Routine inferior vena cava filter (IVCF) retrieval is a common procedure that can be accomplished with different techniques. Simple loop snare retrieval is common; however, snares are single use and many seemingly routine retrievals require more advanced techniques. Rigid endobronchial forceps (EF) retrieval is an effective advanced approach with the ability for the forceps to be sterilized and re-used for multiple procedures. The purpose of this study was to compare the cost effectiveness of snare versus forceps IVCF retrieval techniques at a single institution. This study is a cost minimization analysis including an IRB approved, single-center, retrospective review of all IVCF retrievals from January 2019 to April 2021. Routine IVCF retrieval techniques were categorized as loop snare-only retrieval (SR), forceps-assisted after unsuccessful snare retrieval (S+F), and forceps-only retrieval (FR). Total equipment cost for each technique was determined. Seventy-seven successful routine IVC filter retrieval procedures were performed at our institution during the study period (63 SR, 8 S+F, 6 FR). There were no technical failures. FR was the most cost-effective technique with per-procedure equipment cost of SR, S+F, and FR techniques of $434.30, $556.55, $221.98 respectively. Average equipment cost for the 77 retrievals over the study was $430.46. Had all retrievals been performed using the FR technique, average equipment cost per retrieval would have decreased by $208.48, for a total cost savings of $16,052.72. Utilization of FR technique for all routine IVCF retrievals would result in a meaningful cost savings compared to standard SR and S+F techniques.

BACKGROUND:While large-bore mechanical thrombectomy provides effective venous thrombus removal, often with avoidance of thrombolytics, literature surrounding the application of these devices in pediatric patients is sparse. OBJECTIVE:To report technical success and outcomes following large-bore thrombectomy systems in adolescent patients with deep venous thrombosis. MATERIALS AND METHODS:A retrospective review identified all patients less than 18 years of age undergoing mechanical venous thrombectomy at a single institution between 2018 and 2022. No patients were excluded. Technical success was defined as extraction of thrombus sufficient to restore unimpeded flow in affected segments. Clinical success was defined as resolution of presenting symptoms. RESULTS:Nine consecutive patients (6 females, 3 males; age range 15-17 years) underwent 10 thrombectomy procedures using ClotTriever (n=6; 60%), FlowTriever (n=2; 20%), or both (n=2; 20%). Chronicity of thrombus was categorized as acute (<2 weeks) in 6 (60%), subacute (2-6 weeks) in 1 (10%), and chronic (>6 weeks) in 3 (30%). Distribution of thrombus was lower extremity and/or inferior vena cava (IVC) in 9 (90%) and unilateral axillo-subclavian in 1 (10%). Technical success was achieved in 9 interventions (90%). Clinical success was achieved in 8 patients (88.9%). No patients received thrombolytics. There were no intraprocedural adverse events (AE). Minor complications (Society of Interventional Radiology mild adverse events) were observed in a delayed fashion following 2 interventions (20%). CONCLUSIONS:This preliminary experience demonstrated high rates of technical and clinical success with large-bore deep venous thrombectomy in adolescent patients across a range of thrombus chronicity and locations.

The ellipsoid formula is used to estimate prostate volume but has questionable accuracy for large prostates. We compared CT-based manual segmentation to the ellipsoid formula in patients selected for PAE.

Early cell and gene therapies show promise to achieve positive treatment outcomes, primarily for cancer and hereditary conditions; however, there is a lack of therapeutic options for chronic organ failure, such as chronic kidney disease (CKD).1Approved Cellular and Gene Therapy Products. Food and Drug Administration.https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-productsDate accessed: January 17, 2021Google Scholar,2Advanced Therapy Medicinal Products: Overview. European Medicines Agency.https://www.ema.europa.eu/en/human-regulatory/overview/advanced-therapy-medicinal-products-overviewDate accessed: January 17, 2021Google Scholar CKD represents a growing global health crisis, predicted to affect more than 250 million people with type 2 diabetes as the leading cause in greater than 40% of selected populations and the dominant cause for end-stage kidney disease.3Xie Y. Bowe B. Mokdad A. et al.Analysis of the global burden of disease study highlights the global, regional, and national trends of chronic kidney disease from 1990–2016.Kidney Int. 2018; 94: 567-581Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar,4Centers for Disease Control and PreventionNational Health and Nutrition Examination Survey, 2013–2014.https://nccd.cdc.gov/CKD/detail.aspx?Qnum=Q372Date accessed: January 17, 2021Google Scholar Most CKD therapies are small-molecule medications targeting a biochemical pathway or enzyme modulator in a damaged renal framework. In contrast, preclinical and early clinical CKD cell therapies offer the potential to restore and repair the glomerular-tubular unit to improve intrinsic renal function and reduce secondary comorbidities.5Little M. Kairath P. Regenerative medicine in kidney disease.Kidney Int. 2016; 90: 289-299Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar,6Kelley R. Werdin E. Bruce A. Tubular cell-enriched subpopulations of primary renal cells improves survival and augments kidney function in rodent model of chronic kidney disease.Am J Physiol Renal Physiol. 2010; 299: F1026-F1039Crossref PubMed Scopus (50) Google Scholar Most early-phase cell-based CKD trials use autologous mesenchymal stem cell lines delivered by intravenous injections, yet the probability of mechanistic effects is unpredictable secondary to systemic circulation dilution and blood trapping. Furthermore, in the diabetic kidney, intravenous cell delivery may also be attenuated by underlying fibrosis and microvascular disease. An alternative method of cell delivery is a locoregional injection directly into the diseased kidney. Direct cell injections have been performed with chronic liver disease and, more recently, via transendocardial delivery in heart failure trials, whereas there are limited reports of direct cell injection in kidneys with CKD.7Bartunek J. Terzic A. Davidson B. et al.Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective randomized, double blind, sham-controlled CHART-1 clinical trial.Eur Heart J. 2017; 38: 648-660PubMed Google Scholar, 8Forbes S.J. Gupta S. Dhawan A. Cell therapy for liver disease: from transplantation to cell factory.J Hepatol. 2015; 62: S157-S169Abstract Full Text Full Text PDF PubMed Scopus (178) Google Scholar, 9Stavas J. Diaz-Gonzalez de Ferris M. Johns A. et al.Protocol and baseline data on renal autologous cell therapy injection in adults with chronic kidney disease secondary to congenital anomalies of the kidney and urinary tract. Blood Purif.https://doi.org/10.1159/000512586Date accessed: January 17, 2021Google Scholar,S1 We describe a novel technique and preliminary observations regarding injection safety and feasibility of precision delivery of homologous autologous renal progenitors into the renal cortex of patients with type 2 diabetic CKD. Between October 2017 and November 2020, 87 consecutive direct parenchymal homologous autologous cells injections using a 20/25-gauge coaxial needle system were analyzed in 51 enrolled patients from two phase II trials (RMCL-002 [NCT02836574] and REGEN-003 [NCT03270956]) with type 2 diabetic CKD stages 3-4 who met eligibility criteria (see Supplemental Material). Estimated glomerular filtration rates (eGFR) of enrolled patients were 20 to 50 ml/min per 1.73 m2 (RMCL-002) and 14 to 20 ml/min per 1.73 m2 (REGEN-003). The international normalized ratio for all enrolled patients’ was less than 1.5. Following a percutaneous kidney biopsy from each patient and cell expansion by Good Manufacturing Practice, progenitor cells were formulated in a thermolabile hydrogel concentration of 100 × 106 cells/ml and reinjected into the biopsied kidney 6 weeks later. Renal volume was measured on magnetic resonance imaging to determine cell dose (3–8 ml). Cell injection was performed using computed tomographic (CT) guidance. A coaxial 20-gauge outer guiding needle (COOK, Inc, Bloomington, Indiana) was inserted into the subcapsular parenchyma of the lower pole of the previously biopsied kidney and a 25-gauge inner injection needle (0.51 mm diameter, IMD Inc, Huntsville, Utah) into the renal cortex, within 5 mm from the capsule (Figure 1). For patients with two subsequent injections, the procedure was performed in the same kidney 6 months apart. All procedures were performed by experienced interventional radiologists receiving training and on-site proctoring. Patients underwent conscious sedation and were discharged from the day-surgery unit after recovery. The protocol required hemoglobin, hematocrit, and renal chemistries before and after injection. Intra- and end-procedure intermittent CT scanning took place to guide the injections and assess for bleeding. Renal ultrasonography was performed during post-injection recovery and on day 1 postprocedure to assess for hematoma. Also, patients temporarily refrained from anticoagulation and antiplatelet medications. The primary endpoints were changes in eGFR and complications related to the injection and cell product. Major renal bleeds were defined as those requiring blood transfusion, extended hospitalization, or an interventional procedure. Statistical analyses were performed using R (4.0.5, R Core Team, 2021, Vienna, Austria). This analysis included 87 cell injections in 51 patients (Table 1). Sixty-nine injections were completed in 41 patients and 18 in 10 patients with eGFRs 20 to 50 ml/min per 1.73 m2 (RMCL-002) and 14 to 20 ml/min per 1.73 m2 (REGEN-003), respectively. All patients remained hemodynamically stable throughout the procedure. All locoregional injections into the renal cortex were technically successful, and CT scans documented final needle locations in the subcapsular renal cortex (Figure 1). There were no significant differences in hemoglobin (P = 0.3 [RMCL-002, first injection], P = 0.2 [RMCL-002, second injection], P = 0.2 [REGEN-003, first injection], P = 0.14 [REGEN-003, second injection]) and hematocrit (P = 0.2 [RMCL-002, first injection], P = 0.3 [RMCL-002, second injection], P = 0.3 [REGEN-003, first injection], P > 0.9 [REGEN-003, second injection]) between pre- and post-cell injections (Table 2). Differences in creatinine, blood urea nitrogen, and eGFR were also not significant (Table 2, Figure 2). There were no procedure-related bleeds or cell extravasation documented during the CT-guided injections. However, a delayed subcapsular hematoma that required hospitalization without transfusion was present on a post-injection ultrasound in a female patient (1/1% [1 of 87 patients]) with eGFR of 15 ml/min per 1.73 m2 (REGEN-003).Table 1Baseline characteristics of subjects and laboratory values before the injection of homologous autologous renal progenitor cells∗Values are presented as mean ± standard variation (range) or as n (%).Total (N = 51)RMCL-002 trial†RMCL-002 trial includes patients with eGFR of 20 to 50 ml/min per 1.73 m2. (n = 41)REGEN-003 trial‡REGEN-003 trial includes patients with eGFR of 14 to 20 ml/min per 1.73 m2. (n = 10)PAge, yrs64.5 ± 10.3 (37.0-80.0)66.0 ± 10.6 (37.0-80.0)58.3 ± 5.3 (48.0-65.0)0.007Sex0.14 Women15 (29)10 (24)5 (50) Men36 (71)31 (76)5 (50)BMI, kg/m233.5 ± 6.3 (20.4-52.5)33.1 ± 5.6 (20.4-44.9)35.1 ± 8.5 (23.8-52.5)0.7Number of injections0.7 115 (29)13 (32)2 (20) 236 (71)28 (68)8 (80)Hemoglobin, g/dl12.4 ± 1.8 (8.6-16.6)12.7 ± 1.8 (8.6-16.6)10.9 ± 1.2 (9.7-12.5)0.003Hematocrit, %36.9 ± 5.5 (25.0-52.0)37.8 ± 5.5 (25.0-52.0)33.3 ± 3.8 (27.0-38.0)0.013Platelet count, ×103/μl264.1 ± 95.4 (121.0-509.0)248.9 ± 88.8 (121.0-509.0)326.6 ± 100.8 (167.0-484.0)0.020Total bilirubin, mg/dl0.4 ± 0.2 (0.2-1.1)0.4 ± 0.2 (0.2-1.1)0.3 ± 0.1 (0.2-0.4)0.014ALT, U/l20.0 ± 9.0 (7.0-46.0)21.5 ± 9.1 (10.0-46.0)13.7 ± 5.8 (7.0-23.0)0.011AST, U/l19.8 ± 7.6 (8.0-43.0)21.0 ± 7.6 (8.0-43.0)14.7 ± 5.3 (10.0-27.0)0.006BUN, mg/dl42.2 ± 16.3 (19.0-80.0)38.0 ± 14.3 (19.0-80.0)59.5 ± 12.7 (39.0-78.0)<0.001Creatinine, mg/dl2.2 ± 0.7 (1.2-3.9)2.0 ± 0.6 (1.2-3.5)3.2 ± 0.4 (2.7-3.9)<0.001eGFR, ml/min per 1.73 m231.7 ± 10.8 (13.0-53.0)35.2 ± 9.1 (21.0-53.0)17.5 ± 2.4 (13.0-21.0)<0.001INR1.0 ± 0.1 (0.9-1.3)1.0 ± 0.1 (0.9-1.3)1.0 ± 0.1 (0.9-1.1)0.13PTT, s12.4 ± 12.8 (9.4-102.0)12.8 ± 14.3 (9.4-102.0)10.4 ± 0.5 (9.7-11.3)0.7APTT, s25.2 ± 2.3 (20.5-36.3)25.3 ± 2.5 (20.5-36.3)24.6 ± 0.9 (23.1-25.9)0.4ALT, alanine aminotransferase; APTT, activated partial thromboplastin time; AST, aspartate aminotransferase; BMI, body mass index; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; INR, international normalization ratio; PTT, partial thromboplastin time.∗ Values are presented as mean ± standard variation (range) or as n (%).† RMCL-002 trial includes patients with eGFR of 20 to 50 ml/min per 1.73 m2.‡ REGEN-003 trial includes patients with eGFR of 14 to 20 ml/min per 1.73 m2. Open table in a new tab Table 2Comparison of laboratory test results between before and after injection of homologous autologous renal progenitor cells∗Values are presented as mean ± standard variation (n).Pre-injectionPost-injectionPRMCL-002†RMCL-002 trial included patients with eGFR of 20 to 50 ml/min per 1.73 m2. trial First injection (n = 41)Hemoglobin, g/dl12.0 ± 1.811.9 ± 1.60.3Hematocrit, %36.5 ± 5.536.0 ± 4.50.2BUN, mg/dl39.5 ± 16.038.9 ± 13.60.7Creatinine, mg/dl2.1 ± 0.72.2 ± 0.90.4eGFR, ml/min per1.73 m232.6 ± 10.532.0 ± 10.90.9 Second injection (n = 28)Hemoglobin, g/dl12.3 ± 1.712.5 ± 1.30.2Hematocrit, %38.1 ± 4.737.6 ± 3.90.3BUN, mg/dl36.2 ± 10.035.1 ± 13.00.4Creatinine, mg/dl1.9 ± 0.62.1 ± 0.70.065eGFR, ml/min per 1.73 m235.1 ± 9.432.8 ± 9.50.031REGEN-003‡REGEN-003 trial included patients with eGFR of 14 to 20 ml/min per 1.73 m2. trial First injection (n = 10)Hemoglobin, g/dl10.4 ± 1.110.7 ± 1.10.2Hematocrit, %31.4 ± 3.232.1 ± 4.30.3BUN, mg/dl59.4 ± 15.857.9 ± 15.00.7Creatinine, mg/dl3.5 ± 0.73.5 ± 0.70.6eGFR, ml/min per 1.73 m216.3 ± 3.115.8 ± 2.70.6 Second injection (n = 8)Hemoglobin, g/dl10.4 ± 1.210.0 ± 1.30.14Hematocrit, %30.2 ± 2.930.2 ± 2.9>0.9BUN, mg/dl60.6 ± 14.560.0 ± 16.60.9Creatinine, mg/dl3.8 ± 0.64.0 ± 0.60.4eGFR, ml/min per 1.73 m214.1 ± 2.713.5 ± 3.20.4BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate.∗ Values are presented as mean ± standard variation (n).† RMCL-002 trial included patients with eGFR of 20 to 50 ml/min per 1.73 m2.‡ REGEN-003 trial included patients with eGFR of 14 to 20 ml/min per 1.73 m2. Open table in a new tab ALT, alanine aminotransferase; APTT, activated partial thromboplastin time; AST, aspartate aminotransferase; BMI, body mass index; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; INR, international normalization ratio; PTT, partial thromboplastin time. BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate. We present results on the safety and feasibility of a novel locoregional precision delivery method for a cell-based therapy currently in phase II clinical trials. Cellular-based therapies are a rapidly growing classification of Advanced Therapy Medicinal Products, and these therapies have shown encouraging clinical outcomes, most notably treating hematologic cancers. The most common cell product delivery method is via intravenous injections with the emerging use of direct tissue deposit techniques in benign conditions (eg, orthopedic, dermal, and cardiac indications).S2 Early phase trials are underway using mesenchymal stem cell intravascular injection therapy for CKD regeneration, although the reliability of cell secretory effects on target cells is unknown. Diabetic microvascular disease, systemic recirculation dilution, and lung trapping attenuate the cell quantity to the glomerular-tubule environment, reducing the efficacy and dose accuracy with intravenous injections. Alternately, locoregional injections into the recipient’s renal cortex allow renal progenitor cells to impart direct restorative effects in the microenvironment of effete CKD tubules and glomeruli, primarily. Preclinical trials of progenitor cell injections in multiple CKD animal models showed local and distant nephron repair and improved kidney function6Kelley R. Werdin E. Bruce A. Tubular cell-enriched subpopulations of primary renal cells improves survival and augments kidney function in rodent model of chronic kidney disease.Am J Physiol Renal Physiol. 2010; 299: F1026-F1039Crossref PubMed Scopus (50) Google Scholar,S3,S4 In a phase I, first-in-human trial, six patients underwent laparoscopic renal subcapsular injection of selected renal cells (SRCs).S1 All included patients had type 2 diabetic CKD with a glomerular filtration rate of 15 to 50 ml/min. Post–SRC injection, iohexol clearance and albumin-creatinine ratio remained stable to 12 and 24 months, respectively. Although laparoscopically assisted implantation of SRCs was uneventful, it resulted in surgery-related complications and extended hospital admissions. The procedure was converted to a percutaneous image-guided technique for the phase II trials with a smaller needle platform and moderate sedation to mitigate adverse events and maintain efficacy by cell delivery into the renal cortex. Before needle selection, in vitro testing was performed to determine shear and stress effects on renal epithelial cells injected through smaller bore needles. No harmful effects on cell viability or potency were identified during autologous cell injections through the 25-gauge needle design. The process of cell biodistribution in renal tissues was shown by injecting labeled SRCs into animal kidneys, and cellular movement was established using immunofluorescence and magnetic resonance imaging.S3,S5 The migration of SRCs from the injected renal cortex is mediated by cytokines, which elicit a chemotactic response. The nephron restoration following SRC injection is associated with the integration of cells into areas of damage, inflammation, and fibrosis with local paracrine effects resulting in antifibrotic, anti-inflammatory, and improved renal function.S6 CT-guided percutaneous procedures have proven feasibility and safety for many indications but remain undescribed in the local delivery of cell therapies to treat CKD.S7 In our trials, thin-section CT scans were performed through the kidneys to identify a safe pathway and target in the renal cortex of the lower pole. Despite the small injection needle caliber, CT image reconstructions at 1 to 5 mm allow verification of the needle tip within the thinned renal cortex during each injection while allowing real-time safety surveillance for hematoma development. Renal pathophysiology and related comorbidities of stage 3/4 type 2 diabetic CKD, principally anemia, higher eGFR stage, and females, are risk factors for increased bleeding during percutaneous interventions.S8,S9 Postrenal biopsy bleeding risks have been well-described in previous studies, with wide ranges due to heterogeneity of the disease, biopsy techniques, and hospital status.S9,S10 Although no complications have been published specific to our trial’s intervention, percutaneous biopsy for medical renal disease and tumor masses can furnish a benchmark for risk approximation. Poggio et al.S10 reported an 11% (range, 9% to 16%) rate of hematoma as the most common complication for biopsy of intrinsic renal diseases in a systematic review and meta-analysis. At the same time, other complication-related treatments have been noted, such as transfusion rates (1% to 5.7%), angiographic interventions (0.2% to 0.6%), nephrectomy (0 to 0.1%) and death (0 to 0.06%).S8,S9,S10,S11 Among renal tumor mass biopsy specimens, median overall complication rates were 8.1% (interquartile range, 2.7% to 11.1%), with perirenal hematoma being the most common and a few reporting treatments meeting Clavien Surgical Complication grades greater than IIIa.S7,S12 The accuracy of procedure-related bleeding in our study was verified by pre- and post-injection, and 24-hour follow-up ultrasonography with comparative hemoglobin/hematocrit levels and intraprocedural CT scans to ascertain acute or concealed subclinical hematomas. The low bleeding complication rate of 1.1% in a high-risk CKD population is ascribed to the small-needle platform and CT guidance compared to larger gauge cutting renal biopsy needles with multiple passes. The safety and feasibility of cell delivery are critical factors that maximize the efficacy of cell-based nephron-restorative therapies. Cell product loss during delivery may impact accurate dosing determination and end-organ effects. Few regulatory-approved cell treatments for chronic diseases use direct tissue injection, although late phase III trials are underway in chronic heart failure with transendocardial mechanical mapping injections of mesenchymal-line cells.7Bartunek J. Terzic A. Davidson B. et al.Cardiopoietic cell therapy for advanced ischaemic heart failure: results at 39 weeks of the prospective randomized, double blind, sham-controlled CHART-1 clinical trial.Eur Heart J. 2017; 38: 648-660PubMed Google Scholar, S13 CT-guided needle insertion and cell injection into thinned renal cortices are feasible with low, acceptable rates of bleeding risks. In addition, the percutaneous, minimally invasive nature of the procedure with conscious sedation adds to the safety of cell delivery in high-risk CKD stage 3-4 populations with trajectories toward end-stage kidney disease. Locoregional image-guided delivery of autologous cell therapies in CKD offers the potential for kidney function stabilization or improvement and delay of renal replacement therapies. Future trials are underway. The authors thank all ProKidney trial participants for advancing the science of cell therapy for CKD, Ms. Brenda McGrath for statistics preparation, Dr. Victor Silva Ritter for statistical analysis, and Dr. Maria Díaz-González de Ferris for manuscript review. The trials have been censured by Institutional Review Board approval and participant informed consent. HY and JMS have made substantial contributions to the conception of the manuscript, drafting, and revisions of content, and agreed to be accountable for the accuracy and interpretation of the results data and approved the final version for publication. PDS, PRB, MPL, FSN, GJW, CTH, RDM, RN, EMC, ACE, and BST reviewed and agreed with manuscript content and approved the final version for publication. JMS is employed by ProKidney and an Executive Committee member. All the other authors have declared no conflict of interest. Download .pdf (.19 MB) Help with pdf files Supplementary File (PDF) Supplementary Inclusion and Exclusion Criteria Supplementary References

PURPOSE:An automated segmentation technique (AST) for computed tomography (CT) venography was developed to quantify measures of disease severity before and after stent placement in patients with left-sided nonthrombotic iliac vein compression.MATERIALS AND METHODS:Twenty-one patients with left-sided nonthrombotic iliac vein compression who underwent venous stent placement were retrospectively identified. Pre- and poststent CT venography studies were quantitatively analyzed using an AST to determine leg volume, skin thickness, and water content of fat. These measures were compared between diseased and nondiseased limbs and between pre- and poststent images, using patients as their own controls. Additionally, patients with and without postthrombotic lesions were compared.RESULTS:The AST detected significantly increased leg volume (12,437 cm3 vs 10,748 cm3, P < .0001), skin thickness (0.531 cm vs 0.508 cm, P < .0001), and water content of fat (8.2% vs 5.0%, P < .0001) in diseased left limbs compared with the contralateral nondiseased limbs, on prestent imaging. After stent placement in the left leg, there was a significant decrease in the water content of fat in the right (4.9% vs 2.7%, P < .0001) and left (8.2% vs 3.2%, P < .0001) legs. There were no significant changes in leg volume or skin thickness in either leg after stent placement. There were no significant differences between patients with or without postthrombotic lesions in their poststent improvement across the 3 measures of disease severity.CONCLUSIONS:ASTs can be used to quantify measures of disease severity and postintervention changes on CT venography for patients with lower extremity venous disease. Further investigation may clarify the clinical benefit of such technologies.

Historically, disease severity in venous disease has been derived from patient surveys, which are inherently subjective and qualitative. The purpose of this study is to describe a novel automated segmentation technique used to quantitatively measure disease severity in patients with May-Thurner Syndrome (MTS) from CT venography studies. We retrospectively identified 20 MTS patients (15 chronic DVT; 5 lymphedema) who underwent venous stenting and analyzed these patients' preprocedure and postprocedure CT venography studies using an automated segmentation technique. This technique works by separating the different layers of the leg (i.e. muscle, fat, bone, etc.) using Hounsfield units and deriving quantitative measures of disease severity from these partitions. The derived measurements include water percentage (a surrogate for edema), fat density, leg circumference, and skin thickness. The Wilcoxon signed rank test was employed in the statistical analysis of these data. When comparing the right and left legs of the same patient prior to stenting, the automated sequencing method found a significant difference in all measures of disease severity (P≤0.01), with the left leg showing more severe disease. The differences in all of these variables disappeared in the postprocedural images (P = 0.07, 0.40, 0.47), except leg circumference (pre P = 7.6 × 106, post P = 0.004). This suggests that although edema decreases after stenting, adipogenesis also occurs, leaving the leg enlarged. When comparing images of left legs before and after stenting, the automated segmentation imaging data showed no significant difference in fat density (P = 1), skin thickness (P = 1), and leg circumference (P = 1). However, there was a significant decrease in the percent of water in the leg (P = 0.04) on postprocedure imaging. The water percentage variable showed a significant decrease on postprocedure vs. preprocedure imaging, suggesting a decrease in the amount of edema following stenting. This objective variable is measurable and simple to calculate, making it a promising candidate for a quantitative measure of disease severity in patients with MTS.

For May-Thurner Syndrome (MTS), the degree of left common iliac vein stenosis which causes symptoms remains unknown and the characterization of lower extremity symptoms can be subjective. Determining which patients may benefit from treatment, therefore, is a challenge. The purpose of this study was to demonstrate the feasibility of efficiently obtaining quantitative image-based measures of disease severity from contrast enhanced CT studies of MTS patients. Patients seen and treated for MTS at our single academic institution who obtained contrast enhanced CT of the lower extremities were identified. Representative CT studies were selected, de-identified, and transferred to a research server where they were analyzed in Matlab. Novel segmentation algorithms were created to distinguish fat, muscle, skin, and bone regions for each axial image then used to calculate the total volume of fat, percentage volume of fat (PVF) relative to the total leg volume at that slice, fat density, and leg circumference for each leg. Differences between left and right leg values were compared using paired t-tests. Right leg values were considered internal controls. Following creation of segmentation algorithms, values were successfully obtained from 3 CT studies with results shown the Table. Volume of fat, PVF, fat density, and leg circumference were higher in the left leg compared to right, with PVF being statistically significant, p<0.05. Novel measures of disease severity in MTS can be efficiently obtained from CT data via automated segmentation methods. With further investigation, these values could be used to help guide patient selection and determine effectiveness of therapy.Tabled 1PatientFat Vol Diff (cm3)% Fat DiffFat Density Diff (HU)Leg Circ Diff (cm)A89830.051.062.15B93190.072.243.01C1830.010.180.22 Open table in a new tab

Background: Compared to permanent inferior vena cava (IVC) filters, higher complication rates occur with long-term use of temporary IVC filters. We aimed to identify patient clinical factors at the time of placement that could predict failure to remove a temporary IVC filter.Methods: A retrospective review was performed of both vascular surgery and interventional radiology prospective databases between December 2008 and December 2013. We analyzed a total number of 1,024 consecutive, temporary IVC filters stratified by whether retrieval was attempted or made permanent. Univariate, multivariate, and prediction modeling analyses with internal validation were performed on abstracted data, which included risk factors, treatment modalities, and indications for IVC filter placement.Results: Of 1,024 temporary IVC filters, removal was attempted in 60% and no attempt at removal (kept permanent) in 40%. Of the 619 with attempted removal, the overall successful retrieval rate was 95%. The majority of filters were not attempted to be removed because of persistent filter indications (360 cases). Risk factors associated with IVC filter permanence included male sex, older age, history, or indication of venous thromboembolism (VTE) with inability to anticoagulate, malignancy, and neurologic condition. Risk factors most predictive of permanence in the multivariate model were malignancy (odds ratio [OR]: 3.0, P < 0.001) or neurologic disorder (OR: 2.69, P = 0.0005). Validation revealed our model had a sensitivity of 60.4% and specificity of 69.9%.Conclusions: Our study shows that patients who are more likely to have a temporary IVC filter kept permanent are more likely to be older males with a history of malignancy, neurologic condition, or VTE. These factors are also predictive of permanence and can be used in our predictive model to provide insight into the significant preoperative risk factors that should play into the decision-making process.

Historically, IR procedure reports are free-text documents that provide a procedure narrative but do not capture data for outcomes analysis. Benefits of discrete data field templates (DDFTs) include consistent procedure data capture, automated parsing of reports into databases, and improved ability to track outcomes. There may be reluctance to adopt DDFTs, however, due to concerns of adversely affected workflow. This study evaluates the impact of adoption of DDFTs in a single tertiary care academic institution. DDFTs for all TACE procedures were implemented through a speech recognition system. Surveys were completed by IR attendings and fellows before and 6 months after DDFT implementation. Responses to survey questions were analyzed. Ten IR attendings and five IR fellows completed pre- and post-implementation surveys with results shown in the accompanying table. For IR fellows, the primary creators of procedure reports at our institution, DDFTs were easier to use and faster to complete compared to conventional free text-based report templates. For IR attendings, DDFTs were more difficult to use and more time consuming. For all respondents, DDFTs made it easier to find, retrieve, and utilize data for quality improvement, research, and teaching. Differences in pre- and post-implementation question scores were not found to be statistically significant, likely related to sample size. Discrete data field templates can be implemented into an IR TACE practice with a variable impact on work flow. Improvements in work flow were perceived by users with the most experience creating reports using DDFTs.Tabled 1QuestionCriteriaFellowAttendingPrePostPrePostHow long does it take to dictate a TACE study?1 = <5 min – 5 = >20 min4.23.61.63.3How easy-to-use are the TACE report templates?2.82.22.73.5How easy is it to find, retrieve, and utilize data in your dictations forQI?1 = very easy – 5 = very hard3.23.23.83.1Research?3.42.53.83.1Teaching?32.83.52.9 Open table in a new tab

Compared with permanent filters, higher complication rates occur with long-term use of temporary filters. Our hypothesis is that clinical factors at the time of placement can predict the need for a permanent instead of a temporary filter. An IRB-approved retrospective review was performed of both vascular surgery and interventional radiology prospective databases between 2008 and 2013. Protocols to maximize removal were in place. Patients were placed in group A if retrieval was attempted or group B if no retrieval attempt was made. Clinical factors for both groups were analyzed and compared (Table). Of 1,021 filters, removal was attempted in 60% (group A) and no attempt at removal in 40% (group B). Retrieval rate in group A was 95%. The most common reason removal wasn't attempted was lost follow-up. In the univariate model (Table), factors associated with permanence included male sex, old age, history or indication of venous thromboembolism (VTE) with inability to anticoagulate, malignancy, and neurologic condition. Factors most predictive of permanence in the multivariate model were malignancy (odds ratio, 3.0; P < .001) or neurologic disorder (odds ratio, 2.69; P = .0005). Despite protocols, 40% of temporary filters were not removed. These patients are more likely to be older, male, have a malignancy or history of neurologic condition or VTE. These factors can be used prospectively to aid in deciding whether a permanent and not a temporary filter should be used.TableUnivariate analysis of factors associated with filter permanenceFactorGroup A (n= 619)Group B (n=405)OR (95% CI)PNo. (%)No. (%)Male sex270 (44)225 (62)1.61 (1.25-2.07).00002History of VTE351 (57)273 (67)1.59 (1.22-2.07).0005Malignancy153 (25)200 (49)2.97 (2.27-3.88)<.0001Neurologic condition (CVA, paralysis, dementia)24 (4)35 (8)2.35 (1.38-4.02).002Indication VTE + AC contraindication290 (47)283 (70)2.65 (2.07-3.46)<.0001 VTE + AC complication25 (4)49 (12)3.28 (1.99-5.40)<.0001 VTE + AC failure9 (1)13 (3)2.25 (0.95-5.32).06 High-risk VTE63 (10)20 (5)0.46 (0.27-0.77).003 Prophylaxis232 (37)39 (10)0.17 (0.12-0.25)<.0001AC, Anticoagulation; CI, confidence interval; CVA, cerebrovascular accident (stroke); OR, odds ratio; VTE, venous thromboembolism. Open table in a new tab

Nanoparticles (NP) have emerged as a novel class of therapeutic agents that overcome many of the limitations of current cancer chemotherapeutics. However, a major challenge to many current NP platforms is unfavorable biodistribution, and limited tumor uptake, upon systemic delivery. Delivery, therefore, remains a critical barrier to widespread clinical adoption of NP therapeutics. To overcome these limitations, we have adapted the techniques of image-guided local drug delivery to develop nanoablation and nanoembolization. Nanoablation is a tumor ablative strategy that employs image-guided placement of electrodes into tumor tissue to electroporate tumor cells, resulting in a rapid influx of NPs that is not dependent on cellular uptake machinery or stage of the cell cycle. Nanoembolization involves the image-guided delivery of NPs and embolic agents directly into the blood supply of tumors. We describe the design and testing of our innovative local delivery strategies using doxorubicin-functionalized superparamagnetic iron oxide nanoparticles (DOX-SPIOs) in cell culture, and the N1S1 hepatoma and VX2 tumor models, imaged by high resolution 7T MRI. We demonstrate that local delivery techniques result in significantly increased intratumoral DOX-SPIO uptake, with limited off-target delivery in tumor-bearing animal models. The techniques described are versatile enough to be extended to any NP platform, targeting any solid organ malignancy that can be accessed via imaging guidance.

PurposeUse of IVC filters (IVCF) is under increasing regulatory scrutiny because of device safety and economic considerations. We hypothesize that Interventional Radiology (IR) consultation results in better utilization of optional and permanent IVCFs. This study aims to evaluate the impact of prospective decision-making on IVCF utilization.Materials and MethodsOver a 6-month period, we prospectively studied an IVCF decision-making database at our institution with IRB approval. After IR consultation, each case was classified as concordant (agreement between referring physician and IR regarding permanent or optional filter choice) or discordant (disagreement over filter choice). For all optional IVCFs, the likelihood of retrieval was prospectively estimated at the time of placement by the consulting IR (0–100%). Chi square and t-test were used for statistical analyses. The null hypotheses were rejected at p<0.05.Results66 IVCFs (23 permanent, 43 optional) were placed in 66 patients. 16/66 (24%) decisions were discordant. 7/16 (44%) of the discordant cases received optional filters; of these, 6/7 (86%) were declared permanent by the referring physician; for this group, the IR prospective estimate of retrieval was 6.4% (range 0–15%). 50/66 (76%) decisions were concordant. Of these, 36 patients received an optional IVCF. 29/36 (81%) of concordant optional devices were successfully retrieved (p<0.001). For this group, the IR prospective estimate of retrieval was 88.9% (range 80-100%) (p<0.001). Of the 7 concordant devices not retrieved, 2 patients died, 3 were declared permanent, while 2 are still being actively followed. There were no IVCF placement or retrieval failures. No patients were lost to follow up.ConclusionAfter consultation, IRs can accurately and prospectively determine the likelihood of IVCF retrieval. Significantly higher retrieval rates are achieved as a result of IR consultation on IVCF device choice. IR consultation positively impacts optimization of IVCF device choice, patient safety, and effective utilization. PurposeUse of IVC filters (IVCF) is under increasing regulatory scrutiny because of device safety and economic considerations. We hypothesize that Interventional Radiology (IR) consultation results in better utilization of optional and permanent IVCFs. This study aims to evaluate the impact of prospective decision-making on IVCF utilization. Use of IVC filters (IVCF) is under increasing regulatory scrutiny because of device safety and economic considerations. We hypothesize that Interventional Radiology (IR) consultation results in better utilization of optional and permanent IVCFs. This study aims to evaluate the impact of prospective decision-making on IVCF utilization. Materials and MethodsOver a 6-month period, we prospectively studied an IVCF decision-making database at our institution with IRB approval. After IR consultation, each case was classified as concordant (agreement between referring physician and IR regarding permanent or optional filter choice) or discordant (disagreement over filter choice). For all optional IVCFs, the likelihood of retrieval was prospectively estimated at the time of placement by the consulting IR (0–100%). Chi square and t-test were used for statistical analyses. The null hypotheses were rejected at p<0.05. Over a 6-month period, we prospectively studied an IVCF decision-making database at our institution with IRB approval. After IR consultation, each case was classified as concordant (agreement between referring physician and IR regarding permanent or optional filter choice) or discordant (disagreement over filter choice). For all optional IVCFs, the likelihood of retrieval was prospectively estimated at the time of placement by the consulting IR (0–100%). Chi square and t-test were used for statistical analyses. The null hypotheses were rejected at p<0.05. Results66 IVCFs (23 permanent, 43 optional) were placed in 66 patients. 16/66 (24%) decisions were discordant. 7/16 (44%) of the discordant cases received optional filters; of these, 6/7 (86%) were declared permanent by the referring physician; for this group, the IR prospective estimate of retrieval was 6.4% (range 0–15%). 50/66 (76%) decisions were concordant. Of these, 36 patients received an optional IVCF. 29/36 (81%) of concordant optional devices were successfully retrieved (p<0.001). For this group, the IR prospective estimate of retrieval was 88.9% (range 80-100%) (p<0.001). Of the 7 concordant devices not retrieved, 2 patients died, 3 were declared permanent, while 2 are still being actively followed. There were no IVCF placement or retrieval failures. No patients were lost to follow up. 66 IVCFs (23 permanent, 43 optional) were placed in 66 patients. 16/66 (24%) decisions were discordant. 7/16 (44%) of the discordant cases received optional filters; of these, 6/7 (86%) were declared permanent by the referring physician; for this group, the IR prospective estimate of retrieval was 6.4% (range 0–15%). 50/66 (76%) decisions were concordant. Of these, 36 patients received an optional IVCF. 29/36 (81%) of concordant optional devices were successfully retrieved (p<0.001). For this group, the IR prospective estimate of retrieval was 88.9% (range 80-100%) (p<0.001). Of the 7 concordant devices not retrieved, 2 patients died, 3 were declared permanent, while 2 are still being actively followed. There were no IVCF placement or retrieval failures. No patients were lost to follow up. ConclusionAfter consultation, IRs can accurately and prospectively determine the likelihood of IVCF retrieval. Significantly higher retrieval rates are achieved as a result of IR consultation on IVCF device choice. IR consultation positively impacts optimization of IVCF device choice, patient safety, and effective utilization. After consultation, IRs can accurately and prospectively determine the likelihood of IVCF retrieval. Significantly higher retrieval rates are achieved as a result of IR consultation on IVCF device choice. IR consultation positively impacts optimization of IVCF device choice, patient safety, and effective utilization.

PurposeThe durability and long term reliability of optional inferior vena cava filters (OIVCF) are unknown compared to permanent ICVFs (PICVFs). The FDA now recommends that OIVCFs be removed as soon as their indication resolves. A patient's clinical evolution may dictate that an OIVCF be left in place permanently, but this "conversion" is impossible to predict. Thus, it is difficult to predict when a PIVCF should be used instead of an OIVCF. We aim to test the hypothesis that select clinical factors present at the time of IVCF placement can predict the need for PICVF vs OIVCF.Materials and MethodsUnder IRB approval, we reviewed a prospectively acquired database of all IVCFs 1) placed at our institution by interventional radiologists (IRs) between 12/2008 and 9/2011; and 2) where a decision was made about the IVCF by 9/2011. IVCFs were placed in the Removed group if removal was attempted. IVCFs were placed in the Kept Permanent group if the OIVCF was made permanent, or if patients were lost to follow up. See Table 1 for studied factors. We calculated odds ratios for each factor. We used Fischer's exact test to calculate CIs and p values (p<0.5 significant).Tabled 1Factor/GroupKept Permanent (n=98)Removed (n= 167)Odds Ratio (95% CI)p-valueMean (±SD) Age - yr63.0 (± 14.3)57.1 (± 15.6)<0.001*Gender (Male Sex)66 (67%)74 (44%)2.59 (1.49-4.53)<0.001*Prior History of VTE53 (54%)108 (65%)0.64 (0.38-1.11)0.058Underlying Medical Condition: Malignancy61 (62%)64 (38%)2.65 (1.54-4.59)<0.001*Underlying Medical Condition: Neurological7 (7%)9 (5%)1.35 (0.41-4.23)0.37Indication: VTE + AC Contraindication65 (66%)85 (51%)1.90 (1.10-3.31)0.01*Indication: VTE + AC Complication10 (10%)12 (7%)1.47 (0.54-3.87)0.26Indication: VTE + AC Failure9 (9%)3 (2%)5.53 (1.33-32.33)<0.001*Indication: High Risk VTE10 (10%)32 (19%)0.48 (0.20-1.07).075Indication: Prophylaxis4 (4%)35 (21%)0.16 (0.04-0.47)<0.001* Open table in a new tab ResultsSee Table 1. Five patients were lost to follow-up; 7 patients failed retrieval.ConclusionIn patients whose OIVCFs were kept permanent, it is more likely that they were older, male, had malignancy, and that the indication for their filter was VTE with contraindication to anticoagulation (AC), VTE with AC failure, or was non-prophylactic. OICVFs in patients with each of these factors at time of placement were significantly more likely to be made permanent. PIVCFs use should be considered in these scenarios. PurposeThe durability and long term reliability of optional inferior vena cava filters (OIVCF) are unknown compared to permanent ICVFs (PICVFs). The FDA now recommends that OIVCFs be removed as soon as their indication resolves. A patient's clinical evolution may dictate that an OIVCF be left in place permanently, but this "conversion" is impossible to predict. Thus, it is difficult to predict when a PIVCF should be used instead of an OIVCF. We aim to test the hypothesis that select clinical factors present at the time of IVCF placement can predict the need for PICVF vs OIVCF. The durability and long term reliability of optional inferior vena cava filters (OIVCF) are unknown compared to permanent ICVFs (PICVFs). The FDA now recommends that OIVCFs be removed as soon as their indication resolves. A patient's clinical evolution may dictate that an OIVCF be left in place permanently, but this "conversion" is impossible to predict. Thus, it is difficult to predict when a PIVCF should be used instead of an OIVCF. We aim to test the hypothesis that select clinical factors present at the time of IVCF placement can predict the need for PICVF vs OIVCF. Materials and MethodsUnder IRB approval, we reviewed a prospectively acquired database of all IVCFs 1) placed at our institution by interventional radiologists (IRs) between 12/2008 and 9/2011; and 2) where a decision was made about the IVCF by 9/2011. IVCFs were placed in the Removed group if removal was attempted. IVCFs were placed in the Kept Permanent group if the OIVCF was made permanent, or if patients were lost to follow up. See Table 1 for studied factors. We calculated odds ratios for each factor. We used Fischer's exact test to calculate CIs and p values (p<0.5 significant).Tabled 1Factor/GroupKept Permanent (n=98)Removed (n= 167)Odds Ratio (95% CI)p-valueMean (±SD) Age - yr63.0 (± 14.3)57.1 (± 15.6)<0.001*Gender (Male Sex)66 (67%)74 (44%)2.59 (1.49-4.53)<0.001*Prior History of VTE53 (54%)108 (65%)0.64 (0.38-1.11)0.058Underlying Medical Condition: Malignancy61 (62%)64 (38%)2.65 (1.54-4.59)<0.001*Underlying Medical Condition: Neurological7 (7%)9 (5%)1.35 (0.41-4.23)0.37Indication: VTE + AC Contraindication65 (66%)85 (51%)1.90 (1.10-3.31)0.01*Indication: VTE + AC Complication10 (10%)12 (7%)1.47 (0.54-3.87)0.26Indication: VTE + AC Failure9 (9%)3 (2%)5.53 (1.33-32.33)<0.001*Indication: High Risk VTE10 (10%)32 (19%)0.48 (0.20-1.07).075Indication: Prophylaxis4 (4%)35 (21%)0.16 (0.04-0.47)<0.001* Open table in a new tab Under IRB approval, we reviewed a prospectively acquired database of all IVCFs 1) placed at our institution by interventional radiologists (IRs) between 12/2008 and 9/2011; and 2) where a decision was made about the IVCF by 9/2011. IVCFs were placed in the Removed group if removal was attempted. IVCFs were placed in the Kept Permanent group if the OIVCF was made permanent, or if patients were lost to follow up. See Table 1 for studied factors. We calculated odds ratios for each factor. We used Fischer's exact test to calculate CIs and p values (p<0.5 significant). ResultsSee Table 1. Five patients were lost to follow-up; 7 patients failed retrieval. See Table 1. Five patients were lost to follow-up; 7 patients failed retrieval. ConclusionIn patients whose OIVCFs were kept permanent, it is more likely that they were older, male, had malignancy, and that the indication for their filter was VTE with contraindication to anticoagulation (AC), VTE with AC failure, or was non-prophylactic. OICVFs in patients with each of these factors at time of placement were significantly more likely to be made permanent. PIVCFs use should be considered in these scenarios. In patients whose OIVCFs were kept permanent, it is more likely that they were older, male, had malignancy, and that the indication for their filter was VTE with contraindication to anticoagulation (AC), VTE with AC failure, or was non-prophylactic. OICVFs in patients with each of these factors at time of placement were significantly more likely to be made permanent. PIVCFs use should be considered in these scenarios.

Purpose: The use of inferior vena cava filters (IVCFs) is under increasing scrutiny because of device safety and economic considerations. The aim of this study was to test the hypothesis that interventional radiologist (IR) consultation results in better utilization of optional and permanent filters.Methods: Over 6 months, an IVCF decision-making database at a single institution was prospectively studied. After IR consultation, each case was classified as concordant (agreement between the referring physician and the IR over filter choice) or discordant (disagreement over filter choice). The consulting IR estimated the likelihood of retrieval attempt for all optional filters at the time of placement (0%-100%). Chi-square and t tests were used for statistical analyses. The null hypotheses were rejected at P < .05.Results: Sixty-six IVCFs (23 permanent, 43 optional) were placed in 66 patients. Sixteen of 66 decisions were discordant. In 7 of the 16 discordant cases, patients received optional filters; of these, 6 (86%) were declared permanent by the referring physician. For this group, the IR's prospective estimate of subsequent retrieval was 6.4% (0%-15%; P < .001). Fifty of 66 decisions were concordant. Of these, 36 patients received optional filters. Thirty-one of 36 concordant optional filters (86%) were successfully retrieved (P < .001). For this group, the IR's prospective estimate of subsequent retrieval was 88.3% (80%-100%; P < .001). Of the 5 concordant devices not retrieved, 2 patients died, and 3 devices were declared permanent. There were no IVCF placement or retrieval failures. No patients were lost to follow-up.Conclusions: Interventional radiologists can prospectively predict the likelihood of optional filter retrieval. Significantly higher retrieval rates are achieved as a result of IR consultation. Interventional radiologist consultation positively affects IVCF device choice, patient safety, and effective utilization.

There is a critical unmet need to monitor intratumoral drug uptake non-invasively. Superparamagnetic iron oxide nanoparticles (SPIOs) are agents with dual diagnostic and therapeutic properties that may meet this need. However, systemic (IV) administration results in unfavorable biodistribution with minimal tumor delivery. To overcome this limitation we propose nano-embolization (NE) as the image-guided delivery of SPIOs and embolic agents directly into the blood supply of tumors. It remains unknown if MRI can quantify the amount of NPs delivered to tumors during NE. Using VX2 liver tumors, we tested the hypotheses that a) NE increases uptake of therapeutic SPIOs over IV administration and b) 7T MRI can quantify intratumoral drug delivery. We induced VX2 liver tumors in 20 rabbits, evenly dividing them into NE and control (IV) groups. Both groups received doxorubicin-loaded therapeutic SPIOs at 0.56 mg/kg body weight. For the NE group, SPIOs and ethiodol were delivered into the hepatic artery under fluoroscopy. T2*-weighted gradient echo imaging (Bruker 7T ClinScan MRI) was performed on both groups pre and post-treatment to quantify SPIO delivery and uptake using T2*W mapping. After necropsy, we used ICP-MS as the gold standard to measure SPIO concentrations in normal liver and tumor pathological specimens. We compared SPIO uptake between the groups using ANOVA with post-hoc Tukey analysis, with p<0.05 considered significant. NE significantly increased tumor SPIO uptake 240% over IV delivery alone (340 vs. 140 μg Fe/mg, p<0.05). This correlated with T2*W MRI, which showed a significant T2 signal drop in NE tumors over controls (ΔT2: 47.4 ms vs. 18.9 ms, p<0.05). Furthermore, NE resulted in 75% less off target delivery to healthy liver tissue than IV delivery (p<0.05). NE improves tumor uptake of therapeutic SPIOs over conventional IV administration, with significantly less off-target delivery. 7T MRI can also quantify SPIO uptake non-invasively. To determine the optimal dose of therapeutic nanoparticles to inject, future studies should correlate SPIO delivery with tumor response.

PURPOSE:To test the hypothesis that patient parameters identifiable at the time of inferior vena cava (IVC) filter placement can be used to predict the need for a permanent versus optional filter. MATERIALS AND METHODS:A comprehensive institutional database of details and patient parameters for all optional IVC filters placed at a single institution between December 2008 and July 2011 was reviewed. IVC filters were categorized as removed if removal was attempted or as kept permanent if not. Patient parameters (age, sex, history of venous thromboembolism [VTE], presence of neurologic disease or malignancy, indication for filter placement) were compared between groups by multiple logistic regression analysis, and a prediction model based on these parameters was constructed. RESULTS:A total of 265 optional IVC filters were placed and analyzed; 167 were removed and 98 were kept permanent. In the multivariable model predicting filter disposition, significant factors associated with permanence were age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.05), male sex (OR, 3.01; 95% CI, 1.64-5.54), underlying malignancy (OR, 3.27; 95% CI, 1.77-6.03), and an indication of anticoagulation failure (OR, 8.12; 95% CI, 1.83-36.0). Significant factors associated with removal were history of VTE (OR, 0.39; 95% CI, 0.21-0.74), prophylactic filter placement indication (OR, 0.14; 95% CI, 0.04-0.43), and high-risk VTE (OR, 0.37; 95% CI, 0.15-0.94). The c-statistic for the prediction model based on these parameters was 0.80. CONCLUSIONS:Patient parameters can be used to quantitatively predict an optional IVC filter being kept permanent. These findings can aid in optimization of prospective decision-making in IVC filter placement.

Superparamagnetic Iron Oxide nanoparticles (SPIOs) are an emerging class of agents with diagnostic and therapeutic properties. SPIOs injected systemically (IV) are sequestered by the reticuloendothelial system, with limited tumor uptake. Electroporation (EP) can modulate the influx of therapeutics into cells through the rapid, reversible induction of transmembrane pores. We propose electro-nanotherapy (electro-NT) as the EP of tissues following nanoparticle delivery as a method to increase drug uptake. The purpose of this study was to demonstrate the benefits of this combined locoregional approach in the N1S1 hepatoma model. We hypothesized that electro-NT increases uptake of therapeutic SPIOs over IV injection and that SPIO uptake can be detected with high-resolution 7T MRI. We grew N1S1 tumors in 20 Sprague-Dawley rats, which were evenly divided into electro-NT and control groups. Both groups received doxorubicin functionalized SPIOs, serving as dual imaging and therapeutic agents, at 0.56 mg/kg body weight IV. For the electro-NT group, following SPIO delivery, EP was applied directly to tumors at 500-V/cm field strength (8 pulses, 100-μs pulse duration). T2*-weighted gradient echo imaging (Bruker 7T ClinScan MRI) was performed on both groups pre and post-treatment to detect SPIO delivery and uptake using T2*W mapping. After euthanasia, tumors were harvested for evaluation by ICP-MS for iron concentration. SPIO uptake between the groups were compared with using ANOVA with post-hoc Tukey analysis, with p<0.05 considered significant. Electro-NT significantly increased tumor SPIO uptake over IV delivery alone. Tumors that received electro-NT had a 6.3 fold increase in SPIOs over controls (165 vs. 26.1 μg Fe/mg tissue, p<0.05). This correlated with T2*W MRI, which showed a significant T2 signal drop in electro-NT tumors over controls (T2: 33.5 ms vs. 103.4 ms, p<0.05). Electro-NT considerably improves tumor uptake of therapeutic SPIO over conventional IV administration. 7T MRI is capable of monitoring this SPIO uptake non-invasively. The next experimental steps should determine the efficacy of this new locoregional drug therapy.

The approval of drugs for human use by the US Food and Drug Administration (FDA) through the Center for Drug Evaluation and Research (CDER) is a time-consuming and expensive process, and approval rates are low (DiMasi et al., J Health Econ 22:151-185, 2003; Marchetti and Schellens, Br J Cancer 97:577-581, 2007). In general, the FDA drug approval process can be separated into preclinical, clinical, and postmarketing phases. At each step from the point of discovery through demonstration of safety and efficacy in humans, drug candidates arc closely scrutinized. Advances in nanotechnology are being applied in the development of novel therapeutics that may address a number of shortcomings of conventional small molecule drugs and may facilitate the realization of personalized medicine (Ferrari, Curr Opin Chem Biol 9:343-346, 2005; Ferrari, Nat Rev Cancer 5:161-171, 2005; Ferrari and Downing, BioDrugs 19:203-210, 2005). Appealingly, nanoparticle drug candidates often represent multiplexed formulations (e.g., drug, targeting moiety, and nanoparticle scaffold material). By tailoring the chemistry and identity of variable nanoparticle constituents, it is possible to achieve targeted delivery, reduce side effects, and prepare formulations of unstable (e.g., siRNA) and/or highly toxic drugs (Ferrari, Curr Opin Chem Biol 9:343-346, 2005; Ferrari, Nat Rev Cancer 5:161-171, 2005; Ferrari and Downing, BioDrugs 19:203-210, 2005). With these benefits arise new challenges in all aspects of regulated drug development and testing.This chapter distils the drug development and approval process with an emphasis on special considerations for nanotherapeutics. The chapter concludes with a case study focused on a nanoparticle therapeutic, CALAA-01, currently in human clinical trials, that embodies many of the potential benefits of nanoparticle therapeutics (Davis, Mol Pharm 6:659-668, 2009). By choosing CALAA-01, reference is made to the infancy of the therapeutic nanoparticle field; in 2008, CALAA-01 was the first targeted siRNA nanoparticle therapeutic administered to humans. Certainly, there will be many more that will follow the lead of CALAA-01 and each will have its own unique challenges; however, much can be learned from this drug in the context of nanotherapeutics and the evolving development and approval process as it applies to them.

PurposeElectroporation (EP) is a new ablation technique that causes temporary membrane permeability and transient vascular hypoperfusion. These effects could be used to enhance the local delivery of drugs to target tumors, assuming that the drugs are located within the zone of treatment during ablation. The purpose of this study was to determine the relationship between the timing of delivery of doxorubicin-containing superparamagnetic iron oxide nanoparticles (SPIOs) and EP. In VX2 rabbits, we tested the hypothesis that the onset of EP relative to nanoembolization (NE) with SPIOs affects their intratumoral uptake, and that uptake can be assessed with MRI.Materials and MethodsWe implanted 8 VX2 tumors in the hindlimbs of 5 rabbits. After 2 weeks of tumor growth, we performed T2 TSE MRI for tumor location, and T2*-w MRI for baseline tumor signal intensity. Using a femoral artery catheter approach, we injected SPIOs emulsified in lipiodol into the iliac artery perfusing each hindlimb tumor in a procedure called NE. We performed EP at progressive time points ranging from 5 min before to 3 min after NE. T2*-w MRI detected SPIO uptake via tumor signal changes. After euthanasia, tissues were harvested to assess SPIO uptake using inductively coupled plasma mass spectroscopy (ICP-MS). Mean tumor SPIO concentration was compared between timing groups using ANOVA with post-hoc Tukey analysis, with p<0.05 considered significant.ResultsWhen EP was performed 1.5 to 2.25 min after NE, mean SPIO concentration in the tumor increased 2.9 fold (63.4 vs. 21.9 μg Fe/mg tissue, p<0.05) compared to other time points. T2*-w MRI signal intensity changes correlated with pathologic findings from injected SPIOs. Groups that underwent EP outside this window did not show appreciable tumor T2*-w signal changes.ConclusionThe timing of EP relative to NE significantly affects intratumoral drug uptake. Catheter-based drug delivery using nanoparticle platforms can be detected non-invasively using T2*-w MRI. Future studies that seek to verify the efficacy of combining EP with therapeutic nanoparticles should consider the timing of such drug delivery. PurposeElectroporation (EP) is a new ablation technique that causes temporary membrane permeability and transient vascular hypoperfusion. These effects could be used to enhance the local delivery of drugs to target tumors, assuming that the drugs are located within the zone of treatment during ablation. The purpose of this study was to determine the relationship between the timing of delivery of doxorubicin-containing superparamagnetic iron oxide nanoparticles (SPIOs) and EP. In VX2 rabbits, we tested the hypothesis that the onset of EP relative to nanoembolization (NE) with SPIOs affects their intratumoral uptake, and that uptake can be assessed with MRI. Electroporation (EP) is a new ablation technique that causes temporary membrane permeability and transient vascular hypoperfusion. These effects could be used to enhance the local delivery of drugs to target tumors, assuming that the drugs are located within the zone of treatment during ablation. The purpose of this study was to determine the relationship between the timing of delivery of doxorubicin-containing superparamagnetic iron oxide nanoparticles (SPIOs) and EP. In VX2 rabbits, we tested the hypothesis that the onset of EP relative to nanoembolization (NE) with SPIOs affects their intratumoral uptake, and that uptake can be assessed with MRI. Materials and MethodsWe implanted 8 VX2 tumors in the hindlimbs of 5 rabbits. After 2 weeks of tumor growth, we performed T2 TSE MRI for tumor location, and T2*-w MRI for baseline tumor signal intensity. Using a femoral artery catheter approach, we injected SPIOs emulsified in lipiodol into the iliac artery perfusing each hindlimb tumor in a procedure called NE. We performed EP at progressive time points ranging from 5 min before to 3 min after NE. T2*-w MRI detected SPIO uptake via tumor signal changes. After euthanasia, tissues were harvested to assess SPIO uptake using inductively coupled plasma mass spectroscopy (ICP-MS). Mean tumor SPIO concentration was compared between timing groups using ANOVA with post-hoc Tukey analysis, with p<0.05 considered significant. We implanted 8 VX2 tumors in the hindlimbs of 5 rabbits. After 2 weeks of tumor growth, we performed T2 TSE MRI for tumor location, and T2*-w MRI for baseline tumor signal intensity. Using a femoral artery catheter approach, we injected SPIOs emulsified in lipiodol into the iliac artery perfusing each hindlimb tumor in a procedure called NE. We performed EP at progressive time points ranging from 5 min before to 3 min after NE. T2*-w MRI detected SPIO uptake via tumor signal changes. After euthanasia, tissues were harvested to assess SPIO uptake using inductively coupled plasma mass spectroscopy (ICP-MS). Mean tumor SPIO concentration was compared between timing groups using ANOVA with post-hoc Tukey analysis, with p<0.05 considered significant. ResultsWhen EP was performed 1.5 to 2.25 min after NE, mean SPIO concentration in the tumor increased 2.9 fold (63.4 vs. 21.9 μg Fe/mg tissue, p<0.05) compared to other time points. T2*-w MRI signal intensity changes correlated with pathologic findings from injected SPIOs. Groups that underwent EP outside this window did not show appreciable tumor T2*-w signal changes. When EP was performed 1.5 to 2.25 min after NE, mean SPIO concentration in the tumor increased 2.9 fold (63.4 vs. 21.9 μg Fe/mg tissue, p<0.05) compared to other time points. T2*-w MRI signal intensity changes correlated with pathologic findings from injected SPIOs. Groups that underwent EP outside this window did not show appreciable tumor T2*-w signal changes. ConclusionThe timing of EP relative to NE significantly affects intratumoral drug uptake. Catheter-based drug delivery using nanoparticle platforms can be detected non-invasively using T2*-w MRI. Future studies that seek to verify the efficacy of combining EP with therapeutic nanoparticles should consider the timing of such drug delivery. The timing of EP relative to NE significantly affects intratumoral drug uptake. Catheter-based drug delivery using nanoparticle platforms can be detected non-invasively using T2*-w MRI. Future studies that seek to verify the efficacy of combining EP with therapeutic nanoparticles should consider the timing of such drug delivery.

Pancreatic ductal adenocarcinoma (PDAC) carries the worst prognosis of any cancer. As current treatments offer minimal benefit, entirely new approaches are needed. Gold nanoparticles (AuNPs) can be surface functionalized with anti-sense oligonucleotides (ASOs) to target molecular mechanisms of PDAC. We propose transcatheter intra-arterial (IA) delivery of these AuNPs - a procedure we term “nanoembolization” - as a novel therapy for PDAC. We aimed to test the hypothesis that nanoembolization using therapeutic AuNPs increases intra-tumoral uptake of AuNPs over systemic IV injection in an animal model of PDAC. AuNPs were prepared by citrate reduction of AuCl3. ASOs targeting mRNA of survivin (an inhibitor of apoptosis) were synthesized using phosphoramidite chemistry and attached to the AuNPs. We surgically implanted and grew VX2 tumors in the pancreas of 12 rabbits. Rabbits were randomized into IV or IA delivery groups (n = 6 in each group). For the IV group, AuNPs were injected into the ear vein. For the IA group, we catheterized the gastroduodenal artery using x-ray fluoroscopy and used transcatheter intra-arterial perfusion MRI to confirm catheter placement. AuNPs mixed with emulsion agent ethiodol were then injected. Both groups were kept alive for 4 hours then euthanized. Tissue samples were obtained from each tumor and surrounding pancreas. AuNP concentration in each sample was quantified using inductively coupled plasma mass spectrometry. Mean AuNP concentrations for the two groups were compared using an unpaired t-test. VX2 pancreatic tumors were grown successfully in 12/12 rabbits. IA delivery increased AuNP uptake 42 fold in the tumor periphery, 89 fold in the tumor core and 55 fold in the tumor overall compared to IV (all p