Aqueous Dispersion of Manganese-Zinc Ferrite Nanoparticles Protected by PEG as a T2 MRI Temperature Contrast Agent.

Mixed manganese-zinc ferrite nanoparticles coated with PEG were studied for their potential usefulness in MRI thermometry as temperature-sensitive contrast agents. Particles in the form of an 8.5 nm core coated with a 3.5 nm layer of PEG were fabricated using a newly developed, one-step method. The composition of Mn0.48Zn0.46Fe2.06O4 was found to have a strong thermal dependence of magnetization in the temperature range between 5 and 50 °C. Nanoparticles suspended in an agar gel mimicking animal tissue and showing non-significant impact on cell viability in the biological test were studied with NMR and MRI over the same temperature range. For the concentration of 0.017 mg/mL of Fe, the spin-spin relaxation time T2 increased from 3.1 to 8.3 ms, while longitudinal relaxation time T1 shows a moderate decrease from 149.0 to 125.1 ms. A temperature map of the phantom exposed to the radial temperature gradient obtained by heating it with an 808 nm laser was calculated from T2 weighted spin-echo differential MR images. Analysis of temperature maps yields thermal/spatial resolution of 3.2 °C at the distance of 2.9 mm. The experimental relaxation rate R2 data of water protons were compared with those obtained from calculations using a theoretical model incorporating the motion averaging regime.

Synthesis of Manganese Zinc Ferrite Nanoparticles in Medical-Grade Silicone for MRI Applications.

The aim of this project is to fabricate hydrogen-rich silicone doped with magnetic nanoparticles for use as a temperature change indicator in magnetic resonance imaging-guided (MRIg) thermal ablations. To avoid clustering, the particles of mixed MnZn ferrite were synthesized directly in a medical-grade silicone polymer solution. The particles were characterized by transmission electron microscopy, powder X-ray diffraction, soft X-ray absorption spectroscopy, vibrating sample magnetometry, temperature-dependent nuclear magnetic resonance relaxometry (20 °C to 60 °C, at 3.0 T), and magnetic resonance imaging (at 3.0 T). Synthesized nanoparticles were the size of 4.4 nm ± 2.1 nm and exhibited superparamagnetic behavior. Bulk silicone material showed a good shape stability within the study's temperature range. Embedded nanoparticles did not influence spin-lattice relaxation, but they shorten the longer component of spin-spin nuclear relaxation times of silicone's protons. However, these protons exhibited an extremely high r2* relaxivity (above 1200 L s-1 mmol-1) due to the presence of particles, with a moderate decrease in the magnetization with temperature. With an increased temperature decrease of r2*, this ferro-silicone can be potentially used as a temperature indicator in high-temperature MRIg ablations (40 °C to 60 °C).

Magnetic particle based MRI thermometry at 0.2 T and 3 T.

This study provides insight into the advantages and disadvantages of using ferrite particles embedded in agar gel phantoms as MRI temperature indicators for low-magnetic field scanners. We compare the temperature-dependent intensity of MR images at low-field (0.2 T) to those at high-field (3.0 T). Due to a shorter T1 relaxation time at low-fields, MRI scanners operating at 0.2 T can use shorter repetition times and achieve a significant T2⁎ weighting, resulting in strong temperature-dependent changes of MR image brightness in short acquisition times. Although the signal-to-noise ratio for MR images at 0.2 T MR is much lower than at 3.0 T, it is sufficient to achieve a temperature measurement uncertainty of about ±1.0 °C at 37 °C for a 90 µg/mL concentration of magnetic particles.

One-Step Preparation of Highly Stable Copper-Zinc Ferrite Nanoparticles in Water Suitable for MRI Thermometry.

Superparamagnetic ferrite nanoparticles coated with a polymer layer are widely used for biomedical applications. The objective of this work is to design nanoparticles as a magnetic resonance imaging (MRI) temperature-sensitive contrast agent. Copper-zinc ferrite nanoparticles coated with a poly(ethylene glycol) (PEG) layer are synthesized using a one-step thermal decomposition method in a polymer matrix. The resulting nanoparticles are stable in water and biocompatible. Using Mössbauer spectroscopy and magnetometry, it was determined that the grown nanoparticles exhibit superparamagnetic properties. Embedding these particles into an agarose gel resulted in significant modification of water proton relaxation times T 1, T 2, and T 2* determined by nuclear magnetic resonance measurements. The results of the spin-echo T 2-weighted MR images of an aqueous phantom with embedded Cu0.08Zn0.54Fe2.38O4 nanoparticles in the presence of a strong temperature gradient show a strong correlation between the temperature and the image intensity. The presented results support the hypothesis that CuZn ferrite nanoparticles can be used as a contrast agent for MRI thermometry.

On the optimization of imaging parameters for magnetic resonance imaging thermometry using magnetic microparticles.

Magnetic Resonance Imaging thermometry is an extremely useful technique which allows one to determine, noninvasively, the temperature deep in the tissue in two or three dimensions. Many methods of MR thermometry have been developed, including those that rely on the intrinsic MR properties of tissue and those which depend on the addition of contrast agents injected into the tissue to create temperature dependent MR images. One such method is to introduce magnetic particles whose magnetization's temperature dependence influences the MR properties of the surrounding tissue and obtain temperature from calibrated intensity changes of T2* weighted MR images. One limitation of this method is the temperature resolution which is determined by the rate of change of the magnetization with temperature. One can change the MR response either through varying the particles properties or finding the MR scan parameters which maximize the image contrast due to T2* weighting of images. In this work we calculate the MR signal strength, using known values of T1 and T2* relaxation times for agarose gel phantoms with embedded magnetic particles, and compared this with the temperature dependent intensity of experimental MR images. We seek to optimize the change in signal intensity with temperature by varying the selectable MR scanner parameters: echo time, repetition time, and flip angle. Based on comparison with experimental data we find that the change in signal with temperature can be significantly increased (by as much as 100%) through the appropriate choice of MR scan parameters.

Measurement of sub-zero temperatures in MRI using T1 temperature sensitive soft silicone materials: Applications for MRI-guided cryosurgery.

PURPOSE: One standard method, proton resonance frequency shift, for measuring temperature using magnetic resonance imaging (MRI), in MRI-guided surgeries, fails completely below the freezing point of water. Because of this, we have developed a new methodology for monitoring temperature with MRI below freezing. The purpose of this paper is to show that a strong temperature dependence of the nuclear relaxation time T1 in soft silicone polymers can lead to temperature-dependent changes of MRI intensity acquired with T1 weighting. We propose the use of silicone filaments inserted in tissue for measuring temperature during MRI-guided cryoablations. METHODS: The temperature dependence of T1 in bio-compatible soft silicone polymers was measured using nuclear magnetic resonance spectroscopy and MRI. Phantoms, made of bulk silicone materials and put in an MRI-compatible thermal container with dry ice, allowed temperature measurements ranging from -60°C to + 20°C. T1 -weighted gradient echo images of the phantoms were acquired at spatially uniform temperatures and with a gradient in temperature to determine the efficacy of using these materials as temperature indicators in MRI. Ex vivo experiments on silicone rods, 4 mm in diameter, inserted in animal tissue were conducted to assess the practical feasibility of the method. RESULTS: Measurements of nuclear relaxation times of protons in soft silicone polymers show a monotonic, nearly linear, change with temperature (R2  > 0.98) and have a significant correlation with temperature (Pearson's r > 0.99, p < 0.01). Similarly, the intensity of the MR images in these materials, taken with a gradient echo sequence, are also temperature dependent. There is again a monotonic change in MRI intensity that correlates well with the measured temperature (Pearson's r < -0.98 and p < 0.01). The MRI experiments show that a temperature change of 3°C can be resolved in a distance of about 2.5 mm. Based on MRI images and external sensor calibrations for a sample with a gradient in temperature, temperature maps with 3°C isotherms are created for a bulk phantom. Experiments demonstrate that these changes in MRI intensity with temperature can also be seen in 4 mm silicone rods embedded in ex vivo animal tissue. CONCLUSIONS: We have developed a new method for measuring temperature in MRI that potentially could be used during MRI-guided cryoablation operations, reducing both procedure time and cost, and making these surgeries safer.

Optical Imaging of Magnetic Particle Cluster Oscillation and Rotation in Glycerol.

Magnetic particles have been evaluated for their biomedical applications as a drug delivery system to treat asthma and other lung diseases. In this study, ferromagnetic barium hexaferrite (BaFe12O19) and iron oxide (Fe3O4) particles were suspended in water or glycerol, as glycerol can be 1000 times more viscous than water. The particle concentration was 2.50 mg/mL for BaFe12O19 particle clusters and 1.00 mg/mL for Fe3O4 particle clusters. The magnetic particle cluster cross-sectional area ranged from 15 to 1000 µµm2, and the particle cluster diameter ranged from 5 to 45 µµm. The magnetic particle clusters were exposed to oscillating or rotating magnetic fields and imaged with an optical microscope. The oscillation frequency of the applied magnetic fields, which was created by homemade wire spools inserted into an optical microscope, ranged from 10 to 180 Hz. The magnetic field magnitudes varied from 0.25 to 9 mT. The minimum magnetic field required for particle cluster rotation or oscillation in glycerol was experimentally measured at different frequencies. The results are in qualitative agreement with a simplified model for single-domain magnetic particles, with an average deviation from the model of 1.7 ± 1.3. The observed difference may be accounted for by the fact that our simplified model does not include effects on particle cluster motion caused by randomly oriented domains in multi-domain magnetic particle clusters, irregular particle cluster size, or magnetic anisotropy, among other effects.