The Xyrem® (Sodium Oxybate) Risk Evaluation and Mitigation Strategy (REMS) Program in the USA: Results From 2016 to 2017.

BACKGROUND: Sodium oxybate, which is approved for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy, is available in the USA only through the restricted-distribution Xyrem® Risk Evaluation and Mitigation Strategy Program (Xyrem REMS Program, XRP). The XRP requires prescriber enrollment and certification, patient enrollment, and prescriber attestation of patient counseling. Sodium oxybate is dispensed only by the certified pharmacy. After pharmacist/patient counseling, sodium oxybate is shipped only to enrolled patients, with documentation of safe use. Documentation of enrollments, prescriptions, counseling, shipments, and adverse events in a central database, and risk management reporting of any suspicion of abuse, misuse, or diversion, ensure provider notification and facilitate monitoring. OBJECTIVE: This analysis reports data from the XRP regarding assessment of the risks of serious adverse outcomes that may result from inappropriate prescribing, abuse, misuse, and diversion. METHODS: Data collected from December 2016 to December 2017 were analyzed. RESULTS: Prescriptions were from enrolled prescribers (n = 4524); 17,037 patients received one or more shipment of sodium oxybate. No patients were shipped sodium oxybate under more than one name/identifier or after being disenrolled; no individual patient had overlapping active prescriptions. Sodium oxybate was dispensed in 146,426 shipments containing 375,173 bottles; of those, 13 shipments (0.009%) and 26 bottles (0.007%) were lost in delivery and not recovered. Notifications regarding potential abuse (n = 31), misuse (n = 343), or diversion (n = 22) were discussed with prescribers. Most patients and prescribers were aware of the main safety risks of sodium oxybate. CONCLUSIONS: The XRP maintains controlled access to sodium oxybate; additional prescriber education on safety risks may be warranted.

Design of catheter radio frequency coils using coaxial transmission line resonators for interventional neurovascular MR imaging.

BACKGROUND: It is technically challenging to design compact yet sensitive miniature catheter radio frequency (RF) coils for endovascular interventional MR imaging. METHODS: In this work, a new design method for catheter RF coils is proposed based on the coaxial transmission line resonator (TLR) technique. Due to its distributed circuit, the TLR catheter coil does not need any lumped capacitors to support its resonance, which simplifies the practical design and construction and provides a straightforward technique for designing miniature catheter-mounted imaging coils that are appropriate for interventional neurovascular procedures. The outer conductor of the TLR serves as an RF shield, which prevents electromagnetic energy loss, and improves coil Q factors. It also minimizes interaction with surrounding tissues and signal losses along the catheter coil. To investigate the technique, a prototype catheter coil was built using the proposed coaxial TLR technique and evaluated with standard RF testing and measurement methods and MR imaging experiments. Numerical simulation was carried out to assess the RF electromagnetic field behavior of the proposed TLR catheter coil and the conventional lumped-element catheter coil. RESULTS: The proposed TLR catheter coil was successfully tuned to 64 MHz for proton imaging at 1.5 T. B1 fields were numerically calculated, showing improved magnetic field intensity of the TLR catheter coil over the conventional lumped-element catheter coil. MR images were acquired from a dedicated vascular phantom using the TLR catheter coil and also the system body coil. The TLR catheter coil is able to provide a significant signal-to-noise ratio (SNR) increase (a factor of 200 to 300) over its imaging volume relative to the body coil. CONCLUSIONS: Catheter imaging RF coil design using the proposed coaxial TLR technique is feasible and advantageous in endovascular interventional MR imaging applications.

Intra-Arterial MR Perfusion Imaging of Meningiomas: Comparison to Digital Subtraction Angiography and Intravenous MR Perfusion Imaging.

BACKGROUND AND PURPOSE: To evaluate the ability of IA MR perfusion to characterize meningioma blood supply. METHODS: Studies were performed in a suite comprised of an x-ray angiography unit and 1.5T MR scanner that permitted intraprocedural patient movement between the imaging modalities. Patients underwent intra-arterial (IA) and intravenous (IV) T2* dynamic susceptibility MR perfusion immediately prior to meningioma embolization. Regional tumor arterial supply was characterized by digital subtraction angiography and classified as external carotid artery (ECA) dural, internal carotid artery (ICA) dural, or pial. MR perfusion data regions of interest (ROIs) were analyzed in regions with different vascular supply to extract peak height, full-width at half-maximum (FWHM), relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), and mean transit time (MTT). Linear mixed modeling was used to identify perfusion curve parameter differences for each ROI for IA and IV MR imaging techniques. IA vs. IV perfusion parameters were also directly compared for each ROI using linear mixed modeling. RESULTS: 18 ROIs were analyzed in 12 patients. Arterial supply was identified as ECA dural (n = 11), ICA dural (n = 4), or pial (n = 3). FWHM, rCBV, and rCBF showed statistically significant differences between ROIs for IA MR perfusion. Peak Height and FWHM showed statistically significant differences between ROIs for IV MR perfusion. RCBV and MTT were significantly lower for IA perfusion in the Dural ECA compared to IV perfusion. Relative CBF in IA MR was found to be significantly higher in the Dural ICA region and MTT significantly lower compared to IV perfusion.

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.

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.

Magnetic Resonance-Guided Passive Catheter Tracking for Endovascular Therapy.

The use of MR guidance for endovascular intervention is appealing because of its lack of ionizing radiation, high-contrast visualization of vessel walls and adjacent soft tissues, multiplanar capabilities, and potential to incorporate functional information such as flow, fluid dynamics, perfusion, and cardiac motion. This review highlights state-of-the-art imaging techniques and hardware used for passive tracking of endovascular devices in interventional MR imaging, including negative contrast, passive contrast, nonproton multispectral, and direct current techniques. The advantages and disadvantages of passive tracking relative to active tracking are also summarized.

New-Generation Laser-lithographed Dual-Axis Magnetically Assisted Remote-controlled Endovascular Catheter for Interventional MR Imaging: In Vitro Multiplanar Navigation at 1.5 T and 3 T versus X-ray Fluoroscopy.

PURPOSE: To assess the feasibility of multiplanar vascular navigation with a new magnetically assisted remote-controlled (MARC) catheter with real-time magnetic resonance (MR) imaging at 1.5 T and 3 T and to compare it with standard x-ray guidance in simulated endovascular catheterization procedures. MATERIALS AND METHODS: A 1.6-mm-diameter custom clinical-grade microcatheter prototype with lithographed double-saddle coils at the distal tip was deflected with real-time MR imaging. Two inexperienced operators and two experienced operators catheterized anteroposterior (celiac, superior mesenteric, and inferior mesenteric arteries) and mediolateral (renal arteries) branch vessels in a cryogel abdominal aortic phantom. This was repeated with conventional x-ray fluoroscopy by using clinical catheters and guidewires. Mean procedure times and percentage success data were analyzed with linear mixed-effects regression. RESULTS: The MARC catheter tip was visible at 1.5 T and 3 T. Among inexperienced operators, MARC MR imaging guidance was not statistically different from x-ray guidance at 1.5 T (67% successful vessel selection turns with MR imaging vs 76% with x-ray guidance, P = .157) and at 3 T (75% successful turns with MR imaging vs 76% with x-ray guidance, P = .869). Experienced operators were more successful in catheterizing vessels with x-ray guidance (98% success within 60 seconds) than with 1.5-T (65%, P < .001) or 3-T (75%) MR imaging. Among inexperienced operators, mean procedure time was nearly equivalent by using MR imaging (31 seconds) and x-ray guidance (34 seconds, P = .436). Among experienced operators, catheterization was faster with x-ray guidance (20 seconds) compared with 1.5-T MR imaging (42 seconds, P < .001), but MARC guidance improved at 3 T (31 seconds). MARC MR imaging guidance at 3 T was not significantly different from x-ray guidance for the celiac (P = .755), superior mesenteric (P = .358), and inferior mesenteric (P = .065) arteries. CONCLUSION: Multiplanar navigation with a new MARC catheter with real-time MR imaging at 1.5 T and 3 T is feasible and comparable to x-ray guidance for anteroposterior vessels at 3 T in a vascular phantom.

Digital subtraction MR angiography roadmapping for magnetic steerable catheter tracking.

PURPOSE: To develop a high temporal resolution MR imaging technique that could be used with magnetically assisted remote control (MARC) endovascular catheters. MATERIALS AND METHODS: A technique is proposed based on selective intra-arterial injections of dilute MR contrast at the beginning of a fluoroscopic MR angiography acquisition. The initial bolus of contrast is used to establish a vascular roadmap upon which MARC catheters can be tracked. The contrast to noise ratio (CNR) of the achieved roadmap was assessed in phantoms and in a swine animal model. The ability of the technique to permit navigation of activated MARC catheters through arterial branch points was evaluated. RESULTS: The roadmapping mode proved effective in phantoms for tracking objects and achieved a CNR of 35.7 between the intra- and extra-vascular space. In vivo, the intra-arterial enhancement strategy produced roadmaps with a CNR of 42.0. The artifact produced by MARC catheter activation provided signal enhancement patterns on the roadmap that experienced interventionalists could track through vascular structures. CONCLUSION: A roadmapping approach with intra-arterial contrast-enhanced MR angiography is introduced for navigating the MARC catheter. The technique mitigates the artifact produced by the MARC catheter, greatly limits the required specific absorption rate, permits regular roadmap updates due to the low contrast agent requirements, and proved effective in the in vivo setting. Inc.

Electrostatic focal spot correction for x-ray tubes operating in strong magnetic fields.

PURPOSE: A close proximity hybrid x-ray/magnetic resonance (XMR) imaging system offers several critical advantages over current XMR system installations that have large separation distances (∼5 m) between the imaging fields of view. The two imaging systems can be placed in close proximity to each other if an x-ray tube can be designed to be immune to the magnetic fringe fields outside of the MR bore. One of the major obstacles to robust x-ray tube design is correcting for the effects of the MR fringe field on the x-ray tube focal spot. Any fringe field component orthogonal to the x-ray tube electric field leads to electron drift altering the path of the electron trajectories. METHODS: The method proposed in this study to correct for the electron drift utilizes an external electric field in the direction of the drift. The electric field is created using two electrodes that are positioned adjacent to the cathode. These electrodes are biased with positive and negative potential differences relative to the cathode. The design of the focusing cup assembly is constrained primarily by the strength of the MR fringe field and high voltage standoff distances between the anode, cathode, and the bias electrodes. From these constraints, a focusing cup design suitable for the close proximity XMR system geometry is derived, and a finite element model of this focusing cup geometry is simulated to demonstrate efficacy. A Monte Carlo simulation is performed to determine any effects of the modified focusing cup design on the output x-ray energy spectrum. RESULTS: An orthogonal fringe field magnitude of 65 mT can be compensated for using bias voltages of +15 and -20 kV. These bias voltages are not sufficient to completely correct for larger orthogonal field magnitudes. Using active shielding coils in combination with the bias electrodes provides complete correction at an orthogonal field magnitude of 88.1 mT. Introducing small fields (<10 mT) parallel to the x-ray tube electric field in addition to the orthogonal field does not affect the electrostatic correction technique. However, rotation of the x-ray tube by 30° toward the MR bore increases the parallel magnetic field magnitude (∼72 mT). The presence of this larger parallel field along with the orthogonal field leads to incomplete correction. Monte Carlo simulations demonstrate that the mean energy of the x-ray spectrum is not noticeably affected by the electrostatic correction, but the output flux is reduced by 7.5%. CONCLUSIONS: The maximum orthogonal magnetic field magnitude that can be compensated for using the proposed design is 65 mT. Larger orthogonal field magnitudes cannot be completely compensated for because a pure electrostatic approach is limited by the dielectric strength of the vacuum inside the x-ray tube insert. The electrostatic approach also suffers from limitations when there are strong magnetic fields in both the orthogonal and parallel directions because the electrons prefer to stay aligned with the parallel magnetic field. These challenging field conditions can be addressed by using a hybrid correction approach that utilizes both active shielding coils and biasing electrodes.

Comparing deflection measurements of a magnetically steerable catheter using optical imaging and MRI.

PURPOSE: Magnetic resonance imaging (MRI) is an emerging modality for interventional radiology, giving clinicians another tool for minimally invasive image-guided interventional procedures. Difficulties associated with endovascular catheter navigation using MRI guidance led to the development of a magnetically steerable catheter. The focus of this study was to mechanically characterize deflections of two different prototypes of the magnetically steerable catheter in vitro to better understand their efficacy. METHODS: A mathematical model for deflection of the magnetically steerable catheter is formulated based on the principle that at equilibrium the mechanical and magnetic torques are equal to each other. Furthermore, two different image based methods for empirically measuring the catheter deflection angle are presented. The first, referred to as the absolute tip method, measures the angle of the line that is tangential to the catheter tip. The second, referred to the base to tip method, is an approximation that is used when it is not possible to measure the angle of the tangent line. Optical images of the catheter deflection are analyzed using the absolute tip method to quantitatively validate the predicted deflections from the mathematical model. Optical images of the catheter deflection are also analyzed using the base to tip method to quantitatively determine the differences between the absolute tip and base to tip methods. Finally, the optical images are compared to MR images using the base to tip method to determine the accuracy of measuring the catheter deflection using MR. RESULTS: The optical catheter deflection angles measured for both catheter prototypes using the absolute tip method fit very well to the mathematical model (R(2) = 0.91 and 0.86 for each prototype, respectively). It was found that the angles measured using the base to tip method were consistently smaller than those measured using the absolute tip method. The deflection angles measured using optical data did not demonstrate a significant difference from the angles measured using MR image data when compared using the base to tip method. CONCLUSIONS: This study validates the theoretical description of the magnetically steerable catheter, while also giving insight into different methods and modalities for measuring the deflection angles of the prototype catheters. These results can be used to mechanically model future iterations of the design. Quantifying the difference between the different methods for measuring catheter deflection will be important when making deflection measurements in future studies. Finally, MR images can be used to reliably measure deflection angles since there is no significant difference between the MR and optical measurements.

Magnetically assisted remote-controlled endovascular catheter for interventional MR imaging: in vitro navigation at 1.5 T versus X-ray fluoroscopy.

PURPOSE: To compare in vitro navigation of a magnetically assisted remote-controlled (MARC) catheter under real-time magnetic resonance (MR) imaging with manual navigation under MR imaging and standard x-ray guidance in endovascular catheterization procedures in an abdominal aortic phantom. MATERIALS AND METHODS: The 2-mm-diameter custom clinical-grade microcatheter prototype with a solenoid coil at the distal tip was deflected with a foot pedal actuator used to deliver 300 mA of positive or negative current. Investigators navigated the catheter into branch vessels in a custom cryogel abdominal aortic phantom. This was repeated under MR imaging guidance without magnetic assistance and under conventional x-ray fluoroscopy. MR experiments were performed at 1.5 T by using a balanced steady-state free precession sequence. The mean procedure times and percentage success data were determined and analyzed with a linear mixed-effects regression analysis. RESULTS: The catheter was clearly visible under real-time MR imaging. One hundred ninety-two (80%) of 240 turns were successfully completed with magnetically assisted guidance versus 144 (60%) of 240 turns with nonassisted guidance (P < .001) and 119 (74%) of 160 turns with standard x-ray guidance (P = .028). Overall mean procedure time was shorter with magnetically assisted than with nonassisted guidance under MR imaging (37 seconds ± 6 [standard error of the mean] vs 55 seconds ± 3, P < .001), and time was comparable between magnetically assisted and standard x-ray guidance (37 seconds ± 6 vs 44 seconds ± 3, P = .045). When stratified by angle of branch vessel, magnetic assistance was faster than nonassisted MR guidance at turns of 45°, 60°, and 75°. CONCLUSION: In this study, a MARC catheter for endovascular navigation under real-time MR imaging guidance was developed and tested. For catheterization of branch vessels arising at large angles, magnetically assisted catheterization was faster than manual catheterization under MR imaging guidance and was comparable to standard x-ray guidance.

Safety of retained microcatheters: an evaluation of radiofrequency heating in endovascular microcatheters with nitinol, tungsten, and polyetheretherketone braiding at 1.5 T and 3 T.

BACKGROUND: The use of ethylene-vinyl alcohol copolymer for liquid embolization of cranial vascular lesions has resulted in microcatheter fragments entrapped in patients following endovascular procedures. Undergoing subsequent diagnostic MRI examinations poses a safety concern due to the possibility of radiofrequency heating of the metallic braid incorporated into the microcatheter. Heating of nitinol, tungsten, and polyetheretherketone (PEEK) braided microcatheters was assessed and compared using a phantom model. METHODS: Microcatheters coupled with fluoroptic temperature probes were embedded in a polyacrylamide gel within a head and torso phantom. Experiments were performed at 1.5 T and 3 T, analyzing the effects of different catheter immersion lengths, specific absorption rate (SAR) levels, short clinical scans, long clinical scans, and microcatheter fragment lengths. RESULTS: The maximal increase in temperature for the nitinol braided microcatheter during a 15 min scan was 3.06°C using the T1 fast spin echo sequence at 1.5 T and 0.45°C using the balanced steady state free precession sequence at 3 T. The same scans for fragment lengths of 9, 18, 36, and 72 cm produced maximal temperature rises of 0.68, 0.80, 1.70, and 1.07°C at 1.5 T, respectively. The temperature changes at 3 T for these fragment lengths were 0.66, 0.83, 1.07, and 0.72°C, respectively. The tungsten and PEEK braided microcatheters did not demonstrate heating. CONCLUSIONS: Substantial heating of nitinol braided microcatheters occurred and was a function of SAR level and geometric considerations. SAR and time limitations on MR scanning are proposed for patients with this microcatheter entrapped in their vasculature. In contrast, tungsten and PEEK braided microcatheters showed potential safe use in MRI.

System architecture for a magnetically guided endovascular microcatheter.

Magnetic resonance imaging (MRI) guided minimally invasive interventions are an emerging technology. We developed a microcatheter that utilizes micro-electromagnets manufactured on the distal tip, in combination with the magnetic field of a MRI scanner, to perform microcatheter steering during endovascular surgery. The aim of this study was to evaluate a user control system for operating, steering and monitoring this magnetically guided microcatheter. The magnetically-assisted remote control (MARC) microcatheter was magnetically steered within a phantom in the bore of a 1.5 T MRI scanner. Controls mounted in an interventional MRI suite, along with a graphical user interface at the MRI console, were developed with communication enabled via MRI compatible hardware modules. Microcatheter tip deflection measurements were performed by evaluating MRI steady-state free precession (SSFP) images and compared to models derived from magnetic moment interactions and composite beam mechanics. The magnitude and direction of microcatheter deflections were controlled with user hand, foot, and software controls. Data from two different techniques for measuring the microcatheter tip location within a 1.5 T MRI scanner showed correlation of magnetic deflections to our model (R(2): 0.88) with a region of linear response (R(2): 0.98). Image processing tools were successful in autolocating the in vivo microcatheter tip within MRI SSFP images. Our system showed good correlation to response curves and introduced low amounts of MRI noise artifact. The center of the artifact created by the energized microcatheter solenoid was a reliable marker for determining the degree of microcatheter deflection and auto-locating the in vivo microcatheter tip.

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.

Design optimization of MR-compatible rotating anode x-ray tubes for stable operation.

PURPOSE: Hybrid x-ray/MR systems can enhance the diagnosis and treatment of endovascular, cardiac, and neurologic disorders by using the complementary advantages of both modalities for image guidance during interventional procedures. Conventional rotating anode x-ray tubes fail near an MR imaging system, since MR fringe fields create eddy currents in the metal rotor which cause a reduction in the rotation speed of the x-ray tube motor. A new x-ray tube motor prototype has been designed and built to be operated close to a magnet. To ensure the stability and safety of the motor operation, dynamic characteristics must be analyzed to identify possible modes of mechanical failure. In this study a 3D finite element method (FEM) model was developed in order to explore possible modifications, and to optimize the motor design. The FEM provides a valuable tool that permits testing and evaluation using numerical simulation instead of building multiple prototypes. METHODS: Two experimental approaches were used to measure resonance characteristics: the first obtained the angular speed curves of the x-ray tube motor employing an angle encoder; the second measured the power spectrum using a spectrum analyzer, in which the large amplitude of peaks indicates large vibrations. An estimate of the bearing stiffness is required to generate an accurate FEM model of motor operation. This stiffness depends on both the bearing geometry and adjacent structures (e.g., the number of balls, clearances, preload, etc.) in an assembly, and is therefore unknown. This parameter was set by matching the FEM results to measurements carried out with the anode attached to the motor, and verified by comparing FEM predictions and measurements with the anode removed. The validated FEM model was then used to sweep through design parameters [bearing stiffness (1 × 10(5)-5 × 10(7) N/m), shaft diameter (0.372-0.625 in.), rotor diameter (2.4-2.9 in.), and total length of motor (5.66-7.36 in.)] to increase the fundamental frequency past the operating range at 50 Hz. RESULTS: The first large vibration during the prototype motor operation was obtained at 21.64 ± 0.68 Hz in the power spectrum. An abrupt decrease in acceleration occurred at 21.5 Hz due to struggling against the resonance vibrations. A bearing stiffness of 1.2 × 10(5) N/m in the FEM simulation was used to obtain a critical speed of 21.4 Hz providing 1.1% error. This bearing stiffness value and the 3D model were then confirmed by the experiments with the anode removed, demonstrating an agreement within 6.4% between simulation results and measurements. A calculated first critical frequency (fundamental frequency) of 68.5 Hz was obtained by increasing the bearing stiffness to 1 × 10(7) N/m and increasing the shaft diameter by 68.0%. Reducing the number of bearings in the design permits decreasing the total length of the motor by 1.7 in., and results in a fundamental frequency of 68.3 Hz in concert with additional changes (shaft diameter of 0.625 in., rotor diameter of 2.4 in., and bearing stiffness of 1 × 10(6) N/m). CONCLUSIONS: An FEM model of the x-ray tube motor has been implemented and experimentally validated. A fundamental frequency above the operational rotation speed can be achieved through modification of multiple design parameters, which allows the motor to operate stably and safely in the MR environment during the repeated acceleration/deceleration cycles required for an interventional procedure. The validated 3D FEM model can now be used to investigate trade-offs between generated torque, maximum speed, and motor inertia to further optimize motor design.

Magnetic catheter manipulation in the interventional MR imaging environment.

PURPOSE: To evaluate deflection capability of a prototype endovascular catheter, which is remotely magnetically steerable, for use in the interventional magnetic resonance (MR) imaging environment. MATERIALS AND METHODS: Copper coils were mounted on the tips of commercially available 2.3-3.0-F microcatheters. The coils were fabricated in a novel manner by plasma vapor deposition of a copper layer followed by laser lithography of the layer into coils. Orthogonal helical (ie, solenoid) and saddle-shaped (ie, Helmholtz) coils were mounted on a single catheter tip. Microcatheters were tested in water bath phantoms in a 1.5-T clinical MR scanner, with variable simultaneous currents applied to the coils. Catheter tip deflection was imaged in the axial plane by using a "real-time" steady-state free precession MR imaging sequence. Degree of deflection and catheter tip orientation were measured for each current application. RESULTS: The catheter tip was clearly visible in the longitudinal and axial planes. Magnetic field artifacts were visible when the orthogonal coils at the catheter tip were energized. Variable amounts of current applied to a single coil demonstrated consistent catheter deflection in all water bath experiments. Changing current polarity reversed the observed direction of deflection, whereas current applied to two different coils resulted in deflection represented by the composite vector of individual coil activations. Microcatheter navigation through the vascular phantom was successful through control of applied current to one or more coils. CONCLUSIONS: Controlled catheter deflection is possible with laser lithographed multiaxis coil-tipped catheters in the MR imaging environment.

Magnetically-Assisted Remote Controlled Microcatheter Tip Deflection under Magnetic Resonance Imaging.

X-ray fluoroscopy-guided endovascular procedures have several significant limitations, including difficult catheter navigation and use of ionizing radiation, which can potentially be overcome using a magnetically steerable catheter under MR guidance. The main goal of this work is to develop a microcatheter whose tip can be remotely controlled using the magnetic field of the MR scanner. This protocol aims to describe the procedures for applying current to the microcoil-tipped microcatheter to produce consistent and controllable deflections. A microcoil was fabricated using laser lathe lithography onto a polyimide-tipped endovascular catheter. In vitro testing was performed in a waterbath and vessel phantom under the guidance of a 1.5-T MR system using steady-state free precession (SSFP) sequencing. Various amounts of current were applied to the coils of the microcatheter to produce measureable tip deflections and navigate in vascular phantoms. The development of this device provides a platform for future testing and opportunity to revolutionize the endovascular interventional MRI environment.

Novel motor design for rotating anode x-ray tubes operating in the fringe field of a magnetic resonance imaging system.

PURPOSE: Using hybrid x-ray∕MR (XMR) systems for image guidance during interventional procedures could enhance the diagnosis and treatment of neurologic, oncologic, cardiovascular, and other disorders. The authors propose a close proximity hybrid system design in which a C-arm fluoroscopy unit is placed immediately adjacent to the solenoid magnet of a MR system with a minimum distance of 1.2 m between the x-ray and MR imaging fields of view. Existing rotating anode x-ray tube designs fail within MR fringe field environments because the magnetic fields alter the electron trajectories in the x-ray tube and act as a brake on the induction motor, reducing the rotation speed of the anode. In this study the authors propose a novel motor design that avoids the anode rotation speed reduction. METHODS: The proposed design replaces the permanent magnet stator found in brushed dc motors with the radial component of the MR fringe field. The x-ray tube is oriented such that the radial component of the MR fringe field is orthogonal to the cathode-anode axis. Using a feedback position sensor and the support bearings as electrical slip rings, the authors use electrical commutation to eliminate the need for mechanical brushes and commutators. A vacuum compatible prototype of the proposed motor design was assembled, and its performance was evaluated at various operating conditions. The prototype consisted of a 3.1 in. diameter anode rated at 300 kHU with a ceramic rotor that was 5.6 in. in length and had a 2.9 in. diameter. The material chosen for all ceramic components was MACOR, a machineable glass ceramic developed by Corning Inc. The approximate weight of the entire assembly was 1750 g. The maximum rotation speed, angular acceleration, and acceleration time of the motor design were investigated, as well as the dependence of these parameters on rotor angular offset, magnetic field strength, and field orientation. The resonance properties of the authors' assembly were also evaluated to determine its stability during acceleration, and a pulse width modulation algorithm was implemented to control the rotation speed of the motor. RESULTS: At a magnetic flux density of 41 mT orthogonal to the axis of rotation (on the lower end of the expected flux density in the MR suite) the maximum speed of the motor was found to be 5150 revolutions per minute (rpm). The acceleration time necessary to reach 3000 rpm was found to be approximately 10 s at 59 mT. The resonance frequency of the assembly with the anode attached was 1310 rpm (21.8 Hz) which is far below the desired operating speeds. Pulse width modulation provides an effective method to control the speed of the motor with a resolution of 100 rpm. CONCLUSIONS: The proposed design can serve as a direct replacement to the conventional induction motor used in rotating anode x-ray tubes. It does not suffer from a reduced rotation speed when operating in a MR environment. The presence of chromic steel bearings in the prototype prevented testing at the higher field strengths, and future iterations of the design could eliminate this shortcoming. The prototype assembly demonstrates proof of concept of the authors' design and overcomes one of the major obstacles for a MR compatible rotating anode x-ray tube.