Nanotech Enables Faster, More Powerful MRI
Molecular nanomagnets have been shown to improve the contrast between healthy and diseased tissues in magnetic resonance imaging.
Researchers at the National Institute of Standards and Technology (NIST), Boulder, Colo.; Florida State Univ. (FSU), Tallahassee; the Univ. of Colorado (UC), Boulder; and The Children’s Hospital (TCH), Denver, Colo., have shown that nanoscale magnets in the form of iron-containing molecules can be used to improve the contrast between healthy and diseased tissues in magnetic resonance imaging (MRI) techniques. The disclaimer on this discovery is that the concentration of the nanomagnets needs to be carefully managed.
MRI relies on the relaxation properties of excited hydrogen nuclei in water and lipids. Within a high-power magnetic field, the spins of these hydrogen atoms align either parallel or anti-parallel to the magnetic field according to quantum mechanics. The tissues being imaged are then exposed to pulses of electromagnetic energy (RF pulses) in a plane perpendicular to the magnetic field, which causes some of the magnetically aligned hydrogen nuclei to assume a temporary non-aligned high-energy state. Orthogonal magnetic gradients are then applied to the object being imaged to collect different image voxels.
Various techniques can be used within the MRI control procedures to provide image contrasts between different tissues, such as that between blood and brain tissue within the cranial cavity. These T1-weighted and T2-weighted techniques are routinely used in most imaging procedures. And when T1 and T2 still don’t provide enough contrast, even more sophisticated machine-control techniques can be used such as fat-suppression or chemical shifts.
One contrast alternative
Often, however, in actual clinical testing, a separate contrast agent may need
to be administered to the subject to delineate the areas of interest. This could
be as simple as drinking water to image the stomach. More commonly, however, a
paramagnetic contrast agent, such as a gadolinium (Gd) compound, is administered.
U.S. Food and Drug Administration (FDA)-approved Gd-contrast-enhancing compounds
have been available for MRI procedures since 1988 (Magnevist, manufactured in
Germany for Berlex, Montville, N.J.). Recently, however, there has been research
that shows a possible association between the Gd-contrast compound and the incidence
of a rare disease called nephrogenic systemic fibrosis (NSF) in a small number
of patients with kidney disease.
Previous research in replacements for the Gd-contrast compound focused on clusters of iron molecules. One nanoparticle evaluated is a new class of uniform, biodegradable, and non-toxic superparamagnetic contrast agent, Fe3O4. These particles are usually of varying sizes from several to several hundred nanometers. They are irregular in shape and highly light absorbing. The have no magnetic hysteresis at ambient temperatures, which is characteristic of superparamagnetic materials.
Another example of this kind of molecule is the octanuclear iron cluster of formula Fe8O2 (OH)12 (tacn6)Br8 or abbreviated Fe8—tacn is triazacyclonane which provides a hydrophobic shell that prevents the growth of metal hydroxide-oxide core to an extended lattice. The results of these tests on these single-molecule magnetic materials were inconclusive with one claiming a much greater efficiency of Fe8 for MRI contrast and another claiming a lower efficiency, when compared to the Gd-contrast compound.
The NIST research collaboration noted above, however, recently issued a report (Polyhedron, available online Dec. 14, 2006.) stating that for concentrations below 1.5mM, the Fe8 has a T1 relaxivity (a function of contrast) of 5.4/sec-mM, which is comparable to the generally available Gd-contrast compound. For concentrations above 1.5 mM, the Fe8 has a T1 relaxivity of 1.1/sec-mM, or significantly lower than the Gd-contrast compound. Results for T2 relaxivities were similar. The non-linearity of the Fe8 appears to account for the inconclusive results in the earlier tests that did not take contrast concentration levels into account. While Gd-contrast data are monotonic over the entire concentration range, the Fe8 data exhibits two distinctly linear regions.
The NIST, et al, researchers, utilizing novel magnetic measurements based on SQUID (superconducting quantum interference device) magnetometer evaluations of the decomposition of Fe8 in aqueous solutions, were able to monitor the Fe8 molecules’ magnetic properties as the concentration was varied. The excitation spectra of Fe8 were characterized using SQUID high-frequency EPR (electron paramagnetic resonance). This novel EPR technique uses a SQUID magnetometer to quantitatively measure the spin excitation in response to microwave radiation.
Magnetic advantages
The MRI contrast agents currently in use consist of two types of injectable dyes. Magnetic ions, which alter the nuclear properties of hydrogen in water, offer the advantage of consistent identical designs, but provide low contrasts. The second category encompasses particles of thousands of atoms or crystals, which provide contrast variations in a larger region but have irregular designs and magnetic properties that are difficult to control. By comparison, molecular nanomagnets, such as Fe8, can be designed to have consistent properties and high contrast. In addition, they might be modified to act as “smart” materials whose contrast could be turned on only when bonded to a target molecule or cell. Toxicity, similar to that seen in the Gd-contrast compounds, is not believed to be an issue, because iron is found naturally in the body and other studies have found that these materials are non-toxic at the concentrations used in MRI procedures.
The NIST single molecule magnets for these studies were manufactured at less than 5 nm in dia at FSU, while researchers at UC created nanocrystals in the 10 to 50 nm range. NIST is continuing their research by developing additional methods for manipulating and measuring the magnetic properties of these compounds, while developing the instrumentation needed to understand how contrast agents work and how to control contrast properties. The researchers are correlating the measured properties to the observed MRI response under non-clinical conditions using MRI imaging equipment at The Children’s Hospital for fabricating improved Fe8 contrast compounds.
—Tim Studt
Resources
The Children’s Hospital, Denver, Colo., www.thechildrenshospital.org
Florida State Univ., National High Field Magnet Laboratory, Tallahassee, Fla., www.magnet.fsu.edu
NIST Electromagnetics Div., Boulder, Colo., www.boulder.nist.gov
Univ. of Colorado, Dept. of Chemistry & Biochemistry, Boulder, Colo., http://chemnmr.colorado.edu
Researchers at the National Institute of Standards and Technology (NIST), Boulder, Colo.; Florida State Univ. (FSU), Tallahassee; the Univ. of Colorado (UC), Boulder; and The Children’s Hospital (TCH), Denver, Colo., have shown that nanoscale magnets in the form of iron-containing molecules can be used to improve the contrast between healthy and diseased tissues in magnetic resonance imaging (MRI) techniques. The disclaimer on this discovery is that the concentration of the nanomagnets needs to be carefully managed.
MRI relies on the relaxation properties of excited hydrogen nuclei in water and lipids. Within a high-power magnetic field, the spins of these hydrogen atoms align either parallel or anti-parallel to the magnetic field according to quantum mechanics. The tissues being imaged are then exposed to pulses of electromagnetic energy (RF pulses) in a plane perpendicular to the magnetic field, which causes some of the magnetically aligned hydrogen nuclei to assume a temporary non-aligned high-energy state. Orthogonal magnetic gradients are then applied to the object being imaged to collect different image voxels.
Various techniques can be used within the MRI control procedures to provide image contrasts between different tissues, such as that between blood and brain tissue within the cranial cavity. These T1-weighted and T2-weighted techniques are routinely used in most imaging procedures. And when T1 and T2 still don’t provide enough contrast, even more sophisticated machine-control techniques can be used such as fat-suppression or chemical shifts.
One contrast alternative
|
Previous research in replacements for the Gd-contrast compound focused on clusters of iron molecules. One nanoparticle evaluated is a new class of uniform, biodegradable, and non-toxic superparamagnetic contrast agent, Fe3O4. These particles are usually of varying sizes from several to several hundred nanometers. They are irregular in shape and highly light absorbing. The have no magnetic hysteresis at ambient temperatures, which is characteristic of superparamagnetic materials.
Another example of this kind of molecule is the octanuclear iron cluster of formula Fe8O2 (OH)12 (tacn6)Br8 or abbreviated Fe8—tacn is triazacyclonane which provides a hydrophobic shell that prevents the growth of metal hydroxide-oxide core to an extended lattice. The results of these tests on these single-molecule magnetic materials were inconclusive with one claiming a much greater efficiency of Fe8 for MRI contrast and another claiming a lower efficiency, when compared to the Gd-contrast compound.
The NIST research collaboration noted above, however, recently issued a report (Polyhedron, available online Dec. 14, 2006.) stating that for concentrations below 1.5mM, the Fe8 has a T1 relaxivity (a function of contrast) of 5.4/sec-mM, which is comparable to the generally available Gd-contrast compound. For concentrations above 1.5 mM, the Fe8 has a T1 relaxivity of 1.1/sec-mM, or significantly lower than the Gd-contrast compound. Results for T2 relaxivities were similar. The non-linearity of the Fe8 appears to account for the inconclusive results in the earlier tests that did not take contrast concentration levels into account. While Gd-contrast data are monotonic over the entire concentration range, the Fe8 data exhibits two distinctly linear regions.
The NIST, et al, researchers, utilizing novel magnetic measurements based on SQUID (superconducting quantum interference device) magnetometer evaluations of the decomposition of Fe8 in aqueous solutions, were able to monitor the Fe8 molecules’ magnetic properties as the concentration was varied. The excitation spectra of Fe8 were characterized using SQUID high-frequency EPR (electron paramagnetic resonance). This novel EPR technique uses a SQUID magnetometer to quantitatively measure the spin excitation in response to microwave radiation.
Magnetic advantages
The MRI contrast agents currently in use consist of two types of injectable dyes. Magnetic ions, which alter the nuclear properties of hydrogen in water, offer the advantage of consistent identical designs, but provide low contrasts. The second category encompasses particles of thousands of atoms or crystals, which provide contrast variations in a larger region but have irregular designs and magnetic properties that are difficult to control. By comparison, molecular nanomagnets, such as Fe8, can be designed to have consistent properties and high contrast. In addition, they might be modified to act as “smart” materials whose contrast could be turned on only when bonded to a target molecule or cell. Toxicity, similar to that seen in the Gd-contrast compounds, is not believed to be an issue, because iron is found naturally in the body and other studies have found that these materials are non-toxic at the concentrations used in MRI procedures.
The NIST single molecule magnets for these studies were manufactured at less than 5 nm in dia at FSU, while researchers at UC created nanocrystals in the 10 to 50 nm range. NIST is continuing their research by developing additional methods for manipulating and measuring the magnetic properties of these compounds, while developing the instrumentation needed to understand how contrast agents work and how to control contrast properties. The researchers are correlating the measured properties to the observed MRI response under non-clinical conditions using MRI imaging equipment at The Children’s Hospital for fabricating improved Fe8 contrast compounds.
—Tim Studt
Resources
The Children’s Hospital, Denver, Colo., www.thechildrenshospital.org
Florida State Univ., National High Field Magnet Laboratory, Tallahassee, Fla., www.magnet.fsu.edu
NIST Electromagnetics Div., Boulder, Colo., www.boulder.nist.gov
Univ. of Colorado, Dept. of Chemistry & Biochemistry, Boulder, Colo., http://chemnmr.colorado.edu
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