MRI-guided endovascular intervention: current methods and future potential.

INTRODUCTION: Image-guided endovascular interventions, performed using the insertion and navigation of catheters through the vasculature, have been increasing in number over the years, as minimally invasive procedures continue to replace invasive surgical procedures. Such endovascular interventions are almost exclusively performed under x-ray fluoroscopy, which has the best spatial and temporal resolution of all clinical imaging modalities. Magnetic resonance imaging (MRI) offers unique advantages and could be an attractive alternative to conventional x-ray guidance, but also brings with it distinctive challenges. AREAS COVERED: In this review, the benefits and limitations of MRI-guided endovascular interventions are addressed, systems and devices for guiding such interventions are summarized, and clinical applications are discussed. EXPERT OPINION: MRI-guided endovascular interventions are still relatively new to the interventional radiology field, since significant technical hurdles remain to justify significant costs and demonstrate safety, design, and robustness. Clinical applications of MRI-guided interventions are promising but their full potential may not be realized until proper tools designed to function in the MRI environment are available. Translational research and further preclinical studies are needed before MRI-guided interventions will be practical in a clinical interventional setting.

Evaluating Radioactive Analogs of Doxorubicin to Quantify ChemoFilter Binding and Whole-Body Positron Emission Tomography/Magnetic Resonance Imaging for Drug Biodistribution.

PURPOSE: To evaluate radiolabeled doxorubicin (Dox) analogs as tracers of baseline Dox biodistribution in vivo during hepatic intra-arterial chemotherapy and to assess the efficacy of ChemoFilter devices to bind Dox in vitro. MATERIALS AND METHODS: In an in vitro static experiment, [fluorine-18]N-succinimidyl 4-fluorobenzoate ([18F]SFB) and [fluorine-18]fluorobenzoyl-doxorubicin ([18F]FB-Dox) were added to a beaker containing a filter material (Dowex cation exchange resin, single-stranded DNA (ssDNA) resin, or sulfonated polymer coated mesh). In an in vitro flow model, [18F]FB-Dox was added into a Dox solution in phosphate-buffered saline, and the solution flowed via a syringe column containing the filter materials. In an in vitro flow experiment, using micro-positron emission tomography (PET), images were taken as [18F]SFB and [18F]FB-Dox moved through a phantom. For in vivo biodistribution testing, a catheter was placed into the common hepatic artery of a swine, and [18F]FB-Dox was infused over 30 seconds. A 10-minute dynamic image and three 20-minute static images were acquired using 3T PET/MR imaging. RESULTS: In the in vitro static experiment, [18F]FB-Dox demonstrated 76.7%, 88.0%, and 52.4% binding to the Dowex resin, ssDNA resin, and coated mesh, respectively. In the in vitro flow model, the first-pass binding of [18F]FB-Dox to the Dowex resin, ssDNA resin, and coated mesh was 76.7%, 74.2%, and 76.2%, respectively, and the total bound fraction was 80.9%, 84.6%, and 79.9%, respectively. In the in vitro flow experiment using micro-PET, the phantom demonstrated a greater amount of [18F]FB-Dox bound to both filter cartridges than of the control [18F]SFB. In in vivo biodistribution testing, the first 10 minutes depicted [18F]FB-Dox moving through the right upper quadrant of the abdomen. A region-of-interest analysis showed that the relative amount increased by 2.97 times in the gallbladder and 1.08 times in the kidney. The amount decreased by 0.74 times in the brain and 0.57 times in the heart. CONCLUSIONS: [18F]FB-Dox can be used to assess Dox binding to ChemoFilters as well as in vivo biodistribution. This sets the stage for the evaluation of ChemoFilter effectiveness in reducing systemic toxicity from intra-arterial chemotherapy.

Wireless Resonant Circuits Printed Using Aerosol Jet Deposition for MRI Catheter Tracking.

Interventional magnetic resonance imaging (MRI) could allow for diagnosis and immediate treatment of ischemic stroke; however, such endovascular catheter-based procedures under MRI guidance are inherently difficult. One major challenge is tracking the tip of the catheter, as standard fabrication methods for building inductively coupled coil markers are rigid and bulky. Here, we report a new approach that uses aerosol jet deposition to three-dimensional (3-D) print an inductively coupled RF coil marker on a polymer catheter. Our approach enables lightweight conforming markers on polymer catheters and these low-profile markers allow the catheter to be more safely navigated in small caliber vessels. Prototype markers with an inductor with the geometry of a double helix are incorporated on catheters for in vitro studies, and we show that these markers exhibit good signal amplification. We report temperature measurements and, finally, demonstrate feasibility in a preliminary in vivo experiment. We provide material properties and electromagnetic simulation performance analysis. This paper presents fully aerosol jet-deposited and functional wireless resonant markers on polymer catheters for use in 3T clinical scanners.

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.

Optimization of an endovascular magnetic filter for maximized capture of magnetic nanoparticles.

To computationally optimize the design of an endovascular magnetic filtration device that binds iron oxide nanoparticles and to validate simulations with experimental results of prototype devices in physiologic flow testing. Three-dimensional computational models of different endovascular magnetic filter devices assessed magnetic particle capture. We simulated a series of cylindrical neodymium N52 magnets and capture of 1500 iron oxide nanoparticles infused in a simulated 14 mm-diameter vessel. Device parameters varied included: magnetization orientation (across the diameter, "D", along the length, "L", of the filter), magnet outer diameter (3, 4, 5 mm), magnet length (5, 10 mm), and spacing between magnets (1, 3 mm). Top designs were tested in vitro using 89Zr-radiolabeled iron oxide nanoparticles and gamma counting both in continuous and multiple pass flow model. Computationally, "D" magnetized devices had greater capture than "L" magnetized devices. Increasing outer diameter of magnets increased particle capture as follows: "D" designs, 3 mm: 12.8-13.6 %, 4 mm: 16.6-17.6 %, 5 mm: 21.8-24.6 %; "L" designs, 3 mm: 5.6-10 %, 4 mm: 9.4-15.8 %, 5 mm: 14.8-21.2 %. In vitro, while there was significant capture by all device designs, with most capturing 87-93 % within the first two minutes, compared to control non-magnetic devices, there was no significant difference in particle capture with the parameters varied. The computational study predicts that endovascular magnetic filters demonstrate maximum particle capture with "D" magnetization. In vitro flow testing demonstrated no difference in capture with varied parameters. Clinically, "D" magnetized devices would be most practical, sized as large as possible without causing intravascular flow obstruction.

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.

Improving cardiac resynchronization therapy response with multipoint left ventricular pacing: Twelve-month follow-up study.

BACKGROUND: Cardiac resynchronization therapy (CRT) with multipoint left ventricular (LV) pacing (MultiPoint™ Pacing [MPP], St. Jude Medical) improves acute LV function and LV reverse remodeling at 3 months. OBJECTIVE: The purpose of this study was to test the hypothesis that MPP can also improve LV function at 12 months. METHODS: Consecutive patients receiving a CRT implant (Unify Quadra MP™ or Quadra Assura MP™ CRT-D and Quartet™ LV lead, St. Jude Medical) were randomized to receive pressure-volume (PV) loop optimized biventricular pacing with either conventional cardiac resynchronization therapy (CONV) or MPP. CRT response was defined by a reduction in end-systolic volume (ESV) ≥15% relative to BASELINE as determined by a blinded observer and alive status. RESULTS: Forty-four patients (New York Heart Association class III, ejection fraction [EF] 29% ± 6%, QRS 152 ± 17 ms) were enrolled and randomized to either CONV (N = 22) or MPP (N = 22). During the observation period, 2 patients died of noncardiac causes and 2 patients were lost to follow-up. After 12 months, 12 of 21 patients (57%) in the CONV group and 16 of 21 patients (76%) in the MPP group were classified as CRT responders (P = .33). ESV reduction and EF increase relative to BASELINE were significantly greater with MPP than with CONV (ESV: median -25%, interquartile range [IQR] [-39% to -20%] vs median -18%, IQR [-25% to -2%], P = .03; EF: median +15%, IQR [8% to 20%] vs median +5%, IQR [-1% to 8%], P <.001). CONCLUSION: Sustaining the trend observed 3 months postimplant, PV loop-guided multipoint LV pacing resulted in greater LV reverse remodeling and increased LV function at 12 months compared to PV loop-guided conventional CRT.

Musculoskeletal MRI at 3.0 T and 7.0 T: a comparison of relaxation times and image contrast.

OBJECTIVE: The purpose of this study was to measure and compare the relaxation times of musculoskeletal tissues at 3.0 T and 7.0 T, and to use these measurements to select appropriate parameters for musculoskeletal protocols at 7.0 T. MATERIALS AND METHODS: We measured the T1 and T2 relaxation times of cartilage, muscle, synovial fluid, bone marrow and subcutaneous fat at both 3.0 T and 7.0 T in the knees of five healthy volunteers. The T1 relaxation times were measured using a spin-echo inversion recovery sequence with six inversion times. The T2 relaxation times were measured using a spin-echo sequence with seven echo times. The accuracy of both the T1 and T2 measurement techniques was verified in phantoms at both magnetic field strengths. We used the measured relaxation times to help design 7.0 T musculoskeletal protocols that preserve the favorable contrast characteristics of our 3.0 T protocols, while achieving significantly higher resolution at higher SNR efficiency. RESULTS: The T1 relaxation times in all tissues at 7.0 T were consistently higher than those measured at 3.0 T, while the T2 relaxation times at 7.0 T were consistently lower than those measured at 3.0 T. The measured relaxation times were used to help develop high resolution 7.0 T protocols that had similar fluid-to-cartilage contrast to that of the standard clinical 3.0 T protocols for the following sequences: proton-density-weighted fast spin-echo (FSE), T2-weighted FSE, and 3D-FSE-Cube. CONCLUSION: The T1 and T2 changes were within the expected ranges. Parameters for musculoskeletal protocols at 7.0 T can be optimized based on these values, yielding improved resolution in musculoskeletal imaging with similar contrast to that of standard 3.0 T clinical protocols.

Subject-specific models of susceptibility-induced B0 field variations in breast MRI.

PURPOSE: To rapidly calculate and validate subject-specific field maps based on the three-dimensional shape of the bilateral breast volume. MATERIALS AND METHODS: Ten healthy female volunteers were scanned at 3 Tesla using a multi-echo sequence that provides water, fat, in-phase, out-of-phase, and field map images. A shape-specific binary mask was automatically generated to calculate a computed field map using a dipole field model. The measured and computed field maps were compared by visualizing the spatial distribution of the difference field map, the mean absolute error, and the 80% distribution widths of frequency histograms. RESULTS: The 10 computed field maps had a mean absolute error of 38 Hz (0.29 ppm) compared with the measured field maps. The average 80% distribution widths for the histograms of all of the computed, measured, and difference field maps are 205 Hz, 233 Hz, and 120 Hz, respectively. CONCLUSION: The computed field maps had substantial overall agreement with the measured field maps, indicating that breast MRI field maps can be computed based on the air-tissue interfaces. These estimates may provide a predictive model for field variations and thus have the potential to improve applications in breast MRI.

Nucleic acid and protein mass mapping by live-cell deep-ultraviolet microscopy.

We developed a deep-ultraviolet (UV) microscope capable of imaging cell mitosis and motility at 280 nm for 45 min with minimal UV-induced toxicity, and for 6 h before the onset of visible cell death in cultured human and mouse cells. Combined with computational methods that convert the intensity of each pixel into an estimate of mass, deep-UV microscopy images generate maps of nucleic acid mass, protein mass and fluorescence yield in unlabeled cells.