Magnetic Particle Imaging: Visualization of Instruments for Cardiovascular Intervention

Original research n

Technical DevelopmenTs

Radiology: Volume 265: Number 3—December 2012 n radiology.rsna.org 933

Magnetic Particle imaging: Visualization of Instruments for Cardiovascular Intervention1

Julian Haegele, MD, Dr medJürgen Rahmer, Dipl Phys, Dr rer natBernhard Gleich, Dipl PhysJörn Borgert, Dipl Phys, Dr rer natHanne Wojtczyk, Dipl Phys (Med)Nikolaos PanagiotopoulosThorsten M. Buzug, Dipl Phys, Dr rer natJörg Barkhausen, MD, Dr medFlorian M. Vogt, MD, Dr med

Purpose: To evaluate the feasibility of different approaches of in-strument visualization for cardiovascular interventions guided by using magnetic particle imaging (MPI).

Materials and Methods:

Two balloon (percutaneous transluminal angioplasty) catheters were used. The balloon was filled either with di-luted superparamagnetic iron oxide (SPIO) ferucarbotran (25 mmol of iron per liter) or with sodium chloride. Both catheters were inserted into a vessel phantom that was filled oppositional to the balloon content with sodium chloride or diluted SPIO (25 mmol of iron per liter). In addition, the administration of a 1.4-mL bolus of pure SPIO (500 mmol of iron per liter) followed by 5 mL of sodium chloride through a SPIO-labeled balloon catheter into the sodium chloride–filled vessel phantom was re-corded. Images were recorded by using a preclinical MPI demonstrator. All images were acquired by using a field of view of 3.6 3 3.6 3 2.0 cm.

Results: By using MPI, both balloon catheters could be visualized with high temporal (21.54 msec per image) and sufficient spatial ( 3 mm) resolution without any motion artifacts. The movement through the field of view, the inflation and deflation of the balloon, and the application of the SPIO bolus were visualized at a rate of 46 three-dimensional data sets per second.

Conclusion: Visualization of SPIO-labeled instruments for cardiovas-cular intervention at high temporal resolution as well as monitoring the application of a SPIO-based tracer by using labeled instruments is feasible. Further work is necessary to evaluate different labeling approaches for diagnostic catheters and guidewires and to demonstrate their navi-gation in the vascular system after administration of con-trast material.

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Supplemental material: http://radiology.rsna.org/lookup /suppl/doi:10.1148/radiol.12120424/-/DC1

1 From the Clinic for Radiology and Nuclear Medicine, University Hospital Schleswig Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany (J.H., N.P., J. Barkhausen, F.M.V.); Philips Technology Innovative Technologies, Research Laboratories, Hamburg, Germany (J.R., B.G., J. Borgert); and Institute of Medical Engineering, University of Lübeck, Lübeck, Germany (H.W., T.M.B.). Received February 22, 2012; revision requested March 30; revision received May 21; accepted May 31; final version accepted June 5. Supported by the German Federal Minis-try of Education and Research, grant numbers 13N11090 and 13N11093 and the European Union in cooperation with the State Schleswig-Holstein, grant number 122-10-004. Address correspondence to J.H. (e-mail: [email protected]).

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934 radiology.rsna.org n Radiology: Volume 265: Number 3—December 2012

TECHNICAL DEVELOPMENTS: Magnetic Particle Imaging of Instruments Haegele et al

Main Principle of MPIMPI uses the nonlinear magnetization curve of SPIO particles for signal gen-eration. Basically, a sinusoidal magnetic field (drive field) induces a change of magnetization in the particles. Because of their nonlinear magnetization curve, the emitted electromagnetic signal con-tains not only the excitation frequency but also higher harmonics thereof. As mentioned previously, the strength of the signal is linear to the concentration of the SPIO particles (1). For spatial encoding, a time constant magnetic gradient field (selection field) is used to magnetically saturate all SPIO particles outside a defined point in space, called the field free point. Thus, only the SPIO particles in close vicinity of the field free point generate a signal that can then be allocated to a known po-sition. For three-dimensional imaging, the field free point is moved through the volume of interest by using three orthogonal drive fields applied at differ-ent frequencies (4) (Fig E1 [online]).

One key characteristic and funda-mental difference of MPI compared with other imaging modalities is the high magnetic moment (about 108 times higher than protons) and the fast relaxivity (about 104 times faster than protons in water) of SPIOs (7). This explains not only the potential for high temporal and spatial resolution

assessment, perfusion images of adja-cent organs could be acquired as well. Because of the high data acquisition capabilities, all images can be record-ed in real time.

In addition, single-sided scanner geometry is possible, allowing unre-stricted access to the patient from three sides (5). However, for interven-tional procedures, the visualization of the instruments is an absolute pre-condition. But because MPI depicts SPIO particles, visualization of con-ventional interventional instruments is very complex. Thus, it is easier to label instruments by using SPIOs for use in MPI-guided interventions.

In principle, there are two different ways of visualizing conventional instru-ments: labeling with an SPIO-based enamel or loading a lumen of the in-strument with SPIOs and, in terms of a negative or passive contrast, visual-ization of an unlabeled instrument in tracer-containing volumes (eg, in con-trasted vessels) (6).

Thus, the purpose of the study was to evaluate the feasibility of different approaches of instrument visualization for cardiovascular interventions guided by using MPI.

Materials and Methods

In the framework of the Magnetic Par-ticle Imaging Technology consortium, funded by the German Federal Min-istry of Education and Research, the University of Lübeck and Philips Tech-nology Innovative Technologies (Ham-burg, Germany) maintain a stipulated cooperation and work together in precompetitive research. The images were acquired at the Philips research laboratories in Hamburg by one au-thor (J.H., University of Lübeck) under technical supervision and con-sultancy of other authors (J.R., B.G., and J. Borgert) who are all employees of Philips. The assessment of the data was carried out by and was under the full control of authors (J.H., H.W., and N.P.) under supervision of other authors (T.M.B., J. Barkhausen, and F.M.V.) without any influence of Phil-ips or its employees.

Magnetic particle imaging (MPI) depicts the spatial distribution of superparamagnetic iron ox-

ide (SPIO) particles by using oscillating magnetic fields. It offers high sensitiv-ity combined with high temporal and good spatial resolution down to 0.5 mm (1,2). Thus, MPI is able to visual-ize small structures as well as fast pro-cesses, such as small vessels and organ perfusion (3,4). Furthermore, because MPI is free of ionizing radiation, there is no limit in exposure time.

Owing to these characteristics, MPI is a very interesting technique for cardiovascular imaging. It can over-come disadvantages of established methods such as exposure to ionizing radiation (digital subtraction angiogra-phy and computed tomography [CT]), availability of only two-dimensional information (digital subtraction angi-ography), or limitations in temporal resolution (magnetic resonance [MR] imaging). In addition, MPI allows di-rect quantification of tracer content because of the linear dependence of signal strength on tracer concentra-tion. MPI is a true three-dimensional imaging modality that allows adjust-ment of the field of view (FOV) in any direction. Furthermore, after acquisi-tion of a survey image of an anatomic region, specific areas of interest could be magnified and viewed in detail with higher image quality. For qualitative

Advances in Knowledge

n Magnetic particle imaging is a promising method for cardiovas-cular diagnostics and interven-tions, providing high temporal and good spatial resolution; it delivers high-contrast four-dimensional data of the vascular system and may provide func-tional information on tissue perfusion.

n Active and passive visualization of balloon catheters is possible without motion artifacts.

n The bolus application of contrast material can be imaged three dimensionally with a high tempo-ral resolution.

Published online before print10.1148/radiol.12120424 Content code:

Radiology 2012; 265:933–938

Abbreviations:FOV = field of viewMPI = magnetic particle imagingSPIO = superparamagnetic iron oxide

Author contributions:Guarantors of integrity of entire study, J.H., J.R., F.M.V.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, J.H., H.W., N.P., T.M.B., F.M.V.; exper-imental studies, J.H., J.R., B.G., J.B., H.W., T.M.B., J.B., F.M.V.; statistical analysis, F.M.V.; and manuscript editing, J.H., J.R., J.B., H.W., T.M.B., J.B., F.M.V.

Conflicts of interest are listed at the end of this article.



deflated, and inflated balloon catheter was clearly delineable from the unen-hanced background (Figs 1, 2; Movies 1, 2 [online]). Its cylindrical shape could be distinguished. A slight blur-ring of about two voxel rows occurred at the edges. But even quick move-ment did not lead to further blurring or other motion artifacts.

By using the size of the FOV and the grid size, the dimensions of the displayed balloon could be roughly estimated by counting the contrasted voxels. Because the border of the balloon in each voxel cannot be determined exactly, mislead-ing effects such as a partial volume ef-fect can occur. Consequently, an error of about 1 voxel in the size estimation of the balloon was encountered. The displayed inflated balloon had a dimen-sion of 7 3 21 3 9 voxels. Given a voxel size of 1.2 3 1.2 3 1.0 mm, the esti-mated object size was about 8.4 6 1.2 [standard deviation] 3 25.2 6 1.2 3 9 6 1 mm, compared with the original size of 10 mm in diameter and 30 mm in length. The relatively high deviation of measured and real balloon length can be explained by the distortion of the signal at the edges of the FOV (11). This effect occurs when the object is bigger than the volume that is covered by the field free point. In this case, the balloon was slightly longer than the vol-ume covered by the field free point in the x direction (30 vs 22.4 mm). Taking voxel size, original and imaged object size, and the potential sources of error, as described previously, into account, a spatial resolution of about 1–2 mm in the z direction and 2–3 mm in the x and y direction could be estimated.

Nonlabeled CatheterThe nonlabeled catheter was clearly delineable from the contrasted vessel phantom (Fig 3, Movie 3 [online]). As with the labeled catheter, the edges were slightly blurred, but no motion ar-tifacts occurred.

The diameter of the vessel phan-tom could be estimated in the y direc-tion; according to the voxel grid and FOV, the diameter was about 15.6 mm 6 1.2. For the balloon size in the y and x direction, 8.4 mm 6 1.2 and

acquisition, was carried out identically to that of the labeled catheter.

In addition, the administration of a 1.4-mL bolus of pure SPIO (500 mmol of iron per liter) followed by 5 mL of sodium chloride through a SPIO-labeled balloon catheter into the sodium chlo-ride–filled vessel phantom was record-ed in real time.

Image Acquisition and ReconstructionAll images were acquired by using a preclinical MPI demonstrator (Philips Research, Hamburg, Germany), as de-scribed by Gleich et al (10) (Fig E2 [on-line]). The gradient field strength was 2.5 T/m/µ0 in the z direction and 1.25 T/m/µ0 in the x and y direction. The drive fields were applied with an ampli-tude of 14 mT/µ0 and frequencies around 25 kHz. Thus, the volume directly cov-ered by the field free point trajectory was 2.24 3 2.24 3 1.12 cm. Because signal is also generated in the vicinity of the field free point, image information is encoded and can be reconstructed on a larger FOV. The reconstruction time per volume was about 5–10 seconds.

Imaging ParametersThe FOV was 36 3 36 3 20 mm with a grid of 30 3 30 3 20 voxel, resulting in a voxel size of 1.2 3 1.2 3 1.0 mm. The rectangular size of the FOV is a re-sult of the higher gradient field strength in the z direction. Higher gradient field strength with identical drive field ampli-tude leads to a higher spatial resolution (8) but to a smaller FOV as well.

The ratio of the applied drive field frequencies determines the acquisition time per three-dimensional volume, which was 21.54 msec, resulting in a sample rate of 46 Hz (4).

Results

Labeled CatheterTwo radiologists (J.H. and F.M.V., with 3 and 10 years, respectively, of clinical experience) and two physi-cists (H.W. and T.M.B., with 2 and 18 years, respectively, of experi-ence in medical physics) conducted the image assessment. The labeled,

and high sensitivity but also the great influence of the SPIOs on image qual-ity. The achievable spatial resolution is proportional to the selection field gradient strength and the steepness of the magnetization curve, which in Langevin theory depends cubically on particle core diameter (8). At a gradient strength of 2.5 T/m/µ0, an intrinsic resolution of 1 mm can be expected for particles with a core di-ameter of 30 nm. However, initial ex-periments demonstrated spatial reso-lutions down to 0.5 mm (2), because the reconstructed spatial resolution additionally depends on the available signal-to-noise ratio (9).

Preparation of Instruments and Vessel PhantomsTwo polyvinyl chloride tubes 20 cm in length and with an inner diameter of 16 mm were used as basic vessel phantoms. One was filled with sodium chloride (0.9%), the other with a so-lution of sodium chloride and with the SPIO ferucarbotran (Resovist; Bayer Pharma, Berlin, Germany) (dilution of 1:20, corresponding to 25 mmol of iron per liter). The afferent lumen to the balloon of one percutaneous trans-luminal angioplasty catheter (Fox Plus; Abbott Vascular, Beringen, Switzer-land) (shaft diameter, 1.72 mm; bal-loon diameter, 10 mm; balloon length, 30 mm) was filled with the same SPIO–sodium chloride solution (labeled cath-eter). This catheter was inserted into the vessel phantom containing sodium chloride. The vessel phantom with the catheter was placed in a cylindri-cal spacer and thus positioned in the center of the bore of the MP scanner. Then, the balloon was navigated in the FOV. After the start of the image acquisition, the balloon catheter was moved forward and backward through the FOV, and finally the balloon was in-flated and deflated. A second identical percutaneous transluminal angioplasty catheter was filled with sodium chlo-ride and inserted into the phantom containing the SPIO–sodium chloride solution (nonlabeled catheter). The positioning of the nonlabeled cathe-ter and phantom, as well as the image



a spatial resolution of about 1–2 mm in the z direction and 2–3 mm in the x and y direction can be estimated, tak-ing voxel size and original and imaged

Figure 2

Figure 2: Three-dimensional rendering of SPIO-filled balloon catheter (a) deflated, (b) during inflation, (c) inflated, and (d) while being moved out of the FOV. Contrast agent–free area in d is result of an air bubble in the balloon.

28.8 mm 6 1.2 could be estimated, respectively.

Bolus AdministrationThe passage of the SPIO bolus through the catheter and its exit into the lumen of the vessel phantom was clearly dis-tinguishable (Fig E3, Movie 4 [online]). Shortly afterward, nearly the whole cross section of the vessel phantom was contrasted. Still, it was possible to dis-tinguish tracer from the balloon cathe-ter. Because there was no movement of the solution, the bolus did not disperse evenly as it would have within a vessel with constant or pulsatile flow.

Discussion

Our study aimed to evaluate the fea-sibility of two different approaches to instrument visualization in an MPI set-ting. Our results demonstrated that di-rect and indirect visualization of a com-mercially available interventional device can be achieved with high temporal and sufficient spatial resolution. In addition, we were able to image inflation and de-flation of a balloon, as well as the appli-cation of a contrast agent bolus in real time. This is a first step toward cardio-vascular interventions by using MPI.

Compared with other cross-sec-tional imaging modalities for interven-tional procedures, the gained temporal resolution (46 volumes per second) with MPI is considerably higher than that with interventional MR imaging (about 5 frames per second [12,13]) and C-arm cone beam CT (image acquisition time of about 5 seconds [14]). The high temporal resolution combined with three-dimensional imaging inherent to MPI allows delineation of moving instru-ments independent of the course of the vessel. Despite the fast data acquisition capabilities of MPI, real guidance of in-struments is still challenging, because of image reconstruction time of several seconds. However, it is expected that real-time image reconstruction will be achievable in the near future with the availability of faster computer hardware and optimized software.

The spatial resolution of an MPI system does not correspond exactly

to the voxel size (9,12) but is deter-mined by the selection field gradient and the steepness of the particle mag-netization curve (13). For our images,

Figure 1

Figure 1: (a) Axial, (b) sagittal, and (c) coronal MP images show SPIO-labeled balloon catheter. The catheter is clearly delineable in the FOV (20 3 36 3 36 mm).



increase the FOV is decreasing the gra-dient strength, resulting in a diminished spatial resolution, as long as the drive-field amplitudes are not increased in re-turn. Temporal resolution (acquisition time of a single volume) is not influ-enced by gradient strength or drive-field amplitude, only by the ratio of the three different excitation frequencies. One solution is to move the small FOV (called “patch” in this context) through the volume of interest by using a so-called focus field and to combine the individual patches to a larger FOV (18). Because the focus fields operate at low frequencies up to 100 Hz, patient heating is not an issue. This approach elongates acquisition time but enables imaging of a larger FOV without dimin-ishing spatial resolution and the need for higher drive-field amplitudes.

In the current study, several chal-lenges were not addressed which have to be solved prior to the transition into clinical routine. For percutaneous transluminal angioplasty, guidewires and diagnostic catheters have to be visualized in addition to balloon cath-eters. For these devices, very thin, low friction, and flexible coatings are es-sential to maintain mechanical integ-rity and handling. However, thin coat-ings require a highly concentrated and most effective optimized MPI tracer to emit a sufficiently strong detectable sig-nal. Furthermore, the coating must be nonthrombogenic and biocompatible. In addition, as with MR imaging, the safe use of the instruments has to be ensured. Especially, guidewires acting as antennas may heat up because of the interaction with oscillating electromag-netic fields. However, in this regard, MPI will definitely benefit from the most recent developments in interventional MR imaging. Furthermore, for the guidance of a vascular intervention, the vessel has to be visualized in addition to the devices. This can be achieved by using a tracer bolus to record a road-map corresponding to digital subtrac-tion angiography, as demonstrated in this study. However, the application of a blood pool tracer or labeling eryth-rocytes with SPIOs might be an attrac-tive alternative (19). Although several

and particle properties (detection limit is expected to improve up to 20 nmol of iron per liter for a spatial resolution of about 1 mm) (1,2,4,8). By trading in the high signal-to-noise ratio avail-able with improved sensitivity, even submillimeter spatial resolution can be achieved (9). Because of the high sensi-tivity, objects below 1 mm can already be detected but not fully resolved. How-ever, even with perfect imaging hard-ware, software, and tracers, the superb spatial resolution of C-arm cone beam CT (150 3 150 3 150 µm [16]) cannot be equaled by using MPI.

While temporal and spatial reso-lutions seem to be sufficient for inter-ventional purposes, for in vivo use, the FOV has to be enlarged. To enlarge the FOV without diminishing the temporal resolution, the drive-field amplitudes have to be increased. However, the achievable drive-field amplitudes are limited by power dissipation and poten-tial patient heating or nerve stimulation issues (17,18). Another possibility to

object size into account. The potential spatial resolution of MPI is known to be better (2,4) than demonstrated in this study. However, the limited resolution is owed to prototype hardware (ie, field strength) and not caused by the method itself or intrinsic to the visualization of interventional instruments.

Considering MPI and particle the-ory, the achieved resolution in the z di-rection of 1–2 mm is close to the limit on intrinsic resolution, which is 1 mm for the applied gradient strength of 2.5 T/m/µ0. The spatial resolution of the acquired MP images is comparable to real-time interventional MR imaging, which has already proved feasible to guide interventional procedures in vivo (15). Our results demonstrated the vi-sualization of catheters and balloons ex vivo, and we believe that MPI guidance of interventional procedures is feasible in larger vessels in vivo as well.

Finally, the spatial resolution is sub-ject to improve considerably with the expected progress in scanner hardware

Figure 3

Figure 3: (a) Axial, (b) sagittal, and (c) coronal MP images show nonlabeled balloon catheter (arrow) in SPIO con-trasted lumen of the vessel phantom. The contour of the vessel and the catheter inside the vessel are clearly distin-guishable (FOV, 20 3 36 3 36 mm).



challenges have to be addressed in fur-ther developments, there seems to be no fundamental insoluble obstacles pre-cluding human applications during the next decade.

Our study is an initial step toward MPI-guided cardiovascular interven-tions, demonstrating the feasibility of instrument and vessel visualization for MPI-guided interventions. However, this is not the only attractive applica-tion for MPI in cardiovascular diseases. Because of the high temporal resolu-tion combined with fully quantitative measurements of the tracer concen-tration, MPI imay provide noninvasive quantitative measurements of tissue perfusion without applying ionizing ra-diation. Thus, at a single examination, MPI may allow for a fast and accurate assessment of the vascular anatomy, depict stenoses, help guide the inter-ventional procedure, and help quanti-tatively measure the effects on tissue perfusion before, during, and after the procedure. This will have a major ef-fect on patient care, because the clin-ical decision to perform, for example, coronary interventions can be on the basis of the quantitative evidence of is-chemia rather than a visual estimation of the degree of a stenosis.

Disclosures of Conflicts of Interest: J.H. No conflicts of interest to disclose. J.R. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: author receives money from Philips Technology for patents. Other relation-ships: none to disclose. B.G. Financial activities related to the present article: none to disclose. Financial activities not related to the present ar-ticle: author receives money from Philips Tech-nology for patents. Other relationships: none to disclose. J. Borgert. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: au-thor receives money from Philips Technology for patents. Other relationships: none to disclose. H.W. Financial activities related to the present article: institution receives grant (122-10-004) from European Union and the State Schleswig-Holstein (Programme for the Future-Economy). Financial activities not related to the present ar-

ticle: none to disclose. Other relationships: none to disclose. N.P. No conflicts of interest to dis-close. T.M.B. Financial activities related to the present article: institution receives grant (122-10-004) from European Union and the State Schleswig-Holstein (Programme for the Future-Economy). Financial activities not related to the present article: none to disclose. Other relation-ships: none to disclose. J. Barkhausen. No con-flicts of interest to disclose. F.M.V. No conflicts of interest to disclose.

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Magnetic Particle Imaging: Visualization of Instruments for Cardiovascular Intervention