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).

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.

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.

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.

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.

Early impairment of transmural principal strains in the left ventricular wall after short-term, high-fat feeding of mice predisposed to cardiac steatosis.

BACKGROUND: myocardial lipid accumulation precedes some cardiomyopathies, but little is known of concurrent effects on ventricular mechanics. We tested the hypothesis that intramyocardial lipid accumulation during a short-term, high-fat diet (HFD) affects 2-dimensional strains in the heart. We examined the hearts of nontransgenic (NTG) mice and of transgenic mice predisposed to elevated triacylglyceride (TAG) storage linked to low-level overexpression of peroxisome proliferator activated receptor (PPAR-α). METHODS AND RESULTS: myocardial lipid and transmural principal strains E1 and E2 were determined in vivo with (1)H magnetic resonance spectroscopy/imaging before and after 2 weeks of an HFD in both PPAR-α and NTG littermate mice. Baseline lipid was elevated in PPAR-α compared with NTG mice. An HFD increased mobile lipid by 174% in NTG mice (P<0.05) and by 79% in PPAR-α mice (P<0.05). After an HFD, lipid and TAG were higher in PPAR-α versus NTG mice by 63% and 81%, respectively. However, TAG in PPAR-α mice after an HFD was similar to TAG in PPAR-α mice fed a regular diet, suggesting that the magnetic resonance spectroscopy signal from lipid is not exclusive to TAG. Only at the highest lipid contents, achieved in PPAR-α mice, were strains affected. Endocardial strain was most compromised, with a negative correlation to lipid (P<0.05). CONCLUSIONS: a short-term HFD elevated myocardial lipid measures as determined by magnetic resonance spectroscopy, which became dissociated from TAG content in hearts predisposed to cardiac steatosis. The increased lipid was associated with concurrent, transmural reductions in E1 and E2 strains across the left ventricular wall. Strains were attenuated at the highest levels of lipid accumulation, suggesting a threshold response. Thus, 2-dimensional strains are impaired early and without left ventricular diastolic dysfunction, owing to cardiac steatosis.

Principal strain changes precede ventricular wall thinning during transition to heart failure in a mouse model of dilated cardiomyopathy.

This study was performed to elucidate the relation between in vivo measurements of two-dimensional principal strains and the progression of left ventricle (LV) wall thinning during development of dilated cardiomyopathy in the protein kinase C-epsilon (PKC-epsilon) transgenic (TG) overexpressing mouse heart. Principal two-dimensional strains, E1 and E2, were determined in the LV wall of the anesthetized mouse using cardiac MRI tagging at 14.1 T. PKC-epsilon TG provided a model of pure dilated cardiomyopathy without evidence of hypertrophy (PKC-epsilon TG, n = 6). Ejection fraction, wall thickness, and principal strains were determined at 1-mo intervals in hearts of PKC-epsilon TG vs. age-matched, nontransgenic mice (NTG, n = 5) from age 6 to 13 mo. Through the study, PKC-epsilon TG displayed lower ejection fraction than NTG. At 7 mo, average principal strain E1 in PKC-epsilon TG hearts was lower compared with NTG (PKC-epsilon TG = 0.14 +/- 0.03, NTG = 0.19 +/- 0.03, P < 0.05). The greatest reductions in regional E1 occurred in the lateral segments. The principal strain E2 did not change significantly in either group. At 9 mo, LV wall thinning occurred in PKC-epsilon TG mice (P < 0.01 vs. 8 mo) to 21% below values in NTG (P < 0.001). Average E1 strain diverged between PKC-epsilon TG and NTG hearts by 25-43%. These E1 changes preceded LV wall thinning and predated the eventual transition from a compensated circumstance to the dilated phenotype. The findings indicate a near step function in E1 depression that precedes the onset of LV wall thinning and suggest E1 as a prognostic indicator of dilated cardiomyopathy.

Improved cardiac tagging resolution at ultra-high magnetic field elucidates transmural differences in principal strain in the mouse heart and reduced stretch in dilated cardiomyopathy.

Cardiac tagging resolution for regional principal strains E1 and E2 has been a limiting factor for the study of dilated mouse hearts, in which the left ventricle (LV) wall thickness can drop to below 1 mm. Therefore, high resolution tagging was performed at 14.1 T to enable transmural principal strain measurements across the LV wall of normal mouse hearts and average principal strains in thinned LV walls of a transgenic mouse (PKCepsilon TG) that develops dilated LV. A modified DANTE tagging and fast gradient imaging method produced a tagging grid dimension of 0.33 x 0.33 mm and line thickness under 0.1 mm. In normal mice, average E1 strain in the epicardium was significantly higher than the endocardial E1 (epi = 0.22 +/- 0.10; endo = 0.13 +/- 0.07, p < 0.05), while magnitude of average endocardial E2 was greater than in the epicardium (endo = -0.12 +/- 0.03, epi = -0.08 +/- 0.03; p < 0.001). E1 strain averaged over four segments was reduced in dilated hearts compared to controls (PKCepsilon TG = 0.14 +/- 0.02; control = 0.18 +/- 0.02, p < 0.01), with specific reductions in septal (33%) and lateral (31%, p < 0.01) segments. E2 strain was similar between dilated and control hearts at -0.11 +/- 0.01. Thus, improved tagging resolution demonstrates that stretch (E1), but not compression strains (E2), are reduced as a result of significant LV wall thinning in a mouse model of dilated cardiomyopathy.