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Takeno Y.,Tohoku University | Murakami Y.,Tohoku University | Murakami Y.,RIKEN | Sato T.,Hitachi High-Technologies | And 8 more authors.
Applied Physics Letters | Year: 2014

This study reports on the correlation between crystal orientation and magnetic flux distribution of Fe3O4 nanoparticles in the form of self-assembled rings. High-resolution transmission electron microscopy demonstrated that the nanoparticles were single-crystalline, highly monodispersed, (25nm average diameter), and showed no appreciable lattice imperfections such as twins or stacking faults. Electron holography studies of these superparamagnetic nanoparticle rings indicated significant fluctuations in the magnetic flux lines, consistent with variations in the magnetocrystalline anisotropy of the nanoparticles. The observations provide useful information for a deeper understanding of the micromagnetics of ultrasmall nanoparticles, where the magnetic dipolar interaction competes with the magnetic anisotropy. © 2014 AIP Publishing LLC.

Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 150.00K | Year: 2012

This Small Business Innovation Research (SBIR) Phase I project addresses a fundamental problem with Magnetic Particle Imaging, a promising, yet new imaging modality. MPI uses magnetic nanoparticles (tracers) to generate a signal that can be used for fast, safe, non-invasive 3D imaging in living patients. The problem relates to the magnetic tracers: there are no existing commercial tracers that are suitable for MPI, due partly to a fundamental lack of control over the physical and magnetic properties of tracers when using existing methods of production. We have addressed this problem by identifying the desired tracer properties for any MPI imaging system and developing a method to produce particles with controlled/tailored properties. The proposed research is designed to further improve the performance of our product, both to fine-tune its physical characteristics and improve its stability in a biological environment. We will improve the stability and performance of our tracer agent by developing a new process for encapsulating the magnetic particles with a biocompatible shell. We will also further improve the performance by developing a novel filtering system to isolate desirable tracers based specifically on their suitability for MPI, as determined by their magnetic relaxation.

The broader impact/commercial potential of this proposed project is an enabling technology for MPI. The goal is to develop a high performance solution that can make clinical MPI commercially viable. MPI using safe iron oxide tracers could reduce patient morbidity during the course of treatment for cardiovascular disease, where current imaging methods like x-ray angiography rely heavily on the use of iodinated contrast media even though they may cause nephrogenic systemic fibrosis in patients, especially those with chronic kidney disease. MPI with targeted tracer probes, also offers significant promise for cancer diagnosis and therapy, with outstanding signal to noise ratio and almost perfect contrast (tissue is diamagnetic and generates no signal in MPI). Finally, the projected commercial impact of MPI is significant: billions of dollars are spent on medical imaging tracers each year, with iodine the most commonly used tracer. Ultimately, MPI, which would circumvent a known hazard in iodine contrast agents, has the potential to generate billions in tracer sales.

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 220.32K | Year: 2011

DESCRIPTION (provided by applicant): Magnetic Resonance Imaging (MRI) is an attractive platform for medical imaging because it uses neither harmful radiation nor expensive radio-tracers; however, MRI, even with the aid of suitable contrast agents, is plagued by background noise from the host tissue and lacks the ability to quantify exactly how much contrast agent is present at a given location. Despite the fact that contrast agents are useful in imaging and differentiating abnormal tissues (tumors) from healthy tissues at much larger scales, early detection of a few-thousand cancer cells is difficult due to the lack of contrast differentiating the tumor from surrounding healthy tissue. Additionally, quantification of cells at the disease site is crucial fordevelopment of more site-specific contrast agents that will enable future developments in image-guided therapeutics. Thus, there is a critical need to develop magnetic molecular probes that, unlike contrast agents, can be directly imaged, irrespective of the surrounding tissue, and can be simultaneously targeted to disease sites for early diagnostic imaging. Our goal is to use Magnetic Particle Imaging (MPI), a new medical imaging technology recently introduced by Philips that uses the magnetic relaxationof magnetite nanoparticles in alternating fields, to produce three-dimensional images of the distribution of the nanoparticles in the tissue. The magnetic nanoparticles will have a million times more signal in MPI compared to the nuclear paramagnetism of protons used in MRI. Royal Philips and Bruker Biospin, have jointly announced the development of a preclinical MPI hardware and imaging system, to be marketed in 2011/12. However, commercially available magnetite formulations are grossly inadequate for MPI,both in terms of signal intensity and spatial resolution. In fact, if this critical component, i.e. appropriate magnetite nanoparticle-based molecular probes, that are biocompatible and surface functionalized for facile bioconjugation, and tailored for optimal, performance, are not developed now the enormous potential of MPI may never be realized. Based on our knowhow, we propose to develop the technology of the molecular probes crucially required for the success of MPI in a most timely manner. Our threespecific aims (SA) will focus on (SA1) development of monodispersed and biocompatible magnetic nanoparticles (MNPs) as molecular probes optimized for any specific driving frequency used in MPI, (SA2) functionalize the MNPs for specific targeting to tumor cells and the surrounding vasculature and determine the targeting effectiveness in vitro, and (SA3) demonstrate MPI's ability to detect and quantify our targeted MNPs in vitro using a home-built magnetic spectrometer, thereby setting the stage for Phase IIwork involving in vivo imaging and quantification. PUBLIC HEALTH RELEVANCE: Medical imaging, in its many forms, is a crucial technique used by clinicians for diagnosing diseases and determining the correct treatment options for patients. Diagnosis of cancer, a disease that has resulted in over 550,000 deaths in the United States in 2010 alone (National Cancer Institute; www.cancer.gov), is especially difficult and often detected at much later stages when patient survival chances are low. For early detection of a few-thousand cells, it is important to use nanometer-scale probes (1 nanometer = 1 billionth of a meter) that can specifically target cancer cells and be directly imaged, without any interference or noise from the patient's body. In this project, we will develop functionalized magnetic nanoparticle-based molecular probes, with a million times more signal than nuclear paramagnetism used in MRI, for early detection of cancer using a new and emerging technique called Magnetic Particle Imaging (MPI). Our technology will complement the hardware being developed by Philips, the inventors of MPI. This technology, if successful, will be superior to current imaging techniques such as Magnetic Resonance Imaging (MRI) and has the potential to enable early diagnosis, giving patients a head start in the fight against cancer.

Shah S.A.,University of Washington | Shah S.A.,Forman Christian College | Reeves D.B.,Dartmouth College | Ferguson R.M.,University of Washington | And 3 more authors.
Physical Review B - Condensed Matter and Materials Physics | Year: 2015

Superparamagnetic iron oxide nanoparticles with highly nonlinear magnetic behavior are attractive for biomedical applications like magnetic particle imaging and magnetic fluid hyperthermia. Such particles display interesting magnetic properties in alternating magnetic fields and here we document experiments that show differences between the magnetization dynamics of certain particles in frozen and melted states. This effect goes beyond the small temperature difference (ΔT∼20C) and we show the dynamics to be a mixture of Brownian alignment of the particles and Néel rotation of their moments occurring in liquid particle suspensions. These phenomena can be modeled in a stochastic differential equation approach by postulating log-normal distributions and partial Brownian alignment of an effective anisotropy axis. We emphasize that precise particle-specific characterization through experiments and nonlinear simulations is necessary to predict dynamics in solution and optimize their behavior for emerging biomedical applications including magnetic particle imaging. © 2015 American Physical Society.

Ferguson R.M.,LodeSpin Labs | Khandhar A.P.,LodeSpin Labs | Khandhar A.P.,University of Washington | Kemp S.J.,LodeSpin Labs | And 10 more authors.
IEEE Transactions on Medical Imaging | Year: 2015

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 MPI's 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. © 1982-2012 IEEE.

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