Magnetic Particle Imaging for Magnetic Hyperthermia Treatment: Visualization and Quantification of the Intratumoral Distribution and Temporal Change of Magnetic Nanoparticles in Vivo

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.

Performance Evaluation of Super-Resolution Methods Using Deep-Learning and Sparse-Coding for Improving the Image Quality of Magnified Images in Chest Radiographs

Purpose: To detect small diagnostic signals such as lung nodules in chest radiographs, radiologists magnify a region-of-interest using linear interpolation methods. However, such methods tend to generate over-smoothed images with artifacts that can make interpretation difficult. The purpose of this study was to investigate the effectiveness of super-resolution methods for improving the image quality of magnified chest radiographs. Materials and Methods: A total of 247 chest X-rays were sampled from the JSRT database, then divided into 93 training cases with non-nodules and 154 test cases with lung nodules. We first trained two types of super-resolution methods, sparse-coding super-resolution (ScSR) and super-resolution convolutional neural network (SRCNN). With the trained super-resolution methods, the high-resolution image was then reconstructed using the super-resolution methods from a low-resolution image that was down-sampled from the original test image. We compared the image quality of the super-resolution methods and the linear interpolations (nearest neighbor and bilinear interpolations). For quantitative evaluation, we measured two image quality metrics: peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). For comparative evaluation of the super-resolution methods, we measured the computation time per image. Results: The PSNRs and SSIMs for the ScSR and the SRCNN schemes were significantly higher than those of the linear interpolation methods (p p p Conclusion: Super-resolution methods provide significantly better image quality than linear interpolation methods for magnified chest radiograph images. Of the two tested schemes, the SRCNN scheme processed the images fastest;thus, SRCNN could be clinically superior for processing radiographs in terms of both image quality and processing speed.

Comparative Study of Extracellular and Intracellular Magnetic Hyperthermia Treatments Using Magnetic Particle Imaging

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.

A Novel Therapeutic Strategy Combining Use of Intracellular Magnetic Nanoparticles under an Alternating Magnetic Field and Bleomycin

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.

Usefulness of Magnetic Particle Imaging for Predicting the Therapeutic Effect of Magnetic Hyperthermia

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.

Super-Resolution Imaging of Mammograms Based on the Super-Resolution Convolutional Neural Network

Purpose: To apply and evaluate a super-resolution scheme based on the super-resolution convolutional neural network (SRCNN) for enhancing image resolution in digital mammograms. Materials and Methods: A total of 711 mediolateral oblique (MLO) images including breast lesions were sampled from the Curated Breast Imaging Subset of the Digital Database for Screening Mammography (CBIS-DDSM). We first trained the super-resolution convolutional neural network (SRCNN), which is a deep-learning based super-resolution method. Using this trained SRCNN, high-resolution images were reconstructed from low-resolution images. We compared the image quality of the super-resolution method and that obtained using the linear interpolation methods (nearest neighbor and bilinear interpolations). To investigate the relationship between the image quality of the SRCNN-processed images and the clinical features of the mammographic lesions, we compared the image quality yielded by implementing the SRCNN, in terms of the breast density, the Breast Imaging-Reporting and Data System (BI-RADS) assessment, and the verified pathology information. For quantitative evaluation, peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) were measured to assess the image restoration quality and the perceived image quality. Results: The super-resolution image quality yielded by the SRCNN was significantly higher than that obtained using linear interpolation methods (p p Conclusion: SRCNN can significantly outperform conventional interpolation methods for enhancing image resolution in digital mammography. SRCNN can significantly improve the image quality of magnified mammograms, especially in dense breasts, high-risk BI-RADS assessment groups, and pathology-verified malignant cases.

Application of Magnetic Particle Imaging to Pulmonary Imaging Using Nebulized Magnetic Nanoparticles

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.

Perivascular Fat Attenuation Index on Non-Contrast-Enhanced Cardiac Computed Tomography: Comparison with Coronary Computed Tomography Angiography

Objective: Perivascular fat attenuation index (FAI) measurement on non-contrast-enhanced cardiac computed tomography (NCCT) has not been rigorously validated in previous studies. Herein, we compared perivascular FAI values between NCCT and coronary computed tomography angiography (CCTA). We also investigated the variability and reproducibility of perivascular FAI measurement. Methods: A total of 44 patients who underwent NCCT and CCTA were included in this study. For NCCT, perivascular FAI was measured using three threshold settings: from −30 to −190 Hounsfield Units (HU), −20 to −180 HU, and −10 to −170 HU. For CCTA, perivascular FAI was measured using one threshold setting: from −30 to −190 HU. Perivascular FAI measurements by NCCT were compared with those by CCTA using the paired t-test, and correlations were assessed using Pearson’s correlation coefficient. The intra- and inter-observer variabilities for the measurements with NCCT and CCTA were evaluated with the intraclass correlation coefficient. Results: Perivascular FAI measurements with the threshold setting of −30 to −190 HU were significantly lower on NCCT than on CCTA. There were no significant differences between the perivascular FAI measurements at the remaining thresholds on NCCT and those on CCTA. The perivascular FAI at all thresholds on NCCT correlated significantly with those on CCTA. The intra- and inter-observer agreements were excellent for the measurements on NCCT and CCTA. Conclusion: There were significant differences between the perivascular FAI measurements on NCCT and CCTA. However, the differences could be modified by threshold adjustment.

Lock-in-Amplifier Model for Analyzing the Behavior of Signal Harmonics in Magnetic Particle Imaging

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.

Quantitative Assessment of the Effect of Nitric Oxide Synthase Inhibition on Tumor Vascular Activity Using Dynamic Contrast-Enhanced Computed Tomography

Purpose: The purpose of this study was to develop a method to quantitatively assess the effect of nitric oxide synthase (NOS) inhibition on tumor vascular activity using dynamic contrast-enhanced computed tomography (DCE-CT) and to investigate its usefulness using animal experiments. Mate-rials and Methods: The DCE-CT studies were performed in anesthetized Fisher rats bearing tumors using a 4-row multi-slice CT. The scanning started 4 s before a bolus injection of iodinated contrast agent (CA) (150 mgI/kg) from the tail vein using an automatic injector and lasted 60 s at 1-s in-tervals. The contrast enhancement (CE) images were generated by subtracting the CT images before and after the administration of CA. First, the DCE-CT studies were performed before and 15, 30, and 45 min after administration of N-nitro-L-arginine (L-NNA) (1, 3, and 10 mg/kg) or vehicle, and the relative CE values were calculated by normalizing the CE image at each time point by that obtained from the first DCE-CT study. Second, we investigated the case when L-arginine (L-ARG) (200 mg/kg) and L-NNA (1, 3, and 10 mg/kg) were administered after the first and second DCE-CT studies, respectively. Third, we investigated the case when L-NNA (1, 3, and 10 mg/kg) and L-ARG (200 mg/kg) were administered after the first and second DCE-CT studies, respectively. Finally, we investigated the case when L-NNA (1, 3, and 10 mg/kg) and L-ARG (200 mg/kg) were administered simultaneously after the first DCE-CT study. Results: The relative CE value significantly decreased after L-NNA administration in a dose-dependent manner (p-values = 0.0074 and <0.0001 for 0 vs. 3 mg/kg and 0 vs. 10 mg/kg, respectively, at 15 min, 0.0003 and <0.0001 for 0 vs. 3 mg/kg and 0 vs. 10 mg/kg, respectively, at 30 min, and 0.0367 and 0.0004 for 0 vs. 3 mg/kg and 0 vs. 10 mg/kg, respectively, at 45 min). When L-ARG was administered prior to the administration of 1 mg/kg L-NNA, the relative CE value at 45 min was significantly higher than that at 15 min. When L-ARG was administered after L-NNA administration, there was no significant difference between the relative CE values at 15 min and 45 min. These results suggest that when using L-NNA in combination with L-ARG, their effect on tumor vascular activity differs depending on the order of their administration. When L-NNA and L-ARG were administered simultaneously, there was a tendency for the relative CE value to be higher than that when only L-NNA was administered, at all injected doses of L-NNA. Conclusion: Our method using DCE-CT is useful for monitoring the effect of NOS inhibition on tumor vascular activity and for determining the optimal injected dose and timing of NOS inhibitors for anticancer therapy.

Usefulness of Magnetic Particle Imaging for Monitoring the Effect of Magnetic Targeting

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.

Numerical Analysis of the Magnetization Behavior in Magnetic Resonance Imaging in the Presence of Multiple Chemical Exchange Pools

The purpose of this study was to demonstrate a simple and fast method for solving the time-dependent Bloch-McConnell equations describing the behavior of magnetization in magnetic resonance imaging (MRI) in the presence of multiple chemical exchange pools. First, the time-dependent Bloch- McConnell equations were reduced to a homogeneous linear differential equation, and then a simple equation was derived to solve it using a matrix operation and Kronecker tensor product. From these solutions, the longitudinal relaxation rate (R1ρ) and transverse relaxation rate in the rotating frame (R2ρ) and Z-spectra were obtained. As illustrative examples, the numerical solutions for linear and star-type three-pool chemical exchange models and linear, star- type, and kite-type four-pool chemical exchange models were presented. The effects of saturation time (ST) and radiofrequency irradiation power (ω1) on the chemical exchange saturation transfer (CEST) effect in these models were also investigated. Although R1ρ and R2ρ were not affected by the ST, the CEST effect observed in the Z-spectra increased and saturated with increasing ST. When ω1 was varied, the CEST effect increased with increasing ω1 in R1ρ, R2ρ, and Z-spectra. When ω1 was large, however, the spillover effect due to the direct saturation of bulk water protons also increased, suggesting that these parameters must be determined in consideration of both the CEST and spillover effects. Our method will be useful for analyzing the complex CEST contrast mechanism and for investigating the optimal conditions for CEST MRI in the presence of multiple chemical exchange pools.

Effect of Signal Filtering on Image Quality of Projection-Based Magnetic Particle Imaging

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.

Application of Sparse-Coding Super-Resolution to 16-Bit DICOM Images for Improving the Image Resolution in MRI

Purpose: To improve the image resolution of magnetic resonance imaging (MRI), conventional interpolation methods are commonly used to magnify images via various image processing approaches;however, these methods tend to produce artifacts. While super-resolution (SR) schemes have been introduced as an alternative approach to apply medical imaging, previous studies applied SR only to medical images in 8-bit image format. This study aimed to evaluate the effectiveness of sparse-coding super-resolution (ScSR) for improving the image quality of reconstructed high-resolution MR images in 16-bit digital imaging and communications in medicine (DICOM) image format. Materials and Methods: Fifty-nine T1-weighted images (T1), 84 T2-weighted images (T2), 85 fluid attenuated inversion recovery (FLAIR) images, and 30 diffusion-weighted images (DWI) were sampled from The Repository of Molecular Brain Neoplasia Data as testing datasets, and 1307 non-medical images were sampled from the McGill Calibrated Color Image Database as a training dataset. We first trained the ScSR to prepare dictionaries, in which the relationship between low- and high-resolution images was learned. Using these dictionaries, a high-resolution image was reconstructed from a 16-bit DICOM low-resolution image downscaled from the original test image. We compared the image quality of ScSR and 4 interpolation methods (nearest neighbor, bilinear, bicubic, and Lanczos interpolations). For quantitative evaluation, we measured the peak signal-to-noise ratio (PSNR) and structural similarity (SSIM). Results: The PSNRs and SSIMs for the ScSR were significantly higher than those of the interpolation methods for all 4 MRI sequences (PSNR: p p Conclusion: ScSR provides significantly higher image quality in terms of enhancing the resolution of MR images (T1, T2, FLAIR, and DWI) in 16-bit DICOM format compared to the interpolation methods.

Visualization of Magnetic Nanofibers Using Magnetic Particle Imaging

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&#8451 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.

Usefulness of an Anisotropic Diffusion Method in Cerebral CT Perfusion Study Using Multi-Detector Row CT

Purpose: To present an application of the anisotropic diffusion (AD) method to improve the accuracy of the functional images of perfusion parameters such as cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) generated from cerebral CT perfusion studies using multi-detector row CT (MDCT). Materials and Methods: Continuous scans (1 sec/rotation ×60 sec) consisting of four 5-mm-thick contiguous slices were acquired after an intravenous injection of iodinated contrast material in 6 patients with cerebrovascular disease using an MDCT scanner with a tube voltage of 80 kVp and a tube current of 200 mA. New image data were generated by thinning out the above original images at an interval of 2 sec or 3 sec. The thinned-out images were then interpolated by linear interpolation to generate the same number of images as originally acquired. The CBF, CBV and MTT images were generated using deconvolution analysis based on singular value decomposition. Results: When using the AD method, the correlation coefficient between the MTT values obtained from the original and thinned-out images was significantly improved. Furthermore, the coefficients of variation of the CBF, CBV and MTT values in the white matter significantly decreased as compared to not using the AD method. Conclusion: Our results suggest that the AD method is useful for improving the accuracy of the functional images of perfusion parameters and for reducing radiation exposure in cerebral CT perfusion studies using MDCT.

Feasibility of Improved Attenuation Correction for SPECT Reconstruction in the Presence of Dense Materials Using Dual-Energy Virtual Monochromatic CT: A Phantom Study

Objective: Computed tomography (CT)-based attenuation correction (CTAC) offers the clear benefit of reliable reconstruction of single-photon emission computed tomography (SPECT) images through its ability to achieve object-specific attenuation maps, but artifacts from dense materials often deteriorate CTAC performance. Therefore, we investigate the feasibility of CTAC in the presence of dense materials using dual-energy virtual monochromatic CT data. Methods: A sodium pertechnetate-filled cylindrical uniform phantom, with a pair of undiluted iodine syringes attached, is scanned with a dual-source CT scanner to obtain both single-energy (120 kVp) polychromatic and dual-energy (80 kVp/140 kVp with tin filtering) virtual monochromatic CT images. The single-energy and the dual-energy CT images are then converted to attenuation maps at 141 keV. SPECT images are reconstructed from 99mTc emission data of the phantom using each single-energy and dual-energy attenuation map and incorporating CTAC procedure. A region-of-in- terest analysis is performed to quantitatively compare the attenuation maps between the single-energy and the dual-energy techniques, each at an iodine-free position and a position adjacent to the iodine solutions. Results: At the iodine-free position, the phantom provides a uniform distribution of attenuation maps in both the single-energy and the dual-energy techniques. In the presence of adjacent iodine solutions, however, severe artifacts appeare in the single-energy CT images. These artifacts make attenuation values fluctuate, resulting in erroneous pixel values in the CTAC SPECT images. In contrast, dual-energy CT strongly suppresses the artifacts and hence improves the uniformity of the attenuation maps and the resultant SPECT images. Conclusions: Dual-energy CT with virtual monochromatic reconstruction has the potential to substantially reduce artifacts arising from dense materials. It has the potential to improve the accuracy of attenuation maps and the resultant CTAC SPECT images.

A Simulation Study on the Specific Loss Power in Magnetic Hyperthermia in the Presence of a Static Magnetic Field

Our purpose in this study was to present a method for estimating the specific loss power (SLP) in magnetic hyperthermia in the presence of an external static magnetic field (SMF) and to investigate the SLP values estimated by this method under various diameters (D) of magnetic nanoparticles (MNPs) and amplitudes (H0) and frequencies (f) of an alternating magnetic field (AMF). In our method, the SLP was calculated by solving the magnetization relaxation equation of Shliomis numerically, in which the magnetic field strength at time t (H(t)) was assumed to be given by , with Hs being the strength of the SMF. We also investigated the SLP values in the case when the SMF with a field-free point (FFP) generated by two solenoid coils was used. The SLP value in the quasi steady state (SLPqss) decreased with increasing Hs. The plot of the SLPqss values against the position from the FFP became narrow as the gradient strength of the SMF (Gs) increased. Conversely, it became broad as Gs decreased. These results suggest that the temperature rise and the area of local heating in magnetic hyperthermia can be controlled by varying the Hs and Gs values, respectively. In conclusion, our method will be useful for estimating the SLP in the presence of both the AMF and SMF and for designing an effective local heating system for magnetic hyperthermia in order to reduce the risk of overheating surrounding healthy tissues.

Quantitative Assessment of Protective Effects of Antioxidant Agents against Drug-Induced Nephrotoxicity Using Dynamic Contrast-Enhanced Computed Tomography

Purpose: The purpose of this study was to develop a method for quantifying the extent of renal dysfunction due to drug-induced nephrotoxicity using dynamic contrast-enhanced computed tomography (DCE-CT) and to investigate the protective effects of various antioxidant agents against cis-dichlorodiammineplatinum (cisplatin)-induced nephrotoxicity in rats using this method. Materials and Methods: The DCE-CT studies were performed in 8-week-old male Sprague-Dawley rats. The CT scanning started 4 s before a bolus intravenous injection of iodinated contrast agent (CA) (150 mgI/kg) from the tail vein using an automatic injector and lasted 90 s at 1-s intervals. The contrast clearance per unit renal volume (K1) was estimated from the DCE-CT data using the Patlak model. The renal volume (V) was calculated by manually delineating the kidney on the CT image. The contrast clearance of the entire kid-ney (K) was obtained by . First, to investigate the effect of CA itself, the DCE-CT studies were performed without injecting cisplatin 2, 4, and 7 days after the first DCE-CT study on day 0. Second, to investigate the effect of injected dose of cisplatin, the DCE-CT study was performed after the intraperitoneal (i.p.) injection of cisplatin (1.8 mg/kg) and was repeated every other day for one week. Finally, to investigate the protective effects of antioxidant agents [L-arginine (300 mg/kg), N-acetylcysteine (500 or 1000 mg/kg), methimazole (40 mg/kg), captopril (60 mg/kg), and taurine (750 mg/kg)], the DCE-CT studies were performed on days 0, 2, 4, and 7 after the i.p. injection of cisplatin (3.6 mg/kg). For comparison, the DCE-CT data were also acquired without injecting the antioxidant agents (CDDP group). Results: When cisplatin was not injected, there were no significant changes in the K value as compared to that on day 0 within the studied period. The K valuesignificantly (p < 0.05) decreased with increasing dose of cisplatin. Although some differences were observed in the extent of change in the K value normalized by that on day 0, depending on the antioxidant agents and their injected dose and schedule, the normalized K values on day 7 in the groups injected with the antioxidant agents were significantly higher than those in the CDDP group, suggesting that the antioxidant agents studied here had protective effects against cisplatin-induced nephrotoxicity in varying degrees. Conclusion: Our method appears useful for quantitatively evaluating the protective effects of antioxidant agents against cisplatin-induced nephrotoxicity and for investigating the optimal injected dose and schedule of the agents, because it allows repeated measurements of split renal function in a single animal.

Methods for Estimating Specific Loss Power in Magnetic Hyperthermia Revisited

Our purpose in this study was to present three methods for estimating specific loss power (SLP) in magnetic hyperthermia with use of an alternating magnetic field (AMF) and magnetic nanoparticles (MNPs) and to compare the SLP values estimated by the three methods using simulation studies under various diameters of MNPs (D), amplitudes (H0) and frequencies of AMF (f). In the first method, the SLP was calculated by solving the magnetization relaxation equation of Shliomis numerically (SLP1). In the second method, the SLP was obtained by solving Shliomis’ relaxation equation using the complex susceptibility (SLP2). The third method was based on Rosensweig’s model (SLP3). The SLP3 value changed largely depending on the magnetic field strength (H) in the Langevin parameter (§) and it became maximum (SLP3max) and minimum (SLP3min) when H was 0 and ±H0, respectively. The relative difference between SLP1 and SLP2 was the largest and increased with increasing D and H0, whereas that between SLP1 and was the smallest and was almost constant regardless of D and H0, suggesting that H in ξ should be taken as H0 in estimating the SLP using Rosensweig’s model. In conclusion, this study will be useful for optimizing the parameters of AMF in magnetic hyperthermia and for the optimal design of MNPs for magnetic hyperthermia.