Flexible Metamaterial Wrap for Improved Head Imaging at 3 T MRI With Low-Cost and Easy Fabrication Method.

Magnetic resonance imaging (MRI) requires spatial uniformity of the radiofrequency (RF) field inside the subject for maximum signal-to-noise ratio (SNR) and image contrast. Bulky high permittivity dielectric pads (HPDPs) focus magnetic fields into the region of interest (ROI) and increase RF field uniformity when placed between the patient and RF coils in the MR scanner. Metamaterials could replace HPDPs and reduce system bulkiness, but those in the literature often require a complicated fabrication process and cannot conform to patient body shape. Proposed is a flexible metamaterial for brain imaging made with a scalable fabrication process using conductive paint and a plastic laminate substrate. The effects of single and double-sided placement of the metamaterial around a human head phantom were investigated in a 3 T scanner. When two metamaterial sheets were wrapped around a head phantom (double-sided placement), the total average signal in the resulting image increased by 10.14% compared to placing a single metamaterial sheet underneath the phantom (single-sided placement). The difference between the maximum and minimum signal intensity values decreased by 57% in six different ROIs with double-sided placement compared to single-sided placement.

Validation of a coupled electromagnetic and thermal model for estimating temperatures during magnetic nanoparticle hyperthermia.

PURPOSE: Alternating magnetic field (AMF) tissue interaction models are generally not validated. Our aim was to develop and validate a coupled electromagnetic and thermal model for estimating temperatures in large organs during magnetic nanoparticle hyperthermia (MNH). MATERIALS AND METHODS: Coupled finite element electromagnetic and thermal model validation was performed by comparing the results to experimental data obtained from temperatures measured in homogeneous agar gel phantoms exposed to an AMF at fixed frequency (155 ± 10 kHz). The validated model was applied to a three-dimensional (3D) rabbit liver built from computed tomography (CT) images to investigate the contribution of nanoparticle heating and nonspecific eddy current heating as a function of AMF amplitude. RESULTS: Computed temperatures from the model were in excellent agreement with temperatures calculated using the analytical method (error < 1%) and temperatures measured in phantoms (maximum absolute error <2% at each probe location). The 3D rabbit liver model for a fixed concentration of 5 mg Fe/cm3 of tumor revealed a maximum temperature ∼44 °C in tumor and ∼40 °C in liver at AMF amplitude of ∼12 kA/m (peak). CONCLUSION: A validated coupled electromagnetic and thermal model was developed to estimate temperatures due to eddy current heating in homogeneous tissue phantoms. The validated model was successfully used to analyze temperature distribution in complex rabbit liver tumor geometry during MNH. In future, model validation should be extended to heterogeneous tissue phantoms, and include heat sink effects from major blood vessels.

Development and testing of implanted carbon electrodes for electromagnetic field mapping during neuromodulation.

PURPOSE: Deep brain stimulation electrodes composed of carbon fibers were tested as a means of administering and imaging magnetic resonance electrical impedance tomography (MREIT) currents. Artifacts and heating properties of custom carbon-fiber deep brain stimulation (DBS) electrodes were compared with those produced with standard DBS electrodes. METHODS: Electrodes were constructed from multiple strands of 7-µm carbon-fiber stock. The insulated carbon electrodes were matched to DBS electrode diameter and contact areas. Images of DBS and carbon electrodes were collected with and without current flow and were compared in terms of artifact and thermal effects in phantoms or tissue samples in 7T imaging conditions. Effects on magnetic flux density and current density distributions were also assessed. RESULTS: Carbon electrodes produced magnitude artifacts with smaller FWHM values compared to the magnitude artifacts around DBS electrodes in spin echo and gradient echo imaging protocols. DBS electrodes appeared 269% larger than actual size in gradient echo images, in sharp contrast to the negligible artifact observed in diameter-matched carbon electrodes. As expected, larger temperature changes were observed near DBS electrodes during extended RF excitations compared with carbon electrodes in the same phantom. Magnitudes and distribution of magnetic flux density and current density reconstructions were comparable for carbon and DBS electrodes. CONCLUSION: Carbon electrodes may offer a safer, MR-compatible method for administering neuromodulation currents. Use of carbon-fiber electrodes should allow imaging of structures close to electrodes, potentially allowing better targeting, electrode position revision, and the facilitation of functional imaging near electrodes during neuromodulation.

Magnetic nanoparticle hyperthermia for treating locally advanced unresectable and borderline resectable pancreatic cancers: the role of tumor size and eddy-current heating.

PURPOSE: Tumor volume largely determines the success of local control of borderline resectable and locally advanced pancreatic cancer with current therapy. We hypothesized that a tumor-mass normalized dose of magnetic nanoparticle hyperthermia (MNPH) with alternating magnetic fields (AMFs) reduces the effect of tumor volume for treatment. METHODS: 18 female athymic nude mice bearing subcutaneous MiaPaCa02 human xenograft tumors were treated with MNPH following intratumor injections of 5.5 mg Fe/g tumor of an aqueous suspension of magnetic iron-oxide nanoparticles. Mice were randomly divided into control (n = 5) and treated groups having small (0.15 ± 0.03 cm3, n = 4) or large (0.30 ± 0.06 cm3, n = 5) tumors. We assessed the clinical feasibility of this approach and of pulsed AMF to minimize eddy current heating using a finite-element method to solve a bioheat equation for a human-scale multilayer model. RESULTS: Compared to the control group, both small and large MiaPaCa02 subcutaneous tumors showed statistically significant growth inhibition. Conversely, there was no significant difference in tumor growth between large and small tumors. Both computational and xenograft models demonstrated higher maximum tumor temperatures for large tumors compared to small tumors. Computational modeling demonstrates that pulsed AMF can minimize nonspecific eddy current heating. CONCLUSIONS: MNPH provides an advantage to treat large tumors because the MION dose can be adjusted to increase power. Pulsed AMF, with adjusted treatment time, can enhance MNPH in challenging cases such as low MION dose in the target tissue and/or large patients by minimizing nonspecific eddy current heating without sacrificing thermal dose to the target. Nanoparticle heterogeneity in tumors remains a challenge for continued research.

Design and construction of a Maxwell-type induction coil for magnetic nanoparticle hyperthermia.

Purpose: We describe a modified Helmholtz induction coil, or Maxwell coil, that generates alternating magnetic fields (AMF) having field uniformity (≤10%) within a = 3000 cm3 volume of interest for magnetic hyperthermia research.Materials and methods: Two-dimensional finite element analysis (2D-FEA) was used for electromagnetic design of the induction coil set and to develop specifications for the required matching network. The matching network and induction coil set were fabricated using best available practices and connected to a 120 kW industrial induction heating power supply. System performance was evaluated by magnetic field mapping with a magnetic field probe, and tests were performed using gel phantoms.Results: Tests verified that the system generated a target peak AMF amplitude along the coil axis of ∼35 kA/m (peak) at a frequency of 150 ± 10 kHz while maintaining field uniformity to >90% of peak for a volume of ∼3000 cm3.Conclusions: The induction coil apparatus comprising three independent loops, i.e., Maxwell-type improves upon the performance of simple solenoid and Helmholtz coils by providing homogeneous flux density fields within a large volume while minimizing demands on power and stray fields. Experiments with gel phantoms and analytical calculations show that future translational research efforts should be devoted to developing strategies to reduce the impact of nonspecific tissue heating from eddy currents; and, that an inductor producing a homogeneous field has significant clinical potential for deep-tissue magnetic fluid hyperthermia.

Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia.

PURPOSE: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia. METHODS: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes' bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods. RESULTS: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating. CONCLUSIONS: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.

Increased uptake of doxorubicin by cells undergoing heat stress does not explain its synergistic cytotoxicity with hyperthermia.

Purpose: A proposed mechanism for the enhanced effectiveness of hyperthermia and doxorubicin (Dox) combinations is increased intracellular Dox concentrations resulting from heat-induced cell stress. The purpose of this study was to determine whether specific varied Dox and heat combinations produce measurable effects greater than the additive combination, and whether these effects can be attributed to heat-induced increases in intracellular Dox concentrations. Methods: HCT116, HT29 and CT26 cells were exposed to Dox and water bath heating independently. A clonogenic survival assay was used to determine cell killing and intracellular Dox concentrations were measured in HCT116 cells with mass spectrometry. Cells were exposed to heating at 42 °C (60 min) and 0.5 µg/ml of Dox at varying intervals. Synergy was determined by curve-fitting and isobologram analysis. Results: All cell lines displayed synergistic effects of combined heating and Dox. A maximum synergistic effect was achieved with simultaneous cell exposure to Dox and heat. For exposures at 42 °C, the synergistic effect was most pronounced at Dox concentrations <0.5 µg/ml. Increased intracellular concentrations of Dox in HCT116 cells caused by heat-stress did not generate a concomitant thermal enhancement. Conclusions: Simultaneous exposure of HCT116 cells to heating and Dox is more effective than sequential exposure. Heat-induced cell responses are accompanied by increased intracellular Dox concentrations; however, clonogenic survival data do not support this as the cause for synergistic cytotoxicity.

Magnetic nanoparticle hyperthermia enhances radiation therapy: A study in mouse models of human prostate cancer.

PURPOSE: We aimed to characterise magnetic nanoparticle hyperthermia (mNPH) with radiation therapy (RT) for prostate cancer. METHODS: Human prostate cancer subcutaneous tumours, PC3 and LAPC-4, were grown in nude male mice. When tumours measured 150 mm3 magnetic iron oxide nanoparticles (MIONPs) were injected into tumours to a target dose of 5.5 mg Fe/cm3 tumour, and treated 24 h later by exposure to alternating magnetic field (AMF). Mice were randomly assigned to one of four cohorts to characterise (1) intratumour MIONP distribution, (2) effects of variable thermal dose mNPH (fixed AMF peak amplitude 24 kA/m at 160 ± 5 kHz) with/without RT (5 Gy), (3) effects of RT (RT5: 5 Gy; RT8: 8 Gy), and (4) fixed thermal dose mNPH (43 °C for 20 min) with/without RT (5 Gy). MIONP concentration and distribution were assessed following sacrifice and tissue harvest using inductively coupled plasma mass spectrometry (ICP-MS) and Prussian blue staining, respectively. Tumour growth was monitored and compared among treated groups. RESULTS: LAPC-4 tumours retained higher MIONP concentration and more uniform distribution than did PC3 tumours. AMF power modulation provided similar thermal dose for mNPH and combination therapy groups (CEM43: LAPC-4: 33.6 ± 3.4 versus 25.9 ± 0.8, and PC3: 27.19 ± 0.7 versus 27.50 ± 0.6), thereby overcoming limitations of MIONP distribution and yielding statistically significant tumour growth delay. CONCLUSION: PC3 and LAPC-4 tumours represent two biological models that demonstrate different patterns of nanoparticle retention and distribution, offering a model to make comparisons of these effects for mNPH. Modulating power for mNPH offers potential to overcome limitations of MIONP distribution to enhance mNPH.

Design of standalone wireless impedance matching (SWIM) system for RF coils in MRI.

The radio frequency (RF) power transfer efficiency of transmit coils and the signal-to-noise ratio (SNR) at the receive signal chain are directly dependent on the impedance matching condition presented by a loaded coil, tuned to the Larmor frequency. Sub-optimal impedance condition of receive coils significantly reduces coil sensitivity and image quality. In this study we propose a Standalone Wireless Impedance Matching (SWIM) system for RF coils to automatically compensate for the impedance mismatch caused by the loading effect at the target frequency. SWIM uses a built-in RF generator to produce a calibration signal, measure reflected power as feedback for loading change, and determine an optimal impedance. The matching network consists of a capacitor array with micro-electromechanical system (MEMS) RF switches to electronically cycle through different input impedance conditions. Along with automatic calibration, SWIM can also perform software detuning of RF receive coils. An Android mobile application was developed for real-time reflected power monitoring and controlling the SWIM system via Bluetooth. The SWIM system can automatically calibrate an RF coil in 3 s and the saline sample SNR was improved by 24% when compared to a loaded coil without retuning. Four different tomatoes were imaged to validate the performance of SWIM.

Effort, avolition and motivational experience in schizophrenia: Analysis of behavioral and neuroimaging data with relationships to daily motivational experience.

Recent research suggests that schizophrenia is associated with reduced effort allocation. We examined willingness to expend effort, neural correlates of effort allocation, and the relationship of effort to daily motivational experience in schizophrenia. We recruited 28 individuals with schizophrenia and 30 controls to perform an effort task during fMRI. Individuals with schizophrenia also completed an ecological momentary assessment (EMA) protocol. Individuals with schizophrenia with high negative symptoms were less willing to expend effort for rewards. Daily EMA assessments of motivation were positively associated with effort allocation at a trend-level. Individuals with schizophrenia and controls displayed similar increases in BOLD activation in frontal, cingulate, parietal, and insular regions during effort-based decision-making. However, negative symptoms were associated with reduced BOLD activation in bilateral ventral striatum. These results replicate previous reports of reduced effort allocation in schizophrenia patients with severe negative symptoms, and provide evidence for the role of ventral striatum in effort impairments.

Nanoparticle interactions with immune cells dominate tumor retention and induce T cell-mediated tumor suppression in models of breast cancer.

The factors that influence nanoparticle fate in vivo following systemic delivery remain an area of intense interest. Of particular interest is whether labeling with a cancer-specific antibody ligand ("active targeting") is superior to its unlabeled counterpart ("passive targeting"). Using models of breast cancer in three immune variants of mice, we demonstrate that intratumor retention of antibody-labeled nanoparticles was determined by tumor-associated dendritic cells, neutrophils, monocytes, and macrophages and not by antibody-antigen interactions. Systemic exposure to either nanoparticle type induced an immune response leading to CD8+ T cell infiltration and tumor growth delay that was independent of antibody therapeutic activity. These results suggest that antitumor immune responses can be induced by systemic exposure to nanoparticles without requiring a therapeutic payload. We conclude that immune status of the host and microenvironment of solid tumors are critical variables for studies in cancer nanomedicine and that nanoparticle technology may harbor potential for cancer immunotherapy.

Experimental estimation and analysis of variance of the measured loss power of magnetic nanoparticles.

Magnetic nanoparticles dissipate heat when exposed to alternating magnetic fields (AMFs), making them suitable for cancer hyperthermia. Therapeutic heating applications demand accurate characterization of the heating power dissipated by the particles. Specific loss power (SLP) generated by magnetic nanoparticles is estimated from calorimetric heating measurements. Such measurements require adiabatic conditions, yet they are typically performed in an AMF device with non-adiabatic conditions. We have measured heating from four magnetic nanoparticle constructs using a range of frequencies (150-375 kHz) and magnetic fields (4-44 kA/m). We have extended a method developed to estimate SLP from the inherently non-adiabatic measurements, where we identify data ranges that conform to (quasi)-adiabatic conditions. Each time interval of measurement that met a predetermined criterion was used to generate a value of SLP, and the mean from all estimates was selected as the estimated SLP. Despite the application of rigorous selection criteria, measured temperature data displayed variability at specific heating loads resulting in larger variance of calculated mean SLP values. Overall, the results show a linear dependence of the SLP with AMF frequency, as anticipated by current models. Conversely, measured amplitude-dependent SLP profiles of all studied constructs conform to no predictions of current models.

SIMULATION OF DISCRETE BLOOD VESSEL EFFECTS ON THE THERMAL SIGNATURE OF A MELANOMA LESION.

The effect of the underlying blood vessel on the transient thermal response of the skin surface with and without a melanoma lesion is studied. A 3D computational model of the layers of the skin tissue with cancerous lesion was developed in COMSOL software package. Heat transfer in the skin layers and the lesion is governed by the Pennes bio-heat equation, while the blood vessel is modeled as fully developed pipe flow with constant heat transfer coefficient. The effect of various pertinent parameters, such as diameter of the blood vessel, lateral location of the blood vessel relative to the lesion, flow velocity of the blood, on the skin surface temperature distribution, have been studied in the paper. The results show significant influence of the underlying blood vessel on the temperature of the skin surface and lesion as well as on the surrounding healthy tissue. Thus, a need for development of evaluation criteria for detection of malignant lesions in the presence of blood vessels is is discussed.