In vitro clearance of doxorubicin with a DNA-based filtration device designed for intravascular use with intra-arterial chemotherapy.

To report a novel method using immobilized DNA within mesh to sequester drugs that have intrinsic DNA binding characteristics directly from flowing blood. DNA binding experiments were carried out in vitro with doxorubicin in saline (PBS solution), porcine serum, and porcine blood. Genomic DNA was used to identify the concentration of DNA that shows optimum binding clearance of doxorubicin from solution. Doxorubicin binding kinetics by DNA enclosed within porous mesh bags was evaluated. Flow model simulating blood flow in the inferior vena cava was used to determine in vitro binding kinetics between doxorubicin and DNA. The kinetics of doxorubicin binding to free DNA is dose-dependent and rapid, with 82-96 % decrease in drug concentration from physiologic solutions within 1 min of reaction time. DNA demonstrates faster binding kinetics by doxorubicin as compared to polystyrene resins that use an ion exchange mechanism. DNA contained within mesh yields an approximately 70 % decrease in doxorubicin concentration from solution within 5 min. In the IVC flow model, there is a 70 % drop in doxorubicin concentration at 60 min. A DNA-containing ChemoFilter device can rapidly clear clinical doses of doxorubicin from a flow model in simple and complex physiological solutions, thereby suggesting a novel approach to reduce the toxicity of DNA-binding drugs.

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.

Accuracy of flat panel detector CT with integrated navigational software with and without MR fusion for single-pass needle placement.

PURPOSE: Fluoroscopic systems in modern interventional suites have the ability to perform flat panel detector CT (FDCT) with navigational guidance. Fusion with MR allows navigational guidance towards FDCT occult targets. We aim to evaluate the accuracy of this system using single-pass needle placement in a deep brain stimulation (DBS) phantom. MATERIALS AND METHODS: MR was performed on a head phantom with DBS lead targets. The head phantom was placed into fixation and FDCT was performed. FDCT and MR datasets were automatically fused using the integrated guidance system (iGuide, Siemens). A DBS target was selected on the MR dataset. A 10 cm, 19 G needle was advanced by hand in a single pass using laser crosshair guidance. Radial error was visually assessed against measurement markers on the target and by a second FDCT. Ten needles were placed using CT-MR fusion and 10 needles were placed without MR fusion, with targeting based solely on FDCT and fusion steps repeated for every pass. RESULTS: Mean radial error was 2.75±1.39 mm as defined by visual assessment to the centre of the DBS target and 2.80±1.43 mm as defined by FDCT to the centre of the selected target point. There were no statistically significant differences in error between MR fusion and non-MR guided series. CONCLUSIONS: Single pass needle placement in a DBS phantom using FDCT guidance is associated with a radial error of approximately 2.5-3.0 mm at a depth of approximately 80 mm. This system could accurately target sub-centimetre intracranial lesions defined on MR.

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.

Closed bore XMR (CBXMR) systems for aortic valve replacement: active magnetic shielding of x-ray tubes.

Hybrid closed bore x-ray/MRI systems are being developed to improve the safety and efficacy of percutaneous aortic valve replacement procedures by harnessing the complementary strengths of the x-ray and MRI modalities in a single interventional suite without requiring patient transfer between two rooms. These systems are composed of an x-ray C-arm in close proximity (approximately 1 m) to an MRI scanner. The MRI magnetic fringe field can cause the electron beam in the x-ray tube to deflect. The deflection causes the x-ray field of view to shift position on the detector receptacle. This could result in unnecessary radiation exposure to the patient and the staff in the cardiac catheterization laboratory. Therefore, the electron beam deflection must be corrected. The authors developed an active magnetic shielding system that can correct for electron beam deflection to within an accuracy of 5% without truncating the field of view or increasing exposure to the patient. This system was able to automatically adjust to different field strengths as the external magnetic field acting on the x-ray tube was changed. Although a small torque was observed on the shielding coils of the active shielding system when they were placed in a magnetic field, this torque will not impact their performance if they are securely mounted on the x-ray tube and the C-arm. The heating of the coils of the shielding system for use in the clinic caused by electric current was found to be slow enough not to require a dedicated cooling system for one percutaneous aortic valve replacement procedure. However, a cooling system will be required if multiple procedures are performed in one session.

Closed-bore XMR (CBXMR) systems for aortic valve replacement: x-ray tube imaging performance.

A hybrid closed-bore x-ray/MRI system (CBXMR) is proposed to improve the safety and efficacy of percutaneous aortic valve replacement procedures. In this system, an x-ray C-arm will be positioned about 1 m from the entrance of a 1.5 T MRI scanner. The CBXMR system will harness the complementary strengths of both modalities to guide and deploy a bioprosthetic valve into the aortic annulus of the heart without coronary artery obstruction. A major challenge in constructing this system is ensuring proper operation of a rotating-anode x-ray tube in the MRI magnetic fringe field environment. The electron beam in the x-ray tube responsible for producing x rays can be deflected by the fringe field. However, the clinical impact of electron beam deflection in a magnetic field has not yet been studied. Here, the authors investigated changes in focal spot resolving power, field of view shift, and field of view truncation in x-ray images as a result of electron beam deflection. The authors found that in the fringe field acting on the x-ray tube at the clinical location for the x-ray C-arm (4 mT), focal spot size increased by only 2%, so the fringe field did not limit the resolving power of the x-ray system. The magnetic field also caused the field of view to shift by 3 mm. This shift must be corrected to avoid unnecessary primary radiation exposure to the patient and the staff in the cardiac catheterization laboratory. The fringe field was too weak to cause field of view truncation.

Closed bore XMR (CBXMR) systems for aortic valve replacement: investigation of rotating-anode x-ray tube heat loadability.

In order to improve the safety and efficacy of percutaneous aortic valve replacement procedures, a closed bore hybrid x-ray/MRI (CBXMR) system is proposed in which an x-ray C-arm will be positioned with its isocenter approximately =1 m from the entrance of a clinical MRI scanner. This system will harness the complementary strengths of both modalities to improve clinical outcome. A key component of the CBXMR system will be a rotating anode x-ray tube to produce high-quality x-ray images. There are challenges in positioning an x-ray tube in the magnetic fringe field of the MRI magnet. Here, the effects of an external magnetic field on x-ray tube induction motors of radiography x-ray tubes and the corresponding reduction of x-ray tube heat loadability are investigated. Anode rotation frequency f(aode) was unaffected when the external magnetic field Bb was parallel to the axis of rotation of the anode but decreased when Bb was perpendicular to the axis of rotation. The experimental f(anode) values agreed with predicted values to within +/-3% over a Bb range of 0-30 mT. The MRI fringe field at the proposed location of the x-ray tube mounted on the C-arm (approximately =4 mT) reduced f(anode) by only 1%, so x-ray tube heat loadability will not be compromised when using CBXMR systems for percutaneous aortic valve replacement procedures. Eddy current heating power in the rotor due to an MRI fringe field was found to be two orders of magnitude weaker than the heating power produced on the anode due to a fluoroscopic exposure, so eddy current heating had no effect on x-ray tube heat loadability.