Effect of NC100150 injection on the (1)H NMR linewidth of human whole blood ex vivo: dependency on blood oxygen tension.

The linewidth of the (1)H NMR signal (7.05 T) of human whole blood titrated with a superparamagnetic contrast agent (NC100150 injection) was evaluated at different blood oxygen tensions. In deoxygenated blood and low contrast agent concentrations, NC100150 injection caused a decrease in linewidth. After reaching a minimum, the linewidth increased as the concentration of NC100150 injection increased. At the concentration corresponding to the minimum linewidth, the magnetization of the extracellular space containing the NC100150 injection was equal to that of the paramagnetic (deoxygenated hemoglobin) intracellular space. The minimum linewidth is therefore consistent with a complete elimination of the local microscopic susceptibility effect, the major cause of linebroadening. Additionally, phantom studies were performed at 1.5 T, confirming that the contrast enhancement of NC100150 injection in blood is dependent on oxygen tension. The data suggest that NC100150 injection may be useful in differentiating vessels with varying relative oxygen tensions.

NC100150 Injection, a preparation of optimized iron oxide nanoparticles for positive-contrast MR angiography.

A preparation of monocrystalline iron oxide nanoparticles with an oxidized starch coating, currently in clinical trials (NC100150 Injection; CLARISCAN), was characterized by magnetization measurements, relaxometry, and photon correlation spectroscopy. By combining the results with a measure of iron content, one can obtain the size and magnetic attributes of the iron cores, including the relevant correlation times for outer sphere relaxation (tau(SO) and tau(D)), and information about the interaction of the organic coating with both core and solvent. The results are 6.43 nm for the iron oxide core diameter, a magnetic moment of 4.38x10(-17) erg/G, and a water-penetrable coating region of oxidized oligomeric starch fragments and entrained water molecules. The latter extends the hydrodynamic diameter to 11.9 nm and lowers the average diffusivity of solvent about 64% (which increases tau(D) accordingly). The nanoparticles show little size-polydispersity, evidenced by the lowest value of r(2)/r(1) at 20 MHz reported to date, an asset for magnetic resonance angiography.

'NC100150', a preparation of iron oxide nanoparticles ideal for positive-contrast MR angiography.

A laboratory-scale synthesis of NC100150 (iron oxide particles with an oxidized starch coating) was characterized by magnetization measurements (vibrating sample magnetometry, VSM), relaxometry (1/T1 NMRD profiles and 1/T2 at 10 and 20 MHz), and dynamic light scattering (photon correlation spectroscopy, PCS). The results were related to give a self-consistent physical description of the particles: a water-impenetrable part making up 12% of the total particle volume, 82% of this volume consisting of an iron oxide core and the remaining 18% consisting of an oxidized starch rind; and, a water-penetrable part making up 88% of the total particle volume, consisting of oxidized starch polymers and entrained water molecules. Relating the magnetization to the relaxometry results required that the oxidized starch coating slows the diffusivity of solvent water molecules in the vicinity of the iron oxide cores. The effect of the organic coating on water diffusivity, not previously considered in the application of relaxation theory to iron oxide nanoparticles, is supported by the much greater (factor of about 2) diameter obtained from the dynamic light scattering measurements in comparison to that obtained from the magnetization measurements. The present work shows that three physical techniques--VSM, relaxometry, and PCS--are needed for properly assessing iron oxide nanoparticles for use as contrast agents for magnetic resonance angiography (MRA). It is also shown that NC100150 has a narrow range of diameters and the smallest value of r2/r1 reported to date, an asset for MRA.

Phantom standards with temperature- and field-independent relaxation rates for magnetic resonance imaging.

RATIONALE AND OBJECTIVES: For use as magnetic resonance imaging reference standards, the optimal set of phantoms should cover a wide range of T1 values, with each phantom having a T1 that is stable over time and is independent of temperature and magnetic field strength. To date, no set of phantoms fulfilling these four requirements has been prepared. In the current work, the construction of such optimal phantom standards is attempted. METHODS: Two linear gadolinium DTPA polymers are used: the first with relaxivities that are independent of temperature and magnetic field strength, and the second with relaxivities that are independent of magnetic field strength, but have an opposite temperature dependence from that of the 1/T1 of the diamagnetic matrix (agarose gel or water). Depending on the desired T1, either one or a combination of the two agents is used. RESULTS: Phantom standards were constructed with 1/T1 values that are independent of temperature (20-35 degrees C) and magnetic field strength (0.47-1.2 T) over a wide range of 1/T1 values (> or = 0.95 s-1). Phantom standards prepared in water were found to be stable with respect to 1/T1 for at least 18 months. CONCLUSIONS: Stable phantoms standards have been constructed covering a wide range of T1 values, where the T1 of any particular phantom is independent of temperature and magnetic field strength for magnetic resonance imaging conditions.

Crystal size and properties of superparamagnetic iron oxide (SPIO) particles.

The properties of a superparamagnetic iron oxide (SPIO) model contrast agent have been studied. The test material, HEP-SPIO, contained iron oxide multicrystal agglomerates coated with heparin, polyanionic, naturally occurring glycosaminoglycan. Fractionation of the HEP-SPIO suspension showed the existence of colloidally stable particles ranging from approx. 100 nm down to single crystal sizes. The small (< 20 nm) particles represented the major number fraction of particles present, but only approx. 2% of the total iron oxide mass. The volume weighted average diameter of the individual iron oxide crystals forming the multicrystal agglomerates was found to be 11-12 nm using transmission electron microscopy and vibrating sample magnetometry (VSM) techniques. Comparable results were obtained with X-ray diffraction and Mössbauer spectroscopy. A number of additional SPIO properties could also be determined on a routine VSM, such as the distribution standard deviation for the log-normal distribution of crystal sizes, the magnetic susceptibility, the magnetic remanence, and the intrinsic magnetization (magnetic moment) of the iron oxide. These parameters are useful tools for evaluation of the magnetic characteristics and contrast efficacy of SPIO contrast agents.

Magnetic characterization of iron oxides for magnetic resonance imaging.

The OMP particle and four additional iron oxide samples were investigated in terms of zero field cooled magnetization (ZFCM) curves and hysteresis loops. The observation of superparamagnetic blocking and the absence of magnetic remanence demonstrated that the samples are superparamagnetic at room temperature. The magnitude of the ZFCM peak temperatures are in qualitative agreement with the iron oxide crystal size. One sample deviated from the remaining four in that it had a significantly lower magnetic moment and an irregular ZFCM curve showing the presence of various less magnetic phases. The similar results obtained with the OMP particles and the individual OMP crystallites without the polymer support show that the superparamagnetic properties of the individual OMP crystallites are retained on the OMP particle. Depending on the application, the ZFCM experiment may be viewed as an alternative or a supplement to Mössbauer spectroscopy in studies of the superparamagnetic blocking of iron oxides.