Stroke and cardiovascular disease are major health threats in the United States. Treatment is typically done under X-ray fluoroscopy but MR imaging could provide physiological information and does not have ionizing radiation. An issue with MR is that tools have to be compatible in a magnetic field environment. Hence, the aim is to build an RC with satisfactory tip visualization at various orientations. It will be utilized in a stroke model involving swine where the catheter will be inserted in the femoral artery up to the carotid. There will also be testing the accuracy of the electromagnetic simulation software XFdtd.

A unique material, pyralux (by Dupont), was processed with photolithography to etch the design. The resonators were wrapped around catheters and tuning was done to achieve the proper resonant frequency for 3.0 T and 1.5 T MR scanners. Scans were made with vascular phantoms and mainly MRA (TOF GRE) protocols. Catheters were oriented perpendicular or parallel to the B0 magnetic field. OsiriX and MS excel were used to calculate the SNR of the catheter relative to the background.

Increasing flip angle, starting from 5 degrees and ending at 90 degrees, decreases the SNR and stronger signal is achieved at 1.5T than 3.0T with these parameters. There is not a significant different between SNR with the perpendicular and parallel orientations in the 3.0T. XFdtd successfully demonstrated the relationship between frequency, capacitance, and inductance with a single coil model but not with the double helix. A clot was successfully induced in the femoral artery of a pig and temperature mapping shows insignificant heating hazards.

The goal of the resonator is to visualize the tip, so wider bandwidth would be useful to account for frequency shifts caused by magnetic field disturbances. While choosing the ROI for analysis, selection was based off covering the catheter width and choosing the background such that any artifacts can be accounted for. Although the same TOF GRE sequence in previous successful cases were used, the new sequences tested this year were variable so they were not included in analysis.

From this study, it is shown that the resonator has similar SNR regardless of orientation in the GE 3.0 T scanner. It would be most beneficial to use low flip angles and currently the 1.5 T scanner.

Abstract

Objective: Localized chemotherapy can be more effective at treating cancers than traditional chemotherapy methods. Increased dosage leads to increased systemic toxicity, a critical issue that must be addressed. The ChemoFilter - a temporarily deployable, endovascular device - aims to extract chemotherapeutic agents from the bloodstream in order to reduce adverse side effects in other areas of the body. In this study, we report the binding effectiveness of ion-exchange resins with cisplatin, a commonly administered chemotherapeutic.

Materials and Methods: All experiments were conducted in vitro using cisplatin in distilled water and phosphate buffered saline. Ion-exchange resins (Dowex 50Wx2, Amberlite FPC22, Tulsion T-66, Amberlite IRC, Purolite S930/950) were tested in solution individually and the total amount of free cisplatin in solution was quantified using ultraviolet-visible spectroscopy and inductively coupled plasma mass spectroscopy.

Results: Quantification of cisplatin using UV-visible methods demonstrated that strong acid cation exchangers perform exceptionally well in saline solutions, removing over 90% of free cisplatin within one minute. The concentration of free cisplatin did not drop when reacted with strong cation exchangers in water. Weak acid cation exchangers and chelating resins also displayed no binding of cisplatin in PBS. Assessing the performance of the strong cation exchange resin, Dowex 50Wx2, using ICP-MS showed that ion exchange filtration was comparable in both water and PBS.

Conclusion: The current effectiveness of localized chemotherapy is limited by its corresponding increased systemic toxicity. The ChemoFilter seeks to mitigate the effects of chemotherapeutics on non-targeted areas of the body by extracting or inactivating the chemotherapy agents that pass through it. Our benchtop OPDA method of quantifying cisplatin in solution indicated that strong acid cation exchangers were exceptionally well-suited to the task. However, quantification using ICP-MS revealed that our previous UV-visible method of cisplatin quantification was not compatible with ion exchange resin studies and that these resins may not be very useful at fulfilling the ChemoFilter’s objective of removing cisplatin from solution.

Objective: ChemoFilter is a new class of image-guided temporarily deployable, endovascular catheter based medical device that selectively filters chemotherapeutic agents from the bloodstream to limit systemic toxicities. We report a novel method to filter doxorubicin in blood using genomic DNA as resin.

Materials and Methods: DNA binding experiments were performed in vitro with doxorubicin in PBS solution and porcine serum. Genomic DNA was used for binding experiments, with the DNA either free in solutions or with the DNA encapsulated in packets made with nylon or polyester mesh. Optimum concentration of genomic DNA to filter 50 mg doxorubicin in solution was determined. We then compared the kinetics of filtering doxorubicin by genomic DNA as compared to our previously published ion exchange resin based ChemoFilter.

Results: Doxorubicin concentration was reduced by over 90% within 1 minute with free DNA in PBS and porcine serum. With packaged DNA, doxorubicin concentration was reduced by 50% within 5 minutes in PBS, and 90% within 1 minute in porcine Serum.

Doxorubicin filtering kinetics between DNA and the ion exchange resin Dowex were compared in each binding experiments and the DNA displayed more rapid kinetics in all situations.

Conclusion: We describe a new version of ChemoFilter that uses DNA as the binding agent for DNA binding drugs. DNA ChemoFilter allows selective filtration of DNA binding chemotherapeutic agents and demonstrates more rapid kinetics than previously described ion exchange version of ChemoFilter.

Introduction: Endovascular chemotherapy treatment allows localized delivery adjacent to the target tumor; allowing an increased dosage and decreased leakage to other areas. It also allows for the opportunity to filter chemotherapy escaping the target tumor and entering the bloodstream. The ChemoFilter - a temporarily deployable, endovascular device will do just that; reducing systemic toxicity thus reducing adverse side effects from chemotherapy treatment. This will allow further increased dosage, increased tumor suppression, and increased tolerance to treatment. ChemoFilter has successfully filtered the chemotherapeutic Doxorubicin, but had yet to be tested in other chemotherapeutics. This study evaluates binding with new chemotherapeutics: Cisplatin, Carboplatin, and a cocktail comprised of Cisplatin and Doxorubicin.

Materials and Methods: ChemoFilter prototypes based on: 1.) Genomic DNA and

2.) Dowex (ion-exchange) resin, were evaluated for their ability to bind chemotherapy in vitro in phosphate-buffered saline (PBS). ChemoFilter was tested free in solution and encapsulated in nylon or polyester mesh packets of various dimensions. Concentrations were quantified using inductively coupled plasma mass spectrometry (IPC-MS), ultraviolet-visible spectrophotometry (UV-Vis), or fluorospectrometry. 11C, 13C, and/or 14C radiolabeling Carboplatin began for in vitro and in vivo ChemoFilter quantification. In vitro quantification can include scintillation and/or gamma counting. In vivo may include Positron Emission Tomography (PET) imaging, Hyperpolarized 13C Magnetic Resonance Imaging (MRI), and/or Magnetic Resonance Spectroscopy (MRS) for real-time visualization. Reactions were verified using High Performance Liquid Chromatography (HPLC) for chemical species identification.

Results and Discussion: Results indicate significant and nearly complete, ~99% (p<0.01) clearance of Cisplatin using the DNA ChemoFilter sequestered in Nylon mesh, quantified with gold standard ICP-MS (evidenced at 214 and 265 nm). The Ion-exchange ChemoFilter has significant clearance, within seconds, of both Doxorubicin and Cisplatin mixed in a cocktail solution. However, it appears some Cisplatin is binding to the Nylon Mesh itself. Size, shape, and material of the mesh have been optimized. A potential mechanism for 11C, 13C, or 14C radiolabeling of Carboplatin has been developed and early results have been successful. ChemoFilter works much more efficiently when sequestered in nylon packets of specific geometries. Significant improvements have been made to ChemoFilter, moving the device closer to clinical trials.

Endovascular chemotherapy is an effective treatment option for cancer, however, the therapeutic agents used in this procedure often travel to non-target tissues and cause severe toxicity. Side-effects of chemotherapy range from nausea to life-threatening conditions. A strategy to reduce exposure of healthy tissues and organs to the toxicity of chemotherapeutic agents, such as doxorubicin (DOX), is to remove these drugs from systemic circulation after they have passed through the tumor site. With this goal in mind, different types of ChemoFilter devices have shown promise in alleviating these detrimental side effects. When placed downstream from the targeted tumor during intra-arterial chemotherapy, excess therapeutic agents bind to the device, preventing them from entering systemic circulation. In this study, we evaluated the doxorubicin-binding efficacy of a 3D printed porous cylindrical ChemoFilter device coated with sulfonated pentablock copolymers. Closed-circuit flow models experiments integrating 11 devices (uncoated or coated) at two concentrations of DOX (0.01 mg/mL and 0.05 mg/mL) were conducted. Samples collected from these flow models were used to treat H9c2 cell cultures, a rat embryonic cardiac cell line selected due to DOX cardiotoxicity. After a 24-hour treatment period, cell viability was calculated using the Trypan blue exclusion method. At 0.01 mg/mL DOX and 0.05 mg/mL DOX, the 3D printed polystyrenesulfonate-coated absorbers effectively filtered and eliminated DOX toxicity, increasing the H9c2 cell viability by 12.97% and 23.11%, respectively. These results confirm the ChemoFilter’s ability to successfully absorb DOX in vitro, showing promise for its possible future use in clinical trials.

This project sought to create a deep learning model to detect and track MR-compatible catheter tips under Magnetic Resonance Imaging. Interventional MRI, or iMRI, has many advantages over traditional x-ray angiography methods, yet the path towards adoption is hindered by many obstacles, including the lack of easily visualizable catheter tips. The model, the Faster Region-based Convolutional Neural Network (Faster R-CNN), was chosen due to its well-balanced speed and accuracy over other model architectures. The dataset included MR images of passive and resonant catheter tips alone and as well as passive catheter tips in an abdominal aorta phantom. The Faster R-CNN was trained over many iterations and over the best run it was able to draw bounding boxes over the tip of the catheter with an overall mean average precision of 0.59 and overall average recall of 0.66. Further optimization of training parameters will be needed to create a model that can achieve a better mean average precision. This study opens the possibility of applying artificial intelligence models towards iMRI methods, which helps push towards the goal of proving the safety and efficacy of iMRI procedures. These foundational elements are critical to smoothing the adoption of iMRI for guiding endovascular procedures.

This project sought to evaluate the efficacy of using the EPflex MRline guidewire for endovascular treatment guided by real-time Magnetic Resonance Imaging (MRI). MRI theoretically has numerous advantages over x-ray, the current clinical standard imaging modality for endovascular procedures. The most profound advantage of MRI is the ability to acquire physiological functional information, via perfusion and diffusion measures, for better intervention planning before and during the procedure. The EPflex guidewire was selected

because of its ability to perform in an MRI and x-ray fluoroscopy environment, allowing for relevant and useful comparisons of the guiding imaging modality. An abdominal aorta phantom was used to assess the ability of experienced and inexperienced operators to successfully

navigate the wire under each imaging modality. It was found that x-ray guidance provided statistically faster and more successful navigation attempts than MRI guidance; however, more clinical tests need to be performed in order to assess the clinical significance of these results.

This study represents an important step in the direction of developing safer and more effective imaging systems for guiding endovascular procedures.

Abstract

Introduction: Liver cancer is on the rise in the US with an increase of 2.7% new cases per year and 2.6% increase of death rates (4). The current treatments include surgical, tumor ablation, embolization, radiation, and chemotherapy. Many patients are diagnosed much too late in their progression of liver cancer and cannot undergo surgical treatments. Chemotherapy has become a promising possible treatment for liver cancer although its largest limitation is systemic toxicity. It has been found that 50-70% of the chemotherapy agent is not absorbed by the liver cancer cells and is circulated through the rest of the body (6). This amount of chemotherapy agent in the blood circulation can cause severe cardiac toxicity. Luckily, chemotherapy filter devices are currently being researched and may solve the limitation of systemic toxicity. Current devices include ionic based, magnetic based, and DNA based (6). The experiments described in this paper will be focusing on DNA based chemotherapy filters and Doxorubicin as the chemotherapy agent. The goal of this research is to create a simple and quick assay to measure the efficiency of a functionalized DNA chemotherapy filter device.

Materials and Methods: In order to simulate an in-vivo usage of a DNA chemotherapy filter device, 50 mg of genomic DNA (Salmon sperm, Sigma-Aldrich, St. Louis, MO) was mixed together with 50 mL of 0.05M Doxorubicin in a beaker. The solution was mixed using a magnetic stir bar, allowing the DNA to bind Doxorubicin. In order to optimize the assay, three different types of extraction agents were tested; 0.3M solution of sodium acetate, 10%wt/vol solution of trichloroacetic acid (TCA), and 35%wt/vol solution of silver nitrate. These extraction agents were mixed with the DNA and Doxorubicin solution to analyze how efficient they were at removing bound Doxorubicin from DNA. The resulting samples were analyzed using both a fluorospectrometer (SPECTRA max M2, Molecular Devices) and higher performance liquid chromatography (HPLC) (SPECTRA max M2, Molecular Devices). Finally, all resulting graphs were created using Microsoft Excel (Microsoft Office 2011).

Results and Discussion: It was found that the 35%wt/vol solution of silver nitrate was the most effective in releasing Doxorubicin from DNA. The 10% wt/vol solution of TCA was found to be the second most efficient followed by the 0.3M solution of sodium acetate. Silver nitrate was able to retrieve 98.12% of the Doxorubicin initially bound to DNA according to the HPLC data, and 80.66% according to the fluorospectrometer data. TCA was able to retrieve 79.21% of the initial Doxorubicin from DNA according to the HPLC data and 85.91% according to the fluorospectrometer data. Sodium acetate was able retrieve 74.35% of the initial Doxorubicin from DNA according to the HPLC data and 17.27% according to the fluorospectrometer data. The discrepancy between the HPLC data and the fluorospectrometer data is most likely due to the quenching limitation of the fluorospectrometer causing a lower Doxorubicin concentration reading than the actual concentration. HPLC appears to be the more reliable and accurate device for measuring Doxorubicin concentration in solution (13).

Conclusion: This paper describes a simple and quick method of extracting Doxorubicin from DNA and then measuring the amount of unbound Doxorubicin. This assay will assist in the optimization of a functionalized DNA-based chemotherapy filter device by allowing the users to test how efficient a device is at absorbing excess Doxorubicin in a simple and quick method. This research uses genomic DNA in place of iron oxide bound DNA. The current model of the functionalized DNA-based chemotherapy filter device uses iron oxide bound DNA that allows the DNA to be magnetically bound to the filter device. Future investigations will test this assay using iron oxide bound DNA instead of genomic DNA. This will allow for a more accurate representation of the efficiency of the extraction agents ability to release Doxorubicin from DNA. This is done in order to measure unbound Doxorubicin and thus the amount of Doxorubicin the DNA is able to bind.