Purpose: To investigate the usefulness of magnetic particle imaging (MPI) for predicting the therapeutic effect of magnetic hyperthermia (MH). Materials and Methods: First, we performed phantom experiments to investig...Purpose: To investigate the usefulness of magnetic particle imaging (MPI) for predicting the therapeutic effect of magnetic hyperthermia (MH). Materials and Methods: First, we performed phantom experiments to investigate the relationship between the MPI value and the temperature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). The MPI value was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. Samples filled with various iron concentrations of MNPs (Resovist®) were prepared and were imaged using our MPI scanner. These samples were also heated using the AMF, and the specific loss power (SLP) and volume-specific loss power (vSLP) were calculated from the initial slope of the time-dependent temperature rise. Second, we performed animal experiments using tumor-bearing mice, which were divided into untreated (n = 10) and treated groups (n = 20). The tumors in the treated group were injected with Resovist®?at an iron concentration of 250 mM (n = 10) or 500 mM (n = 10), and received MH for 20 min, during which the temperatures in the tumor and rectum were measured. The relative tumor volume growth (RTVG) was calculated from (V15 -?V0)/V0, where V0 and V15 represented the tumor volume on day 0 and day 15 after MH, respectively. Results: In phantom experiments, the MPI value had significant correlations with the iron concentration of MNPs (r = 0.997), temperature rise (r = 0.981), and vSLP (r = 0.961). In animal experiments, the MPI value had significant correlations with the temperature rise in the tumor (r = 0.731) and RTVG (r = ﹣0.687). Conclusion: Our preliminary results suggest that MPI is useful for predicting the therapeutic effect of MH.展开更多
Purpose: To investigate the feasibility of applying magnetic particle imaging (MPI) to pulmonary imaging using nebulized magnetic nanoparticles (MNPs) and to quantify the mucociliary clearance in the lung, using small...Purpose: To investigate the feasibility of applying magnetic particle imaging (MPI) to pulmonary imaging using nebulized magnetic nanoparticles (MNPs) and to quantify the mucociliary clearance in the lung, using small animal experiments. Materials and Methods: Intrapulmonary administration of MNPs was performed in seven-week-old male ICR (Institute of Cancer Research) mice (n = 8) using a nebulized microsprayer connected to a high-pressure syringe containing 50 μL of MNPs (500 mM Resovist®). We imaged the lungs using our MPI scanner 2.5 hours, 1 day, 3 days, and 7 days after the intrapulmonary administration of MNPs. The average MPI value was calculated by drawing a region of interest (ROI) on the lungs by taking the threshold value for extracting the contour as 20% of the maximum MPI value within the ROI. The MPI value was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. Mice were sacrificed immediately after the last MPI and X-ray CT studies on day 7, and 5 lobes of the lung in each mouse were extracted to confirm the accumulation of iron using Berlin blue staining. Results: We could visualize the distribution of MNPs in the lungs as positive contrast using MPI with use of nebulized MNPs. The presence of iron in the lung was confirmed by Berlin blue staining. The average MPI value decreased with time and tended to saturate. The clearance rate was calculated to be 0.505 day−1 from the time course of the average MPI value in the lungs. Conclusion: Our preliminary results suggest that MPI can be applied to pulmonary imaging by nebulizing MNPs and can be useful for quantifying the mucociliary clearance in the lung.展开更多
The purpose of this study was to present a lock-in-amplifier model for analyzing the behavior of signal harmonics in magnetic particle imaging (MPI) and some simulation results based on this model. In the lock-in-ampl...The purpose of this study was to present a lock-in-amplifier model for analyzing the behavior of signal harmonics in magnetic particle imaging (MPI) and some simulation results based on this model. In the lock-in-amplifier model, the signal induced by magnetic nanoparticles (MNPs) in a receiving coil was multiplied with a reference signal, and was then fed through a low-pass filter to extract the DC component of the signal (output signal). The MPI signal was defined as the mean of the absolute value of the output signal. The magnetization and particle size distribution of MNPs were assumed to obey the Langevin theory of paramagnetism and a log-normal distribution, respectively, and the strength of the selection magnetic field (SMF) in MPI was assumed to be given by the product of the gradient strength of the SMF and the distance from the field-free region (x). In addition, Gaussian noise was added to the signal induced by MNPs using normally-distributed random numbers. The relationships between the MPI signal and x were calculated for the odd- and even-numbered harmonics and were investigated for various time constants of the low-pass filter used in the lock-in amplifier and particle sizes and their distributions of MNPs. We found that the behavior of the MPI signal largely depended on the time constant of the low-pass filter and the particle size of MNPs. This lock-in-amplifier model will be useful for better understanding, optimizing, and developing MPI, and for designing MNPs appropriate for MPI.展开更多
Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method c...Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method called magnetic particle imaging (MPI) has been introduced. MPI allows imaging of the spatial distribution of MNPs. The purpose of this study was to investigate the feasibility of visualizing and quantifying the intratumoral distribution and temporal change of MNPs and predicting the therapeutic effect of MHT using MPI. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, mice were divided into untreated (n = 10) and treated groups (n = 27). The tumors in the treated group were directly injected with MNPs (Resovist?) with iron concentrations of 500 mM (A, n = 9), 400 mM (B, n = 8), and 250 mM (C, n = 10), respectively, and MHT was performed using an AMF with a frequency of 600 kHz and a peak amplitude of 3.5 kA/m. The mice in the treated group were scanned using our MPI scanner immediately before, immediately after, 7 days, and 14 days after MHT. We drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels by taking the threshold value for extracting the contour as 40% of the maximum MPI value (pixel value) within the ROI. These parameters in the untreated group were taken as zero. We also measured the relative tumor volume growth (RTVG) defined by (V-V0)/V0, where V0 and V are the tumor volumes immediately before and after MHT, respectively. Results: The average, maximum, and total MPI values decreased up to 7 days after MHT and remained almost constant thereafter in all groups, whereas the number of pixels tended to increase with time. The RTVG values in Groups A and B were significantly lower than those in the control group 3 days or more and 5 days or more after MHT, respectively. The above four parameters were significantly inversely correlated with the RTVG values 5, 7, and 14 days after MHT. Conclusion: MPI can visualize and quantify the intratumoral distribution and temporal change of MNPs before and after MHT. Our results suggest that MPI will be useful for predicting the therapeutic effect of MHT and for the treatment planning of MHT.展开更多
Purpose: Magnetic targeting refers to the attachment of therapeutic agents to magnetizable particles such as magnetic nanoparticles (MNPs) and then applying magnetic fields to concentrate them to the targeted region s...Purpose: Magnetic targeting refers to the attachment of therapeutic agents to magnetizable particles such as magnetic nanoparticles (MNPs) and then applying magnetic fields to concentrate them to the targeted region such as solid tumors. The purpose of this study was to investigate the usefulness of magnetic particle imaging (MPI) for monitoring the effect of magnetic targeting using tumor-bearing mice. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, the mice were divided into treated (n = 8) and untreated groups (n = 8). The tumors in the treated group were directly injected with MNPs (Resovist?, 250 mM) and a neodymium magnet was attached to the tumor surface, whereas the magnet was not attached to the tumor in the untreated group. The mice were imaged using our MPI scanner and the average and maximum MPI values were obtained by drawing a region of interest (ROI) on the tumor, with the threshold value for extracting the contour of the tumor being taken as 40% of the maximum MPI value in the ROI. The relative tumor volume growth (RTVG) was calculated from (V ? V0)/V0, where V0 and V represented the tumor volume immediately before and after the injection of MNPs, respectively. Results: The average and maximum MPI values in the treated group were significantly higher than those in the untreated group 3 days after the injection of MNPs, suggesting the effectiveness of magnetic targeting. There were no significant differences in RTVG between the two groups. Conclusion: Our preliminary results suggest that MPI is useful for monitoring the effect of magnetic targeting.展开更多
Magnetic particle imaging(MPI)is an emerging molecular imaging technique with high sensitivity and temporal-spatial resolution.Image reconstruction is an important research topic in MPI,which converts an induced volta...Magnetic particle imaging(MPI)is an emerging molecular imaging technique with high sensitivity and temporal-spatial resolution.Image reconstruction is an important research topic in MPI,which converts an induced voltage signal into the image of superparamagnetic iron oxide particles concentration distribution.MPI reconstruction primarily involves system matrix-and x-space-based methods.In this review,we provide a detailed overview of the research status and future research trends of these two methods.In addition,we review the application of deep learning methods in MPI reconstruction and the current open sources of MPI.Finally,research opinions on MPI reconstruction are presented.We hope this review promotes the use of MPI in clinical applications.展开更多
Purpose: Magnetic particle imaging (MPI) allows for imaging of the spatial distribution of magnetic nanoparticles (MNPs) in positive contrast, with high sensitivity, high spatial resolution, and high imaging speed. It...Purpose: Magnetic particle imaging (MPI) allows for imaging of the spatial distribution of magnetic nanoparticles (MNPs) in positive contrast, with high sensitivity, high spatial resolution, and high imaging speed. It is necessary to increase the signal-to-noise ratio to enhance the reliability of MPI. The purpose of this study was to investigate the effect of signal filtering on the image quality and quantitativity in projection-based MPI using phantoms. Materials and Methods: We fabricated two kinds of phantom (cylindrical tube phantom with a diameter of 6 mm and A-shaped phantom) and evaluated the effect of signal filtering in terms of root-mean-square (RMS) granularity and the correlation coefficient between iron concentrations of MNPs and average MPI values for four filter modes (THRU, BPF, BEF, and LPF). In the THRU mode, the signal input was output without passing through the filter. In the BPF mode, only the third-harmonic signal was passed using a band-pass filter (central frequency: 1200 Hz, band width: 1/3 octave). In the BEF mode, the first-harmonic signal was eliminated using a band-elimination filter (central frequency: 400 Hz, band width: 1/3 octave). In the LPF mode, only the signal with a frequency less than the third-harmonic frequency was passed using a low-pass filter (cut-off frequency: 1200 Hz, -24 ± 2 dB/octave). The RMS granularity was obtained by calculating standard deviations of the pixel values in the MPI image without MNPs, whereas average MPI values were obtained by drawing a circular region of interest with a diameter of 6 mm on the MPI image of the cylindrical tube phantom. Results: When using the filtered back-projection (FBP) method with a ramp filter for image reconstruction, the RMS granularity and correlation coefficient decreased in the order of THRU, BPF, BEF, and LPF. In the BPF mode, however, some artifacts were observed. When using the maximum likelihood-expectation maximization (ML-EM) algorithm with an iteration number of 15, the correlation coefficient decreased in the order of THRU, BPF, BEF, and LPF, whereas the RMS granularity did not largely depend on the filter mode and was significantly (p Conclusion: The BEF mode is adequate for the FBP method in projection-based MPI, whereas THRU is a best option in use of the ML-EM algorithm.展开更多
The purpose of this study was to evaluate the effectiveness of intracellular magnetic hyperthermia treatment (MHT) in comparison with that of extracellular MHT using magnetic particle imaging (MPI). Colon-26 cells wer...The purpose of this study was to evaluate the effectiveness of intracellular magnetic hyperthermia treatment (MHT) in comparison with that of extracellular MHT using magnetic particle imaging (MPI). Colon-26 cells were implanted subcutaneously into the backs of 8-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, the mice were divided into control (n = 10), extracellular MHT (n = 8), and intracellular MHT groups (n = 7). In the control group, MHT was not performed. In the extracellular MHT and intracellular MHT groups, the tumors were injected directly with magnetic nanoparticles (MNPs) (400 mM Resovist®) and were heated for 20 min using an alternating magnetic field. During MHT, the temperatures of the tumor and rectum were measured using optical fiber thermometers. In the extracellular MHT group, MHT was performed 15 min after the injection of MNPs, whereas MHT was performed one day after the injection of MNPs in the intracellular MHT group. In both groups, MPI images were obtained using our MPI scanner immediately before, immediately after, and 7 and 14 days after MHT. After the MPI studies, we drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels within the ROI. Transmission electron microscopic (TEM) images were also obtained from resected tumors. In all groups, tumor volume was measured every day and the relative tumor volume growth (RTVG) was calculated. The TEM images showed that almost all the MNPs were aggregated in the extracellular space in the extracellular MHT group, whereas they were contained within the intracellular space in the intracellular MHT group. Although the temperature of the tumor in the intracellular MHT group was significantly lower than that in the extracellular MHT group, the RTVG value in the intracellular MHT group was significantly lower than that in the control group 2 days or more after MHT and that in the extracellular MHT group 3, 4, and 5 days after MHT. The average MPI value normalized by that immediately before MHT in the intracellular MHT group was significantly higher than that in the extracellular MHT group immediately and 7 days after MHT. The maximum and total MPI values normalized by those immediately before MHT in the intracellular MHT group were significantly higher than those in the extracellular MHT group 7 days after MHT, suggesting that the temporal change of MNPs within the tumor in the intracellular MHT group was smaller than that in the extracellular MHT group. Our results suggest that intracellular MHT is more cytotoxic than extracellular MHT in spite of a lower temperature rise of tumors, and that MPI is useful for evaluating the difference in the temporal change of MNPs in the tumor between extracellular MHT and intracellular MHT.展开更多
Purpose: Magnetic nanofibers (MNFs) are nanofibers impregnated with magnetic nanoparticles (MNPs). Magnetic particle imaging (MPI) is a recently introduced imaging method that allows im-aging of the spatial distributi...Purpose: Magnetic nanofibers (MNFs) are nanofibers impregnated with magnetic nanoparticles (MNPs). Magnetic particle imaging (MPI) is a recently introduced imaging method that allows im-aging of the spatial distribution of MNPs. The purpose of this study was to develop MNFs and to investigate the feasibility of visualizing them using MPI and of heating them using an alternating magnetic field (AMF). Materials and Methods: First, chitosan nanofibers were cross-linked with glu-taraldehyde vapor in a sealed vial for 24 hours. Next, they were mixed with various concentrations of MNPs and the mixture was stirred for 1 hour using a magnetic stirrer. After the mixture was re-frigerated at –80℃ for 24 hours, it was freeze-dried for 24 hours. The morphology of the resultant MNFs was characterized by scanning electron microscopy, and the magnetic properties were meas-ured using a vibrating sample magnetometer. After these measurements, we imaged the MNFs us-ing our MPI scanner, and investigated the correlation between the pixel values of the MPI image and the concentration of MNPs or the number of MNF sheets. We also heated the MNFs using AMF, and measured the temperature rise using an infrared thermometer. Results: The MNFs were suc-cessfully visualized using our MPI scanner, and the pixel values of the MPI image showed excellent correlation with the concentration of MNPs (r = 0.992) and the number of MNF sheets (r = 0.997). A significant temperature rise was observed under AMF, and the initial slope of the time-dependent temperature rise showed excellent correlation with the concentration of MNPs (r = 0.994) and the number of MNF sheets (r = 0.979). Conclusion: The MNFs developed in this study can be visualized using MPI and can be applied to magnetic hyperthermia. They will be useful in biomedicine including cancer therapy and tissue regeneration.展开更多
Ferumoxytol, an iron replacement product, is a new type of superparamagnetic iron oxide ap- proved by the US Food and Drug Administration. Herein, we assessed the feasibility of tracking transplanted human adipose-der...Ferumoxytol, an iron replacement product, is a new type of superparamagnetic iron oxide ap- proved by the US Food and Drug Administration. Herein, we assessed the feasibility of tracking transplanted human adipose-derived stem cells labeled with ferumoxytol in middle cerebral artery occlusion-injured rats by 3.0 T MRI in vivo. 1 × 104 human adipose-derived stem cells labeled with ferumoxytol-heparin-protamine were transplanted into the brains of rats with middle cerebral artery occlusion. Neurologic impairment was scored at 1, 7, 14, and 28 days after transplantation. T2-weighted imaging and enhanced susceptibility-weighted angiography were used to observe transplanted cells. Results of imaging tests were compared with results of Prussian blue staining. The modified neurologic impairment scores were significantly lower in rats transplanted with cells at all time points except I day post-transplantation compared with rats without transplantation. Regions with hypointense signals on T2-weighted and enhanced susceptibility-weighted angiography images corresponded with areas stained by Prussian blue, suggesting the presence of superparamagnetic iron oxide particles within the engrafted cells. Enhanced susceptibility-weighted angiography image exhibited better sensitivity and contrast in tracing ferumoxytol-heparin-protamine-labeled human adipose-derived stem ceils compared with T2-weighted imaging in routine MRI.展开更多
To assess a novel cell manipulation technique of tissue engineering with respect to its ability to augment superparamagnetic iron oxide particles (SPIO) labeled mesenchymal stem cells (MSCs) density at a localized...To assess a novel cell manipulation technique of tissue engineering with respect to its ability to augment superparamagnetic iron oxide particles (SPIO) labeled mesenchymal stem cells (MSCs) density at a localized cartilage defect site in an in vitro phantom by applying magnetic force. Meanwhile, non-invasive imaging techniques were use to track SPIO-labeled MSCs by magnetic resonance imaging (MRI). Human bone marrow MSCs were cultured and labeled with SPIO. Fresh degenerated human osteochondral fragments were obtained during total knee arthroplasty and a cartilage defect was created at the center. Then, the osteochondral fragments were attached to the sidewalls of culture flasks filled with phosphate-buffered saline (PBS) to mimic the human joint cavity. The SPIO-labeled MSCs were injected into the culture flasks in the presence of a 0.57 Tesla (T) magnetic force. Before and 90 min after cell targeting, the specimens underwent T2-weighted turbo spin-echo (SET2WI) sequence of 3.0 T MRI. MRI results were compared with histological findings. Macroscopic observation showed that SPIO-labeled MSCs were steered to the target region of cartilage defect. MRI revealed significant changes in signal intensity (P0.01). HE staining exibited that a great number of MSCs formed a three-dimensional (3D) cell "sheet" structure at the chondral defect site. It was concluded that 0.57 T magnetic force permits spatial delivery of magnetically labeled MSCs to the target region in vitro. High-field MRI can serve as an very sensitive non-invasive technique for the visualization of SPIO-labeled MSCs.展开更多
Purpose: The purpose of this study was to present a novel therapeutic strategy combining use of intracellular magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF) and bleomycin (BLM), and to evaluat...Purpose: The purpose of this study was to present a novel therapeutic strategy combining use of intracellular magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF) and bleomycin (BLM), and to evaluate its therapeutic effect using tumor-bearing mice. Materials and Methods: MNPs (Resovist?, 1.05 mg iron) were incorporated into the hemagglutinating virus of Japan-envelope (HVJ-E) vector (~5 × 109 particles) (HVJ-E/MNPs) by centrifugation at 10,000 × g for 5 min at 4°C. Tumor-bearing mice were prepared by inoculating Colon-26 cells subcutaneously into the backs of BALB/c mice. When the tumor volume reached ~100 mm3, HVJ-E/MNPs and/or BLM were injected directly into the tumor. The AMF was applied to the mice one hour after the injection of agents (AMF treatment). The mice injected with HVJ-E/MNPs were imaged using our magnetic particle imaging (MPI) scanner immediately (13 min) before, immediately (22 min) after, and 3, 7, and 14 days after the injection of agents, and the temporal changes of the average and maximum MPI pixel values in the tumor were quantitatively evaluated. The therapeutic effect was evaluated by calculating the relative tumor volume growth (RTVG) from the tumor volumes measured each day. Transmission electron microscopic (TEM) observation of resected tumors was also performed to confirm the intracellular distribution of MNPs. Results: The AMF treatment combined with BLM significantly decreased the RTVG value compared with AMF treatment alone at 9 to 14 days, and BLM alone at 3 to 5 days after AMF treatment. The average and maximum MPI pixel values in the tumor were almost constant for 14 days. TEM observation confirmed that most of the HVJ-E/MNPs were internalized into tumor cells within one hour after injection. Conclusion: A novel therapeutic strategy with use of AMF treatment and BLM was presented, and the time-dependent change of MNPs in tumors was evaluated using MPI. The present results suggest that this novel strategy can suppress tumor volume growth over AMF treatment or BLM alone, and can be performed repeatedly with a single injection of HVJ-E/MNPs. They also suggest that HVJ-E is effective for internalizing MNPs into cancer cells and that MPI allows for longitudinal monitoring of the distribution of MNPs in tumors.展开更多
Multifunctional fluorescent magnetic nanoparticles (Fe3O4@SiO2-PLLA-RhB/FA) with cell recognition ability were synthesized through conjugation of magnetic nanoparticles with folic acid (FA) and Rhodamine B. To ver...Multifunctional fluorescent magnetic nanoparticles (Fe3O4@SiO2-PLLA-RhB/FA) with cell recognition ability were synthesized through conjugation of magnetic nanoparticles with folic acid (FA) and Rhodamine B. To verity their potential biomedical applications, biocompatibility as well as cell imaging applications of the multifunctional nanoparticles were further investigated. Results showed that these fluorescent magnetic nanoparticles are well bio- compatible with NIH-3T3 cells and HeLa cells. More importantly, these nanoparticles could be selectively taken up by HeLa cells (FA receptor positive) as evidenced by laser scanning confocal microscopy, suggesting their potential for biological imaging applications. Given their excellent biocompatibility and multifunctional characteristics, weexpect that the fluorescent magnetic nanoparticles could be promising for various biomedical applications.展开更多
In the present study,we report a fabrication of dual-mode carbon coated gadolinia C@Gd_(2)O_(3)particles by a facile hydrothermal synthesis method without using any organic solvents.The prepared C@Gd_(2)O_(3)particles...In the present study,we report a fabrication of dual-mode carbon coated gadolinia C@Gd_(2)O_(3)particles by a facile hydrothermal synthesis method without using any organic solvents.The prepared C@Gd_(2)O_(3)particles have a core-shell structure and a narrow size distribution in the range of 261±27 nm.The fluorescent properties of the prepared C@Gd_(2)O_(3)particles were accessed by a room-temperature photoluminescence study,while the longitudinal relaxivity(r1)was examined by using a clinical 1.5 T MRI scanner.A murine fibroblast L-929 cell line was used to examine the cytotoxicity and capability of the prepared C@Gd_(2)O_(3)particles for the fluorescent labeling.The obtained results show that the prepared C@Gd_(2)O_(3)particles could be used as a dual-mode contrast agent for magnetic resonance and fluorescence imaging.展开更多
Magnetic particle imaging(MPI)is an emerging technique to visualize the spatial distribution of super-paramagnetic iron oxide with high temporal–spatial resolution,high sensitivity,unlimited image depth,and true quan...Magnetic particle imaging(MPI)is an emerging technique to visualize the spatial distribution of super-paramagnetic iron oxide with high temporal–spatial resolution,high sensitivity,unlimited image depth,and true quantitative information.MPI is based on the nonlinear response of superparamagnetic iron oxide in an alter-nating magnetic field without tissue background noise.It is a promising imaging modality for various applica-tions,including vascular imaging,cell tracking,tumor imaging,and catheter navigation.Many applications of liver imaging could be improved or created with MPI.In this review,we cover the principle and construction of MPI,we evaluate the features and advantages of MPI with relation to its own rationale and via comparison with other imaging modalities,and we review MPI liver imaging applications with a view toward assisting hepatic researchers in drawing inspiration.展开更多
文摘Purpose: To investigate the usefulness of magnetic particle imaging (MPI) for predicting the therapeutic effect of magnetic hyperthermia (MH). Materials and Methods: First, we performed phantom experiments to investigate the relationship between the MPI value and the temperature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). The MPI value was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. Samples filled with various iron concentrations of MNPs (Resovist®) were prepared and were imaged using our MPI scanner. These samples were also heated using the AMF, and the specific loss power (SLP) and volume-specific loss power (vSLP) were calculated from the initial slope of the time-dependent temperature rise. Second, we performed animal experiments using tumor-bearing mice, which were divided into untreated (n = 10) and treated groups (n = 20). The tumors in the treated group were injected with Resovist®?at an iron concentration of 250 mM (n = 10) or 500 mM (n = 10), and received MH for 20 min, during which the temperatures in the tumor and rectum were measured. The relative tumor volume growth (RTVG) was calculated from (V15 -?V0)/V0, where V0 and V15 represented the tumor volume on day 0 and day 15 after MH, respectively. Results: In phantom experiments, the MPI value had significant correlations with the iron concentration of MNPs (r = 0.997), temperature rise (r = 0.981), and vSLP (r = 0.961). In animal experiments, the MPI value had significant correlations with the temperature rise in the tumor (r = 0.731) and RTVG (r = ﹣0.687). Conclusion: Our preliminary results suggest that MPI is useful for predicting the therapeutic effect of MH.
文摘Purpose: To investigate the feasibility of applying magnetic particle imaging (MPI) to pulmonary imaging using nebulized magnetic nanoparticles (MNPs) and to quantify the mucociliary clearance in the lung, using small animal experiments. Materials and Methods: Intrapulmonary administration of MNPs was performed in seven-week-old male ICR (Institute of Cancer Research) mice (n = 8) using a nebulized microsprayer connected to a high-pressure syringe containing 50 μL of MNPs (500 mM Resovist®). We imaged the lungs using our MPI scanner 2.5 hours, 1 day, 3 days, and 7 days after the intrapulmonary administration of MNPs. The average MPI value was calculated by drawing a region of interest (ROI) on the lungs by taking the threshold value for extracting the contour as 20% of the maximum MPI value within the ROI. The MPI value was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. Mice were sacrificed immediately after the last MPI and X-ray CT studies on day 7, and 5 lobes of the lung in each mouse were extracted to confirm the accumulation of iron using Berlin blue staining. Results: We could visualize the distribution of MNPs in the lungs as positive contrast using MPI with use of nebulized MNPs. The presence of iron in the lung was confirmed by Berlin blue staining. The average MPI value decreased with time and tended to saturate. The clearance rate was calculated to be 0.505 day−1 from the time course of the average MPI value in the lungs. Conclusion: Our preliminary results suggest that MPI can be applied to pulmonary imaging by nebulizing MNPs and can be useful for quantifying the mucociliary clearance in the lung.
文摘The purpose of this study was to present a lock-in-amplifier model for analyzing the behavior of signal harmonics in magnetic particle imaging (MPI) and some simulation results based on this model. In the lock-in-amplifier model, the signal induced by magnetic nanoparticles (MNPs) in a receiving coil was multiplied with a reference signal, and was then fed through a low-pass filter to extract the DC component of the signal (output signal). The MPI signal was defined as the mean of the absolute value of the output signal. The magnetization and particle size distribution of MNPs were assumed to obey the Langevin theory of paramagnetism and a log-normal distribution, respectively, and the strength of the selection magnetic field (SMF) in MPI was assumed to be given by the product of the gradient strength of the SMF and the distance from the field-free region (x). In addition, Gaussian noise was added to the signal induced by MNPs using normally-distributed random numbers. The relationships between the MPI signal and x were calculated for the odd- and even-numbered harmonics and were investigated for various time constants of the low-pass filter used in the lock-in amplifier and particle sizes and their distributions of MNPs. We found that the behavior of the MPI signal largely depended on the time constant of the low-pass filter and the particle size of MNPs. This lock-in-amplifier model will be useful for better understanding, optimizing, and developing MPI, and for designing MNPs appropriate for MPI.
文摘Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the tem-perature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Re-cently, a new imaging method called magnetic particle imaging (MPI) has been introduced. MPI allows imaging of the spatial distribution of MNPs. The purpose of this study was to investigate the feasibility of visualizing and quantifying the intratumoral distribution and temporal change of MNPs and predicting the therapeutic effect of MHT using MPI. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, mice were divided into untreated (n = 10) and treated groups (n = 27). The tumors in the treated group were directly injected with MNPs (Resovist?) with iron concentrations of 500 mM (A, n = 9), 400 mM (B, n = 8), and 250 mM (C, n = 10), respectively, and MHT was performed using an AMF with a frequency of 600 kHz and a peak amplitude of 3.5 kA/m. The mice in the treated group were scanned using our MPI scanner immediately before, immediately after, 7 days, and 14 days after MHT. We drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels by taking the threshold value for extracting the contour as 40% of the maximum MPI value (pixel value) within the ROI. These parameters in the untreated group were taken as zero. We also measured the relative tumor volume growth (RTVG) defined by (V-V0)/V0, where V0 and V are the tumor volumes immediately before and after MHT, respectively. Results: The average, maximum, and total MPI values decreased up to 7 days after MHT and remained almost constant thereafter in all groups, whereas the number of pixels tended to increase with time. The RTVG values in Groups A and B were significantly lower than those in the control group 3 days or more and 5 days or more after MHT, respectively. The above four parameters were significantly inversely correlated with the RTVG values 5, 7, and 14 days after MHT. Conclusion: MPI can visualize and quantify the intratumoral distribution and temporal change of MNPs before and after MHT. Our results suggest that MPI will be useful for predicting the therapeutic effect of MHT and for the treatment planning of MHT.
文摘Purpose: Magnetic targeting refers to the attachment of therapeutic agents to magnetizable particles such as magnetic nanoparticles (MNPs) and then applying magnetic fields to concentrate them to the targeted region such as solid tumors. The purpose of this study was to investigate the usefulness of magnetic particle imaging (MPI) for monitoring the effect of magnetic targeting using tumor-bearing mice. Materials and Methods: Colon-26 cells (1 × 106 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, the mice were divided into treated (n = 8) and untreated groups (n = 8). The tumors in the treated group were directly injected with MNPs (Resovist?, 250 mM) and a neodymium magnet was attached to the tumor surface, whereas the magnet was not attached to the tumor in the untreated group. The mice were imaged using our MPI scanner and the average and maximum MPI values were obtained by drawing a region of interest (ROI) on the tumor, with the threshold value for extracting the contour of the tumor being taken as 40% of the maximum MPI value in the ROI. The relative tumor volume growth (RTVG) was calculated from (V ? V0)/V0, where V0 and V represented the tumor volume immediately before and after the injection of MNPs, respectively. Results: The average and maximum MPI values in the treated group were significantly higher than those in the untreated group 3 days after the injection of MNPs, suggesting the effectiveness of magnetic targeting. There were no significant differences in RTVG between the two groups. Conclusion: Our preliminary results suggest that MPI is useful for monitoring the effect of magnetic targeting.
基金This work was supported in part by the National Key Research and Development Program of China,Nos.2017YFA0700401 and 2017YFA0205200the National Natural Science Foundation of China,Nos.62027901,81827808,81527805,and 81671851+2 种基金the CAS Youth Innovation Promotion Association,No.2018167the CAS Key Technology Talent Programand the Project of High-Level Talents Team Introduction in Zhuhai City,No.Zhuhai HLHPTP201703。
文摘Magnetic particle imaging(MPI)is an emerging molecular imaging technique with high sensitivity and temporal-spatial resolution.Image reconstruction is an important research topic in MPI,which converts an induced voltage signal into the image of superparamagnetic iron oxide particles concentration distribution.MPI reconstruction primarily involves system matrix-and x-space-based methods.In this review,we provide a detailed overview of the research status and future research trends of these two methods.In addition,we review the application of deep learning methods in MPI reconstruction and the current open sources of MPI.Finally,research opinions on MPI reconstruction are presented.We hope this review promotes the use of MPI in clinical applications.
文摘Purpose: Magnetic particle imaging (MPI) allows for imaging of the spatial distribution of magnetic nanoparticles (MNPs) in positive contrast, with high sensitivity, high spatial resolution, and high imaging speed. It is necessary to increase the signal-to-noise ratio to enhance the reliability of MPI. The purpose of this study was to investigate the effect of signal filtering on the image quality and quantitativity in projection-based MPI using phantoms. Materials and Methods: We fabricated two kinds of phantom (cylindrical tube phantom with a diameter of 6 mm and A-shaped phantom) and evaluated the effect of signal filtering in terms of root-mean-square (RMS) granularity and the correlation coefficient between iron concentrations of MNPs and average MPI values for four filter modes (THRU, BPF, BEF, and LPF). In the THRU mode, the signal input was output without passing through the filter. In the BPF mode, only the third-harmonic signal was passed using a band-pass filter (central frequency: 1200 Hz, band width: 1/3 octave). In the BEF mode, the first-harmonic signal was eliminated using a band-elimination filter (central frequency: 400 Hz, band width: 1/3 octave). In the LPF mode, only the signal with a frequency less than the third-harmonic frequency was passed using a low-pass filter (cut-off frequency: 1200 Hz, -24 ± 2 dB/octave). The RMS granularity was obtained by calculating standard deviations of the pixel values in the MPI image without MNPs, whereas average MPI values were obtained by drawing a circular region of interest with a diameter of 6 mm on the MPI image of the cylindrical tube phantom. Results: When using the filtered back-projection (FBP) method with a ramp filter for image reconstruction, the RMS granularity and correlation coefficient decreased in the order of THRU, BPF, BEF, and LPF. In the BPF mode, however, some artifacts were observed. When using the maximum likelihood-expectation maximization (ML-EM) algorithm with an iteration number of 15, the correlation coefficient decreased in the order of THRU, BPF, BEF, and LPF, whereas the RMS granularity did not largely depend on the filter mode and was significantly (p Conclusion: The BEF mode is adequate for the FBP method in projection-based MPI, whereas THRU is a best option in use of the ML-EM algorithm.
文摘The purpose of this study was to evaluate the effectiveness of intracellular magnetic hyperthermia treatment (MHT) in comparison with that of extracellular MHT using magnetic particle imaging (MPI). Colon-26 cells were implanted subcutaneously into the backs of 8-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm3, the mice were divided into control (n = 10), extracellular MHT (n = 8), and intracellular MHT groups (n = 7). In the control group, MHT was not performed. In the extracellular MHT and intracellular MHT groups, the tumors were injected directly with magnetic nanoparticles (MNPs) (400 mM Resovist®) and were heated for 20 min using an alternating magnetic field. During MHT, the temperatures of the tumor and rectum were measured using optical fiber thermometers. In the extracellular MHT group, MHT was performed 15 min after the injection of MNPs, whereas MHT was performed one day after the injection of MNPs in the intracellular MHT group. In both groups, MPI images were obtained using our MPI scanner immediately before, immediately after, and 7 and 14 days after MHT. After the MPI studies, we drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels within the ROI. Transmission electron microscopic (TEM) images were also obtained from resected tumors. In all groups, tumor volume was measured every day and the relative tumor volume growth (RTVG) was calculated. The TEM images showed that almost all the MNPs were aggregated in the extracellular space in the extracellular MHT group, whereas they were contained within the intracellular space in the intracellular MHT group. Although the temperature of the tumor in the intracellular MHT group was significantly lower than that in the extracellular MHT group, the RTVG value in the intracellular MHT group was significantly lower than that in the control group 2 days or more after MHT and that in the extracellular MHT group 3, 4, and 5 days after MHT. The average MPI value normalized by that immediately before MHT in the intracellular MHT group was significantly higher than that in the extracellular MHT group immediately and 7 days after MHT. The maximum and total MPI values normalized by those immediately before MHT in the intracellular MHT group were significantly higher than those in the extracellular MHT group 7 days after MHT, suggesting that the temporal change of MNPs within the tumor in the intracellular MHT group was smaller than that in the extracellular MHT group. Our results suggest that intracellular MHT is more cytotoxic than extracellular MHT in spite of a lower temperature rise of tumors, and that MPI is useful for evaluating the difference in the temporal change of MNPs in the tumor between extracellular MHT and intracellular MHT.
文摘Purpose: Magnetic nanofibers (MNFs) are nanofibers impregnated with magnetic nanoparticles (MNPs). Magnetic particle imaging (MPI) is a recently introduced imaging method that allows im-aging of the spatial distribution of MNPs. The purpose of this study was to develop MNFs and to investigate the feasibility of visualizing them using MPI and of heating them using an alternating magnetic field (AMF). Materials and Methods: First, chitosan nanofibers were cross-linked with glu-taraldehyde vapor in a sealed vial for 24 hours. Next, they were mixed with various concentrations of MNPs and the mixture was stirred for 1 hour using a magnetic stirrer. After the mixture was re-frigerated at –80℃ for 24 hours, it was freeze-dried for 24 hours. The morphology of the resultant MNFs was characterized by scanning electron microscopy, and the magnetic properties were meas-ured using a vibrating sample magnetometer. After these measurements, we imaged the MNFs us-ing our MPI scanner, and investigated the correlation between the pixel values of the MPI image and the concentration of MNPs or the number of MNF sheets. We also heated the MNFs using AMF, and measured the temperature rise using an infrared thermometer. Results: The MNFs were suc-cessfully visualized using our MPI scanner, and the pixel values of the MPI image showed excellent correlation with the concentration of MNPs (r = 0.992) and the number of MNF sheets (r = 0.997). A significant temperature rise was observed under AMF, and the initial slope of the time-dependent temperature rise showed excellent correlation with the concentration of MNPs (r = 0.994) and the number of MNF sheets (r = 0.979). Conclusion: The MNFs developed in this study can be visualized using MPI and can be applied to magnetic hyperthermia. They will be useful in biomedicine including cancer therapy and tissue regeneration.
基金supported by the Science and Technology Plan Project of Dalian City in China,No.2014E14SF186
文摘Ferumoxytol, an iron replacement product, is a new type of superparamagnetic iron oxide ap- proved by the US Food and Drug Administration. Herein, we assessed the feasibility of tracking transplanted human adipose-derived stem cells labeled with ferumoxytol in middle cerebral artery occlusion-injured rats by 3.0 T MRI in vivo. 1 × 104 human adipose-derived stem cells labeled with ferumoxytol-heparin-protamine were transplanted into the brains of rats with middle cerebral artery occlusion. Neurologic impairment was scored at 1, 7, 14, and 28 days after transplantation. T2-weighted imaging and enhanced susceptibility-weighted angiography were used to observe transplanted cells. Results of imaging tests were compared with results of Prussian blue staining. The modified neurologic impairment scores were significantly lower in rats transplanted with cells at all time points except I day post-transplantation compared with rats without transplantation. Regions with hypointense signals on T2-weighted and enhanced susceptibility-weighted angiography images corresponded with areas stained by Prussian blue, suggesting the presence of superparamagnetic iron oxide particles within the engrafted cells. Enhanced susceptibility-weighted angiography image exhibited better sensitivity and contrast in tracing ferumoxytol-heparin-protamine-labeled human adipose-derived stem ceils compared with T2-weighted imaging in routine MRI.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30870639)
文摘To assess a novel cell manipulation technique of tissue engineering with respect to its ability to augment superparamagnetic iron oxide particles (SPIO) labeled mesenchymal stem cells (MSCs) density at a localized cartilage defect site in an in vitro phantom by applying magnetic force. Meanwhile, non-invasive imaging techniques were use to track SPIO-labeled MSCs by magnetic resonance imaging (MRI). Human bone marrow MSCs were cultured and labeled with SPIO. Fresh degenerated human osteochondral fragments were obtained during total knee arthroplasty and a cartilage defect was created at the center. Then, the osteochondral fragments were attached to the sidewalls of culture flasks filled with phosphate-buffered saline (PBS) to mimic the human joint cavity. The SPIO-labeled MSCs were injected into the culture flasks in the presence of a 0.57 Tesla (T) magnetic force. Before and 90 min after cell targeting, the specimens underwent T2-weighted turbo spin-echo (SET2WI) sequence of 3.0 T MRI. MRI results were compared with histological findings. Macroscopic observation showed that SPIO-labeled MSCs were steered to the target region of cartilage defect. MRI revealed significant changes in signal intensity (P0.01). HE staining exibited that a great number of MSCs formed a three-dimensional (3D) cell "sheet" structure at the chondral defect site. It was concluded that 0.57 T magnetic force permits spatial delivery of magnetically labeled MSCs to the target region in vitro. High-field MRI can serve as an very sensitive non-invasive technique for the visualization of SPIO-labeled MSCs.
文摘Purpose: The purpose of this study was to present a novel therapeutic strategy combining use of intracellular magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF) and bleomycin (BLM), and to evaluate its therapeutic effect using tumor-bearing mice. Materials and Methods: MNPs (Resovist?, 1.05 mg iron) were incorporated into the hemagglutinating virus of Japan-envelope (HVJ-E) vector (~5 × 109 particles) (HVJ-E/MNPs) by centrifugation at 10,000 × g for 5 min at 4°C. Tumor-bearing mice were prepared by inoculating Colon-26 cells subcutaneously into the backs of BALB/c mice. When the tumor volume reached ~100 mm3, HVJ-E/MNPs and/or BLM were injected directly into the tumor. The AMF was applied to the mice one hour after the injection of agents (AMF treatment). The mice injected with HVJ-E/MNPs were imaged using our magnetic particle imaging (MPI) scanner immediately (13 min) before, immediately (22 min) after, and 3, 7, and 14 days after the injection of agents, and the temporal changes of the average and maximum MPI pixel values in the tumor were quantitatively evaluated. The therapeutic effect was evaluated by calculating the relative tumor volume growth (RTVG) from the tumor volumes measured each day. Transmission electron microscopic (TEM) observation of resected tumors was also performed to confirm the intracellular distribution of MNPs. Results: The AMF treatment combined with BLM significantly decreased the RTVG value compared with AMF treatment alone at 9 to 14 days, and BLM alone at 3 to 5 days after AMF treatment. The average and maximum MPI pixel values in the tumor were almost constant for 14 days. TEM observation confirmed that most of the HVJ-E/MNPs were internalized into tumor cells within one hour after injection. Conclusion: A novel therapeutic strategy with use of AMF treatment and BLM was presented, and the time-dependent change of MNPs in tumors was evaluated using MPI. The present results suggest that this novel strategy can suppress tumor volume growth over AMF treatment or BLM alone, and can be performed repeatedly with a single injection of HVJ-E/MNPs. They also suggest that HVJ-E is effective for internalizing MNPs into cancer cells and that MPI allows for longitudinal monitoring of the distribution of MNPs in tumors.
基金The authors gratefully acknowledge the financial support of the National Natural Science Foundation of China (Nos. 21374053, 51573086).
文摘Multifunctional fluorescent magnetic nanoparticles (Fe3O4@SiO2-PLLA-RhB/FA) with cell recognition ability were synthesized through conjugation of magnetic nanoparticles with folic acid (FA) and Rhodamine B. To verity their potential biomedical applications, biocompatibility as well as cell imaging applications of the multifunctional nanoparticles were further investigated. Results showed that these fluorescent magnetic nanoparticles are well bio- compatible with NIH-3T3 cells and HeLa cells. More importantly, these nanoparticles could be selectively taken up by HeLa cells (FA receptor positive) as evidenced by laser scanning confocal microscopy, suggesting their potential for biological imaging applications. Given their excellent biocompatibility and multifunctional characteristics, weexpect that the fluorescent magnetic nanoparticles could be promising for various biomedical applications.
基金supported by the 2014 Post-Doc,Development Program of Pusan National Universitysupported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIP)(No.2014R1A2A1A11051146).
文摘In the present study,we report a fabrication of dual-mode carbon coated gadolinia C@Gd_(2)O_(3)particles by a facile hydrothermal synthesis method without using any organic solvents.The prepared C@Gd_(2)O_(3)particles have a core-shell structure and a narrow size distribution in the range of 261±27 nm.The fluorescent properties of the prepared C@Gd_(2)O_(3)particles were accessed by a room-temperature photoluminescence study,while the longitudinal relaxivity(r1)was examined by using a clinical 1.5 T MRI scanner.A murine fibroblast L-929 cell line was used to examine the cytotoxicity and capability of the prepared C@Gd_(2)O_(3)particles for the fluorescent labeling.The obtained results show that the prepared C@Gd_(2)O_(3)particles could be used as a dual-mode contrast agent for magnetic resonance and fluorescence imaging.
文摘Magnetic particle imaging(MPI)is an emerging technique to visualize the spatial distribution of super-paramagnetic iron oxide with high temporal–spatial resolution,high sensitivity,unlimited image depth,and true quantitative information.MPI is based on the nonlinear response of superparamagnetic iron oxide in an alter-nating magnetic field without tissue background noise.It is a promising imaging modality for various applica-tions,including vascular imaging,cell tracking,tumor imaging,and catheter navigation.Many applications of liver imaging could be improved or created with MPI.In this review,we cover the principle and construction of MPI,we evaluate the features and advantages of MPI with relation to its own rationale and via comparison with other imaging modalities,and we review MPI liver imaging applications with a view toward assisting hepatic researchers in drawing inspiration.