Simultaneous spatial and temporal regularization in low-dose dynamic contrast-enhanced CT cerebral perfusion studies.

PURPOSE: To apply total generalized variation (TGV) and its combination with low-rank and sparse decomposition (LRSD) (LTGV) to cerebral perfusion studies using low-dose dynamic contrast-enhanced (DCE) CT and to quantitatively evaluate their performances through comparisons with those without any regularizers and those of total variation (TV) and its combination with LRSD (LTV) using simulation and clinical data. METHODS: The simulation study used a realistic digital brain phantom. Low-dose DCE-CT images were reconstructed using the regularizers and primal-dual algorithm. Subsequently, cerebral perfusion parameter (CPP) images were generated from them. Thereafter, their quality was evaluated based on the peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM). Further, the accuracy of CPP estimation was evaluated through a linear regression analysis between the CPP values obtained by the above regularizers and those obtained from the noise-free DCE-CT images. In addition, the mean and standard deviation of the CPP were calculated (region analysis). In the clinical study, low-dose DCE-CT images were generated using normal-dose images acquired from a patient, and CPP images were generated from them similar to that in the simulation study. RESULTS: When using LTV and LTGV, both PSNR and SSIM were higher than those of the other methods with increasing regularization parameter values. The results of the linear regression and region analyses demonstrated that TGV generally exhibited the best performance, followed by LTGV, and finally that of TV was significantly different from those of the other regularizers. Despite an overall consistency between the simulation and clinical results, certain inconsistencies appeared owing to the difference in generating low-dose DCE-CT images. CONCLUSIONS: The results implied that TGV and LTGV were useful in improving the accuracy of CPP estimation using low-dose DCE-CT. This study provides an improved understanding of the performance of regularizers and is expected to aid in the selection of a suitable regularizer for low-dose DCE-CT perfusion studies.

Quantitative evaluation of simultaneous spatial and temporal regularization in dynamic contrast-enhanced MRI of the liver using Gd-EOB-DTPA.

The purpose of this study was to quantitatively evaluate the usefulness of simultaneous spatial and temporal regularization using total variation (TV), total generalized variation (TGV), a combination of low-rank decomposition (LRD) and TV (LRD+TV), a combination of LRD and TGV (LRD+TGV), and nuclear norm (NN) when applied to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rats with concanavalin A (ConA)-induced acute hepatic injury. The rats were divided into three groups: normal control (NC) (n = 10), ConA10 (n = 8), and ConA20 (n = 7). Rats in the ConA10 and ConA20 groups were intravenously injected with 10 and 20 mg/kg of ConA, respectively; those in the NC group were intravenously injected with the same volume of saline. DCE-MRI studies were performed using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA; 0.025 mmol Gd/kg) as a contrast agent (CA), 24 h after the ConA or saline injection. After the DCE-MRI study, we generated zero-filled and undersampled k-space data from the original images using a pseudoradial sampling scheme with 4 to 64 spokes. We subsequently reconstructed images from these data using the above regularizers and calculated the signal-to-error ratio (SERimg) and structural similarity index measure (SSIM) using the original and reconstructed images. We also calculated the area under the curve (AUC), rate of CA washout (λw), maximum relative enhancement (REmax), and time to REmax (Tmax) from time-intensity curves using an empirical mathematical model (EMM) and the signal-to-error ratio for curve fitting (SERfit) from the original and fit curves. We also compared the parameters obtained using the pseudoradial and Cartesian sampling schemes in the NC group. When using LRD+TV and LRD+TGV, both SERimg and SSIM were greater than those for the other regularizers at all spoke numbers studied; the SERfit for TGV was the greatest. When using TGV and LRD+TGV, in the majority of cases the AUCs did not significantly differ from those obtained from the original images, whereas those for LRD+TV and NN were significantly less at several spoke numbers. The λw for NN was significantly greater at numerous spoke numbers in the NC group; the REmax values for LRD+TV and NN were significantly less at several spoke numbers in all groups. The Tmax values for TV, TGV, and LRD+TGV were significantly greater at numerous spoke numbers in the NC group. Although there were significant differences in SERimg and SSIM between the pseudoradial and Cartesian sampling schemes, the kinetic parameters obtained by the EMM did not significantly differ between the two sampling schemes, with certain exceptions. In conclusion, our results suggest that simultaneous spatial and temporal regularization using TGV or LRD+TGV is useful for accelerating DCE-MRI without significant reduction in the accuracy of the kinetic parameter estimation, even at extremely low sampling factors.

New image-restoration method using a simultaneous algebraic reconstruction technique: comparison with the Richardson-Lucy algorithm.

We developed a new image-restoration method that incorporates the point spread function (PSF) into the simultaneous algebraic reconstruction technique (SART-PSF). Additionally, through simulation studies, we investigated the usefulness of the method in comparison with the Richardson-Lucy (RL) algorithm. In the simulation studies, degraded images were generated by convolving magnetic resonance imaging-based brain images with PSF and adding Gaussian or Poisson noise to them to simulate various noise levels. The effects of the number of iterations N, noise, and PSF error on the processed images were quantitatively evaluated using the percent root mean square error (PRMSE) and mean structural similarity index (mSSIM). After applying the SART-PSF to images degraded using Gaussian noise, the PRMSE value and increase thereof, when N was increased, were smaller than those when using the RL algorithm. The mSSIM value was higher and its decrease upon increasing N was smaller than that of the RL algorithm. When Poisson noise was assumed, the differences in PRMSE and mSSIM between both methods were smaller than those when Gaussian noise was assumed. When the PSF error was negative, its effect on PRMSE and mSSIM was similar for both methods. However, when it was positive, the deterioration of these parameters for the SART-PSF was less than that for the RL algorithm in both the Gaussian and Poisson noise cases. The results suggest that the SART-PSF is more robust against noise and a PSF error than the RL algorithm and, thus, can be used as an alternative to the RL algorithm.

Simultaneous correction of sensitivity and spatial resolution in projection-based magnetic particle imaging.

PURPOSE: The purpose of this study was to develop a method to simultaneously correct the spatial resolution and inhomogeneous sensitivity of a receiving coil in projection-based magnetic particle imaging - and to investigate its efficacy through simulation and experimental studies. METHODS: Magnetic particle imaging (MPI) images were reconstructed using the simultaneous algebraic reconstruction technique (SART), and simultaneous corrections to sensitivity and spatial resolution were performed by incorporating the sensitivity map of the receiving coil and the system function into the SART algorithm. After each SART update, the regularization method - with total variation (TV) minimization - was used to suppress noise amplification and artifact generation. For comparison, MPI images were also reconstructed using the filtered backprojection (FBP) method and the FBP-truncated singular value decomposition (TSVD) method, in which the system function was deconvolved from the projection data using TSVD. In simulation studies, the sensitivity map of a second-order, gradiometer-type receiving coil was generated using the Biot-Savart law, while the system function was obtained by calculating the MPI signals induced by magnetic nanoparticles at various distances from a field-free line (FFL), using a lock-in-amplifier model. The effects of a regularization parameter for TV minimization (α), number of iterations (N), and signal-to-noise ratio (SNR) of the MPI signals on the reconstructed MPI images of a numerical phantom were evaluated, using the image profiles and percent root mean square error (PRMSE). Experimental studies involved the calculation of the system function using a tube phantom. Projection data for an A-shaped phantom were acquired using our MPI scanner, and their MPI images were reconstructed from the projection data, as described above. RESULTS: When both the sensitivity and spatial resolution were corrected (SART-SR), the quality of the reconstructed images was seen to have improved, compared to when the spatial resolution was not corrected - or when the FBP and FBP-TSVD methods were used. When SNR was low (20), a larger α value yielded a better image. The minimum PRMSE occurred at N ≈ 200-400 and increased with increasing N thereafter. When SNR was high (100), the image quality was generally not dependent on the α value within its studied range. The PRMSE decreased slowly with increasing N, and tended to converge to a constant value. The full width at half maximum (FWHM) of the profile was obtained from the A-shaped phantom, reconstructed using the SART-SR algorithm with α = 0.05 and N = 1000. The FWHM value of the tube (2 mm diameter) in the A-shaped phantom image was found to be 2.2 mm on average, whereas those calculated from the images obtained by the FBP and FBP-TSVD methods were 4.4 and 3.0 mm on average, respectively. Spatial resolution improved when using the FBP-TSVD method as compared to the FBP method but image distortion and artifacts were observed. CONCLUSIONS: Although further studies are necessary to optimize the parameters used in the SART algorithm and in TV minimization, the present results suggest that the proposed method is useful for improving the image quality of projection-based MPI.

A Novel Cellular Imaging Method Using Hemagglutinating Virus of Japan-Envelope (HVJ-E) Vector and Magnetic Particle Imaging.

The purpose of this study was to develop a novel cellular imaging method using the hemagglutinating virus of Japan-envelope (HVJ-E) vector and magnetic particle imaging (MPI). First, we determined the concentration of magnetic nanoparticles (MNPs) suitable for encapsulation into the HVJ-E vector (HVJ-MNPs). Colon-26 cells were labeled with HVJ-MNPs, MNPs conjugated with protamine (Pro-MNPs) or MNPs alone (Res-MNPs), and their labeling efficiencies were evaluated. Second, HVJ-MNPs, Pro-MNPs or Res-MNPs were injected directly into the tumors of tumorbearing mice and the MPI images were obtained using our MPI scanner. The temporal change of the MNPs in the tumor was quantitatively evaluated by calculating the average MPI value. In addition, the microstructures of the resected tumor tissues were observed using a transmission electron microscope (TEM). The amount of iron encapsulated into HVJ-E and the encapsulation efficiency, saturated and decreased linearly with increasing amount of added iron, respectively. The labeling efficiency of HVJ-MNPs was significantly higher than those of Res-MNPs and Pro-MNPs. In animal studies, the average MPI value in the HVJ-MNP group remained almost constant up to 14 days, whereas those in the Res-MNP and Pro-MNP groups significantly decreased at 1 day or later, compared with that at 1 hour after the injection of the agents. In the TEM studies, earlier uptake of HVJ-MNPs in the cytoplasm was observed compared with Res-MNPs and Pro-MNPs. Our results suggest that the present method is useful for cellular imaging and tracking, and that HVJ-E is effective in internalizing MNPs into cells, during cellular imaging using MPI.

Magnetic Nanoparticles in Macrophages and Cancer Cells Exhibit Different Signal Behavior on Magnetic Particle Imaging.

Cell labeling with magnetic nanoparticles (MNPs) is a promising method of cell tracking. In particular, a novel quantitative tomography method called magnetic particle imaging (MPI) has the potential to estimate the number of successfully transplanted MNP-labeled cells, thereby helping predict clinical outcomes. However, the biological factors that shape the MPI signals of MNPs during cell labeling are not well understood. To better understand these factors, the MPI signals of MNPs in various extracellular and intracellular conditions were assessed. Firstly, carboxydextran-coated MNPs (Resovist®) in the presence or absence of the transfection agents heparin and/or protamine were subjected to dynamic light scattering analysis and magnetic particle spectroscopy. Secondly, RAW264 macrophages and Colon26 carcinoma cells were labeled with Resovist® by using their intrinsic phagocytic activity or with the assistance of the transfection agents, respectively, after which the cells were visualized by our MPI scanner and transmission electron microscopy, and their absolute amounts of intracellular iron were measured by thiocyanate colorimetry. The MPI pixel values were normalized to intracellular iron concentrations. Finally, the effect of cell lysis on the MPI signal was assessed with magnetic particle spectroscopy. The presence of protamine, but not heparin, increased the hydrodynamic diameter of the MNPs and inhibited their MPI signals. Cell uptake drastically decreased the normalized MPI pixel values. This was particularly marked in the colon cancer cells. The transfection agents did not further alter the MPI signal of the MNP-labeled colon cancer cells. Transmission electron microscopy showed that there was much more MNP aggregation in colon cancer cells than in macrophages. After the MNP-labeled cells were lysed, the MPI signal recovered partially. In conclusion, MPI pixel values can be influenced by the cell-labeling process and cellular uptake. The MPI signals from intracellular magnetic nanoparticles may also differ depending on the cell type.

Longitudinal observations of progressive cardiac dysfunction in a cardiomyopathic animal model by self-gated cine imaging based on 11.7-T magnetic resonance imaging.

The purpose of this study was to longitudinally assess left ventricular function and wall thickness in a hamster model of cardiomyopathy using 11.7-T magnetic resonance imaging (MRI). MRI were performed for six cardiomyopathic J2N-k hamsters and six J2N-n hamsters at 5, 10, 15, and 20 weeks of age. Echocardiography was also performed at 20 weeks. The ejection fraction (EF) at 15 and 20 weeks of age in J2N-k hamsters showed a significant decrease compared with those in controls. Conversely, the end-systolic and end-diastolic volumes in cardiomyopathic hamsters showed a significant increase compared with those in controls. Moreover, the heart walls of J2N-k hamsters at 15 and 20 weeks were thicker than those of controls at end-systole; however, there were no significant differences at end-diastole. Optical microscopy with Masson's trichrome staining depicted no fibrosis in the control myocardium, although it showed interstitial fibrosis in the 20-week-old J2N-k cardiomyopathic myocardium. There were no differences in EF and the wall thickness observed on MRI and those observed on echocardiography. These results indicate the presence of systolic dysfunction in cardiomyopathic hamsters. Self-gated cine imaging based on 11.7-T MRI can be used for serial measurements of cardiac function and wall thickness in a cardiomyopathic model.

Mapping of left ventricle wall thickness in mice using 11.7-T magnetic resonance imaging.

BACKGROUND: The left ventricle (LV) wall thickness is an important and routinely measured cardiologic parameter. Here we introduce three-dimensional (3D) mapping of LV wall thickness and function using a self-gated magnetic resonance (MR) sequence for ultra-high-field 11.7-T MR cine imaging of mouse hearts. METHODS AND RESULTS: Six male C57BL/6-j mice were subjected to 11.7-T MR imaging (MRI). Three standard views-short axis, long axis four-chamber, and long axis two-chamber-and eight consecutive short axis scans from the apex to base were performed for each mouse. The resulting 11 self-gated cine images were used for fast low-angle shot analysis with a navigator echo over an observation period of approximately 35min. The right ventricle (RV) and LV were identified in the short axis and four-chamber views. On 3D color-coded maps, the interventricular septum wall (diastole: 0.94±0.05mm, systole: 1.20±0.09mm) and LV free wall (diastole: 1.07±0.15mm, systole: 1.79±0.11mm) thicknesses were measured. CONCLUSION: This 3D wall thickness mapping technique can be used to observe regional wall thickness at the end-diastole and end-systole. Self-gated cine imaging based on ultra-high-field MRI can be used to accurately and easily measure cardiac function and wall thickness in normal mouse hearts. As in the preclinical study, this versatile and simple method will be clinically useful for the high-field-MRI evaluation of cardiac function and wall thickness.

Differentiation of myocardial ischemia and infarction assessed by dynamic computed tomography perfusion imaging and comparison with cardiac magnetic resonance and single-photon emission computed tomography.

OBJECTIVES: To evaluate the feasibility of myocardial blood flow (MBF) by computed tomography from dynamic CT perfusion (CTP) for detecting myocardial ischemia and infarction assessed by cardiac magnetic resonance (CMR) or single-photon emission computed tomography (SPECT). METHODS: Fifty-three patients who underwent stress dynamic CTP and either SPECT (n = 25) or CMR (n = 28) were retrospectively selected. Normal and abnormal perfused myocardium (ischemia/infarction) were assessed by SPECT/CMR using 16-segment model. Sensitivity and specificity of CT-MBF (mL/g/min) for detecting the ischemic/infarction and severe infarction were assessed. RESULTS: The abnormal perfused myocardium and severe infarction were seen in SPECT (n = 90 and n = 19 of 400 segments) and CMR (n = 223 and n = 36 of 448 segments). For detecting the abnormal perfused myocardium, sensitivity and specificity were 80 % (95 %CI, 71-90) and 86 % (95 %CI, 76-91) in SPECT (cut-off MBF, 1.23), and 82 % (95 %CI, 76-88) and 87 % (95 %CI, 80-92) in CMR (cut-off MBF, 1.25). For detecting severe infarction, sensitivity and specificity were 95 % (95 %CI, 52-100) and 72 % (95 %CI, 53-91) in SPECT (cut-off MBF, 0.92), and 78 % (95 %CI, 67-97) and 80 % (95 %CI, 58-86) in CMR (cut-off MBF, 0.98), respectively. CONCLUSIONS: Dynamic CTP has a potential to detect abnormal perfused myocardium and severe infarction assessed by SPECT/CMR using comparable cut-off MBF. KEY POINTS: • CT-MBF accurately reflects the severity of myocardial perfusion abnormality. • CT-MBF provides good diagnostic accuracy for detecting myocardial perfusion abnormalities. • CT-MBF may assist in stratifying severe myocardial infarction in abnormal perfusion myocardium.

Development and Characterization of Novel LipoCEST Agents Based on Thermosensitive Liposomes.

PURPOSE: To develop a novel probe for chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) based on thermosensitive liposomes (lipoCEST) for theranostics, in which diagnostics and therapy are integrated into a single platform. METHODS: We developed two kinds of lipoCEST agents. The first kind encapsulated dysprosium (Dy)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-Na·3NaCl, terbium-DOTA-Na·3NaCl, or thulium-DOTA-Na·3NaCl into the inner cavity of thermosensitive liposomes, while the second kind encapsulated Dy-DOTA-Na and incorporated amphiphilic metal complex [thulium-diethylenetriamine pentaacetic acid-bis (stearylamide) (Tm-DTPA-BSA)] as a membrane constituent. The nuclear magnetic resonance (NMR)- and Z-spectra of these lipoCEST agents were acquired at various temperatures on a 9.4T MRI scanner. To investigate their applicability to the drug release induced by hyperthermia, we also encapsulated a fluorescent dye (calcein) into the inner cavity of liposomes and measured calcein release after warming them. RESULTS: The intra- and extraliposomal water signals could be differentiated in all agents from their NMR- and Z-spectra. The agent incorporating Tm-DTPA-BSA showed the largest chemical shift (approximately 15 ppm) derived from the intraliposomal water protons. The calcein retained in this agent was successfully released at 44°C. The agent incorporating 30 mol% of Tm-DTPA-BSA in its membrane released more calcein at 42-44ºC than that of the agent incorporating 10 mol%. CONCLUSION: We developed novel thermosensitive lipoCEST agents and characterized them. Our preliminary results suggest that they are useful and can be applied to theranostics.

Series: Utilization of Differential Equations and Methods for Solving Them in Medical Physics (3).

In this issue, simultaneous differential equations were introduced. These differential equations are often used in the field of medical physics. The methods for solving them were also introduced, which include Laplace transform and matrix methods. Some examples were also introduced, in which Laplace transform and matrix methods were applied to solving simultaneous differential equations derived from a three-compartment kinetic model for analyzing the glucose metabolism in tissues and Bloch equations for describing the behavior of the macroscopic magnetization in magnetic resonance imaging.In the next (final) issue, partial differential equations and various methods for solving them will be introduced together with some examples in medical physics.

Series: Utilization of Differential Equations and Methods for Solving Them in Medical Physics (4).

Partial differential equations are often used in the field of medical physics. In this (final) issue, the methods for solving the partial differential equations were introduced, which include separation of variables, integral transform (Fourier and Fourier-sine transforms), Green's function, and series expansion methods. Some examples were also introduced, in which the integral transform and Green's function methods were applied to solving Pennes' bioheat transfer equation and the Fourier series expansion method was applied to Navier-Stokes equation for analyzing the wall shear stress in blood vessels.Finally, the author hopes that this series will be helpful for people who engage in medical physics.

Kinetic analysis of superparamagnetic iron oxide nanoparticles in the liver of body-temperature-controlled mice using dynamic susceptibility contrast magnetic resonance imaging and an empirical mathematical model.

The purpose of this study was to develop a method for analyzing the kinetic behavior of superparamagnetic iron oxide nanoparticles (SPIONs) in the murine liver under control of body temperature using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and an empirical mathematical model (EMM). First, we investigated the influence of body temperature on the kinetic behavior of SPIONs in the liver by controlling body temperature using our temperature-control system. Second, we investigated the kinetic behavior of SPIONs in the liver when mice were injected with various doses of GdCl3, while keeping the body temperature at 36°C. Finally, we investigated it when mice were injected with various doses of zymosan, while keeping the body temperature at 36°C. We also investigated the effect of these substances on the number of Kupffer cells by immunohistochemical analysis using the specific surface antigen of Kupffer cells (CD68). To quantify the kinetic behavior of SPIONs in the liver, we calculated the upper limit of the relative enhancement (A), the rates of early contrast uptake (α) and washout or late contrast uptake (ß), the parameter related to the slope of early uptake (q), the area under the curve (AUC), the maximum change of transverse relaxation rate (ΔR2) (ΔR2(max)), the time to ΔR2(max) (Tmax), and ΔR2 at the last time point (ΔR2(last)) from the time courses of ΔR2 using the EMM. The ß and Tmax values significantly decreased and increased, respectively, with decreasing body temperature, suggesting that the phagocytic activity of Kupffer cells is significantly affected by body temperature. The AUC, ΔR2(max), and ΔR2(last) values decreased significantly with increasing dose of GdCl3, which was consistent with the change in the number of CD68-positive cells. They increased with increasing dose of zymosan, which was also consistent with the change in the number of CD68-positive cells. These results suggest that AUC, ΔR2(max), and ΔR2(last) reflect the number of Kupffer cells. In conclusion, we presented a method for analyzing the kinetic behavior of SPIONs in the liver using DSC-MRI and EMM, and investigated the influence of body temperature, GdCl3, and zymosan using body-temperature-controlled mice. The present study suggests that control of body temperature is essential for investigating the kinetic behavior of SPIONs in the liver and that our method will be applicable and useful for quantifying the responses of Kupffer cells to various drugs under control of body temperature.

[Series: Utilization of Differential Equations and Methods for Solving Them in Medical Physics (2)].

In this issue, symbolic methods for solving differential equations were firstly introduced. Of the symbolic methods, Laplace transform method was also introduced together with some examples, in which this method was applied to solving the differential equations derived from a two-compartment kinetic model and an equivalent circuit model for membrane potential. Second, series expansion methods for solving differential equations were introduced together with some examples, in which these methods were used to solve Bessel's and Legendre's differential equations. In the next issue, simultaneous differential equations and various methods for solving these differential equations will be introduced together with some examples in medical physics.

Factors affecting the chemical exchange saturation transfer of Creatine as assessed by 11.7 T MRI.

Chemical exchange saturation transfer (CEST) is a new contrast enhancement approach for imaging exogenous or endogenous substances such as creatine (Cr), amide protons, and glutamate in the human body. An increase in field strength is beneficial for CEST imaging because of the increased chemical shift and longer longitudinal relaxation time (T1). In high-field magnetic resonance imaging (MRI), establishing and evaluating the CEST effect is important for optimizing the magnetization transfer (MT) saturation radio frequency (RF) pulses. In this study, the CEST effect on Cr was evaluated at different concentrations in pH phantoms by appropriately selecting MT saturation RF pulses using 11.7 T MRI. The results showed that the CEST efficiency increased gradually with increasing applied saturation RF pulse power and that it was affected by the number of saturation RF pulses and their bandwidths. However, spillover effects were observed with higher saturation RF pulse powers. In conclusion, we successfully performed in vitro Cr CEST imaging under optimized conditions of MT saturation RF pulses.

Brain and arterial abnormalities following prenatal X-ray irradiation in mice assessed by magnetic resonance imaging and angiography.

The present study aimed to quantitatively characterize changes in the whole brain and arterial morphology in response to prenatal ionizing irradiation. Magnetic resonance imaging (MRI) and angiography (MRA) were used to evaluate brain and arterial abnormalities in 8-week-old male mice prenatally exposed to X-ray radiation at a dose of 0.5 or 1.0 Gy on embryonic day (E) 13. Irradiated mice demonstrated decreased brain volume, increased ventricular volume, and arterial malformation. Additionally, MRA signal intensity and arterial thickness in the anterior cerebral artery, middle cerebral artery, and basilar artery were lower in radiation-exposed mice than in control mice. MRI and MRA are useful tools for assessing brain and arterial abnormalities after prenatal exposure to radiation.

Diffusion tensor imaging of brain abnormalities induced by prenatal exposure to radiation in rodents.

We assessed brain abnormalities in rats exposed prenatally to radiation (X-rays) using magnetic resonance imaging (MRI) and histological experiments. Pregnant rats were divided into 4 groups: the control group (n = 3) and 3 groups that were exposed to different radiation doses (0.5, 1.0, or 1.5 Gy; n = 3 each). Brain abnormalities were assessed in 32 neonatal male rats (8 per group). Ex vivo T2-weighted imaging and diffusion tensor imaging (DTI) were performed using 11.7-T MRI. The expression of markers of myelin production (Kluver-Barrera staining, KB), nonpyramidal cells (calbindin-D28k staining, CaBP), and pyramidal cells (staining of the nonphosphorylated heavy-chain neurofilament SMI-32) were histologically evaluated. Decreased brain volume, increased ventricle volume, and thinner cortices were observed by MRI in irradiated rats. However, no abnormalities in the cortical 6-layered structure were observed via KB staining in radiation-exposed rats. The DTI color-coded map revealed a dose-dependent reduction in the anisotropic signal (vertical direction), which did not represent reduced numbers of pyramidal cells; rather, it indicated a signal reduction relative to the vertical direction because of low nerve cell density in the entire cortex. We conclude that DTI and histological experiments are useful tools for assessing cortical and hippocampal abnormalities after prenatal exposure to radiation in rats.

Radiotherapy treatment planning with contrast-enhanced computed tomography: feasibility of dual-energy virtual unenhanced imaging for improved dose calculations.

BACKGROUND: In radiotherapy treatment planning, intravenous administration of an iodine-based contrast agent during computed tomography (CT) improves the accuracy of delineating target volumes. However, increased tissue attenuation resulting from the high atomic number of iodine may result in erroneous dose calculations because the contrast agent is absent during the actual procedure. The purpose of this proof-of-concept study was to present a novel framework to improve the accuracy of dose calculations using dual-energy virtual unenhanced CT in the presence of an iodine-based contrast agent. METHODS: Simple phantom experiments were designed to assess the feasibility of the proposed concept. By utilizing a "second-generation" dual-source CT scanner equipped with a tin filter for improved spectral separation, four CT datasets were obtained using both a water phantom and an iodine phantom: "true unenhanced" images with attenuation values of 2 ± 11 Hounsfield Units (HU), "enhanced" images with attenuation values of 274 ± 23 HU, and two series of "virtual unenhanced" images synthesized from dual-energy scans of the iodine phantom, each with a different combination of tube voltages. Two series of virtual unenhanced images demonstrated attenuation values of 12 ± 29 HU (with 80 kVp/140 kVp) and 34 ± 10 HU (with 100 kVp/140 kVp) after removing the iodine component from the contrast-enhanced images. Dose distributions of the single photon beams calculated from the enhanced images and two series of virtual unenhanced images were compared to those from true unenhanced images as a reference. RESULTS: The dose distributions obtained from both series of virtual unenhanced images were almost equivalent to that from the true unenhanced images, whereas the dose distribution obtained from the enhanced images indicated increased beam attenuation caused by the high attenuation characteristics of iodine. Compared to the reference dose distribution from the true unenhanced images, the dose distribution pass rates from both series of virtual unenhanced images were greater than 90%, while those from the enhanced images were less than approximately 50-60%. CONCLUSIONS: Dual-energy virtual unenhanced CT improves the accuracy of dose distributions in radiotherapy treatment planning by removing the iodine component from contrast-enhanced images.

Reconstruction of semiautomated cardiac regions of interest using iodine-123 metaiodobenzylguanidine myocardial scintigraphy.

INTRODUCTION: Analysis using cardiac iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy with regions of interest (ROIs) is useful for assessing myocardial sympathetic activity. However, manual placement of the cardiac ROI is sometimes difficult because myocardial MIBG uptake is reduced in patients with heart failure. A new method was developed to reconstruct the semiautomated cardiac ROI in a sympathetic denervated heart. MATERIALS AND METHODS: Using dynamic planar data, a summed image was generated and the matrix size was changed. Then, the radial count profiles originating from the center of the left ventricle were generated to extract the myocardial count profiles. An asymmetric Gaussian distribution was fitted to each profile and the epicardial border was defined by the threshold method. This program was tested in 50 patients, and its reproducibility was validated when compared with the manual tracing method. RESULTS: The semiautomated method yielded a better quality image compared with the standard image with higher counts. Cardiac ROIs were generated successfully in each patient within normal limits. The intraobserver and interobserver agreements were excellent (P<0.0001 each). This approach showed a significantly higher consistency in measuring the heart-to-mediastinum ratio as compared with the manual tracing method (P<0.05). CONCLUSION: The semiautomated method is useful in generating cardiac ROIs with high reproducibility in myocardial MIBG imaging.

Enhanced heat shock protein 25 immunoreactivity in cranial nerve motoneurons and their related fiber tracts in rats prenatally-exposed to X-irradiation.

Alterations in histoarchitecture of the brainstem were examined immunohistochemically in 4-week-old rats with a single whole body X-irradiation at a dose of 0.5, 1.0, or 1.5 Gy on embryonic day (ED) 15 using anti-heat shock protein 25 (HSP25). HSP25 immunostaining was seen in the neuronal perikarya of cranial nerve motoneurons, that is, the motor and mesencephalic nuclei of the trigeminal nerve, facial nucleus, abducens nucleus and accessory facial nucleus in the pons, and the ambiguous nucleus, dorsal nucleus of vagus nerve and hypoglossus nucleus in the medulla oblongata of intact controls. In 0.5 to 1.5 Gy-irradiated rats, HSP25 immunostaining in those neurons was more intense than in controls, while the most intense immunostaining was marked in 1.5 Gy-irradiated rats. HSP25 immunostaining was also apparent in the spinal tract of the trigeminal nerve and facial nerve tracts in 0.5 to 1.5 Gy-irradiated rats, but was faint in controls. Interestingly, HSP25 immunostaining was aberrantly enhanced in dendritic arbors in the magnocellular region of medial vestibular nucleus of 0.5-1.5 Gy-irradiated rats. Those arbors were identified as excitatory secondary vestibulo-ocular neurons by double immunofluorescence for HSP25 and SMI-32. The results suggest an increase of HSP25 expression in cranial nerve motoneurons and their related fiber tracts from prenatal exposure to ionizing irradiation. This may be an adaptive response to chronic hypoxia due to malformed brain arteries caused by prenatal ionizing irradiation.