Capacity Prioritization Initiative Reduced the Wait Time for Port Placement and Facilitated Increased Volume of Port Placements at a Large County Health System.

DESCRIPTION OF THE PROBLEM: Wait time from request to placement of ports in interventional radiology had increased from 14 to 27 days over a 4-month period. The goal of this project was to reduce the wait time by 15% within 4 months while accommodating additional volume. INSTITUIONAL APPROACH TO ADDRESS PROBLEM: Capacity analysis revealed 2 bottlenecks: (1) inadequate provider capacity for preprocedural visits in interventional radiology clinic and (2) inadequate number of spots for port placement in the angiography schedule. The intervention consisted of: (1) 2 reserved slots in the attending physician's morning clinic schedule and (2) 3 daily guaranteed spots for port placement in the angiography suite. Both changes were integrated into the electronic medical record scheduling system. DESCRIPTION OF OUTCOMES: After the intervention, per biweekly period, the number of port requests increased by 17% (Preintervention: 16.6 ± 3.1, Postintervention: 20.1 ± 4.1, P = 0.03), the number of completed clinic visits increased by 19% (Preintervention: 16.7 ± 5.1, Postintervention: 20.5 ± 3.6, P = 0.05), and the number of port placements increased by 19% (Preintervention: 16.9 ± 3.9, Postintervention: 21.0 ± 3.5, P = 0.02). The average wait time from request to placement decreased by 22% (Preintervention: 22.2 ± 4.4 days, Postintervention: 18.3 ± 3.4 days, P = 0.03), driven by a 49% decrease in wait time between request and clinic visit (Preintervention: 11.0 ± 2.3 days, Postintervention: 7.4 ± 1.0 days, P = 0.03). CONCLUSIONS: Prioritization of clinic and angiography suite capacity, integrated into the electronic scheduling system, significantly reduced the wait time for port placement, even with significant increases in the volume of port requests.

Comparison of radiofrequency and microwave ablation and identification of risk factors for primary treatment failure and local progression.

PURPOSE: To compare percutaneous radiofrequency ablation (RFA) and microwave ablation (MWA) for treatment of Hepatocellular carcinoma (HCC) and to identify risk factors for treatment failure and local progression. METHODS: 145 unique HCC [87 (60%) RFA, 58 (40%) MWA] were retrospectively reviewed from a single tertiary medical center. Adverse events were classified as severe, moderate, or mild according to the Society of Interventional Radiology Adverse Event Classification system. Primary and secondary efficacy, as well as local progression, were determined using mRECIST. Predictors of treatment failure and time to local progression were analyzed using generalized estimating equations and Cox regression, respectively. RESULTS: Technical success was achieved in 143/145 (99%) HCC. There were 1 (0.7%) severe and 2 (1.4%) moderate adverse events. Of the 143 technically successful initial treatments, 136 (95%) completed at least one follow-up exam. Primary efficacy was achieved in 114/136 (84%). 9/22 (41%) primary failures underwent successful repeat ablation, so secondary efficacy was achieved in 128/136 (90%) HCC. Local progression occurred in 24 (19%) HCC at a median of 25 months (95% CI = 19-32 months). There was no difference in technical success, primary efficacy, or time to local progression between RFA and MWA. In HCC treated with MWA, same-day biopsy was associated with primary failure (RR = 9.0, 95% CI: 1.7-47, P = 0.015), and proximity to the diaphragm or gastrointestinal tract was associated with local progression (HR = 2.40, 95% CI:1.5-80, P = 0.017). CONCLUSION: There was no significant difference in primary efficacy or time to local progression between percutaneous RFA and MWA.

Lower extremity endovenous reconstruction for symptomatic occlusive disease in pediatric patients: techniques, clinical outcomes, and long-term stent patencies.

BACKGROUND: Endovascular stent reconstruction is the standard of care for chronic venous occlusive disease in adults, but it has not been reported in pediatric patients. OBJECTIVE: This study reports the technical success, complications, clinical outcomes, and stent patency of iliocaval stent reconstruction for chronic iliocaval thrombosis in pediatric patients. MATERIALS AND METHODS: Fourteen patients, 13 (93%) male with a mean age of 16.4 years (range: 8-20 years), underwent iliocaval stent reconstruction for chronic iliocaval thrombosis. The mean number of prothrombotic risk factors was 2.5 (range: 0-4), including 7 (50%) patients with inferior vena cava atresia. At initial presentation, the Clinical, Etiology, Anatomy, and Pathophysiology classification (CEAP) score was C3 in 2 (14%) patients, C4 in 11 (79%) patients, and C6 in 1 (7.1%) patient. Time course of presenting symptoms included chronic (>4 weeks) (n=7; 50%) and acute worsening of chronic symptoms (2-4 weeks) (n=7; 50%). Aspects of recanalization and reconstruction, stenting technical success, complications, clinical outcomes and stent patency were recorded. Clinical success was defined as a 1-point decrease in the CEAP. Primary, primary-assisted, and secondary patency were defined by Cardiovascular and Interventional Radiological Society of Europe guidelines. RESULTS: Most procedures employed three access sites (range: 2-4). Intravascular ultrasound was employed in 11 (79%) procedures. Blunt and sharp recanalization techniques were used in 12 (86%) and 2 (14%) patients, respectively. Stenting technical success was 100%. Two (14%) minor adverse events occurred and mean post-procedure hospitalization was 2.8 days (range: 1-8 days). Clinical success rates at 2 weeks, 6 months and 12 months were 85%, 82%, and 83%, respectively. At a mean final clinical follow-up of 88 months (range: 16-231 months), clinical success was 93%. Estimated 6- and 12-month primary stent patencies were 86% and 64%, respectively. Six- and 12-month primary-assisted and secondary stent patency rates were both 100%. CONCLUSION: Iliocaval stent reconstruction is an effective treatment for symptomatic chronic iliocaval thrombosis in pediatric patients with high rates of technical success, 6- and 12-month clinical success, and 6- and 12-month primary-assisted and secondary patency rates.

Total endovenous recanalization and stent reconstruction for naïve non-inferior vena cava filter-associated chronic iliocaval occlusive disease: Placement of 352 venous stents in 69 debilitated patients.

The aim of this study was to report the technical success, adverse events, clinical outcomes, and long-term stent patency of iliocaval stent reconstruction for naïve, non-inferior vena cava (IVC) filter-related, chronic iliocaval thrombosis. A total of 69 patients, including 47 (68%) men, with a mean age of 36 years (range: 8-71 years), underwent first-time iliocaval stent reconstruction for non-IVC filter-associated iliocaval thrombosis. The mean number of prothrombotic risk factors was 2.2 (range: 0-5), including 30 (43%) patients with IVC atresia. Upon initial presentation, the Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) classification was C3 in 55 (80%) patients, C4 in four (5.8%) patients, C5 in one (1.4%) patient, and C6 in seven (10%) patients. Technical aspects of stent reconstruction, technical success, adverse events, 2-week and 6, 12, and 24-month clinical response, and 6, 12, and 24-month primary, primary-assisted, and secondary stent patency rates were recorded. Technical success was defined as recanalization and stent deployment. Adverse events were reported according to the Society of Interventional Radiology classification system. Clinical success was defined as a 1-point decrease in CEAP classification and stent patency was defined by the Cardiovascular and Interventional Radiological Society guidelines. The technical success rate was 100%. There were 352 venous stents deployed during stent reconstructions. One (1.4%) severe, four (5.8%) moderate, and four (5.8%) minor adverse events occurred and median post-procedure hospitalization was 1 day (range: 1-45 days). Clinical success at 2 weeks and 6, 12, and 24 months was 76%, 85%, 87%, and 100%, respectively. The estimated 6, 12, and 24-month primary patency rates were 91%, 88%, and 62%, respectively. The estimated 6, 12, and 24-month primary-assisted patency rates were 98%, 95%, and 81%, respectively. The estimated 6, 12, and 24-month secondary-assisted patency rates were all 100%. In conclusion, iliocaval stent reconstruction is an effective treatment for non-IVC filter-associated chronic iliocaval thrombosis with high rates of technical success, clinical responses, and stent patency.

Approach, Technical Success, Complications, and Stent Patency of Sharp Recanalization for the Treatment of Chronic Venous Occlusive Disease: Experience in 123 Patients.

PURPOSE: To report the technical success and complications following sharp recanalization of chronic venous occlusions. MATERIALS AND METHODS: A total of 123 patients, including 75 (61.0%) men and 48 (39.0%) women, with mean age of 50.5 ± 17.5 years (range 19-90 years), underwent sharp recanalization of chronic venous occlusions. The etiologies of occlusion were chronic deep venous thrombosis (n = 43; 35.0%), prior central venous access (n = 39; 31.7%), indwelling cardiac leads (n = 21; 17.1%), and occluded venous stents (n = 20; 16.3%). The sites of venous occlusion included 59/123 (48.0%) thoracic central veins, 37 (30.1%) non-thoracic central veins, and 27 (22.0%) peripheral veins. Median length of occlusion was 3.2 ± 1.4 cm (range 1.3-10.9 cm). RESULTS: Sharp recanalization was most commonly attempted with transseptal needles in 108/123 (87.8%), with a mean number of 1.2 ± 0.4 crossing devices per patient (range 1-4 devices). Targeting devices included a loop snare (n = 92; 74.8%), partially deployed Wallstent (n = 21; 17.1%), partially deployed Amplatzer vascular plug (n = 8; 6.5%), and an angioplasty balloon (n = 3; 2.4%). Technical success was achieved in 111 (90.2%) patients. There were 3 (2.4%) severe, 1 (0.8%) moderate, and 7 (5.7%) minor adverse events. Severe adverse events included 1 case each of pericardial tamponade, hemothorax, and inferior vena cava filter occlusion. 88 (71.5%) patients had venous stents placed; at the last follow-up examination, 68/86 (79.0%) stents were patent. CONCLUSION: Sharp recanalization has a high technical success and low rate of adverse events in the recanalization of chronic venous occlusions.

Acute Limb Ischemia Therapies: When and How to Treat Endovascularly.

Acute limb ischemia is an emergent limb and life-threatening condition with high morbidity and mortality. An understanding of the presentation, clinical evaluation, and initial workup, including noninvasive imaging evaluation, is critical to determine an appropriate management strategy. Modern series have shown endovascular revascularization for acute limb ischemia to be safe and effective with success rates approaching surgical series and with similar, or even decreased, perioperative morbidity and mortality. A thorough understanding of endovascular techniques, associated pharmacology, and perioperative care is paramount to the endovascular management of patients presenting with acute limb ischemia. This article discusses the diagnosis and strategies for endovascular treatment of acute limb ischemia.

Impact of Anemia and Transfusion on Readmission and Length of Stay After Spinal Surgery: A Single-center Study of 1187 Operations.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To determine whether receipt of blood transfusion and preoperative anemia are associated with increased rates of 30-day all-cause readmission, and secondarily with a prolonged hospital stay after spinal surgery. SUMMARY OF BACKGROUND DATA: Increased focus on health care quality has led to efforts to determine postsurgical readmission rates and predictors of length of postoperative hospital stay. Although there are still no defined outcome measures specific to spinal surgery to which providers are held accountable, efforts to identify appropriate measures and to determine modifiable risk factors to optimize quality are ongoing. METHODS: Records from 1187 consecutive spinal surgeries at Northwestern Memorial Hospital in 2010 were retrospectively reviewed and data were collected that described the patient, surgical procedure, hospital course, complications, and readmissions. Presence or absence of transfusion during the surgery and associated hospital course was treated as a binary variable. Multivariate negative binomial regression and logistic regression were used to model length of stay and readmission, respectively. RESULTS: Nearly one fifth (17.8%) of surgeries received transfusions, and the overall readmission rate was 6.1%. After controlling for potential confounders, we found that the presence of a transfusion was associated with a 60% longer hospital stay [adjusted incidence rate ratio=1.60 (1.34-1.91), P<0.001], but was not significantly associated with an increased rate of readmission [adjusted odds ratio=0.81 (0.39-1.70), P=0.582]. Any degree of preoperative anemia was associated with increased length of stay, but only severe anemia was associated with an increased rate of readmission. CONCLUSIONS: Both receipt of blood transfusion and any degree of preoperative anemia were associated with increased length of hospital stay after controlling for other variables. Severe anemia, but not receipt of blood transfusion, was associated with increased rate of readmission. Our findings may help define actions to reduce length of stay and decrease rates of readmission.

Single-Center Comparison of Overall Survival and Toxicities in Patients with Infiltrative Hepatocellular Carcinoma Treated with Yttrium-90 Radioembolization or Drug-Eluting Embolic Transarterial Chemoembolization.

PURPOSE: To compare overall survival and toxicities after yttrium-90 (90Y) radioembolization and chemoembolization with drug-eluting embolics (DEE) in patients with infiltrative hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Retrospective review of 50 patients with infiltrative HCC without main portal vein invasion who were treated with 90Y radioembolization (n = 26) or DEE chemoembolization (n = 24) between March 2007 and August 2012 was completed. Infiltrative tumors were defined by cross-sectional imaging as masses that lacked well-demarcated boundaries, and treatment allocations were made by a multidisciplinary tumor board. Median age was 63 years; median tumor diameter was 9.0 cm; and there were no significant differences between groups in performance status, severity of liver disease, or HCC stage. Toxicities were graded by Common Terminology Criteria for Adverse Events v4.03. Overall survival from treatment was assessed by Kaplan-Meier analysis, with analysis of potential predictors of survival with log-rank test. RESULTS: There was no difference in the average number of procedures performed in each treatment group (DEE, 1.5 ± 1.1; 90Y, 1.6 ± 0.5; P = .97), and technical success was achieved in all cases. Abdominal pain (73% vs 33%; P = .004) and fever (38% vs 8%; P = .01) were more frequent after DEE chemoembolization. There was no significant difference in median overall survival between treatment groups after treatment (DEE, 9.9 months; 90Y, 8.1 months; P = .11). CONCLUSIONS: 90Y radioembolization and DEE chemoembolization provided similar overall survival in the treatment of infiltrative HCC without main portal vein invasion. Abdominal pain and fever were more frequent after DEE chemoembolization.

Long-Term Percutaneous Nephrostomy Management of Malignant Urinary Obstruction: Estimation of Optimal Exchange Frequency and Estimation of the Financial Impact of Patient Compliance.

PURPOSE: To estimate the least costly routine exchange frequency for percutaneous nephrostomies (PCNs) placed for malignant urinary obstruction, as measured by annual hospital charges, and to estimate the financial impact of patient compliance. MATERIALS AND METHODS: Patients with PCNs placed for malignant urinary obstruction were studied from 2011 to 2013. Exchanges were classified as routine or due to 1 of 3 complication types: mechanical (tube dislodgment), obstruction, or infection. Representative cases were identified, and median representative charges were used as inputs for the model. Accelerated failure time and Markov chain Monte Carlo models were used to estimate distribution of exchange types and annual hospital charges under different routine exchange frequency and compliance scenarios. RESULTS: Long-term PCN management was required in 57 patients, with 87 total exchange encounters. Median representative hospital charges for pyelonephritis and obstruction were 11.8 and 9.3 times greater, respectively, than a routine exchange. The projected proportion of routine exchanges increased and the projected proportion of infection-related exchanges decreased when moving from a 90-day exchange with 50% compliance to a 60-day exchange with 75% compliance, and this was associated with a projected reduction in annual charges. Projected cost reductions resulting from increased compliance were generally greater than reductions resulting from changes in exchange frequency. CONCLUSIONS: This simulation model suggests that the optimal routine exchange interval for PCN exchange in patients with malignant urinary obstruction is approximately 60 days and that the degree of reduction in charges likely depends more on patient compliance than exact exchange interval.

Analysis of the RENAL and mRENAL Scores and the Relative Importance of Their Components in the Prediction of Complications and Local Progression after Percutaneous Renal Cryoablation.

PURPOSE: To determine if modified RENAL (mRENAL) score and its individual components have superior predictive value relative to the RENAL nephrometry score in prediction of complications and recurrence after percutaneous renal cryoablation. MATERIALS AND METHODS: Primary masses treated with CT-guided percutaneous renal cryoablation between June 2007 and May 2016 were retrospectively reviewed. RENAL and mRENAL scores were used to stratify masses into low, medium, and high complexity tertiles. Complications were characterized by SIR criteria. Predictors of complications and local progression were analyzed using multivariate logistic regression and Kaplan-Meier analysis. RESULTS: There were 95 renal cryoablation procedures in 86 patients. Of ablations, 89 had at least 1 follow-up imaging study, with median follow-up of 29 months. There were 11 (12.4%) complications, including 5 (6.5%) major complications. Mass complexity, as measured by mRENAL complexity tertile, was associated with increased risk of complications on multivariate analysis (P = .045). Endophytic location was the only individual ordinal component of the RENAL and mRENAL scores associated with complications (P = .021). Local progression occurred in 7 (8.3%) masses. Complexity as measured by either scoring system was not associated with local progression. Only diameter > 3 cm was associated with increased risk of local progression (hazard ratio = 9.9, 95% confidence interval = 2.1-45, P = .003). CONCLUSIONS: mRENAL score was predictive of complications and tumor size was predictive of recurrence. Use of mRENAL score for complications and tumor size for recurrence should allow for simpler risk stratification and more accurate patient counseling.

An Outcome and Cost Analysis Comparing Single-Level Minimally Invasive Transforaminal Lumbar Interbody Fusion Using Intraoperative Fluoroscopy versus Computed Tomography-Guided Navigation.

BACKGROUND: Minimally invasive transforaminal lumbar interbody fusion (TLIF) has undergone significant evolution since its conception as a fusion technique to treat lumbar spondylosis. Minimally invasive TLIF is commonly performed using intraoperative two-dimensional fluoroscopic x-rays. However, intraoperative computed tomography (CT)-based navigation during minimally invasive TLIF is gaining popularity for improvements in visualizing anatomy and reducing intraoperative radiation to surgeons and operating room staff. This is the first study to compare clinical outcomes and cost between these 2 imaging techniques during minimally invasive TILF. METHODS: For comparison, 28 patients who underwent single-level minimally invasive TLIF using fluoroscopy were matched to 28 patients undergoing single-level minimally invasive TLIF using CT navigation based on race, sex, age, smoking status, payer type, and medical comorbidities (Charlson Comorbidity Index). The minimum follow-up time was 6 months. The 2 groups were compared in regard to clinical outcomes and hospital reimbursement from the payer perspective. RESULTS: Average surgery time, anesthesia time, and hospital length of stay were similar for both groups, but average estimated blood loss was lower in the fluoroscopy group compared with the CT navigation group (154 mL vs. 262 mL; P = 0.016). Oswestry Disability Index, back visual analog scale, and leg visual analog scale scores similarly improved in both groups (P > 0.05) at 6-month follow-up. Cost analysis showed that average hospital payments were similar in the fluoroscopy versus the CT navigation groups ($32,347 vs. $32,656; P = 0.925) as well as payments for the operating room (P = 0.868). CONCLUSIONS: Single minimally invasive TLIF performed with fluoroscopy versus CT navigation showed similar clinical outcomes and cost at 6 months.

Percutaneous Cryoablation for the Treatment of Primary and Metastatic Lung Tumors: Identification of Risk Factors for Recurrence and Major Complications.

PURPOSE: To identify risk factors for local recurrence and major complications associated with percutaneous cryoablation of lung tumors. MATERIALS AND METHODS: All cases between April 2007 and September 2014 at 1 institution were retrospectively reviewed. Procedures were performed using computed tomography guidance and a double freeze-thaw protocol. Tumor progression was determined via World Health Organization guidelines, and complications were classified using SIR reporting standards. Measures of efficacy were calculated via Kaplan-Meier analysis. Predictors of local progression and major complications were identified by Cox proportional hazards and logistic regression. RESULTS: There were 47 tumors (25 primary, 22 metastatic) treated with median follow-up of 11.1 months. Mean diameter before treatment was 2.4 cm, and an average of 2.1 cryoprobes were used per procedure. Major complications (most commonly, pneumothorax requiring chest tube) occurred in 12 (25%) cases, and minor complications occurred in 13 (27%) cases. Median time to local progression was 14 months (16 mo for primary tumors and 10 mo for metastatic tumors), and median overall survival was 33 months (43 mo for patients with primary tumors and 22 mo for patients with metastatic tumors). On multivariate analysis, tumor diameter > 3 cm was associated with local progression (hazard ratio = 3.2, P = .013), and use of multiple cryoprobes (relative risk [RR] = 7.2, P = .045) and previous local therapy (RR = 15, P = .030) were associated with major complications. CONCLUSIONS: Percutaneous cryoablation of lung tumors is technically feasible with a complication rate comparable to other percutaneous ablation techniques. Percutaneous cryoablation is more efficacious and has fewer complications when offered to patients with small, previously untreated lesions.

Utility of Readmission Rates as a Quality of Care Measure and Predictors of Readmission Within 30 Days After Spinal Surgery: a Single-Center, Multivariate Analysis.

STUDY DESIGN: A retrospective review. OBJECTIVE: The aim of this study was to establish clinically relevant readmission rates that permit accurate comparisons, improve risk-stratification, and direct efforts to minimize readmissions. SUMMARY OF BACKGROUND DATA: The 30-day hospital readmission rate is a quality of care measure that is now being used to compare hospitals in a publicly available manner. METHODS: Records from 1187 consecutive spinal surgeries at Northwestern Memorial Hospital in 2010 were retrospectively reviewed and data were collected that described the patient, surgical procedure, hospital course, complications, and readmissions. The primary outcome of interest was readmission to the hospital within 30 days. Potential risk factors were examined for association with the outcome first via bivariate analysis, with significant predictors further examined by a multivariable model. Identified readmissions were independently reviewed by attending spinal neurosurgeons not involved with the cases to determine whether the readmissions were procedure related or procedure unrelated with respect to accepted criteria. RESULTS: The overall readmission rate was 6.1%. Of these readmissions, 37.5% were deemed procedure related upon attending review, leading to a procedure-related readmission rate of 2.3%. Upon multivariate analysis, only 3 variables were found to be significant predictors of readmission: 2 or more patient comorbidities [odds ratio (OR) 3.72, 95% confidence interval (95% CI) 1.62-8.56], an admission to the ICU (OR 2.68, 95% CI 1.45-4.95), and each additional spinal level involved (OR 1.11, 95% CI 1.02-1.21). CONCLUSIONS: Our study suggests that predictors for all-cause 30-day readmission following spinal procedures include number of spinal levels performed during the surgery, number of patient comorbidities present at the time of surgery, and whether the admission required an ICU stay. Future work should focus on developing best practices to modify medical risk factors and comorbidities that have the potential to decrease 30-day readmission rates. LEVEL OF EVIDENCE: 3.

MR imaging enables measurement of therapeutic nanoparticle uptake in rat N1-S1 liver tumors after nanoablation.

PURPOSE: To test the hypothesis that magnetic resonance (MR) imaging can quantify intratumoral superparamagnetic iron oxide (SPIO) nanoparticle uptake after nanoablation. MATERIALS AND METHODS: SPIO nanoparticles functionalized with doxorubicin were synthesized. N1-S1 hepatomas were successfully induced in 17 Sprague-Dawley rats distributed into three dosage groups. Baseline tumor R2* values (the reciprocal of T2*) were determined using 7-tesla (T) MR imaging. After intravenous injection of SPIO nanoparticles, reversible electroporation (1,300 V/cm, 8 pulses, 100-µs pulse duration) was applied. Imaging of rats was performed to determine tumor R2* values after the procedure, and change in R2* (ΔR2*) was calculated. Inductively coupled plasma mass spectrometry was used to determine intratumoral iron (Fe) concentration after the procedure, which served as a proxy for SPIO nanoparticle uptake. Mean tumor Fe concentration [Fe] and ΔR2* for each subject were assessed for correlation with linear regression, and mean [Fe] for each dosage group was compared with analysis of variance. RESULTS: ΔR2* significantly correlated with tumor SPIO nanoparticle uptake after nanoablation (r = 0.50, P = .039). On average, each 0.1-ms(-1) increase in R2* corresponded to a 0.1394-mM increase in [Fe]. There was no significant difference in mean SPIO nanoparticle uptake among dosage groups (P = .57). CONCLUSIONS: Intratumoral SPIO nanoparticle uptake after nanoablation can be successfully quantified noninvasively with 7-T MR imaging. Imaging can be used as a method to estimate localized drug delivery after nanoablation.

Seven-tesla magnetic resonance imaging accurately quantifies intratumoral uptake of therapeutic nanoparticles in the McA rat model of hepatocellular carcinoma: preclinical study in a rodent model.

OBJECTIVES: After inducing McA tumors in Sprague-Dawley rats (McA-SD), the following hypotheses were tested: first, that hypervascular McA tumors grown in Sprague-Dawley rats provide a suitable platform to investigate drug delivery; and second, that high-field MRI can be used to measure intratumoral uptake of DOX-SPIOs. MATERIALS AND METHODS: McA cells were implanted into the livers of 18 Sprague-Dawley rats. In successfully inoculated animals, 220-µL DOX-SPIOs were delivered to tumors via the intravenous or intra-arterial route. Pretreatment and posttreatment T2*-weighted images were obtained using 7-T MRI, and change in R2* value (ΔR2*) was obtained from mean signal intensities of tumors in these images. Tumor iron concentration ([Fe]), an indicator of DOX-SPIO uptake, was measured using mass spectroscopy. The primary outcome variable was the Pearson correlation between ΔR2* and [Fe]. RESULTS: Tumors grew successfully in 13 of the 18 animals (72%). Mean (SD) maximum tumor diameter was 0.83 (0.25) cm. The results of phantom studies revealed a strong positive correlation between ΔR2* and [Fe], with r = 0.98 (P < 0.01). The results of in vivo drug uptake studies demonstrated a positive correlation between ΔR2* and [Fe], with r = 0.72 (P = 0.0004). CONCLUSIONS: The McA tumors grown in the Sprague-Dawley rats demonstrated uptake of nanoparticle-based therapeutic agents. Magnetic resonance imaging quantification of intratumoral uptake strongly correlated with iron concentrations in pathological specimens, suggesting that MRI may be used to quantify uptake of iron-oxide nanotherapeutics.

Image-guided local delivery strategies enhance therapeutic nanoparticle uptake in solid tumors.

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.

Quantifying functional group interactions that determine urea effects on nucleic acid helix formation.

Urea destabilizes helical and folded conformations of nucleic acids and proteins, as well as protein-nucleic acid complexes. To understand these effects, extend previous characterizations of interactions of urea with protein functional groups, and thereby develop urea as a probe of conformational changes in protein and nucleic acid processes, we obtain chemical potential derivatives (µ23 = dµ2/dm3) quantifying interactions of urea (component 3) with nucleic acid bases, base analogues, nucleosides, and nucleotide monophosphates (component 2) using osmometry and hexanol-water distribution assays. Dissection of these µ23 values yields interaction potentials quantifying interactions of urea with unit surface areas of nucleic acid functional groups (heterocyclic aromatic ring, ring methyl, carbonyl and phosphate O, amino N, sugar (C and O); urea interacts favorably with all these groups, relative to interactions with water. Interactions of urea with heterocyclic aromatic rings and attached methyl groups (as on thymine) are particularly favorable, as previously observed for urea-homocyclic aromatic ring interactions. Urea m-values determined for double helix formation by DNA dodecamers near 25 °C are in the range of 0.72-0.85 kcal mol(-1)m(-1) and exhibit little systematic dependence on nucleobase composition (17-42% GC). Interpretation of these results using the urea interaction potentials indicates that extensive (60-90%) stacking of nucleobases in the separated strands in the transition region is required to explain the m-value. Results for RNA and DNA dodecamers obtained at higher temperatures, and literature data, are consistent with this conclusion. This demonstrates the utility of urea as a quantitative probe of changes in surface area (ΔASA) in nucleic acid processes.