Jeffrey K. Yang

Development and Validation of Endovascular Chemotherapy Filter Device for Removing High-Dose Doxorubicin: Preclinical Study

To develop a novel endovascular chemotherapy filter (CF) able to remove excess drug from the blood during intra-arterial chemotherapy delivery (IAC), thus preventing systemic toxicities and thereby enabling higher dose IAC. A flow circuit containing 2.5 mL of ion-exchange resin was constructed. Phosphate-buffered saline (PBS) containing 50 mg doxorubicin (Dox) was placed in the flow model with the hypothesis that doxorubicin would bind rapidly to resin. To simulate IAC, 50 mg of doxorubicin was infused over 10 min into the flow model containing resin. Similar testing was repeated with porcine serum. Doxorubicin concentrations were measured over 60 min and compared to controls (without resin). Single-pass experiments were also performed. Based on these experiments, an 18F CF was constructed with resin in its tip. In a pilot porcine study, the device was deployed under fluoroscopy. A control hepatic doxorubicin IAC model (no CF placed) was developed in another animal. A second CF device was created with a resin membrane and tested in the infrarenal inferior vena cava (IVC) of a swine. In the PBS model, resin bound 76% of doxorubicin in 10 min, and 92% in 30 min (P < 0.001). During IAC simulation, 64% of doxorubicin bound in 10 min and 96% in 60 min (P < 0.001). On average, 51% of doxorubicin concentration was reduced during each pass in single pass studies. In porcine serum, 52% of doxorubicin bound in 10 min, and 80% in 30 min (P < 0.05). CF device placement and administration of IAC were successful in three animals. No clot was present on the resin within the CF following the in vivo study. The infrarenal IVC swine study demonstrated promising results with up to 85% reduction in peak concentration by the CF device. An endovascular CF device was developed and shown feasible in vitro. An in vivo model was established with promising results supporting high-capacity rapid doxorubicin filtration from the blood that can be further evaluated in future studies.

In Vitro Capture of Small Ferrous Particles with a Magnetic Filtration Device Designed for Intravascular Use with Intraarterial Chemotherapy: Proof-of-Concept Study.

PURPOSE To establish that a magnetic device designed for intravascular use can bind small iron particles in physiologic flow models. MATERIALS AND METHODS Uncoated iron oxide particles 50-100 nm and 1-5 µm in size were tested in a water flow chamber over a period of 10 minutes without a magnet (ie, control) and with large and small prototype magnets. These same particles and 1-µm carboxylic acid-coated iron oxide beads were likewise tested in a serum flow chamber model without a magnet (ie, control) and with the small prototype magnet. RESULTS Particles were successfully captured from solution. Particle concentrations in solution decreased in all experiments (P < .05 vs matched control runs). At 10 minutes, concentrations were 98% (50-100-nm particles in water with a large magnet), 97% (50-100-nm particles in water with a small magnet), 99% (1-5-µm particles in water with a large magnet), 99% (1-5-µm particles in water with a small magnet), 95% (50-100-nm particles in serum with a small magnet), 92% (1-5-µm particles in serum with a small magnet), and 75% (1-µm coated beads in serum with a small magnet) lower compared with matched control runs. CONCLUSIONS This study demonstrates the concept of magnetic capture of small iron oxide particles in physiologic flow models by using a small wire-mounted magnetic filter designed for intravascular use.

Global Spinal Alignment in Cervical Kyphotic Deformity: The Importance of Head Position and Thoracolumbar Alignment in the Compensatory Mechanism

BACKGROUND Previous studies have evaluated cervical kyphosis (C-kypho) using cervical curvature or chin-brow vertical angle, but the relationship between C-kypho and global spinal alignment is currently unknown. OBJECTIVE To elucidate global spinal alignment and compensatory mechanisms in primary symptomatic C-kypho using full-spine radiography. METHODS In this retrospective multicenter study, symptomatic primary C-kypho patients (Cerv group; n = 103) and adult thoracolumbar deformity patients (TL group; n = 119) were compared. We subanalyzed Cerv subgroups according to sagittal vertical axis (SVA) values of C7 (SVAC7 positive or negative [C7P or C7N]). Various Cobb angles (°) and SVAs (mm) were evaluated. RESULTS SVAC7 values were -20.2 and 63.6 mm in the Cerv group and TL group, respectively (P < .0001). Various statistically significant compensatory curvatures were observed in the Cerv group, namely larger lumbar lordosis (LL) and thoracic kyphosis. The C7N group had significantly lower SVACOG (center of gravity of the head) and SVAC7 (32.9 and -49.5 mm) values than the C7P group (115.9 and 45.1 mm). Sagittal curvatures were also different in T4-12, T10-L2, LL4-S, and LL. The value of pelvic incidence (PI)-LL was different (C7N vs C7P; -2.2° vs 9.9°; P < .0003). Compensatory sagittal curvatures were associated with potential for shifting of SVAC7 posteriorly to adjust head position. PI-LL affected these compensatory mechanisms. CONCLUSION Compensation in symptomatic primary C-kypho was via posterior shifting of SVAC7, small T1 slope, and large LL. However, even in C-kypho patients, lumbar degeneration might affect global spinal alignment. Thus, global spinal alignment with cervical kyphosis is characterized as head balanced or trunk balanced.

O-016 Development and Validation of an Endovascular Chemotherapy Filter Device for Removing High-Dose Doxorubicin from the Blood: In Vivo Porcine Study

Purpose A novel disposable endovascular chemotherapy filter (CF) device was developed to remove excess doxorubicin (Dox) from the blood during intra-arterial chemotherapy delivery to prevent systemic toxicities. Previous proof-of-concept established the capacity of the filter to bind Dox in swine serum in vitro. In this study, CF navigation, deployment and in vivo Dox binding was evaluated in the porcine inferior vena cava (IVC). Materials and methods An 18 Fr CF device was constructed with an ion-exchange membrane attached to an expandable 28 mm diameter Nitinol frame. Under X-ray fluoroscopy and contrast venography, the CF was percutaneously introduced via the internal jugular vein and deployed in the porcine infrarenal IVC. 50 mg of Dox (2 mg/ml) was injected over 10 min in the IVC below the CF device. Venous catheters with tips proximal and distal to the CF device in the infrarenal IVC obtained pressures and blood samples for Dox concentrations over 90 min across the CF device membrane. Results The CF device was successfully introduced and deployed in the infrarenal IVC in vivo. Visualization under X-ray fluoroscopy verified the proper placement and mechanical expansion of the Nitinol framework. In a 90 min study, the device was biocompatible, not leading to hemodynamic disturbances: pressure measurements taken throughout the experiment yielded a max gradient of 17 mmHg across the CF membrane. Venography demonstrated non-flow-limiting thrombus associated with the CF device after 90 min of deployment (swine were not heparinized). Significant Dox binding was noted with an 85%, 74%, and 83% decrease in relative pre- versus post-filter Dox concentrations at times 3, 10, and 30 min, respectively after Dox injection. Conclusion: We developed a biocompatible CF device that can be safely introduced, deployed, and removed from the IVC in vivo. The CF device demonstrated significant Dox binding, and could serve as a platform technology in drug therapy to allow for higher regional doses of drug while limiting systemic toxicity. In future in vivo experiments, animals or the CF device itself may be heparinized in order to prevent thrombosis. When fully developed, indications for this device could include head and neck cancer, with the device deployed in the superior vena cava or internal jugular veins during selective IA chemotherapy. Disclosures A. Patel: 1; C; NIH-NCI. 4; C; ChemoFilter. A. Chin: 1; C; NIH-NCI. 4; C; ChemoFilter. J. Yang: None. B. Thorne: None. M. Saeed: None. M. Wilson: 1; C; NIH-NIBIB, NIH-NCI. 4; C; ChemoFilter. S. Hetts: 1; C; NIH-NIBIB, NIH-NCI, Siemens, Covidien. 2; C; Stryker, Penumbra, Silk Road Medical, Medina Medical. 4; C; ChemoFilter, Medina Medical, DriftCoast.

Endovascular MR-guided Renal Embolization by Using a Magnetically Assisted Remote-controlled Catheter System

Purpose To assess the feasibility of a magnetically assisted remote-controlled (MARC) catheter system under magnetic resonance (MR) imaging guidance for performing a simple endovascular procedure (ie, renal artery embolization) in vivo and to compare with x-ray guidance to determine the value of MR imaging guidance and the specific areas where the MARC system can be improved. Materials and Methods In concordance with the Institutional Animal Care and Use Committee protocol, in vivo renal artery navigation and embolization were tested in three farm pigs (mean weight 43 kg ± 2 [standard deviation]) under real-time MR imaging at 1.5 T. The MARC catheter device was constructed by using an intramural copper-braided catheter connected to a laser-lithographed saddle coil at the distal tip. Interventionalists controlled an in-room cart that delivered electrical current to deflect the catheter in the MR imager. Contralateral kidneys were similarly embolized under x-ray guidance by using standard clinical catheters and guidewires. Changes in renal artery flow and perfusion were measured before and after embolization by using velocity-encoded and perfusion MR imaging. Catheter navigation times, renal parenchymal perfusion, and renal artery flow rates were measured for MR-guided and x-ray-guided embolization procedures and are presented as means ± standard deviation in this pilot study. Results Embolization was successful in all six kidneys under both x-ray and MR imaging guidance. Mean catheterization time with MR guidance was 93 seconds ± 56, compared with 60 seconds ± 22 for x-ray guidance. Mean changes in perfusion rates were 4.9 au/sec ± 0.8 versus 4.6 au/sec ± 0.6, and mean changes in renal flow rate were 2.1 mL/min/g ± 0.2 versus 1.9 mL/min/g ± 0.2 with MR imaging and x-ray guidance, respectively. Conclusion The MARC catheter system is feasible for renal artery catheterization and embolization under real-time MR imaging in vivo, and quantitative physiologic measures under MR imaging guidance were similar to those measured under x-ray guidance, suggesting that the MARC catheter system could be used for endovascular procedures with interventional MR imaging. (©) RSNA, 2016.

Interventional magnetic resonance imaging guided carotid embolectomy using a novel resonant marker catheter: demonstration of preclinical feasibility

To assess the visualization and efficacy of a wireless resonant circuit (wRC) catheter system for carotid artery occlusion and embolectomy under real-time MRI guidance in vivo, and to compare MR imaging modality with x-ray for analysis of qualitative physiological measures of blood flow at baseline and after embolectomy. The wRC catheter system was constructed using a MR compatible PEEK fiber braided catheter (Penumbra, Inc, Alameda, CA) with a single insulated longitudinal copper loop soldered to a printed circuit board embedded within the catheter wall. In concordance with IACUC protocol (AN103047), in vivo carotid artery navigation and embolectomy were performed in four farm pigs (40–45 kg) under real-time MRI at 1.5T. Industry standard clots were introduced in incremental amounts until adequate arterial occlusion was noted in a total of n=13 arteries. Baseline vasculature and restoration of blood flow were confirmed via MR and x-ray imaging, and graded by the Thrombolysis in Cerebral Infarction (TICI) scale. Wilcoxon signed-rank tests were used to analyze differences in recanalization status between DSA and MRA imaging. Successful recanalizations (TICI 2b/3) were compared to clinical rates reported in literature via binomial tests. The wRC catheter system was visible both on 5° sagittal bSSFP and coronal GRE sequence. Successful recanalization was demonstrated in 11 of 13 occluded arteries by DSA analysis and 8 of 13 by MRA. Recanalization rates based on DSA (0.85) and MRA (0.62) were not significantly different from the clinical rate of mechanical aspiration thrombectomy reported in literature. Lastly, a Wilcoxon signed rank test indicated no significant difference between TICI scores analyzed by DSA and MRA. With demonstrated compatibility and visualization under MRI, the wRC catheter system is effective for in vivo endovascular embolectomy, suggesting progress towards clinical endovascular interventional MRI.