Superparamagnetic iron oxide nanoparticles (SPIONs) have a high potential for use in clinical diagnostic and therapeutic applications. In vivo distribution of SPIONs can be imaged with the Magnetic Particle Imaging (MPI) method, which uses an inhomogeneous magnetic field with a field free region (FFR). The spatial distribution of the SPIONs are obtained by scanning the FFR inside the field of view (FOV) and sensing SPION related magnetic field disturbance. MPI magnets can be configured to generate a field free point (FFP), or a field free line (FFL) to scan the FOV. FFL scanners provide more sensitivity, and are also more suitable for scanning large regions compared to FFP scanners. Interventional procedures will benefit greatly from FFL based open magnet configurations. Here, we present the first open-sided MPI system that can electronically scan the FOV with an FFL to generate tomographic MPI images. Magnetic field measurements show that FFL can be rotated electronically in the horizontal plane and translated in three dimensions to generate 3D MPI images. Using the developed scanner, we obtained 2D images of dot and cylinder phantoms with varying iron concentrations between 11 µg/ml and 770 µg/ml. We used a measurement based system matrix image reconstruction method that minimizes 1-norm and total variation in the images. Furthermore, we present 2D imaging results of two 4 mm-diameter vessel phantoms with 0% and 75% stenosis. The experiments show high quality imaging results with a resolution down to 2.5 mm for a relatively low gradient field of 0.6 T/m. Index Terms-Magnetic particle imaging, field free line, open magnetic particle imaging scanner, tomography, magnetic nanoparticles. I. INTRODUCTION S UPERPARAMAGNETIC iron oxide nanoparticles (SPIONs) have been proposed as biocompatible agents for a wide variety of biomedical applications such as magnetic resonance angiography, perfusion imaging, lymph
Purpose: Thermal ablation with transcranial MRI-guided focused ultrasound (FUS) is currently limited to central brain targets because of heating and other beam effects caused by the presence of the skull. Recently, it was shown that it is possible to ablate tissues without depositing thermal energy by driving intravenously administered microbubbles to inertial cavitation using low-duty-cycle burst sonications. A recent study demonstrated that this ablation method could ablate tissue volumes near the skull base in nonhuman primates without thermally damaging the nearby bone. However, blood–brain disruption was observed in the prefocal region, and in some cases, this region contained small areas of tissue damage. The objective of this study was to analyze the experimental model with simulations and to interpret the cause of these effects. Methods: The authors simulated prior experiments where nonthermal ablation was performed in the brain in anesthetized rhesus macaques using a 220 kHz clinical prototype transcranial MRI-guided FUS system. Low-duty-cycle sonications were applied at deep brain targets with the ultrasound contrast agent Definity. For simulations, a 3D pseudospectral finite difference time domain tool was used. The effects of shear mode conversion, focal steering, skull aberrations, nonlinear propagation, and the presence of skull base on the pressure field were investigated using acoustic and elastic wave propagation models. Results: The simulation results were in agreement with the experimental findings in the prefocal region. In the postfocal region, however, side lobes were predicted by the simulations, but no effects were evident in the experiments. The main beam was not affected by the different simulated scenarios except for a shift of about 1 mm in peak position due to skull aberrations. However, the authors observed differences in the volume, amplitude, and distribution of the side lobes. In the experiments, a single element passive cavitation detector was used to measure the inertial cavitation threshold and to determine the pressure amplitude to use for ablation. Simulations of the detector’s acoustic field suggest that its maximum sensitivity was in the lower part of the main beam, which may have led to excessive exposure levels in the experiments that may have contributed to damage in the prefocal area. Conclusions: Overall, these results suggest that case-specific full wave simulations before the procedure can be useful to predict the focal and the prefocal side lobes and the extent of the resulting bioeffects produced by nonthermal ablation. Such simulations can also be used to optimally position passive cavitation detectors. The disagreement between the simulations and the experiments in the postfocal region may have been due to shielding of the ultrasound field due to microbubble activity in the focal region. Future efforts should include the effects of microbubble activity and vascularization on the pressure field.
Magnetic particle imaging (MPI) is a relatively new medical imaging modality, which detects the nonlinear response of magnetic nanoparticles (MNPs) that are exposed to external magnetic fields. The system matrix (SM) method for MPI image reconstruction requires a time consuming system calibration scan prior to image acquisition, where a single MNP sample is measured at each voxel position in the field-of-view (FOV). The scanned sample has the maximum size of a voxel so that the calibration measurements have relatively poor signal-to-noise ratio (SNR). In this paper, we present the coded calibration scene (CCS) framework, where we place multiple MNP samples inside the FOV in a random or pseudo-random fashion. Taking advantage of the sparsity of the SM, we reconstruct the SM by solving a convex optimization problem with alternating direction method of multipliers using CCS measurements. We analyze the effects of filling rate, number of measurements, and SNR on the SM reconstruction using simulations and demonstrate different implementations of CCS for practical realization. We also compare the imaging performance of the proposed framework with that of a standard compressed sensing SM reconstruction that utilizes a subset of calibration measurements from a single MNP sample. The results show that CCS significantly reduces calibration time while increasing both the SM reconstruction and image reconstruction performances.
This study investigated thermal ablation and skull-induced heating with a 230 kHz transcranial MRI-guided focused ultrasound (TcMRgFUS) system in nonhuman primates. We evaluated real-time acoustic feedback and aimed to understand whether cavitation contributed to the heating and the lesion formation. In four macaques, we sonicated thalamic targets at acoustic powers of 34–560 W (896–7590 J). Tissue effects evaluated with MRI and histology were compared to MRI-based temperature and thermal dose measurements, acoustic emissions recorded during the experiments, and acoustic and thermal simulations. Peak temperatures ranged from 46-57°C, and lesions were produced in 5/8 sonicated targets. A linear relationship was observed between the applied acoustic energy and both the focal and brain surface heating. Thermal dose thresholds were 15–50 cumulative equivalent minutes at 43°C, similar to prior studies at higher frequencies. Histology was also consistent with earlier studies of thermal effects in the brain. The system successfully controlled the power level and maintained a low level of cavitation activity. Increased acoustic emissions observed in 3/4 animals occurred when the focal temperature rise exceeded approximately 16°C. Thresholds for thermally-significant subharmonic and wideband emissions were 129 and 140W, respectively, corresponding to estimated pressure amplitudes of 2.1 and 2.2 MPa. Simulated focal heating was consistent with the measurements for sonications without thermally-significant acoustic emissions; otherwise it was consistently lower than the measurements. Overall, these results suggest that the lesions were produced by thermal mechanisms. The detected acoustic emissions, however, and their association with heating suggest that cavitation might have contributed to the focal heating. Compared to earlier work with a 670 kHz TcMRgFUS system, the brain surface heating was substantially reduced and the focal heating was higher with this 230 kHz system, suggesting that a reduced frequency can increase the treatment envelope for TcMRgFUS and potentially reduce the risk of skull heating.
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