Mateus José Martins

Application of hyperthermia induced by superparamagnetic iron oxide nanoparticles in glioma treatment

Gliomas are a group of heterogeneous primary central nervous system (CNS) tumors arising from the glial cells. Malignant gliomas account for a majority of malignant primary CNS tumors and are associated with high morbidity and mortality. Glioblastoma is the most frequent and malignant glioma, and despite the recent advances in diagnosis and new treatment options, its prognosis remains dismal. New opportunities for the development of effective therapies for malignant gliomas are urgently needed. Magnetic hyperthermia (MHT), which consists of heat generation in the region of the tumor through the application of magnetic nanoparticles subjected to an alternating magnetic field (AMF), has shown positive results in both preclinical and clinical assays. The aim of this review is to assess the relevance of hyperthermia induced by magnetic nanoparticles in the treatment of gliomas and to note the possible variations of the technique and its implication on the effectiveness of the treatment. We performed an electronic search in the literature from January 1990 to October 2010, in various databases, and after application of the inclusion criteria we obtained a total of 15 articles. In vitro studies and studies using animal models showed that MHT was effective in the promotion of tumor cell death and reduction of tumor mass or increase in survival. Two clinical studies showed that MHT could be applied safely and with few side effects. Some studies suggested that mechanisms of cell death, such as apoptosis, necrosis, and antitumor immune response were triggered by MHT. Based on these data, we could conclude that MHT proved to be efficient in most of the experiments, and that the improvement of the nanocomposites as well as the AMF equipment might contribute toward establishing MHT as a promising tool in the treatment of malignant gliomas.

Optimization of Saddle Coils for Magnetic Resonance Imaging

In Nuclear Magnetic Resonance (NMR) experiments, besides the apparatus designed to acquire the NMR signal, it is necessary to generate a radio frequency electromagnetic field using a device capable to transduce electromagnetic power into a transverse magnetic field. We must generate this transverse homogeneous magnetic field inside the region of interest with minimum power consumption. Many configurations have been proposed for this task, from coils to resonators. For low field intensity ( <0.5 T) and small sample dimensions (<30 cm), the saddle coil configuration has been widely used. In this work we present a simplified method for calculating the magnetic field distribution in these coils considering the current density profile. We propose an optimized saddle configuration as a function of the dimensions of the region of interest, taking into account the uniformity and the sensitivity. In order to evaluate the magnetic field uniformity three quantities have been analyzed: Non-uniformity, peak-to-peak homogeneity and relative uniformity. Some experimental results are presented to validate our calculation.

Tumor growth analysis by magnetic resonance imaging of the C6 glioblastoma model with prospects for the assessment of magnetohyperthermia therapy

OBJECTIVE The objective was to establish a pattern of tumor growth of the C6 model of glioblastoma multiform in Wistar rats via magnetic resonance imaging (MRI) for the subsequent verification of tumor volume reduction due to magnetic hyperthermia therapy. METHODS Young male Wistar rats weighing between 250 and 300 g were used for the C6 model. After the rats were anesthetized (55 mg/ kg ketamine and 11 mg/kg xylazine), C6 lineage tumorigenic cells suspended in culture medium (10(5) cells in 10 microl) were stereotaxically injected into the right frontal cortex (bregma coordinates: 2.0 mm anteroposterior, 3.0 mm laterolateral, and 2.5 mm depth) of the rats using a Hamilton syringe. For the control group, the rats were injected with culture medium without cells. MRI scans were performed at 14, 21, and 28 d after the injection using a 2.0 T MRI scanner (Bruker BioSpec, Germany). The animals were anesthetized with 55 mg/kg ketamine and 11 mg/kg xylazine before being examined. Coronal multilayers were acquired using a standard spin echo sequence with the following parameters: repetition/echo time = 4.000 ms/67.1 ms, field of view = 3.50, matrix = 192, slice thickness = 0.4 mm, and slice separation = 0 mm. RESULTS The MRI analysis enabled a clear visualization of the tumor mass, and it was possible to establish the tumor volume parameters on the various days that were examined. The volume at 14 d after induction was 13.7 +/- 2.5 mm3. On days 21 and 28, the tumor volumes were 31.7 +/- 6.5 mm3 and 122.1 +/- 11.8 mm3, respectively. CONCLUSION These results demonstrated that it is possible to evaluate the C6 model tumor volume in rats, which will allow for the future implementation and verification of magnetic hyperthermia therapy.

Deuterium microimages and microvolume localized spectroscopy at 9.4T

Deuterium (2H) microscopic images with resolution of tens of microns and localized 2H spectra with volumes in the micro liter range have been obtained on a Varian 400 MHz (9.4T) wide bore spectrometer equipped with a 50 G/cm gradient system. In order to realize 2H experiments at 61.4 MHz, a simple RF coil was built. 2H-Microimaging experiments have been carried out with SE and FLASH pulse sequences and localized 2H-spectroscopy has been tested on a phantom, which consists of a 2×2×2 mm3 cube with CD3OD immersed in D2O. Results show that non-invasive investigation of biological samples is possible. As an example for a biological application, the absorption process of D2O in a plant fragment (Mikania Cordifolia) has been monitored by acquiring consecutive SE microimages along various hours.