Alberto Tannús

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.

BISTRO: an outer-volume suppression method that tolerates RF field inhomogeneity.

A technique is described for performing frequency‐selective signal suppression with a high degree of tolerance to RF field inhomogeneity. The method is called B1‐insensitive train to obliterate signal (BISTRO). BISTRO consists of multiple amplitude‐ and frequency‐modulated (FM) pulses interleaved with spoiler gradients. BISTRO was developed for the purpose of accomplishing band‐selective signal removal, as in water suppression and outer‐volume suppression (OVS), in applications requiring the use of an inhomogeneous RF transmitter, such as a surface coil. In the present work, Bloch simulations were used to illustrate the principles and theoretical performance of BISTRO. Its performance for OVS was evaluated experimentally using MRI and spectroscopic imaging of phantoms and in vivo animal and human brain. By using FM pulses featuring offset‐independent adiabaticity, BISTRO permitted high‐quality, broadband suppression with one (or two) discrete borders demarcating the edge(s) of the suppression band. Simulations and experiments demonstrated the ability to operate BISTRO with reasonably attainable peak RF power levels and with average RF energy deposition similar to other multipulse OVS techniques. Magn Reson Med 45:1095–1102, 2001.

Magnetic resonance imaging quantification of regional cerebral blood flow and cerebrovascular reactivity to carbon dioxide in normotensive and hypertensive rats

Hypertension afflicts 25% of the general population and over 50% of the elderly. In the present work, arterial spin labeling MRI was used to non-invasively quantify regional cerebral blood flow (CBF), cerebrovascular resistance and CO(2) reactivity in spontaneously hypertensive rats (SHR) and in normotensive Wistar Kyoto rats (WKY), at two different ages (3 months and 10 months) and under the effects of two anesthetics, α-chloralose and 2% isoflurane (1.5 MAC). Repeated CBF measurements were highly consistent, differing by less than 10% and 18% within and across animals, respectively. Under α-chloralose, whole brain CBF at normocapnia did not differ between groups (young WKY: 61 ± 3ml/100g/min; adult WKY: 62 ± 4ml/100g/min; young SHR: 70 ± 9ml/100g/min; adult SHR: 69 ± 8ml/100g/min), indicating normal cerebral autoregulation in SHR. At hypercapnia, CBF values increased significantly, and a linear relationship between CBF and PaCO(2) levels was observed. In contrast, 2% isoflurane impaired cerebral autoregulation. Whole brain CBF in SHR was significantly higher than in WKY rats at normocapnia (young SHR: 139 ± 25ml/100g/min; adult SHR: 104 ± 23ml/100g/min; young WKY: 55± 9ml/100g/min; adult WKY: 71 ± 19ml/100g/min). CBF values increased significantly with increasing CO(2); however, there was a clear saturation of CBF at PaCO(2) levels greater than 70mmHg in both young and adult rats, regardless of absolute CBF values, suggesting that isoflurane interferes with the vasodilatory mechanisms of CO(2). This behavior was observed for both cortical and subcortical structures. Under either anesthetic, CO(2) reactivity values in adult SHR were decreased, confirming that hypertension, when combined with age, increases cerebrovascular resistance and reduces cerebrovascular compliance.

Muscle Atrophy and Functional Deficits of Knee Extensors and Flexors in People With Chronic Stroke

Background Further clarification is needed with regard to the degree of atrophy in individual muscle groups and its possible relationship to joint torque deficit poststroke. Objective The purpose of this study was to investigate quadriceps and hamstring muscle volume and strength deficits of the knee extensors and flexors in people with chronic hemiparesis compared with a control group. Design This was a cross-sectional study. Methods Thirteen individuals with hemiparesis due to chronic stroke (hemiparetic group) and 13 individuals who were healthy (control group) participated in this study. Motor function, quadriceps and hamstring muscle volume, and maximal concentric and eccentric contractions of the knee extensors and flexors were assessed. Results Only the quadriceps muscle of the paretic limb showed reduced muscle volume (24%) compared with the contralateral (nonparetic) limb. There were no differences in muscle volume between the hemiparetic and control groups. The peak torque of the paretic-limb knee extensors and flexors was reduced in both contraction modes and velocities compared with the nonparetic limb (36%–67%) and with the control group (49%–75%). The nonparetic limb also showed decreased extensor and flexor peak torque compared with the control group (17%–23%). Power showed similar deficits in strength (12%–78%). There were significant correlations between motor function and strength deficits (.54–.67). Limitations Magnetic resonance imaging coil length did not allow measurement of the proximal region of the thigh. Conclusions There were different responses between quadriceps and hamstring muscle volumes in the paretic limb that had quadriceps muscle atrophy only. However, both paretic and nonparetic limbs showed knee extensor and flexor torque and power reduction.

Asymmetrical gradient coil for head imaging.

This work presents a novel approach to develop dedicated transverse gradient coils for head imaging. The proposed coil design is based on the stochastic optimization of an asymmetrical stream function and improves the matching between the region‐of‐interest and the homogeneous gradient volume. Additionally, the electric field produced by these asymmetrical coils is 30% lower than that produced by standard symmetrical designs, which minimizes the risk of magnetostimulation of nerves in fast imaging techniques. A prototype of the asymmetrical gradient coil was built to test the method and magnetic field produced by the prototype was measured. Magnetic field measurements and electrical parameters of coils are in good agreement with theoretical calculations. Magn Reson Med 48:707–714, 2002.

MAGNETIC RESONANCE IMAGING AS A NON-INVASIVE TECHNIQUE FOR INVESTIGATING 3-D PREFERENTIAL FLOW OCCURRING WITHIN STRATIFIED SOIL SAMPLES

Abstract The soil fingering phenomenon was investigated using magnetic resonance imaging (MRI) as an appropriate technique. A cubic 15 × 15 × 15-cm 3 double-layer sand column was built in order to simulate the stratified soil. The column was imaged in a 500 Gauss NMR tomograph [IFQSC, USP, Sao Carlos (SP)]. After reaching the water steady-state flow several coronal, transverse and sagittal images of the column were obtained. For each case seven slices, 1.8 cm thick and separated by 2.0 cm center to center, were collected providing three-dimensional information regarding to the number of fingers, their sizes and diameters. To study the fingering dynamics employing MRI concepts, another kind of experiment was performed by following only the water front (no image reconstruction), using spin-echo signals with phase encoding along vertical axis (gravitational direction), but with phase encoding gradients switched off. Sixteen acquisitions of seven transverses of 2 cm thick slices, were performed in a 3-min experiment. After suitable treatment, the water front and the horizontal distribution at each measured time during the water infiltration process was obtained. Normalizing the signal intensities to the soil column dimensions and using computational graphic resources, made it possible to quantify the number of fingers and their spatial and temporal variability. The results elect MRI as a valuable tool for non-invasively investigating the dynamics of soil fingering phenomenon.

Changes in Hippocampal Volume are Correlated with Cell Loss but Not with Seizure Frequency in Two Chronic Models of Temporal Lobe Epilepsy

Kainic acid (KA) or pilocarpine (PILO) have been used in rats to model human temporal lobe epilepsy (TLE) but the distribution and severity of structural lesions between these two models may differ. Magnetic resonance imaging (MRI) studies have used quantitative measurements of hippocampal T2 (T2HP) relaxation time and volume, but simultaneous comparative results have not been reported yet. The aim of this study was to compare the MRI T2HP and volume with histological data and frequency of seizures in both models. KA- and PILO-treated rats were imaged with a 2 T MRI scanner. T2HP and volume values were correlated with the number of cells, mossy fiber sprouting, and spontaneous recurrent seizures (SRS) frequency over the 9 months following status epilepticus (SE). Compared to controls, KA-treated rats had unaltered T2HP, pronounced reduction in hippocampal volume and concomitant cell reduction in granule cell layer, CA1 and CA3 at 3 months post SE. In contrast, hippocampal volume was unchanged in PILO-treated animals despite detectable increased T2HP and cell loss in granule cell layer, CA1 and CA3. In the following 6 months, MRI hippocampal volume remained stable with increase of T2HP signal in the KA-treated group. The number of CA1 and CA3 cells was smaller than age-matched CTL group. In contrast, PILO group had MRI volumetric reduction accompanied by reduction in the number of CA1 and CA3 cells. In this group, T2HP signal was unaltered at 6 or 9 months after status. Reductions in the number of cells were not progressive in both models. Notably, the SRS frequency was higher in PILO than in the KA model. The volumetry data correlated well with tissue damage in the epileptic brain, suggesting that MRI may be useful for tracking longitudinal hippocampal changes, allowing the assessment of individual variability and disease progression. Our results indicate that the temporal changes in hippocampal morphology are distinct for both models of TLE and that these are not significantly correlated to the frequency of SRS.

Modeling epileptogenesis and temporal lobe epilepsy in a non-human primate.

Here we describe a new non-human primate model of temporal lobe epilepsy (TLE) to better investigate the cause/effect relationships of human TLE. Status epilepticus (SE) was induced in adult marmosets by pilocarpine injection (250mg/kg; i.p.). The animals were divided in 2 groups: acute (8h post-SE) and chronic (3 and 5 months post-SE). To manage the severity of SE, animals received diazepam 5min after the SE onset (acute group: 2.5 or 1.25mg/kg; i.p.; chronic group/; 1.25mg/kg; i.p). All animals were monitored by video and electrocorticography to assess SE and subsequent spontaneous recurrent seizures (SRS). To evaluate brain injury produced by SE or SRS we used argyrophil III, Nissl and neo-Timm staining techniques. Magnetic resonance image was also performed in the chronic group. We observed that pilocarpine was able to induce SE followed by SRS after a variable period of time. Prolonged SE episodes were associated with brain damage, mostly confined to the hippocampus and limbic structures. Similar to human TLE, anatomical disruption of dentate gyrus was observed after SRS. Our data suggest that pilocarpine marmoset model of epilepsy has great resemblance to human TLE, and could provide new tools to further evaluate the subtle changes associated with human epilepsy.

Pseudolikelihood Equations for Potts MRF Model Parameter Estimation on Higher Order Neighborhood Systems

This letter presents pseudolikelihood equations for the estimation of the Potts Markov random field model parameter on higher order neighborhood systems. The derived equation for second-order systems is a significantly reduced version of a recent result found in the literature (from 67 to 22 terms). Also, with the proposed method, a completely original equation for Potts model parameter estimation in third-order systems was obtained. These equations allow the modeling of less restrictive contextual systems for a large number of applications in a computationally feasible way. Experiments with both simulated and real remote sensing images provided good results.

Manganese-enhanced magnetic resonance imaging detects mossy fiber sprouting in the pilocarpine model of epilepsy

Purpose:  Mossy fiber sprouting (MFS) is a frequent finding following status epilepticus (SE). The present study aimed to test the feasibility of using manganese‐enhanced magnetic resonance imaging (MEMRI) to detect MFS in the chronic phase of the well‐established pilocarpine (Pilo) rat model of temporal lobe epilepsy (TLE).