Justin J. Konkle

Magnetic Particle Imaging With Tailored Iron Oxide Nanoparticle Tracers

Magnetic particle imaging (MPI) shows promise for medical imaging, particularly in angiography of patients with chronic kidney disease. As the first biomedical imaging technique that truly depends on nanoscale materials properties, MPI requires highly optimized magnetic nanoparticle tracers to generate quality images. Until now, researchers have relied on tracers optimized for MRI T2*-weighted imaging that are sub-optimal for MPI. Here, we describe new tracers tailored to MPIs unique physics, synthesized using an organic-phase process and functionalized to ensure biocompatibility and adequate in vivo circulation time. Tailored tracers showed up to 3 × greater signal-to-noise ratio and better spatial resolution than existing commercial tracers in MPI images of phantoms.

Projection X-Space Magnetic Particle Imaging

Projection magnetic particle imaging (MPI) can improve imaging speed by over 100-fold over traditional 3-D MPI. In this work, we derive the 2-D x-space signal equation, 2-D image equation, and introduce the concept of signal fading and resolution loss for a projection MPI imager. We then describe the design and construction of an x-space projection MPI scanner with a field gradient of 2.35 T/m across a 10 cm magnet free bore. The system has an expected resolution of 3.5 × 8.0 mm using Resovist tracer, and an experimental resolution of 3.8 × 8.4 mm resolution. The system images 2.5 cm × 5.0 cm partial field-of views (FOVs) at 10 frames/s, and acquires a full field-of-view of 10 cm × 5.0 cm in 4 s. We conclude by imaging a resolution phantom, a complex “Cal” phantom, mice injected with Resovist tracer, and experimentally confirm the theoretically predicted x-space spatial resolution.

A Convex Formulation for Magnetic Particle Imaging X-Space Reconstruction.

Magnetic Particle Imaging (mpi) is an emerging imaging modality with exceptional promise for clinical applications in rapid angiography, cell therapy tracking, cancer imaging, and inflammation imaging. Recent publications have demonstrated quantitative mpi across rat sized fields of view with x-space reconstruction methods. Critical to any medical imaging technology is the reliability and accuracy of image reconstruction. Because the average value of the mpi signal is lost during direct-feedthrough signal filtering, mpi reconstruction algorithms must recover this zero-frequency value. Prior x-space mpi recovery techniques were limited to 1d approaches which could introduce artifacts when reconstructing a 3d image. In this paper, we formulate x-space reconstruction as a 3d convex optimization problem and apply robust a priori knowledge of image smoothness and non-negativity to reduce non-physical banding and haze artifacts. We conclude with a discussion of the powerful extensibility of the presented formulation for future applications.

Twenty-fold acceleration of 3D projection reconstruction MPI

Abstract We experimentally demonstrate a 20-fold improvement in acquisition time in projection reconstruction (PR) magnetic particle imaging (MPI) relative to the state-of-the-art PR MPI imaging results. We achieve this acceleration in our imaging system by introducing an additional Helmholtz electromagnet pair, which creates a slow shift (focus) field. Because of magnetostimulation limits in humans, we show that scan time with three-dimensional (3D) PR MPI is theoretically within the same order of magnitude as 3D MPI with a field free point; however, PR MPI has an order of magnitude signal-to-noise ratio gain.

Development of a field free line magnet for projection MPI

The field free line (FFL) magnet has the potential to greatly increase signal to noise ratio (SNR) or to decrease scan time for magnetic particle imaging (MPI). The use of an FFL will decrease scan time by reducing image dimensionality from a 3D image to a projection image. Alternatively, in comparison to a 3D scan of equal scan time, an FFL scanner will increase SNR through more signal averages. An FFL magnet would enable projection imaging as is used in projection x-ray and is common in angiography. The Philips and Lubeck groups have pioneered the design of field free line magnets for MPI and have shown that they can achieve power efficiency similar to that of a field free point, the standard in MPI. Current FFL magnet designs have not been optimized for characteristics such as gradient efficiency and gradient magnitude homogeneity. This work shows a 2.25 T/m Halbach quadrupole permanent magnet design that produces a homogeneous magnetic field along the field free line. Along the FFL, we experimentally measured a field maximum of 2mT within the imaging field of view (FOV), and we experimentally measured that the gradient perpendicular to the FFL deviates by a maximum of 3.4%. In future work, we plan to produce an x-space MPI image using the FFL magnet. We also plan to improve upon this design using optimization techniques.

Low drive field amplitude for improved image resolution in magnetic particle imaging

PURPOSE Magnetic particle imaging (MPI) is a new imaging technology that directly detects superparamagnetic iron oxide nanoparticles. The technique has potential medical applications in angiography, cell tracking, and cancer detection. In this paper, the authors explore how nanoparticle relaxation affects image resolution. Historically, researchers have analyzed nanoparticle behavior by studying the time constant of the nanoparticle physical rotation. In contrast, in this paper, the authors focus instead on how the time constant of nanoparticle rotation affects the final image resolution, and this reveals nonobvious conclusions for tailoring MPI imaging parameters for optimal spatial resolution. METHODS The authors first extend x-space systems theory to include nanoparticle relaxation. The authors then measure the spatial resolution and relative signal levels in an MPI relaxometer and a 3D MPI imager at multiple drive field amplitudes and frequencies. Finally, these image measurements are used to estimate relaxation times and nanoparticle phase lags. RESULTS The authors demonstrate that spatial resolution, as measured by full-width at half-maximum, improves at lower drive field amplitudes. The authors further determine that relaxation in MPI can be approximated as a frequency-independent phase lag. These results enable the authors to accurately predict MPI resolution and sensitivity across a wide range of drive field amplitudes and frequencies. CONCLUSIONS To balance resolution, signal-to-noise ratio, specific absorption rate, and magnetostimulation requirements, the drive field can be a low amplitude and high frequency. Continued research into how the MPI drive field affects relaxation and its adverse effects will be crucial for developing new nanoparticles tailored to the unique physics of MPI. Moreover, this theory informs researchers how to design scanning sequences to minimize relaxation-induced blurring for better spatial resolution or to exploit relaxation-induced blurring for MPI with molecular contrast.

A 7 T/M 3D X-space MPI mouse and rat scanner

This prototype system has already produced high quality images with spatial resolutions very similar to the theoretically predicted resolution across mouse and rat sized FOVs. We have imaged both plastic and biological imaging phantoms, as well as ex vivo mice (not shown). Some early images are shown below in Fig. 1b-c. Imaging times are comparable to micro-MRI: full mouse and rat images (up to 12 cm × 5 cm × 5 cm) require between 2-5 minutes per image.

Third Generation X-Space MPI Mouse and Rat Scanner

Here we describe the construction of our third generation x-space MPI scanner, the fifth MPI scanner built at UC Berkeley. The scanner has two goals, (1) High-resolution native MPI resolution using x-space reconstruction, and (2) extended FOV suitable for mice and rats. In this paper we describe our design criteria, and we show the initial characterizations of the 7 T/m gradient field.

Experimental 3D X-Space Magnetic Particle Imaging Using Projection Reconstruction

Tomographic imaging using a shifted and rotated field free line (FFL) with filtered backprojection image reconstruction can approach an order of magnitude SNR improvement over a field free point (FFP) given equal scan time. In this paper, we demonstrate a projection reconstruction x-space imager. The imager consists of a 2.4 T/m permanent magnet FFL gradient, a Helmholtz pair of off-the-shelf electromagnets, a solenoidal transmit coil and a gradiometer receive coil. A motor driven rotary table rotates the sample and the system acquires multiple projection images at evenly spaced angles between zero degrees and 180 degrees. Filtered back-projection is used to reconstruct a three-dimensional tomographic image stack. Sample rotation, which is sometimes employed in commercial mouse CT scanners, has been used to test this method. Later systems may rotate the gradient similar to a human-sized CT gantry or may generate an electronically rotated FFL gradient. In previous work, we have shown an MPI capable FFL scanner. Here, we show 3D experimental results of our PR-MPI scanner using acrylic USPIO imaging phantoms and post-mortem mice.

Projection X-Space MPI Mouse Scanner

Here we describe the construction and images of the first projection x-space MPI scanner. The scanner is a side-access quadrupole design, and generates a 2.35 T/m main field gradient. The system excites the sample and receives signal in one axis, and reconstructs full-body images using x-space reconstruction. The resulting images are of high quality, and we demonstrate linear and shift invariance of the imaging system by imaging a resolution phantom and mice injected with Resovist.