A prediction model for magnetic particle imaging-based magnetic hyperthermia applied to a brain tumor model.

BACKGROUND AND OBJECTIVE: Brain tumor is a global health concern at the moment. Thus far, the only treatments available are radiotherapy and chemotherapy, which have several drawbacks such as low survival rates and low treatment efficacy due to obstruction of the blood-brain barrier. Magnetic hyperthermia (MH) using magnetic nanoparticles (MNPs) is a promising non-invasive approach that has the potential for tumor treatment in deep tissues. Due to the limitations of the current drug-targeting systems, only a small proportion of the injected MNPs can be delivered to the desired area and the rest are distributed throughout the body. Thus, the application of conventional MH can lead to damage to healthy tissues. METHODS: Magnetic particle imaging (MPI)-guided treatment platform for MH is an emerging approach that can be used for spatial localization of MH to arbitrarily selected regions by using the MPI magnetic field gradient. Although the feasibility of this method has been demonstrated experimentally, a multidimensional prediction model, which is of crucial importance for treatment planning, has not yet been developed. Hence, in this study, the time dependent magnetization equation derived by Martsenyuk, Raikher, and Shliomis (which is a macroscopic equation of motion derived from the Fokker-Planck equation for particles with Brownian relaxation mechanism) and the bio-heat equations have been used to develop and investigate a three-dimensional model that predicts specific loss power (SLP), its spatio-thermal resolution (temperature distribution), and the fraction of damage in brain tumors. RESULTS: Based on the simulation results, the spatio-thermal resolution in focused heating depends, in a complex manner, on several parameters ranging from MNPs properties to magnetic fields characteristics, and coils configuration. However, to achieve a high performance in focused heating, the direction and the relative amplitude of the AC magnetic heating field with respect to the magnetic field gradient are among the most important parameters that need to be optimized. The temperature distribution and fraction of the damage in a simple brain model bearing a tumor were also obtained. CONCLUSIONS: The complexity in the relationship between the MNPs properties and fields parameter imposes a trade-off between the heating efficiency of MNPs and the accuracy (resolution) of the focused heating. Therefore, the system configuration and field parameters should be chosen carefully for each specific treatment scenario. In future, the results of the model are expected to lead to the development of an MPI-guided MH treatment platform for brain tumor therapy. However, for more accurate quantitative results in such a platform, a magnetization dynamics model that takes into account coupled Néel-Brownian relaxation mechanism in the MNPs should be developed.

Highly Optimized Iron Oxide Embedded Poly(Lactic Acid) Nanocomposites for Effective Magnetic Hyperthermia and Biosecurity.

INTRODUCTION: Iron oxide magnetic nanoparticles (IONPs) have attracted considerable attention for various biomedical applications owing to their ease of synthesis, strong magnetic properties, and biocompatibility. In particular, IONPs can generate heat under an alternating magnetic field, the effects of which have been extensively studied for magnetic hyperthermia therapy. However, the development of IONPs with high heating efficiency, biocompatibility, and colloidal stability in physiological environments is still required for their safe and effective application in biomedical fields. METHODS: We synthesized magnetic IONP/polymer nanocomposites (MNCs) by embedding IONPs in a poly(L-lactic acid) (PLA) matrix via nanoemulsion. The IONP contents (Fe: 9-22 [w/w]%) in MNCs were varied to investigate their effects on the magnetic and hyperthermia performances based on their optimal interparticle interactions. Further, we explored the stability, cytocompatibility, biodistribution, and in vivo tissue compatibility of the MNCs. RESULTS: The MNCs showed enhanced heating efficiency with over two-fold increase compared to nonembedded bare IONPs. The relationship between the IONP content and heating performance in MNCs was nonmonotonous. The highest heating performance was obtained from MNC2, which contain 13% Fe (w/w), implying that interparticle interactions in MNCs can be optimized to achieve high heating performance. In addition, the MNCs exhibited good colloidal stability under physiological conditions and maintained their heating efficiency during 48 h of incubation in cell culture medium. Both in vitro and in vivo studies revealed excellent biocompatibility of the MNC. CONCLUSION: Our nanocomposites, comprising biocompatible IONPs and PLA, display improved heating efficiency, good colloidal stability, and cytocompatibility, and thus will be beneficial for diverse biomedical applications, including magnetic hyperthermia for cancer treatment.

Theoretical Analysis for Using Pulsed Heating Power in Magnetic Hyperthermia Therapy of Breast Cancer.

In magnetic hyperthermia, magnetic nanoparticles (MNPs) are used to generate heat in an alternating magnetic field to destroy cancerous cells. This field can be continuous or pulsed. Although a large amount of research has been devoted to studying the efficiency and side effects of continuous fields, little attention has been paid to the use of pulsed fields. In this simulation study, Fourier's law and COMSOL software have been utilized to identify the heating power necessary for treating breast cancer under blood flow and metabolism to obtain the optimized condition among the pulsed powers for thermal ablation. The results showed that for small source diameters (not larger than 4 mm), pulsed powers with high duties were more effective than continuous power. Although by increasing the source domain the fraction of damage caused by continuous power reached the damage caused by the pulsed powers, it affected the healthy tissues more (at least two times greater) than the pulsed powers. Pulsed powers with high duty (0.8 and 0.9) showed the optimized condition and the results have been explained based on the Arrhenius equation. Utilizing the pulsed powers for breast cancer treatment can potentially be an efficient approach for treating breast tumors due to requiring lower heating power and minimizing side effects to the healthy tissues.

Theoretical Analysis for Wireless Magnetothermal Deep Brain Stimulation Using Commercial Nanoparticles.

A wireless magnetothermal stimulation (WMS) is suggested as a fast, tetherless, and implanted device-free stimulation method using low-radio frequency (100 kHz to 1 MHz) alternating magnetic fields (AMF). As magnetic nanoparticles (MNPs) can transduce alternating magnetic fields into heat, they are targeted to a region of the brain expressing the temperature-sensitive ion channel (TRPV1). The local temperature of the targeted area is increased up to 44 °C to open the TRPV1 channels and cause an influx of Ca2+ sensitive promoter, which can activate individual neurons inside the brain. The WMS has initially succeeded in showing the potential of thermomagnetics for the remote control of neural cell activity with MNPs that are internally targeted to the brain. In this paper, by using the steady-state temperature rise defined by Fourier's law, the bio-heat equation, and COMSOL Multiphysics software, we investigate most of the basic parameters such as the specific loss power (SLP) of MNPs, the injection volume of magnetic fluid, stimulation and cooling times, and cytotoxic effects at high temperatures (43-44 °C) to provide a realizable design guideline for WMS.

Effects of Vibrotactile Biofeedback Coding Schemes on Gait Symmetry Training of Individuals With Stroke.

Variations in biofeedback coding schemes for postural control, in recent research, have shown significant differences in performance outcomes due to variations in coding schemes. However, the application of vibrotactile biofeedback coding schemes to gait symmetry training is not well explored. In this paper, we devised various vibrotactile biofeedback modes and identified their efficacy during gait symmetry training of individuals suffering from hemiparesis due to stroke. These modes are composed of variations in vibration type (on-time or intensity), and relation type (proportional or inversely-proportional) with the error in symmetry ratio. Eight individuals with stroke participated in walking trials. From dependent t-tests on the collected data, we found improved achievement of temporal gait symmetry while utilizing all the provided biofeedback modes compared to no biofeedback (P < 0.001). Furthermore, two-way repeated measures ANOVA revealed statistically significant difference in symmetry ratio for main effect of vibration type (P-value = 0.016, partial eta squared = 0.585). The participants performed better with modes of biofeedback with varying vibration on-times. Furthermore, participants showed better performance when the biofeedback varied proportionally with the error. These findings suggest that biofeedback coding schemes may have a significant effect on the performance of gait training.

Evaluating the Effects of Kinesthetic Biofeedback Delivered Using Reaction Wheels on Standing Balance.

Aging, injury, or ailments can contribute to impaired balance control and increase the risk of falling. Provision of light touch augments the sense of balance and can thus reduce the amount of body sway. In this study, a wearable reaction wheel-based system is used to deliver light touch-based balance biofeedback on the subject's back. The system can sense torso tilt and, using reaction wheels, generates light touch. A group of 7 healthy young individuals performed balance tasks under 12 trial combinations based on two conditions each of standing stance and surface types and three of biofeedback device status. Torso tilt data, collected from a waist-mounted smartphone during all the trials, were analyzed to determine the efficacy of the system. Provision of biofeedback by the device significantly reduced RMS of mediolateral (ML) trunk tilt (p < 0.05) and ML trunk acceleration (p < 0.05). Repeated measures ANOVA revealed significant interaction between stance and surface on reduction in RMS of ML trunk tilt, AP trunk tilt, ML trunk acceleration, and AP trunk acceleration. The device shows promise for further applications such as virtual reality interaction and gait rehabilitation.

A novel balance training system using multimodal biofeedback.

BACKGROUND: A biofeedback-based balance training system can be used to provide the compromised sensory information to subjects in order to retrain their sensorimotor function. In this study, the design and evaluation of the low-cost, intuitive biofeedback system developed at Gyeongsang National University is extended to provide multimodal biofeedback for balance training by utilization of visual and haptic modalities. METHODS: The system consists of a smartphone attached to the waist of the subject to provide information about tilt of the torso, a personal computer running a purpose built software to process the smartphone data and provide visual biofeedback to the subject by means of a dedicated monitor and a dedicated Phantom Omni(®) device for haptic biofeedback. For experimental verification of the system, eleven healthy young participants performed balance tasks assuming two distinct postures for 30 s each while acquiring torso tilt. The postures used were the one foot stance and the tandem Romberg stance. For both the postures, the subjects stood on a foam platform which provided a certain amount of ground instability. RESULTS: Post-experiment data analysis was performed using MATLAB(®) to analyze reduction in body sway. Analysis parameters based on the projection of trunk tilt information were calculated in order to ascertain the reduction in body sway and improvements in postural control. Two-way analysis of variance (ANOVA) showed no statistically significant interactions between postures and biofeedback. Post-hoc analysis revealed statistically significant reduction in body sway on provision of biofeedback. Subjects exhibited maximum body sway during no biofeedback trial, followed by either haptic or visual biofeedback and in most of the trials the multimodal biofeedback of visual and haptic together resulted in minimization of body sway, thus indicating that the multimodal biofeedback system worked well to provide significant (p < 0.05) assistance in postural control. CONCLUSIONS: A multimodal biofeedback system can offer more customized training methods and hence provide therapists with a comprehensive solution for a diverse array of patients. It is necessary to identify the long-term effects of this novel biofeedback system. In the future, the balance training schemes for individuals with upright balance issues will be studied.

Cancer pain control for advanced cancer patients by using autonomic nerve pharmacopuncture.

OBJECTIVES: The purpose of this study is to report a case series of advanced cancer patients whose cancer pain was relieved by using autonomic nerve pharmacopuncture (ANP) treatment. ANP is a subcutaneous injection therapy of mountain ginseng pharmacopuncture (MGP) along the acupoints on the spine (Hua-Tuo-Jia-Ji-Xue; 0.5 cun lateral to the lower border of the spinous processes of vertebrae) to enhance the immune system and to balance autonomic nerve function. METHODS: Patients with three different types of cancer (gastric cancer, lung cancer, colon cancer with distant metastases) with cancer pain were treated with ANP. 1 mL of MGP was injected into the bilateral Hua-Tuo-Jia-Ji-Xue on the T1-L5 sites (total 12 ─ 20 mL injection) of each patient's dorsum by using the principle of symptom differentiation. During ANP treatment, the visual analogue scale (VAS) for pain was used to assess their levels of cancer pain; also, the dosage and the frequency of analgesic use were measured. RESULTS: The cancer pain levels of all three patients improved with treatment using ANP. The VAS scores of the three patients decreased as the treatment progressed. The dosage and the frequency of analgesics also gradually decreased during the treatment period. Significantly, no related adverse events were found. CONCLUSION: ANP has shown benefit in controlling cancer pain for the three different types of cancer investigated in this study and in reducing the dosage and the frequency of analgesics. ANP is expected to be beneficial for reducing cancer pain and, thus, to be a promising new treatment for cancer pain.