current preferred imaging method is vena cavography. Before filter selection and placement, the infrarenal IVC length and diameter should be measured, the location and number of renal veins determined, IVC anomalies (eg, duplication) defined, and intrinsic IVC disease such as preexisting thrombus or extrinsic compression excluded. The ideal placement for the prevention of lower extremity and pelvic venous thromboembolism is the infrarenal IVC. The apex or superior aspect of any filtration device should be at or immediately inferior to the level of the renal veins according to the manufacturers’ recommendations. In specific clinical circumstances, other target locations may be appropriate. Percutaneous caval interruption is commonly accomplished through right femoral and right internal jugular vein approaches; however, other peripheral and central venous access sites can be used. Filters can be placed in veins other than the vena cava to prevent thromboembolism. Implant sites have included iliac veins, subclavian veins, superior vena cava, and IVC (suprarenal and infrarenal). This document will provide quality improvement guidelines for filter placement within the inferior vena cava because of the limited data available for implantation sites other than the IVC. The patient’s clinical condition, the type of filter available, the alternative access sites available, and the expertise of the treating physician should always be considered when the decision to place an IVC filter has been made. These guidelines are written to be used in quality improvement programs to assess percutaneous interruption of the IVC to prevent pulmonary embolism. The most important processes of care are (a) patient selecThis article first appeared in J Vasc Interv Radiol 2001; 12:137–141.

Intraarterial Gadolinium-enhanced 2D and 3D MR Angiography: A Preliminary Study

PURPOSE To evaluate, in phantom and canine models, intraarterial gadolinium-enhanced two-dimensional (2D) and three-dimensional (3D) magnetic resonance angiography (MRA). MATERIALS AND METHODS The in vitro experiments examined gadodiamide solutions ranging in gadolinium (Gd) concentration from 0.1% to 100%. A spoiled gradient-recalled echo (SPGR) sequence was used with various repetition time/echo time (TR/TE) parameters. Signal was measured to determine which concentration yielded the highest signal. For in vivo experiments, pigtail catheters were placed in the abdominal aortae of two dogs. Intraarterial injections of 20-30 mL of 0.5%-25% Gd solutions were performed. We acquired images with use of 2D and 3D SPGR techniques. Depiction of the abdominal aortae and renal vessels was assessed qualitatively and quantitatively. RESULTS Phantom experiments demonstrated that a 2%-6% solution of Gd produced the highest MR signal, depending on the imaging parameters. In the canine model, a 2% Gd solution was best for 2D techniques, whereas 7%-14% Gd solutions were optimal for 3D techniques. CONCLUSIONS Intraarterial contrast material-enhanced 2D and 3D MRA can be successfully implemented with use of dilute Gd. Dilution permits the administration of more intraarterial injections per day, without exceeding the dose limit, compared with intravenous Gd-enhanced MRA. Intraarterial injections also limit scan synchronization and contrast material dispersion issues. This technique may have application in MR-guided endovascular procedures.

MRI visible drug eluting magnetic microspheres for transcatheter intra-arterial delivery to liver tumors

Magnetic resonance imaging (MRI)-visible amonafide-eluting alginate microspheres were developed for targeted arterial-infusion chemotherapy. These alginate microspheres were synthesized using a highly efficient microfluidic gelation process. The microspheres included magnetic clusters formed by USPIO nanoparticles to permit MRI and a sustained drug-release profile. The biocompatibility, MR imaging properties and amonafide release kinetics of these microspheres were investigated during in vitro studies. A xenograft rodent model was used to demonstrate the feasibility to deliver these microspheres to liver tumors using hepatic transcatheter intra-arterial infusions and potential to visualize the intra-hepatic delivery of these microspheres to both liver tumor and normal tissues with MRI immediately after infusion. This approach offer the potential for catheter-directed drug delivery to liver tumors for reduced systemic toxicity and superior therapeutic outcomes.

Aldoketoreductase family 1B10 (AKR1B10) as a biomarker to distinguish hepatocellular carcinoma from benign liver lesions.

Hepatocellular carcinoma (HCC) is one of the most common highly aggressive malignant tumors worldwide. Aldoketoreductase 1B10 (AKR1B10) was first isolated from HCC and further identified to be over-expressed in many cancers from various organs. AKR1B10 contributes to detoxification of xenobiotics by lipid peroxidation and metabolizes physiological substrates such as farnesal, retinal, and carbonyls. Metabolizing these lipid substrates plays a crucial role in promoting carcinogenesis. In the present study, immunohistochemical analysis was performed to determine the prevalence/pattern of AKR1B10 expression in HCC and its usefulness to differentiate benign liver lesions from HCC. Oncogenic function of AKR1B10 was examined in hepatocellular carcinoma cells in vitro using Western blotting and shRNA knockdown approaches, with emphasis on cell apoptosis and response to chemotherapy. Immunohistochemistry analysis revealed AKR1B10 was overexpressed in 97% (86/89) of hepatocellular carcinomas, with minimal to no expression in adjacent hepatic tissue, while hepatic adenomas and focal nodular hyperplasia did not exhibit expression of AKR1B10. shRNA-mediated silencing of AKR1B10 expression in hepatocellular carcinoma cells resulted in (1) increased cell apoptosis, (2) decreased colony formation and size, and (3) enhanced cytoreductive response following exposure to doxorubicin chemotherapy. Our findings provide first time evidence that AKR1B10 is a unique biomarker involved in hepatocellular carcinogenesis via modulation of proliferation, cell apoptosis and chemoresistance and is a potential promising biomarker to differentiate HCCs from benign hepatic lesions.

Comparison of gradient-echo and steady-state free precession for coronary artery magnetic resonance angiography using a gadolinium-based intravascular contrast agent.

Objectives:Intravascular contrast agents may offer longer imaging times and better vessel visualization over conventional extravascular agents for magnetic resonance coronary angiography. The purpose of this study was to evaluate the effect of intravascular contrast (B-22956/1) on coronary visualization. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were compared in inversion-recovery (IR)-prepared FLASH (fast low-angle shot) and IR-trueFISP (true fast imaging with steady-state precession) sequences before and after contrast. Materials and Methods:Numeric simulations were performed to compare blood signals in IR-trueFISP and IR-FLASH sequences. Coronary imaging was performed in 15 swine. Results:Postcontrast CNR was improved 23% with breathhold IR-FLASH and 55% with breathhold IR-trueFISP as compared with precontrast trueFISP. With free-breathing, long TR IR-FLASH provided 131% and 55.8% higher SNR and 132% and 58.7% increased CNR compared with IR-FLASH with shorter TR and IR-trueFISP, respectively. Conclusion:Intravascular contrast agents improve CNR and vessel visualization in coronary magnetic resonance angiography with IR-FLASH and IR-trueFISP.

Multimodality Imaging to Assess Immediate Response to Irreversible Electroporation in a Rat Liver Tumor Model

PURPOSE To compare changes on ultrasonographic (US), computed tomographic (CT), and magnetic resonance (MR) images after irreversible electroporation (IRE) ablation of liver and tumor tissues in a rodent hepatoma model. MATERIALS AND METHODS Studies received approval from the institutional animal care and use committee. Forty-eight rats were used, and N1-S1 tumors were implanted in 24. Rats were divided into groups and allocated for studies with each modality. Imaging was performed in normal liver tissues and tumors before and after IRE. MR imaging was performed in one group before and after IRE after hepatic vessel ligation. US images were graded to determine echogenicity changes, CT attenuation was measured (in Hounsfield units), and MR imaging signal-to-noise ratio (SNR) was measured before and after IRE. Student t test was used to compare attenuation and SNR measurements before and after IRE (P < .05 indicated a significant difference). RESULTS IRE ablation produced greater alterations to echogenicity in normal tissues than in tumors. Attenuation in ablated liver tissues was reduced compared with that in control tissues (P < .001), while small attenuation differences between ablated (42.11 HU ± 2.11) and control (45.14 HU ± 2.64) tumors trended toward significance (P = .052). SNR in ablated normal tissues was significantly altered after IRE (T1-weighted images: pre-IRE, 145.95 ± 24.32; post-IRE, 97.80 ± 18.03; P = .004; T2-weighted images, pre-IRE, 47.37 ± 18.31; post-IRE, 90.88 ± 37.15; P = .023). In tumors, SNR differences before and after IRE were not significant. No post-IRE signal changes were observed after hepatic vessel ligation. CONCLUSION IRE induces rapid changes on gray-scale US, unenhanced CT, and MR images. These changes are readily visible and may assist a performing physician to delineate ablation zones from the unablated surrounding parenchyma.

Assessment and optimization of electroporation-assisted tumoral nanoparticle uptake in a nude mouse model of pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a particularly lethal form of cancer. In 2012, the incidence of PDAC was 43,920. Five-year survival for patients with PDAC is around 6%, regardless of staging, making PDAC one of the deadliest forms of cancer. One reason for this dismal prognosis is chemoresistance to the current first-line therapy, gemcitabine. There are multiple factors that contribute to the chemoresistance observed in pancreatic cancer. Among them, desmoplasia has been increasingly seen as a significant contributor to chemoresistance. To overcome desmoplastic chemoresistance, several novel methods of treatment have been developed. Electroporation is one such novel treatment. High electrical fields are applied to cells to create pores that increase cell permeability. It has been previously demonstrated that electroporation enhances the therapeutic efficacy of anticancer drugs in pancreatic tumor models. Nanoparticle-based drug delivery systems constitute a second novel method to overcome desmoplastic chemoresistance. Due to their intrinsic design advantages, nanoparticles have been shown to increase the effectiveness of chemotherapeutic agents, while further reducing or even eliminating side effects. To date, there have been no studies evaluating the cumulative effect of combining both nanoparticle and electroporation strategies to overcome chemoresistance in PDAC. Our preliminary studies assessed the in vitro and in vivo uptake of doxorubicin-loaded iron oxide nanoparticles as a function of electroporation voltage and timing of administration in pancreatic adenocarcinoma cells. Our studies demonstrated that addition of electroporation to administration of nanoparticles significantly increased the amount of intracellular iron oxide nanoparticle uptake by a PANC-1 cell line in an athymic nude mouse model of PDAC. Further, electroporation-assisted nanoparticle uptake could be significantly altered by changing the timing of application of electroporation.

Fluorescence-Based Endoscopic Imaging of Thomsen-Friedenreich Antigen to Improve Early Detection of Colorectal Cancer

Thomsen–Friedenreich (TF) antigen belongs to the mucin‐type tumor‐associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF‐associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio‐imaging index for the probe. The nanobeacon exhibited specificity for TF‐associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio‐imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level.

SPIO-labeled Yttrium Microspheres for MR Imaging Quantification of Transcatheter Intrahepatic Delivery in a Rodent Model.

PURPOSE To investigate the qualitative and quantitative impacts of labeling yttrium microspheres with increasing amounts of superparamagnetic iron oxide (SPIO) material for magnetic resonance (MR) imaging in phantom and rodent models. MATERIALS AND METHODS Animal model studies were approved by the institutional Animal Care and Use Committee. The r2* relaxivity for each of four microsphere SPIO compositions was determined from 32 phantoms constructed with agarose gel and in eight concentrations from each of the four compositions. Intrahepatic transcatheter infusion procedures were performed in rats by using each of the four compositions before MR imaging to visualize distributions within the liver. For quantitative studies, doses of 5, 10, 15, or 20 mg 2% SPIO-labeled yttrium microspheres were infused into 24 rats (six rats per group). MR imaging R2* measurements were used to quantify the dose delivered to each liver. Pearson correlation, analysis of variance, and intraclass correlation analyses were performed to compare MR imaging measurements in phantoms and animal models. RESULTS Increased r2* relaxivity was observed with incremental increases of SPIO microsphere content. R2* measurements of the 2% SPIO-labeled yttrium microsphere concentration were well correlated with known phantom concentrations (R(2) = 1.00, P < .001) over a broader linear range than observed for the other three compositions. Microspheres were heterogeneously distributed within each liver; increasing microsphere SPIO content produced marked signal voids. R2*-based measurements of 2% SPIO-labeled yttrium microsphere delivery were well correlated with infused dose (intraclass correlation coefficient, 0.98; P < .001). CONCLUSION MR imaging R2* measurements of yttrium microspheres labeled with 2% SPIO can quantitatively depict in vivo intrahepatic biodistribution in a rat model.