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Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor and the third leading cause of cancer death worldwide. Most patients are diagnosed at an advanced stage, and systemic chemotherapy is the preferred treatment modality for advanced HCC. Curcumin (CUR) is a polyphenolic antineoplastic drug with low toxicity obtained from plants. However, its low bioavailability and poor solubility limit its functionality. In this study, radiofrequency- (RF) enhanced responsive nanoflowers (NFs), containing superparamagnetic ferric oxide nanoclusters (Fe3O4 NCs), - CUR layer, - and MnO2 (CUR-Fe@MnO2 NFs), were verified to have a thermal therapeutic effect. Transmission electron microscopy was used to characterize the CUR-Fe@MnO2 NFs, which appeared flower-like with a size of 96.27 nm. The in vitro experimental data showed that RF enhanced the degradation of CUR-Fe@MnO2 NFs to release Mn2+ and CUR. The cytotoxicity test results indicated that after RF heating, the CUR-Fe@MnO2 NFs significantly suppressed HCC cell proliferation. Moreover, CUR-Fe@MnO2 NFs were effective T 1/T 2 contrast agents for molecular magnetic resonance imaging due to the release of Mn2+ and Fe3O4 NCs.

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Radio frequency (RF) hyperthermia focuses on raising the target area temperature to a value exceeding 45°C. Collagen is stimulated when the temperature rises to 45°C at the dermal layer, resulting in skin tightening. However, most studies on RF hyperthermia have focused on tumor ablation or using electrodes to radiate an electromagnetic field, which is highly inefficient. This study proposed a non-invasive RF hyperthermia skin-tightening system with a compact metamaterial-filled waveguide aperture antenna. The proposed RF system increased the temperature by 11.6°C and 35.3°C with 20 and 80 W of 2.45 GHz RF power, respectively, within 60 s and exhibited a very focused effective area. Furthermore, a metamaterial was proposed to reduce the size of the waveguide aperture antenna and focus the electromagnetic field in the near-field region. The proposed metamaterial-filled waveguide aperture antenna was compact, measuring 10 mm × 17.4 mm, with a peak gain of 2.2 dB at 2.45 GHz. The measured hyperthermia performance indicated that the proposed RF system exhibited better power- and time-efficient hyperthermia performance than other RF hyperthermia systems in the cosmetic skin lifting commercial market. The proposed RF hyperthermia systems will be applied into a new generation of beauty cosmetic devices.

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The efficacy of a hyperthermia treatment depends on the delivery of well-controlled heating; hence, accurate temperature monitoring is essential for ensuring effective treatment. For deep pelvic hyperthermia, there are no comprehensive and systematic reports on MR thermometry. Moreover, data inclusion generally lacks objective selection criteria leading to a high probability of bias when comparing results. Herein, we studied whether imaging-based data inclusion predicts accuracy and could serve as a tool for prospective patient selection. The accuracy of the MR thermometry in patients with locally advanced cervical cancer was benchmarked against intraluminal temperature. We found that gastrointestinal air motion at the start of the treatment, quantified by the Jaccard similarity coefficient, was a good predictor for MR thermometry accuracy. The results for the group that was selected for low gastrointestinal air motion improved compared to the results for all patients by 50% (accuracy), 26% (precision), and 80% (bias). We found an average MR thermometry accuracy of 2.0 °C when all patients were considered and 1.0 °C for the selected group. These results serve as the basis for comprehensive benchmarking of novel technologies. The Jaccard similarity coefficient also has good potential to prospectively determine in which patients the MR thermometry will be valuable.

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In hyperthermia, the general opinion is that pre-treatment optimization of treatment settings requires a patient-specific model. For deep pelvic hyperthermia treatment planning (HTP), tissue models comprising four tissue categories are currently discriminated. For head and neck HTP, we found that more tissues are required for increasing accuracy. In this work, we evaluated the impact of the number of segmented tissues on the predicted specific absorption rate (SAR) for the pelvic region. Highly detailed anatomical models of five healthy volunteers were selected from a virtual database. For each model, seven lists with varying levels of segmentation detail were defined and used as an input for a modeling study. SAR changes were quantified using the change in target-to-hotspot-quotient and maximum SAR relative differences, with respect to the most detailed patient model. The main finding of this study was that the inclusion of high water content tissues in the segmentation may result in a clinically relevant impact on the SAR distribution and on the predicted hyperthermia treatment quality when considering our pre-established thresholds. In general, our results underline the current clinical segmentation protocol and help to prioritize any improvements.

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Purpose: Thermal intervention is a potent sensitizer of cells to chemo- and radiotherapy in cancer treatment. Glioblastoma multiforme (GBM) is a potential clinical target, given the cancer's aggressive nature and resistance to current treatment options. The annular phased array (APA) technique employing electromagnetic waves in the radiofrequency (RF) range allows for localized temperature increase in deep seated target volumes (TVs). Reports on clinical applications of the APA technique in the brain are still missing. Ultrahigh field magnetic resonance (MR) employs higher frequencies than conventional MR and has potential to provide focal temperature manipulation, high resolution imaging and noninvasive temperature monitoring using an integrated RF applicator (ThermalMR). This work examines the applicability of RF applicator concepts for ThermalMR of brain tumors at 297 MHz (7.0 Tesla).Methods: Electromagnetic field (EMF) simulations are performed for clinically realistic data based on GBM patients. Two algorithms are used for specific RF energy absorption rate based thermal intervention planning for small and large TVs in the brain, aiming at maximum RF power deposition or RF power uniformity in the TV for 10 RF applicator designs.Results: For both TVs , the power optimization outperformed the uniformity optimization. The best results for the small TV are obtained for the 16 element interleaved RF applicator using an elliptical antenna arrangement with water bolus. The two row elliptical RF applicator yielded the best result for the large TV.Discussion: This work investigates the capacity of ThermalMR to achieve targeted thermal interventions in model systems resembling human brain tissue and brain tumors.

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Targeted radiofrequency (RF) heating induced hyperthermia has a wide range of applications, ranging from adjunct anti-cancer treatment to localized release of drugs. Focal RF heating is usually approached using time-consuming nonconvex optimization procedures or approximations, which significantly hampers its application. To address this limitation, this work presents an algorithm that recasts the problem as a semidefinite program and quickly solves it to global optimality, even for very large (human voxel) models. The target region and a desired RF power deposition pattern as well as constraints can be freely defined on a voxel level, and the optimum application RF frequencies and time-multiplexed RF excitations are automatically determined. 2D and 3D example applications conducted for test objects containing pure water (rtarget = 19 mm, frequency range: 500-2000 MHz) and for human brain models including brain tumors of various size (r1 = 20 mm, r2 = 30 mm, frequency range 100-1000 MHz) and locations (center, off-center, disjoint) demonstrate the applicability and capabilities of the proposed approach. Due to its high performance, the algorithm can solve typical clinical problems in a few seconds, making the presented approach ideally suited for interactive hyperthermia treatment planning, thermal dose and safety management, and the design, rapid evaluation, and comparison of RF applicator configurations.

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Magnetic fluid hyperthermia (MFH) treatment makes use of a suspension of superparamagnetic iron oxide nanoparticles, administered systemically or locally, in combination with an externally applied alternating magnetic field, to ablate target tissue by generating heat through a process called induction. The heat generated above the mammalian euthermic temperature of 37°C induces apoptotic cell death and/or enhances the susceptibility of the target tissue to other therapies such as radiation and chemotherapy. While most hyperthermia techniques currently in development are targeted towards cancer treatment, hyperthermia is also used to treat restenosis, to remove plaques, to ablate nerves and to alleviate pain by increasing regional blood flow. While RF hyperthermia can be directed invasively towards the site of treatment, non-invasive localization of heat through induction is challenging. In this review, we discuss recent progress in the field of RF magnetic fluid hyperthermia and introduce a new diagnostic imaging modality called magnetic particle imaging that allows for a focused theranostic approach encompassing treatment planning, treatment monitoring and spatially localized inductive heating.

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PURPOSE: The objective of this study is to determine the effect of physical changes on MR temperature imaging at 7.0T and to examine proton-resonance-frequency related changes of MR phase images and T1 related changes of MR magnitude images, which are obtained for MR thermometry at various magnetic field strengths. MATERIALS AND METHODS: An MR-compatible capacitive-coupled radio-frequency hyperthermia system was implemented for heating a phantom and swine muscle tissue, which can be used for both 7.0T and 3.0T MRI. To determine the effect of flip angle correction on T1-based MR thermometry, proton resonance frequency, apparent T1, actual flip angle, and T1 images were obtained. For this purpose, three types of imaging sequences are used, namely, T1-weighted fast field echo with variable flip angle method, dual repetition time method, and variable flip angle method with radio-frequency field nonuniformity correction. RESULTS: Signal-to-noise ratio of the proton resonance frequency shift-based temperature images obtained at 7.0T was five-fold higher than that at 3.0T. The T1 value increases with increasing temperature at both 3.0T and 7.0T. However, temperature measurement using apparent T1-based MR thermometry results in bias and error because B1 varies with temperature. After correcting for the effect of B1 changes, our experimental results confirmed that the calculated T1 increases with increasing temperature both at 3.0T and 7.0T. CONCLUSION: This study suggests that the temperature-induced flip angle variations need to be considered for accurate temperature measurements in T1-based MR thermometry.

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BACKGROUND: Radiofrequency (RF) interstitial hyperthermia has recently been shown to be a beneficial treatment modality for human malignant gliomas. It has also been shown that the thermal threshold dose for histopathological damage in the rat brain was heating at 41 degreesCfor 30 min. In the present study, we investigated apoptosis and necrosis of the neuronal cells in the brains of Fischer rats at different times after interstitial heating with lower than the thermal threshold dose. We also measured the isopeptide bond formation in neuronal cells showing apoptosis or necrosis. METHODS: The applicator needles of the RF interstitial heating device, connected to the Thermotron IV was applied to heat the brain at 39, 40, and 41 degreesCfor 30 minutes. Sham-heated control rats were treated the same as the heated rats. The sham-heated animals and those heated at 40 degreesCfor 30 min were sacrificed at 4, 72, 120, and 168 hours after heating, respectively, and the animals heated at 39 and 41 degreesCfor 30 minutes were sacrificed at 168 hours after heating. Coronally sectioned brain tissue, encompassing the heated lesions, were studied immunohistochemically for the expression of TGase1, TGase2, and TGase3, isopeptide. TUNEL assay was performed to examine apoptosis. RESULTS: Immunohistochemical studies showed that in the brains heated at 40 degreesCfor 30 minutes, necrosis with the maximal nuclear isopeptide-positive neuronal cells of the cerebral cortex were seen at 4 hours; The maximal number of isopep-tide- positive neuronal cells showing apoptosis was at 168 hours. CONCLUSIONS: Necrosis of neuronal cells following mild interstitial hyperthermia was maximal at 4 hours and apoptosis was maximal at 168 hours. Neuronal cells showing necrosis or apoptosis formed isopeptide bonds in their nuclei.

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