XMEA: A New Hybrid Diamond Multielectrode Array for the In Situ Assessment of the Radiation Dose Enhancement by Nanoparticles.

This work presents a novel multielectrode array (MEA) to quantitatively assess the dose enhancement factor (DEF) produced in a medium by embedded nanoparticles. The MEA has 16 nanocrystalline diamond electrodes (in a cell-culture well), and a single-crystal diamond divided into four quadrants for X-ray dosimetry. DEF was assessed in water solutions with up to a 1000 µg/mL concentration of silver, platinum, and gold nanoparticles. The X-ray detectors showed a linear response to radiation dose (r2 ≥ 0.9999). Overall, platinum and gold nanoparticles produced a dose enhancement in the medium (maximum of 1.9 and 3.1, respectively), while silver nanoparticles produced a shielding effect (maximum of 37%), lowering the dose in the medium. This work shows that the novel MEA can be a useful tool in the quantitative assessment of radiation dose enhancement due to nanoparticles. Together with its suitability for cells' exocytosis studies, it proves to be a highly versatile device for several applications.

Forearm Posture Affects the Corticospinal Excitability of Intrinsic and Extrinsic Hand Muscles in Dominant and Nondominant Sides.

Different forearm postures can modulate corticospinal excitability. However, there is no consensus on whether handedness plays a role in such a mechanism. This study investigated the effects of 3 forearm postures (pronation, neutral, and supination) on the corticospinal excitability of muscles from the dominant and nondominant upper limbs. Surface electromyography was recorded from the abductor digiti minimi, flexor pollicis brevis, and flexor carpi radialis from both sides of 12 right-handed volunteers. Transcranial magnetic stimulation pulses were applied to each muscle's hotspot in both cerebral hemispheres. Motor-evoked potential peak-to-peak amplitude and latency and resting motor threshold were measured. The data were evaluated by analysis of variance. The level of significance was set at 5%. The resting motor threshold was similar for the 3 muscles and both sides. Motor-evoked potential peak-to-peak amplitude from flexor pollicis brevis was lower during supination, and the dominant upper limb latency was longer. The flexor carpi radialis presented lower motor-evoked potential peak-to-peak amplitudes for neutral and shorter latencies during supination. Abductor digiti minimi seemed not to be affected by posture or side. Different muscles from dominant and nondominant sides may undergo corticospinal modulation, even distally localized from a particular joint and under rest.

Forearm and Hand Muscles Exhibit High Coactivation and Overlapping of Cortical Motor Representations.

Most of the motor mapping procedures using navigated transcranial magnetic stimulation (nTMS) follow the conventional somatotopic organization of the primary motor cortex (M1) by assessing the representation of a particular target muscle, disregarding the possible coactivation of synergistic muscles. In turn, multiple reports describe a functional organization of the M1 with an overlapping among motor representations acting together to execute movements. In this context, the overlap degree among cortical representations of synergistic hand and forearm muscles remains an open question. This study aimed to evaluate the muscle coactivation and representation overlapping common to the grasping movement and its dependence on the stimulation parameters. The nTMS motor maps were obtained from one carpal muscle and two intrinsic hand muscles during rest. We quantified the overlapping motor maps in size (area and volume overlap degree) and topography (similarity and centroid Euclidean distance) parameters. We demonstrated that these muscle representations are highly overlapped and similar in shape. The overlap degrees involving the forearm muscle were significantly higher than only among the intrinsic hand muscles. Moreover, the stimulation intensity had a stronger effect on the size compared to the topography parameters. Our study contributes to a more detailed cortical motor representation towards a synergistic, functional arrangement of M1. Understanding the muscle group coactivation may provide more accurate motor maps when delineating the eloquent brain tissue during pre-surgical planning.

Electron Spin Resonance Dosimetry Studies of Irradiated Sulfite Salts.

The study of new materials for radiation dosimetry is important to improve the present state of the art and to help in cases of accidents for retrospective dosimetry. Sulfites are compounds that contain a sulfur ion, widely used in the food industry. Due to the significant application of these compounds, sulfites are interesting candidates for accidental dosimetry, as fortuitous radiation detectors. The presence of the SO3- anion enables its detection by electron spin resonance (ESR) spectroscopy. The Dose-Response behavior, signal stability and other spectral features were investigated for sodium sulfite, sodium bisulfite, sodium metabisulfite and potassium metabisulfite, all in crystalline forms. The ESR spectrum of salts presented stability and proportional response with dose, presenting potential for dosimetry applications.

Gel and thermoluminescence dosimetry for dose verifications of a real anatomy simulated prostate conformal radiation treatment in the presence of metallic femoral prosthesis.

This study aims to verify the dose delivery of prostate radiotherapy treatments in an adult pelvic phantom with two metallic hip and femur prosthesis using a four-field box technique. The prostate planned target volume (PTV) tridimensional (3D) dose distribution was evaluated using gel dosimetry, and thermoluminescent dosimeters (TLD) were used for point-dose measurements outside it. Both results were compared to the treatment planning system (TPS) dose calculation without using heterogeneity corrections to evaluate the influence of the metal in the dose distribution. MAGIC-f gel dosimeter (Methacrylic and Ascorbic acid in Gelatin Initiated by Copper with Formaldehyde) associated with magnetic resonance imaging was used. TLD were positioned at several points at the bone metal interface and the sacrum region. The comparison of the gel measured and the TPS calculated dose distributions were done using gamma analysis (3%/3 mm), and a pass rate of 93% was achieved. The TLD dose values at the bone-metal interface showed variations from the planned dose. However, at the sacrum region, where the beams did not intercept the prosthesis, there was a good agreement between TPS planning and TLD measurements. Our results show how the combination of 3D dosimetry and measurements at specific points in the phantom allowed a comprehensive view of the dose distribution and identified that care must also be paid to regions outside the PTV.

2D Quantitative Imaging of Magnetic Nanoparticles by an AC Biosusceptometry Based Scanning Approach and Inverse Problem.

The use of magnetic nanoparticles (MNPs) in biomedical applications requires the quantitative knowledge of their quantitative distribution within the body. AC Biosusceptometry (ACB) is a biomagnetic technique recently employed to detect MNPs in vivo by measuring the MNPs response when exposed to an alternate magnetic field. The ACB technique presents some interesting characteristics: non-invasiveness, low operational cost, high portability, and no need for magnetic shielding. ACB conventional methods until now provided only qualitative information about the MNPs' mapping in small animals. We present a theoretical model and experimentally demonstrate the feasibility of ACB reconstructing 2D quantitative images of MNPs' distributions. We employed an ACB single-channel scanning approach, measuring at 361 sensor positions, to reconstruct MNPs' spatial distributions. For this, we established a discrete forward problem and solved the ACB system's inverse problem. Thus, we were able to determine the positions and quantities of MNPs in a field of view of 5×5×1 cm3 with good precision and accuracy. The results show the ACB system's capabilities to reconstruct the quantitative spatial distribution of MNPs with a spatial resolution better than 1 cm, and a sensitivity of 1.17 mg of MNPs fixed in gypsum. These results show the system's potential for biomedical application of MNPs in several studies, for example, electrochemical-functionalized MNPs for cancer cell targeting, quantitative sensing, and possibly in vivo imaging.

Tissue reaction and anti-biofilm action of new biomaterial composed of latex from Hancornia speciosa Gomes and silver nanoparticles.

In this work, the natural latex extracted from Harconia speciosa was incorporated with silver nanoparticles (AgNP) to compose a functional biomaterial associating the intrinsic angiogenic activity of the latex and the antimicrobial activity of AgNP. Tissue reaction after subcutaneous implantation in dorsum of rats of membranes without AgNP and with 0.05%, 0.4% AgNP was compared at 3, 7 and 25 days. No statistically significant difference in the tissue response of the different biomaterials was observed, indicating that AgNP did not interfere with the inflammatory reaction (p > 0.05) or with the angiogenic activity of latex. Biomembranes were also tested against bacterial biofilm formation by Staphylococcus aureus and the antimicrobial activity of the new biomaterial can be found with bacteria crenation (0.05% AgNP) and no biofilm deposition (0.4% AgNP). Therefore, this biomaterial has interesting properties for the tissue repair process and may be feasible for future applications as dressing.

Monosodium glutamate for accidental, retrospective, and medical dosimetry using electron spin resonance.

The risk of a radiation episode has increased in the last years due to several reasons. In case of a nuclear incident, as with the use of an improvised nuclear device, determination of the radiation doses received by the victims is of utmost importance to define the appropriate medical treatment or to monitor the late effects of radiation. Dose assessment in case of accidents can be performed using commonplace materials found in the accident area. In this paper, the dosimetric properties of monosodium glutamate are investigated by electron spin resonance spectroscopy (ESR), for retrospective and accidental dosimetry. The spectroscopic parameters were optimized to achieve higher signal intensity and better signal-to-noise ratio. As a result, the lowest detectable dose was 0.1 Gy, and monosodium glutamate showed a linear dose-response curve for doses ranging from 0.1 Gy to 10 kGy. The dosimetric signal was monitored from minutes right after irradiation, until 1 year. No changes in the signal intensity were observed over this period, meaning that doses could be assessed immediately after radiation exposure and can still be reconstructed long after the accident. This property also implies that late effects due to victim's radiation exposure could be better monitored and understood. ESR signal intensity for samples irradiated with a photon energy below 100 keV was decreased by only 27% and no dose-rate dependence was noticed. Therefore, the ability to measure doses as low as 0.1 Gy, the high stability of the dosimetric signal, as well as independence on dose rate, tissue equivalence, low-cost, and wide commercial availability make monosodium glutamate a very good dosimetric material not only for retrospective and accidental but also for medical dosimetry.

Real-time liver uptake and biodistribution of magnetic nanoparticles determined by AC biosusceptometry.

We describe the development of a joint in vivo/ex vivo protocol to monitor magnetic nanoparticles in animal models. Alternating current biosusceptometry (ACB) enables the assessment of magnetic nanoparticle accumulation, followed by quantitative analysis of concentrations in organs of interest. We present a study of real-time liver accumulation, followed by the assessment of sequential biodistribution using the same technique. For quantification, we validated our results by comparing all of the data with electron spin resonance (ESR). The ACB had viable temporal resolution and accuracy to differentiate temporal parameters of liver accumulation, caused by vasculature extravasation and macrophages action. The biodistribution experiment showed different uptake profiles for different doses and injection protocols. Comparisons with the ESR system indicated a correlation index of 0.993. We present the ACB system as an accessible and versatile tool to monitor magnetic nanoparticles, allowing in vivo and real-time evaluations of distribution and quantitative assessments of particle concentrations.

Enhancing and quenching luminescence with gold nanoparticle films: the influence of substrate on the luminescent properties.

Gold nanoparticle (AuNP) films were sputtered over glass and aluminum substrates to enhance optically stimulated luminescence (OSL), a luminescent technique employed for radiation detection, from x-ray irradiated NaCl nanocrystals. The AuNP films deposited over glass led to enhanced-OSL emission, whereas the AuNP films deposited on aluminum substrates quenched the OSL emission. The enhanced-OSL intensity is proportional to the optical density of the film's plasmon resonance band at the stimulation wavelength. For the case of the AuNP/aluminum films, the luminescence quenching diminishes, and OSL intensity partially recovers upon increasing the distance between the AuNPs and the aluminum substrates, and between the luminescent nanocrystals and the AuNP films. These results suggest that plasmonic interactions between the emitter nanocrystals, the localized surface plasmons (LSP) of the AuNPs, and the substrate are responsible for the OSL enhancement and quenching. In this sense, the substrate dictates whether LSP relaxation occurs by radiative or non-radiative transisitions, leading to enhanced or quenched OSL, respectively. Therefore, besides showing that AuNP films can enhance and/or tune the sensitivity of luminescent radiation detectors, and demonstrating OSL as a new technique to investigate mechanisms of plasmon-enhanced luminescence, these results bring insights on how substrates strongly modify the optical properties of AuNP films.

Dating of fossil human teeth and shells from Toca do Enoque site at Serra das Confusões National Park, Brazil.

This work reports the dating of a fossil human tooth and shell found at the archaeological site Toca do Enoque located in Serra das Confusões National Park (Piauí, Brazil). Many prehistoric paintings have been found at this site. An archaeological excavation unearthed three sepulchers with human skeletons and some shells. Two Brazilian laboratories, in Ribeirão Preto (USP) and Recife (UFPE), independently performed Electron Spin Resonance (ESR) measurements to date the tooth and the shell and obtain the equivalent dose received by each sample. The laboratories determined similar ages for the tooth and the shell (~4.8 kyBP). The results agreed with C-14 dating of the shell and other samples (charcoal) collected in the same sepulcher. Therefore, this work provides a valid inter-comparison of results by two independent ESR-dating laboratories and between two dating methods; i.e., C-14 and ESR, showing the validity of ESR dating for this range of ages.

Dating human occupation at Toca do Serrote das Moendas, São Raimundo Nonato, Piauí-Brasil by electron spin resonance and optically stimulated luminescence.

Excavation of Toca do Serrote das Moendas, in Piauí state, Brazil revealed a great quantity of fossil wild fauna associated with human remains. In particular, fossils of a cervid (Blastocerus dichotomus) were found, an animal frequently pictured in ancient rock wall paintings. In a well-defined stratum, two loose teeth of this species were found in close proximity to human bones. The teeth were independently dated by electron spin resonance (ESR) in two laboratories. The ages obtained for the teeth were 29 ± 3 ka (thousands of years) and 24 ± 1 ka. The concretion layer capping this stratum was dated by optically stimulated luminescence (OSL) of the quartz grains to 21 ± 3 ka. As these values were derived independently in three different laboratories, using different methods and equipment, these results are compelling evidence of early habitation in this area.

Clinical applications of alanine/electron spin resonance dosimetry.

This paper discusses the clinical applications of electron spin resonance (ESR) dosimetry focusing on the ESR/alanine system. A review of few past studies in this area is presented offering a critical overview of the challenges and opportunities for extending this system into clinical applications. Alanine/ESR dosimetry fulfills many of the required properties for several clinical applications such as water-equivalent composition, independence of the sensitivity for the energy range used in therapy and high precision. Improvements in sensitivity and the development of minidosimeters coupled with the use of a spectrometer of higher microwave frequency expanded the possibilities for clinical applications to the new modalities of radiotherapy (intensity-modulated radiation therapy and radiosurgery) and to the detection of low doses such as those present in some radiological image procedures.

The effect of temperature on the synthesis of magnetite nanoparticles by the coprecipitation method.

Magnetic nanoparticles, such as magnetite (Fe3O4), exhibit superparamagnetic properties below 15 nm at room temperature. They are being explored for medical applications, and the coprecipitation technique is preferred for cost-effective production. This study investigates the impact of synthesis temperature on the nanoparticles' physicochemical characteristics. Two types of magnetic analysis were conducted. Samples T 40, T 50, and T 60 displayed superparamagnetic behavior, as evidenced by the magnetization curves. The experiments verified the development of magnetic nanoparticles with an average diameter of approximately dozens of nanometers, as determined by various measurement methods such as XDR, Raman, and TEM. Raman spectroscopy showed the characteristic bands of the magnetite phase at 319, 364, 499, and 680 cm-1. This was confirmed in the second analysis with the ZFC-FC curves, which showed that the samples' blocking temperatures were below ambient temperature. ZFC-FC curves revealed a similar magnetization of about 30 emu/g when applying a magnetic field of 5 kOe.

Ferrite Shield to Enhance the Performance of Optically Pumped Magnetometers for Fetal Magnetocardiography.

Fetal magnetocardiography (fMCG) has proven to be an important tool for the prenatal monitoring of electrical cardiac activity; however, the high cost of superconducting quantum instrumentation (SQUID) poses a limitation for the dissemination of fMCG as a routine clinical technique. Recently, optically pumped magnetometers (OPMs) operating within person-sized, cylindrical shields have made fMCG more practical, but environmental magnetic interference entering through the shield opening substantially degrades the quality of fMCG signals. The goal of this study was to further attenuate these interferences by placing the OPM array within a small ferrite shield. FMCG recordings were made with and without the ferrite shield in ten subjects inside a person-sized, three-layer mu-metal cylindrical shield. Although the fetal signal was slightly attenuated, the environmental interference was reduced substantially, and maternal interference was also diminished. This increased the signal-to-noise ratio significantly and improved the resolution of the smaller waveform components. The performance improvement was highest in the axial direction and compensated for a major weakness of open-ended, person-sized shields. The ferrite shield is especially beneficial for the deployment of triaxial OPM sensors, which require effective shielding in all directions.

MarLe: Markerless estimation of head pose for navigated transcranial magnetic stimulation.

Navigated transcranial magnetic stimulation (nTMS) is a valuable tool for non-invasive brain stimulation. Currently, nTMS requires fixing of markers on the patient's head. Head marker displacements lead to changes in coil placement and brain stimulation inaccuracy. A markerless neuronavigation method is needed to increase the reliability of nTMS and simplify the nTMS protocol. In this study, we introduce and release MarLe, a Python markerless head tracker neuronavigation software for TMS. This novel software uses computer-vision techniques combined with low-cost cameras to estimate the head pose for neuronavigation. A coregistration algorithm, based on a closed-form solution, was designed to track the patient's head and the TMS coil referenced to the individual's brain image. We show that MarLe can estimate head pose based on real-time video processing. An intuitive pipeline was developed to connect the MarLe and nTMS neuronavigation software. MarLe achieved acceptable accuracy and stability in a mockup nTMS experiment. MarLe allows real-time tracking of the patient's head without any markers. The combination of face detection and a coregistration algorithm can overcome nTMS head marker displacement concerns. MarLe can improve reliability, simplify, and reduce the protocol time of brain intervention techniques such as nTMS.

Hybrid Nanoparticles of Citrate-Coated Manganese Ferrite and Gold Nanorods in Magneto-Optical Imaging and Thermal Therapy.

The development of nanomaterials has drawn considerable attention in nanomedicine to advance cancer diagnosis and treatment over the last decades. Gold nanorods (GNRs) and magnetic nanoparticles (MNPs) have been known as commonly used nanostructures in biomedical applications due to their attractive optical properties and superparamagnetic (SP) behaviors, respectively. In this study, we proposed a simple combination of plasmonic and SP properties into hybrid NPs of citrate-coated manganese ferrite (Ci-MnFe2O4) and cetyltrimethylammonium bromide-coated GNRs (CTAB-GNRs). In this regard, two different samples were prepared: the first was composed of Ci-MnFe2O4 (0.4 wt%), and the second contained hybrid NPs of Ci-MnFe2O4 (0.4 wt%) and CTAB-GNRs (0.04 wt%). Characterization measurements such as UV-Visible spectroscopy and transmission electron microscopy (TEM) revealed electrostatic interactions caused by the opposing surface charges of hybrid NPs, which resulted in the formation of small nanoclusters. The performance of the two samples was investigated using magneto-motive ultrasound imaging (MMUS). The sample containing Ci-MnFe2O4_CTAB-GNRs demonstrated a displacement nearly two-fold greater than just using Ci-MnFe2O4; therefore, enhancing MMUS image contrast. Furthermore, the preliminary potential of these hybrid NPs was also examined in magnetic hyperthermia (MH) and photoacoustic imaging (PAI) modalities. Lastly, these hybrid NPs demonstrated high stability and an absence of aggregation in water and phosphate buffer solution (PBS) medium. Thus, Ci-MnFe2O4_CTAB-GNRs hybrid NPs can be considered as a potential contrast agent in MMUS and PAI and a heat generator in MH.

ESR dosimetry with lithium, potassium, and sodium compounds.

This work consists of a first investigation of materials that could be used as ESR dosimeters with doses up to 5 Gy aiming possible applications that would include retrospective dosimetry or dosimetry in specific applications. The characteristics considered were radiological properties close to that of soft tissues, evaluated through their effective atomic number and mass attenuation coefficient, ESR signal dependence on the irradiation dose, sensitivity to dose in the range of ∼5 Gy when exposed to a 50 kV x-ray source and signal stability over a 30-day period. A total of 16 compounds of lithium, potassium and sodium were analyzed, including the already known dosimeter material, lithium formate. Among them, lithium carbonate, lithium phosphate, sodium formate, sodium acetate, sodium citrate, sodium dithionite, sodium carbonate, showed eligible characteristics. After analyzing the ESR dose-response curves, the molecules that showed greater sensitivity to radiation in descending order are: sodium formate, sodium acetate, sodium citrate and sodium dithionite, however, lower than lithium formate. Sodium formate and sodium citrate presented ESR signals with high stability, similar to lithium formate, with fading of ∼3% in 30 days, different from sodium acetate, which showed a 19% reduction. Sodium citrate also presents radiological properties close to soft tissue. Therefore, considering all properties, in the set of the new materials studied in this work, sodium citrate is a promising material for ESR dosimetry.

TMS with fast and accurate electronic control: Measuring the orientation sensitivity of corticomotor pathways.

BACKGROUND: Transcranial magnetic stimulation (TMS) coils allow only a slow, mechanical adjustment of the stimulating electric field (E-field) orientation in the cerebral tissue. Fast E-field control is needed to synchronize the stimulation with the ongoing brain activity. Also, empirical models that fully describe the relationship between evoked responses and the stimulus orientation and intensity are still missing. OBJECTIVE: We aimed to (1) develop a TMS transducer for manipulating the E-field orientation electronically with high accuracy at the neuronally meaningful millisecond-level time scale and (2) devise and validate a physiologically based model describing the orientation selectivity of neuronal excitability. METHODS: We designed and manufactured a two-coil TMS transducer. The coil windings were computed with a minimum-energy optimization procedure, and the transducer was controlled with our custom-made electronics. The electronic E-field control was verified with a TMS characterizer. The motor evoked potential amplitude and latency of a hand muscle were mapped in 3° steps of the stimulus orientation in 16 healthy subjects for three stimulation intensities. We fitted a logistic model to the motor response amplitude. RESULTS: The two-coil TMS transducer allows one to manipulate the pulse orientation accurately without manual coil movement. The motor response amplitude followed a logistic function of the stimulus orientation; this dependency was strongly affected by the stimulus intensity. CONCLUSION: The developed electronic control of the E-field orientation allows exploring new stimulation paradigms and probing neuronal mechanisms. The presented model helps to disentangle the neuronal mechanisms of brain function and guide future non-invasive stimulation protocols.

Three-Dimensional Dosimetry by Optical-CT and Radiochromic Gel Dosimeter of a Multiple Isocenter Craniospinal Radiation Therapy Procedure.

Craniospinal irradiation (CSI) is a complex radiation technique employed to treat patients with primitive neuroectodermal tumors such as medulloblastoma or germinative brain tumors with the risk of leptomeningeal spread. In adults, this technique poses a technically challenging planning process because of the complex shape and length of the target volume. Thus, it requires multiple fields and different isocenters to guarantee the primary-tumor dose delivery. Recently, some authors have proposed the use IMRT technique for this planning with the possibility of overlapping adjacent fields. The high-dose delivery complexity demands three-dimensional dosimetry (3DD) to verify this irradiation procedure and motivated this study. We used an optical CT and a radiochromic Fricke-xylenol-orange gel with the addition of formaldehyde (FXO-f) to evaluate the doses delivered at the field junction region of this treatment. We found 96.91% as the mean passing rate using the gamma analysis with 3%/2 mm criteria at the junction region. However, the concentration of fail points in a determined region called attention to this evaluation, indicating the advantages of employing a 3DD technique in complex dose-distribution verifications.