Synthesis, Characterization and Magnetic Hyperthermia of Monodispersed Cobalt Ferrite Nanoparticles for Cancer Therapeutics.

Magnetic nanoparticles such as cobalt ferrite are investigated under clinical hyperthermia conditions for the treatment of cancer. Cobalt ferrite nanoparticles (CFNPs) synthesized by the thermal decomposition method, using nonionic surfactant Triton-X100, possess hydrophilic polyethylene oxide chains acting as reducing agents for the cobalt and iron precursors. The monodispersed nanoparticles were of 10 nm size, as confirmed by high-resolution transmission electron microscopy (HR-TEM). The X-ray diffraction patterns of CFNPs prove the existence of cubic spinel cobalt ferrites. Cs-corrected scanning transmission electron microscopy-high-angle annular dark-field imaging (STEM-HAADF) of CFNPs confirmed their multi-twinned crystallinity due to the presence of atomic columns and defects in the nanostructure. Magnetic measurements proved that the CFNPs possess reduced remnant magnetization (MR/MS) (0.86), which justifies cubic anisotropy in the system. Microwave-based hyperthermia studies performed at 2.45 GHz under clinical conditions in physiological saline increased the temperature of the CFNP samples due to the transformation of radiation energy to heat. The specific absorption rate of CFNPs in physiological saline was 68.28 W/g. Furthermore, when triple-negative breast cancer cells (TNBC) in the presence of increasing CFNP concentration (5 mg/mL to 40 mg/mL) were exposed to microwaves, the cell cytotoxicity was enhanced compared to CFNPs alone.

Computerized lesion segmentation of breast ultrasound based on marker-controlled watershed transformation.

PURPOSE: This paper presents a computerized segmentation method for breast lesions on ultrasound (US) images. METHODS: It consists of first applying a contrast-enhanced approach, i.e., a contrast-limited adaptive histogram equalization. Then, aiming at removing speckle and enhancing the lesion boundary, an anisotropic diffusion filter, guided by texture descriptors derived from a set of Gabor filters, is applied. To eliminate the distant pixels that do not belong to the tumor, the resulting filtered image is multiplied by a constraint Gaussian function. By doing so, both the segmentation and the marker functions are generated and could be used in the marker-controlled watershed transformation algorithm to create potential lesion boundaries. Finally, to determine the lesion contour, the average radial derivative function is evaluated. The proposed method was tested with 50 breast US images and 60 simulated "ultrasound-like" images. Accuracy and precision of the segmentation method were then assessed. For the accuracy, three parameters were used: Overlap ratio (OR), normalized residual value (nrv), and proportional distance (PD) between contours. RESULTS: The average results for US images were OR = 0.86 +/- 0.05, nrv = 0.16 +/- 0.06, and PD = 6.58 +/- 2.52%. For simulated ultrasound-like images, a better performance (OR = 0.92 +/- 0.01, nrv = 0.08 +/- 0.01, and PD = 3.20 +/- 0.53%) was achieved. CONCLUSIONS: The segmentation method proposed was capable of delineating the lesion contours with high accuracy in comparison to both the radiologists' delineations and the true delineations of simulated images. Moreover, this method was also found to be robust to human-dependent parameters variations.

Wearable Active Electrode for sEMG Monitoring Using Two-Channel Brass Dry Electrodes with Reduced Electronics.

Gel-based electrodes are employed to record sEMG signals for prolonged periods. These signals are used for the control of myoelectric prostheses, clinical analysis, or sports medicine. However, when the gel dries, the electrode-skin impedance increases considerably. Using dry active electrodes (AEs) to compensate variations of impedance is an alternative for long-term recording. This work describes the optimization of the electronic design of a conventional AE by removing the impedance coupling stage and two filters. The proposed work consisted of 5 stages: electrodes, amplification (X250), 2.2 Vdc offset, low-pass filter, and ADC with USART communication. The device did not need the use of electrolytic gel. The measurements of CMRR (96 dB), amplitude of the output sEMG signal (∼1.6 Vp-p), and system bandwidth (15-450 Hz) were performed in order to confirm the reliability of the device as an sEMG signal acquisition system. The SNR values from seven movements performed by eleven volunteers were compared in order to measure the repeatability of the measurements (average 30.32 dB for a wrist flexion). The SNR for wrist flexion measured with the proposed and the commercial system was compared; the values were 49 dB and 60 dB, respectively.

Feasibility of Using a Novel 2.45 GHz Double Short Distance Slot Coaxial Antenna for Minimally Invasive Cancer Breast Microwave Ablation Therapy: Computational Model, Phantom, and In Vivo Swine Experimentation.

Microwave ablation (MWA) by using coaxial antennas is a promising alternative for breast cancer treatment. A double short distance slot coaxial antenna as a newly optimized applicator for minimally invasive treatment of breast cancer is proposed. To validate and to analyze the feasibility of using this method in clinical treatment, a computational model, phantom, and breast swine in vivo experimentation were carried out, by using four microwave powers (50 W, 30 W, 20 W, and 10 W). The finite element method (FEM) was used to develop the computational model. Phantom experimentation was carried out in breast phantom. The in vivo experimentation was carried out in a 90 kg swine sow. Tissue damage was estimated by comparing control and treated micrographs of the porcine mammary gland samples. The coaxial slot antenna was inserted in swine breast glands by using image-guided ultrasound. In all cases, modeling, in vivo and phantom experimentation, and ablation temperatures (above 60°C) were reached. The in vivo experiments suggest that this new MWA applicator could be successfully used to eliminate precise and small areas of tissue (around 20-30 mm2). By modulating the power and time applied, it may be possible to increase/decrease the ablation area.

Design and evaluation of surface functionalized superparamagneto-plasmonic nanoparticles for cancer therapeutics.

Designing a multifunctional nanomaterial is always considered as a biggest concern in the field of nanomedicine which aims to promote versatile action in a single use from tracking to therapeutics. Therefore, metallic nanoparticles are well exploited as a major platform with the assemblage of surface modifications which can be effectively engaged for plenty of applications. Here, in this work, we have successfully amalgamated gold coated magnetite core-shell nanoparticles along with bio-functionalization of folic acid and doxorubicin to explore its possibility as a distinct nanocargo for cancer nanotheranostics. This unique combination of both magnetic and optical properties makes its function to be more precise. For example, in case of in-vitro drug-release studies more than 75% of drug moieties are released at acidic pH 5.4 and exactly fitting in first order rate kinetics. As gold shell retains the superparamagnetic nature of the core it exhibited high r2 values, and because of large relaxivities (r2/r1) ratio, they are confirmed as T2-weighted contrast agent by MRI. Finally, under microwave of 2.45GHz exhibited enough heat which can induce both apoptosis & necrosis leading to cell death. Thus, we conclude that our nanoparticle can be a multitool for diagnosis and therapeutics for various human diseases.

Experimental Verification of Modeled Thermal Distribution Produced by a Piston Source in Physiotherapy Ultrasound.

Objectives. To present a quantitative comparison of thermal patterns produced by the piston-in-a-baffle approach with those generated by a physiotherapy ultrasonic device and to show the dependency among thermal patterns and acoustic intensity distributions. Methods. The finite element (FE) method was used to model an ideal acoustic field and the produced thermal pattern to be compared with the experimental acoustic and temperature distributions produced by a real ultrasonic applicator. A thermal model using the measured acoustic profile as input is also presented for comparison. Temperature measurements were carried out with thermocouples inserted in muscle phantom. The insertion place of thermocouples was monitored with ultrasound imaging. Results. Modeled and measured thermal profiles were compared within the first 10 cm of depth. The ideal acoustic field did not adequately represent the measured field having different temperature profiles (errors 10% to 20%). Experimental field was concentrated near the transducer producing a region with higher temperatures, while the modeled ideal temperature was linearly distributed along the depth. The error was reduced to 7% when introducing the measured acoustic field as the input variable in the FE temperature modeling. Conclusions. Temperature distributions are strongly related to the acoustic field distributions.

Plasmonic/Magnetic Multifunctional nanoplatform for Cancer Theranostics.

A multifunctional magneto-plasmonic CoFe2O4@Au core-shell nanoparticle was developed by iterative-seeding based method. This nanocargo consists of a cobalt ferrite kernel as a core (Nk) and multiple layers of gold as a functionalizable active stratum, (named as Nk@A after fifth iteration). Nk@A helps in augmenting the physiological stability and enhancing surface plasmon resonance (SPR) property. The targeted delivery of Doxorubicin using Nk@A as a nanopayload is demonstrated in this report. The drug release profile followed first order rate kinetics optimally at pH 5.4, which is considered as an endosomal pH of cells. The cellular MR imaging showed that Nk@A is an efficient T2 contrast agent for both L6 (r2-118.08 mM-1s-1) and Hep2 (r2-217.24 mM-1s-1) cells. Microwave based magnetic hyperthermia studies exhibited an augmentation in the temperature due to the transformation of radiation energy into heat at 2.45 GHz. There was an enhancement in cancer cell cytotoxicity when hyperthermia combined with chemotherapy. Hence, this single nanoplatform can deliver 3-pronged theranostic applications viz., targeted drug-delivery, T2 MR imaging and hyperthermia.

Modeling the thermo-acoustic effects of thermal-dependent speed of sound and acoustic absorption of biological tissues during focused ultrasound hyperthermia.

PURPOSE: To evaluate the effects of thermal dependence of speed of sound (SOS) and acoustic absorption of biological tissues during noninvasive focused ultrasound (US) hyperthermia therapy. METHODS: A finite element (FE) model was used to simulate hyperthermia therapy in the liver by noninvasive focused US. The model consisted of an ultrasonic focused transducer radiating a four-layer biological medium composed of skin, fat, muscle, and liver. The acoustic field and temperature distribution along the layers were obtained after 15 s of hyperthermia therapy using the bio-heat equation. The model solution was found with and without the thermal dependence of SOS and acoustic absorption of biological tissues. RESULTS: The inclusion of the thermal dependence of the SOS generated an increment of 0.4 mm in the longitudinal focus axis of the acoustic field. Moreover, results indicate an increment of the hyperthermia area (zone with temperature above 43 °C), and a maximum temperature difference of almost 3.5 °C when the thermal dependence of absorption was taken into account. CONCLUSION: The increment of the achieved temperatures at the treatment zone indicated that the effects produced by the thermal dependence of SOS and absorption must be accounted for when planning hyperthermia treatment in order to avoid overheating undesired regions.

Development and characterisation of electromechanical muscles for driving trans-humeral myoelectric prostheses.

Recently, attempts have been made to construct actuators with similar behaviour to natural muscles. However the results have been inadequate for application to practical prostheses. For example, muscle wire, which has too low an efficiency to be powered by batteries and McKibben muscles which require two power supplies, one electric and one pneumatic. Electrochemical muscles are still in the development stage and cannot yet be used for prostheses. In this paper, a new electromechanical actuator is presented, which provides rectilinear movement and linear characteristics. This electromechanical actuator is based on a ball screw and rare earth magnet coreless motors. The system has been characterised and some of the most important results are that it produces a force of 167N while developing a velocity of 7x10(-3)m/s. The force developed is proportional to the current drained. Its efficiency is about 32%, its total mass 0.19kg and it is light and compact enough to be used in practical clinical prosthesis.

A comparison of direct and pattern recognition control for a two degree-of-freedom above elbow virtual prosthesis.

Individuals with a transhumeral amputation have a large functional deficit and require basic functions out of their prosthesis. Myoelectric prostheses have used amplitude control techniques for decades to restore one or two degrees of freedom to these patients. Pattern recognition control has also been investigated for transhumeral amputees, but in recent years, has been more focused on transradial amputees or high-level patients who have received targeted muscle reinnervation. This study seeks to use the most recent advances in pattern recognition control and investigate techniques that could be applied to the majority of the transhumeral amputee population that has not had the reinnervation surgery to determine if pattern recognition systems may provide them with improved control. In this study, able-bodied control subjects demonstrated that highly accurate two degree-of-freedom pattern recognition systems may be trained using four EMG channels. Such systems may be used to better control a prosthesis in real-time when compared to conventional amplitude control with mode switching.

Influence of temperature variations on the average grayscale of B-mode images of HIFU-induced lesions.

The aim of this work is to understand how the variations in grayscale values of B-mode ultrasound (US) images can be used as an approach for non-invasive temperature estimation. In order to obtain real-time monitoring of HIFU treatment, an US imaging system and HIFU were synchronized. Images were acquired using an electronic convex imaging probe. An 8% BSA tissue-mimicking polyacrylamide gel was used for the experiments. First, the HIFU power was set to 10 W. The application of HIFU resulted in the appearance of hyperechoic regions that were used to place a thermocouple tip at the focal spot by means of US imaging. Afterwards, the power was gradually increased up to 40 W for 4 min. The temperature sampling rate was set to 5 Hz. For each temperature sample the synchronization system captured one frame. The region of interest (ROI) was manually selected and a set of morphological operations were implemented in order to obtain the shape and size of the thermal lesion. From here, the average grayscale (AGS) and area of the thermal lesion were calculated to assess temperature quantification. The AGS parameter showed a maximum correlation coefficient of 0.6626 as a function of temperature whereas the thermal lesion appeared. In contrast, area values showed a greater correlation coefficient of 0.9122. In conclusion, temperature shows a non-linear behavior with respect to the parameters estimated due to the nature of the thermal lesion formation by HIFU exposure.

Validation of a transit time blood flow meter used for coronary bypass surgery.

The validation of a blood flow meter is presented. This flow meter is based on the transit time method that uses two ultrasound transducers and a reflector. The measuring is based on the time difference of the upstream and the downstream ultrasound transit time. The validation was based on the norm ANSI Std. N42.17A-2003 of blood flow protocol. We used a flow simulator system with 3 mm pipe, bi-distilled and desgasificated water as fluid. Flow simulator system uses a constant flow pump, regulated by a valve, and a peristaltic flow pump, regulated by a variable voltage source, like flow source through the pipe.

Tracking training evolution: patient with upper limb amputation above the elbow.

This article describes a patient training evolution to achieve myoelectric control in the remnant limb. The methodology is divided in two main stages: (i) the training procedure, where the patient is submitted to a protocol for educating the muscles of the remnant limb, and (ii) myoelectric signal acquisition and analysis, in order to measure the patient evolution to reach different contraction levels along the training sessions. After three training stages, the results suggest that the patient gradually achieved strength control over the muscles of the remnant limb.

Using 'stall detection' as an auxiliary mechanism for sensing obstacles and hand grasping in arm prosthesis.

This paper proposes a novel method for sensing obstacles and hand grasping activities in electromechanical arm prosthesis. The described method is based on indirectly sensing 'Stall' condition in prosthesis actuators through hall-effect sensors already embedded on its dc motors, thus not requiring external sensors. To test the proposed methodology, an electromechanical arm prosthesis of 3 degrees of freedom (DOF), plus 'open-close' of hand, which is being developed at CINVESTAV Mexico, was used. At the end of this paper, experimental measurements performed on the tested prosthesis, using and non using 'Stall Detection', are shown. We demonstrated that methodology can be used successfully for "sensing obstacles", but it cannot be used alone for "hand grasping". In any case, this technique demonstrated to be a good method to simplify and strengthen control of prosthesis.

A performance analysis of echographic ultrasonic techniques for non-invasive temperature estimation in hyperthermia range using phantoms with scatterers.

Optimization of efficiency in hyperthermia requires a precise and non-invasive estimation of internal distribution of temperature. Although there are several research trends for ultrasonic temperature estimation, efficient equipments for its use in the clinical practice are not still available. The main objective of this work was to research about the limitations and potential improvements of previously reported signal processing options in order to identify research efforts to facilitate their future clinical use as a thermal estimator. In this document, we have a critical analysis of potential performance of previous ultrasonic research trends for temperature estimation inside materials, using different processing techniques proposed in frequency, time and phase domains. It was carried out in phantom with scatterers, assessing at their specific applicability, linearity and limitations in hyperthermia range. Three complementary evaluation indexes: technique robustness, Mat-lab processing time and temperature resolution, with specific application protocols, were defined and employed for a comparative quantification of the behavior of the techniques. The average increment per degrees C and mm was identified for each technique (3 KHz/ degrees C in the frequency analysis, 0.02 rad/ degrees C in the phase domain, while increments in the time domain of only 1.6 ns/ degrees C were found). Their linearity with temperature rising was measured using linear and quadratic regressions and they were correlated with the obtained data. New improvements in time and frequency signal processing in order to reveal the potential thermal and spatial resolutions of these techniques are proposed and their subsequent improved estimation results are shown for simulated and measured A-scans registers. As an example of these processing novelties, an excellent potential resolution of 0.12 degrees C into hyperthermia range, with near-to-linear frequency dependence, could be achieved. Specifically defined "numerical" and physical multi-scatter phantoms are described, which mimic ultrasound velocity in tissues of about 1560 m/s @ 35 degrees C and have a quasi-uniform internal scattering structure designed to assure standard signal patterns adequate for processing comparisons in the same time and sound velocity conditions for all the techniques analyzed, and to obtain easily repeatable multi-pulse echo-patterns. A perfect lineal dependence (100% of correlation coefficient) between the unitary average increment measured by each technique and temperature rising was observed while working with simulated A-scan registers, where all the parameters are under an accurate control. Nevertheless a very small quadratic tendency appeared in the results obtained from experimental echo registers, which are more similar to a real tissues case. It would be an interesting future work to analyze the behavior of these techniques in real tissues in order to confirm or reject this light quadratic tendency. Finally, new methods were detailed and applied in order to precisely quantify the advantages of each estimation technique; their respective intrinsic limitations were also underlined.

Therapy ultrasound equipment characterization: Comparison of three techniques.

Methods for characterizing ultrasonic therapy equipment rapidly and easily have to be implemented in order to avoid damages to patients; the existent methods measure different parameters in the ultrasonic beam that can be used to determine if the equipment works appropriately. In this paper, a comparison of three methods to characterize the ultrasonic beam is presented. The first one is a C-scan with microprobe which uses a hydrophone for measuring the signal and a positioning system. The second method is the IR-thermography which uses a phantom to absorb the ultrasonic energy and to convert it into heat. Here, the heat distribution is obtained with an IR camera. The third method uses a sheet of thermochromic liquid crystals (TLC) as sensor and a phantom to absorb the energy. The heat distribution is obtained with a normal camera because the TLCs change their color as a function of temperature. The results indicate that each technique has its own benefits, but the most important parameters can be obtained with only one of them.

An electronic tongue using potentiometric all-solid-state PVC-membrane sensors for the simultaneous quantification of ammonium and potassium ions in water.

The simultaneous determination of NH(4)(+) and K(+) in solution has been attempted using a potentiometric sensor array and multivariate calibration. The sensors used are rather non-specific and of all-solid-state type, employing polymeric (PVC) membranes. The subsequent data processing is based on the use of a multilayer artificial neural network (ANN). This approach is given the name "electronic tongue" because it mimics the sense of taste in animals. The sensors incorporate, as recognition elements, neutral carriers belonging to the family of the ionophoric antibiotics. In this work the ANN type is optimized by studying its topology, the training algorithm, and the transfer functions. Also, different pretreatments of the starting data are evaluated. The chosen ANN is formed by 8 input neurons, 20 neurons in the hidden layer and 2 neurons in the output layer. The transfer function selected for the hidden layer was sigmoidal and linear for the output layer. It is also recommended to scale the starting data before training. A correct fit for the test data set is obtained when it is trained with the Bayesian regularization algorithm. The viability for the determination of ammonium and potassium ions in synthetic samples was evaluated; cumulative prediction errors of approximately 1% (relative values) were obtained. These results were comparable with those obtained with a generalized regression ANN as a reference algorithm. In a final application, results close to the expected values were obtained for the two considered ions, with concentrations between 0 and 40 mmol L(-1).