Using ferromagnetic nanoparticles with low Curie temperature for magnetic resonance imaging-guided thermoablation

Vít Herynek,1 Karolína Turnovcová,2 Pavel Veverka,3 Tereza Dědourková,4,5 Pavel Žvátora,6 Pavla Jendelová,2 Andrea Gálisová,1 Lucie Kosinová,7 Klára Jiráková,2 Eva Syková2 1MR-Unit, Radiodiagnostic and Interventional Radiology Department, Institute for Clinical and Experimental Medicine, Prague, 2Department of Neuroscience, Institute of Experimental Medicine, 3Department of Magnetics and Superconductors, Institute of Physics, Czech Academy of Sciences, Prague, 4Department of Inorganic Technology, Faculty of Chemical Technology, University of Pardubice, 5SYNPO, akciová společnost, Pardubice, 6Department of Analytical Chemistry, Institute of Chemical Technology, 7Diabetes Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic Introduction: Magnetic nanoparticles (NPs) represent a tool for use in magnetic resonance imaging (MRI)-guided thermoablation of tumors using an external high-frequency (HF) magnetic field. To avoid local overheating, perovskite NPs with a lower Curie temperature (Tc) were proposed for use in thermotherapy. However, deposited power decreases when approaching the Curie temperature and consequently may not be sufficient for effective ablation. The goal of the study was to test this hypothesis. Methods: Perovskite NPs (Tc =66°C–74°C) were characterized and tested both in vitro and in vivo. In vitro, the cells suspended with NPs were exposed to a HF magnetic field together with control samples. In vivo, a NP suspension was injected into a induced tumor in rats. Distribution was checked by MRI and the rats were exposed to a HF field together with control animals. Apoptosis in the tissue was evaluated. Results and discussion: In vitro, the high concentration of suspended NPs caused an increase of the temperature in the cell sample, leading to cell death. In vivo, MRI confirmed distribution of the NPs in the tumor. The temperature in the tumor with injected NPs did not increase substantially in comparison with animals without particles during HF exposure. We proved that the deposited power from the NPs is too small and that thermoregulation of the animal is sufficient to conduct the heat away. Histology did not detect substantially higher apoptosis in NP-treated animals after ablation. Conclusion: Magnetic particles with low Tc can be tracked in vivo by MRI and heated by a HF field. The particles are capable of inducing cell apoptosis in suspensions in vitro at high concentrations only. However, their effect in the case of extracellular deposition in vivo is questionable due to low deposited power and active thermoregulation of the tissue. Keywords: perovskite nanoparticles, hyperthermia, high-frequency magnetic field, MRI, tumor ablatio

TOPICAL CORTICOSTEROIDS BUT NOT CALCINEURIN INHIBITORS INDUCED ATROPHY AFTER FOUR WEEKS

Reflectance confocal microscopy (RCM) is a non-invasive, in vivo technique for real-time imaging of the epidermis and superficial dermis at the cellular resolution. We performed a pilot study focusing on the evaluation of the effect of topical corticosteroids and calcineurin inhibitors on the epidermis of patients with atopic dermatitis (AD). The effect was assessed by RCM. A total of 45 patients with AD took part in the study. Patients were selected according to the standardized protocol and divided into two groups. Twenty-three patients used methylprednisolone aceponat topically on the skin with lesions of AD once a day for three months (group A). Twenty-one patients applied topical tacrolimus on the skin with lesions of AD twice a day for three months (B). RCM imaging was performed on the day of intiating the study (T0), then after one (T1), two (T2) and three months (T3). In group A, there was a visible decrease of the stratum corneum and the epidermis thickness which was statistically significant. In comparison, in group B, such changes were not noted and the differences between the groups in time course were statistically significant. In group A, an increase in the percentage of blurred keratinocytes in the stratum spinosum was also recorded, especially between the first (T0) and the second visit (T1). RCM is a useful method for evaluating the changes in epidermis due to the different topical treatment in patients with AD

TOPICAL CORTICOSTEROIDS BUT NOT CALCINEURIN INHIBITORS INDUCED ATROPHY AFTER FOUR WEEKS

Reflectance confocal microscopy (RCM) is a non-invasive, in vivo technique for real-time imaging of the epidermis and superficial dermis at the cellular resolution. We performed a pilot study focusing on the evaluation of the effect of topical corticosteroids and calcineurin inhibitors on the epidermis of patients with atopic dermatitis (AD). The effect was assessed by RCM. A total of 45 patients with AD took part in the study. Patients were selected according to the standardized protocol and divided into two groups. Twenty-three patients used methylprednisolone aceponat topically on the skin with lesions of AD once a day for three months (group A). Twenty-one patients applied topical tacrolimus on the skin with lesions of AD twice a day for three months (B). RCM imaging was performed on the day of intiating the study (T0), then after one (T1), two (T2) and three months (T3). In group A, there was a visible decrease of the stratum corneum and the epidermis thickness which was statistically significant. In comparison, in group B, such changes were not noted and the differences between the groups in time course were statistically significant. In group A, an increase in the percentage of blurred keratinocytes in the stratum spinosum was also recorded, especially between the first (T0) and the second visit (T1). RCM is a useful method for evaluating the changes in epidermis due to the different topical treatment in patients with AD

How to Reduce Fluid-Injection-Induced Seismicity

The recent growth in energy technologies and the management of subsurface reservoirs has led to increased human interaction with the Earth's crust. One consequence of this is the overall increase of anthropogenic earthquakes. To manage fluid-injection-induced seismicity, in this study, we propose to use an advanced fluid-injection scheme. First, long-term fluid-injection experiments are separated from short-term fluid-injection experiments. Of the short-term experiments, enhanced geothermal systems stimulations have shown a higher propensity to produce larger seismic events compared to hydraulic fracturing in oil and gas. Among the factors discussed for influencing the likelihood of an induced seismic event to occur are injection rate, cumulative injected volume, wellhead pressure, injection depth, stress state, rock type, and proximity to faults. We present and discuss the concept of fatigue hydraulic fracturing at different scales in geothermal applications. In contrast to the conventional hydraulic fracturing with monotonic injection of high-pressure fluids, in fatigue hydraulic fracturing, the fluid is injected in pressure cycles with increasing target pressure, separated by depressurization phases for relaxing the crack tip stresses. During pressurization phases, the target pressure level is modified by pulse hydraulic fracturing generated with a second pump system. This combination of two pumps with multiple-flow rates may allow a more complex fracture pattern to be designed, with arresting and branching fractures, forming a broader fracture process zone. Small-scale laboratory fluid-injection tests on granite cores and intermediate-scale fluid-injection experiments in a hard rock underground test siteare described. At laboratory scale, cyclic fluid-injection tests with acoustic emission analysis arereported with subsequent X-ray CT fracture pattern analysis. At intermediate scale, in a controlled underground experiment at constant depth with well-known stress state in granitic rock, we test advanced fluid-injection schemes. The goal is to optimize the fracture network and mitigate larger seismic events. General findings in granitic rock, independent of scale, are summarized. First, the fracture breakdown pressure in fatigue hydraulic testing is lower than that in the conventional hydraulic fracturing. Second, compared to continuous injection, the magnitude of the largest induced seismic event seems to be systematically reduced by cyclic injection. Third, the fracture pattern in fatigue testing is different from that in the conventional injection tests at high pressures. Cyclic fracture patterns seem to result from chiefly generated low energy grain boundary cracks forming a wider process zone. Fourth, cyclic injection increases the permeability of the system. A combination of cyclic progressive and pulse pressurization leads to the best hydraulic performance of all schemes tested. One advantage of fatigue testing is the fact that this soft stimulation method can be applied in circumstances where the conventional stimulation might otherwise be abandoned based on site-specific seismic hazard estimates.Y