Nanoparticle technology for the 21st Century
Magnetic Particle Imaging (MPI) is a tomographic imaging technique that measures the magnetic fields generated by magnetic particles in a tracer.
In recent decades, tomographic imaging methods such as computed tomography (CT) magnetic resonance imaging (MRI) and positron-emission tomography (PET) have become important tools for the diagnosis of a large number of diseases. While PET provides high sensitivity in static imaging based on tracer materials, MRI and CT offer intrinsic tissue contrast at high spatial resolution and are capable of dynamic imaging. However, despite recent advances, real-time imaging of 3D volumes using MR remains challenging. CT, as well as x-ray fluoroscopy, offers higher temporal resolution, but applies ionizing radiation.
Recently, a new imaging modality called magnetic particle imaging (MPI) has been presented. It offers quantitative 3D real-time imaging of ferromagnetic nano-particles at spatial resolutions comparable to established modalities. Therefore, it could become the modality of choice for diagnoses requiring fast dynamic information, e.g., blood flow in the case of coronary artery disease.
Magnetic particle imaging (MPI) is a tomographic imaging technique that measures the magnetic fields generated by superparamagnetic nanoparticles (iron oxide) as tracers. Philips Research have used the technique to achieve resolutions finer than one millimeter. Magnetic particle imaging has potential applications in medicine and material science.
In comparison to the classic setup as ‘a cave’, the University of Lübeck in Germany is developing a single-sided MPI scanner. The single-sided MPI scanner could be used like an ultrasound device.
The MPI method directly detects the bulk magnetization from an SPIO whose saturation magnetization approaches 0.6 T. The MPI method has extraordinary promise for sensitivity and contrast because this bulk SPIO magnetization is 10 million times more intense than the nuclear paramagnetism of water detected with a 7 Tesla MRI scanner. Philips Research have used the technique to achieve resolutions finer than one millimeter.
Until now, only dynamic 2D phantom experiments with high tracer concentrations have been demonstrated. These first in vivo 3D real-time MPI scans are presented revealing details of a beating mouse heart using a clinically approved concentration of a commercially available MRI contrast agent. A temporal resolution of 21.5 ms is achieved at a 3D field of view of 20.4 × 12 × 16.8 mm3 with a spatial resolution sufficient to resolve all heartchambers. With these abilities, MPI has taken a huge step toward medical application.
The superparamagnetic nanofluid used in magnetic particle imaging is superparamagnetic iron oxide (SPIO). This fluid is very responsive to even weak magnetic fields, and all of the magnetic moments will line up in the direction of an induced magnetic field. These particles can be used because the human body does not contain anything which will create magnetic interference in imaging.
• High resolution (~0.4 mm)
• Fast image results (~20 ms)
• No radiation
• No iodine
• No background noise (high contrast)
SPIO tracers have shown exceptional utility in human MRI studies for liver and lymph node cancer detection and are routinely used in animal MRI experiments to tag and track cells. MRI detects the presence of SPIO nanoparticles indirectly, typically by detecting the dephasing of the signal from the nuclear paramagnetism of water surrounding the SPIO. Consequently, the detection limit is typically low, but there has been some progress in MRI detection of single SPIO tagged cells under ideal conditions. Numerous groups have developed positive and negative contrast methods, which aim to localize and quantify SPIO concentrations. MPI's goal in detecting nanomolar concentrations of SPIO particles would provide a 200-fold gain in sensitivity over MRI with positive contrast, and should enable reliable tracking of tens of tagged cells in vivo.
Because the human body contains no naturally occurring magnetic materials visible to MPI, there is no background signal. After injection, the nanoparticles therefore appear as bright signals in the images, from which anoparticle concentrations can be calculated. By combining high spatial resolution with short image acquisition times (as short as 1/50th of a second), Magnetic Particle Imaging can capture dynamic concentration changes as the nanoparticles are swept along by the blood stream. This could ultimately allow MPI scanners to perform a wide range of functional cardiovascular measurements in a single scan. These could include measurements of coronary blood supply, myocardial perfusion, and the heart's ejection fraction, wall motion and flow speeds.
The technology enables unprecedented real-time images of arterial blood flow and volumetric heart motion. This represents a major step forward in taking Magnetic Particle Imaging from a theoretical concept to an imaging tool to help improve diagnosis and therapy planning for many of the world's major diseases, such as heart disease, stroke and cancer.
"A novel non-invasive cardiac imaging technology is required to further unravel and characterize the disease processes associated with atherosclerosis, in particular those associated with vulnerable plaque formation which is a major risk factor for stroke and heart attacks," says Professor Valentin Fuster, M.D., Ph.D., director of the Mount Sinai Heart Center, New York. "Through its combined speed, resolution and sensitivity, Magnetic Particle Imaging technology has great potential for this application, and the latest in-vivo imaging results represent a major breakthrough."
"We are the first in the world to demonstrate that Magnetic Particle Imaging can be used to produce real-time in-vivo images that accurately capture cardiovascular activity," says Henk van Houten, senior vice president of Philips Research and head of the Healthcare research program.
"By adding important functional information to the anatomical data obtained from existing modalities such as CT and MR, Philips' MPI technology has the potential to significantly help in the diagnosis and treatment planning of major diseases such as atherosclerosis and congenital heart defects."
The results obtained from Philips' experimental MPI scanner mark an important step towards the development of a whole-body system for use on humans. Some of the technical challenges in scaling up the system relate to the magnetic field generation required for human applications. Others lie in the measurement and processing of the extremely weak signal emitted by the nanoparticles.
Beyond cell tracking, MPI's excellent resolution and sensitivity would have medical applications including angiography using venous injections of SPIOs, examining allograft rejection, and tracking inflammation.
Compiled by Dr JD Sandham