X‐Space MPI: Magnetic Nanoparticles for Safe Medical Imaging

Department of Bioengineering, University of California Berkeley, Berkeley, CA 94720-1762, USA.
Advanced Materials (Impact Factor: 17.49). 07/2012; 24(28):3870-7. DOI: 10.1002/adma.201200221
Source: PubMed


One quarter of all iodinated contrast X-ray clinical imaging studies are now performed on Chronic Kidney Disease (CKD) patients. Unfortunately, the iodine contrast agent used in X-ray is often toxic to CKD patients' weak kidneys, leading to significant morbidity and mortality. Hence, we are pioneering a new medical imaging method, called Magnetic Particle Imaging (MPI), to replace X-ray and CT iodinated angiography, especially for CKD patients. MPI uses magnetic nanoparticle contrast agents that are much safer than iodine for CKD patients. MPI already offers superb contrast and extraordinary sensitivity. The iron oxide nanoparticle tracers required for MPI are also used in MRI, and some are already approved for human use, but the contrast agents are far more effective at illuminating blood vessels when used in the MPI modality. We have recently developed a systems theoretic framework for MPI called x-space MPI, which has already dramatically improved the speed and robustness of MPI image reconstruction. X-space MPI has allowed us to optimize the hardware for fi ve MPI scanners. Moreover, x-space MPI provides a powerful framework for optimizing the size and magnetic properties of the iron oxide nanoparticle tracers used in MPI. Currently MPI nanoparticles have diameters in the 10-20 nanometer range, enabling millimeter-scale resolution in small animals. X-space MPI theory predicts that larger nanoparticles could enable up to 250 micrometer resolution imaging, which would represent a major breakthrough in safe imaging for CKD patients.

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    • "Patient safety is an important motivation for a proper choice of magnetic particulate systems designed for both diagnosis and therapy (theranostics). To exemplify , iodine or gadolinium tracers are hazardous for patients with chronic kidney disease, therefore their use as contrast agents is a public health safety concern and requires a safer replacement, such as iron oxide nanoparticles (IONPs) [11]. Complex nanosystems of coated and multiple functionalized superparamagnetic iron oxide nanoparticles started to become the most important tools of nanomedicine [7] [9] [12] [13], as they represent the best compromise between good magnetic properties and very reduced toxicity, evidenced by extensive in vitro and in vivo tests [14] and by quantitative evaluation of biodistribution and local therapeutic effects [12] [15]. "
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    ABSTRACT: Recent developments in nanotechnology and application of magnetic nanoparticles, in particular in magnetic iron oxide nanosystems, offer exciting possibilities for nanomedicine. Facile and precise synthesis procedures, high magnetic response, tunable morphologies and multiple bio-functionalities of single- and multi-core magnetic particles designed for nanomedicine applications are thoroughly appraised. This review focuses on the structural and magnetic characterization of the cores, the synthesis of single- and multicore iron oxide NPs, especially the design of the latter, as well as their protection, stabilization and functionalization by desired coating in order to protect against the corrosion of core, to prevent non-specific protein adsorption and particle aggregation in biological media, and to provide binding sites for targeting and therapeutic agents. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 08/2015; DOI:10.1016/j.bbrc.2015.08.030 · 2.30 Impact Factor
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    • "The idea of magnetic particle imaging (MPI) based on harmonic fields was first demonstrated in 2005 [20]. Various important achievements have been reported since that time including three dimensional realtime imaging [21], the use of intermodulation to create harmonics at frequencies other than multiples of the primary field [22] [23], xspace based imaging [24] [25], inclusion of a direct current (DC) field component to create even harmonics [26] [27], improvements in the magnetic characteristics of mNPs [28], the use of field free lines [29] [30] [31], a one-sided MPI system [32], an MPI system without a field free point [33], an alternative field free point [34], use in medical applications [21] [35] and a model-based imaging approach [36]. We previously introduced the susceptibility magnitude imaging (SMI) method that achieves mNP imaging with an array of drive coils, fluxgate magnetometers, and compensation coils using linear magnetic susceptibility measurements [37]. "
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    ABSTRACT: This study demonstrates a method for improving the resolution of susceptibility magnitude imaging (SMI) using spatial information that arises from the nonlinear magnetization characteristics of magnetic nanoparticles (mNPs). In this proof-of-concept study of nonlinear SMI, a pair of drive coils and several permanent magnets generate applied magnetic fields and a coil is used as a magnetic field sensor. Sinusoidal alternating current (AC) in the drive coils results in linear mNP magnetization responses at primary frequencies, and nonlinear responses at harmonic frequencies and intermodulation frequencies. The spatial information content of the nonlinear responses is evaluated by reconstructing tomographic images with sequentially increasing voxel counts using the combined linear and nonlinear data. Using the linear data alone it is not possible to accurately reconstruct more than 2 voxels with a pair of drive coils and a single sensor. However, nonlinear SMI is found to accurately reconstruct 12 voxels (R(2) = 0.99, CNR = 84.9) using the same physical configuration. Several time-multiplexing methods are then explored to determine if additional spatial information can be obtained by varying the amplitude, phase and frequency of the applied magnetic fields from the two drive coils. Asynchronous phase modulation, amplitude modulation, intermodulation phase modulation, and frequency modulation all resulted in accurate reconstruction of 6 voxels (R(2) > 0.9) indicating that time multiplexing is a valid approach to further increase the resolution of nonlinear SMI. The spatial information content of nonlinear mNP responses and the potential for resolution enhancement with time multiplexing demonstrate the concept and advantages of nonlinear SMI.
    Journal of Magnetism and Magnetic Materials 03/2015; 378:267-277. DOI:10.1016/j.jmmm.2014.11.049 · 1.97 Impact Factor
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    • "One of the most promising uses of mNPs in medicine is as an imaging contrast agent. Significant research has resulted in the development of methods such as magnetic particle imaging (MPI) [3] [4] [5] [6], magnetic resonance imaging MRI methods such as Sweep Imaging with Fourier Transform (SWIFT) [7] [8], magnetic relaxometry (MRX) [9] [10] [11] [12] [13] [14] [15] [16] [17] and AC susceptibility detection [18] [19] [20] [21] [22] [23]. A particularly relevant study to the present work describes the use of magnetic relaxometry and an array of SQUID sensors and drive coils to spatially localize mNPs using excitation fields in the microtesla range [9]. "
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    ABSTRACT: This study demonstrates a method for alternating current (AC) susceptibility imaging (ASI) of magnetic nanoparticles (mNPs) using low cost instrumentation. The ASI method uses AC magnetic susceptibility measurements to create tomographic images using an array of drive coils, compensation coils and fluxgate magnetometers. Using a spectroscopic approach in conjunction with ASI, a series of tomographic images can be created for each frequency measurement set and is termed sASI. The advantage of sASI is that mNPs can be simultaneously characterized and imaged in a biological medium. System calibration was performed by fitting the in-phase and out-of-phase susceptibility measurements of an mNP sample with a hydrodynamic diameter of 100 nm to a Brownian relaxation model (R2=0.96). Samples of mNPs with core diameters of 10 and 40 nm and a sample of 100 nm hydrodynamic diameter were prepared in 0.5 ml tubes. Three mNP samples were arranged in a randomized array and then scanned using sASI with six frequencies between 425 and 925 Hz. The sASI scans showed the location and quantity of the mNP samples (R2=0.97). Biological compatibility of the sASI method was demonstrated by scanning mNPs that were injected into a pork sausage. The mNP response in the biological medium was found to correlate with a calibration sample (R2=0.97, p<0.001). These results demonstrate the concept of ASI and advantages of sASI.
    Journal of Magnetism and Magnetic Materials 02/2015; 375:164–176. DOI:10.1016/j.jmmm.2014.10.011 · 1.97 Impact Factor
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