Establishment of a mouse model of 70% lethal dose by total-body irradiation / 한국실험동물학회지

Whereas increasing concerns about radiation exposure to nuclear disasters or side effects of anticancer radiotherapy, relatively little research for radiation damages or remedy has been done. The purpose of this study was to establish level of LD70/30 (a lethal dose for 70% of mice within 30 days) by total-body γ irradiation (TBI) in a mouse model. For this purpose, at first, 8-week-old male ICR and C57BL/6N mice from A and B companies were received high dose (10, 11, 12 Gy) TBI. After irradiation, the body weight and survival rate were monitored for 30 days consecutively. In next experiment, 5-week-old male ICR and C57BL/6N mice from B company were received same dose irradiation. Results showed that survival rate and body weight change rate in inbred C57BL/6N mice were similar between A and B company. In ICR mice, however, survival rate and body weight change rate were completely different among the companies. Significant difference of survival rate both ICR and C57BL6N mice was not observed in between 5-week-old and 8-week-old groups receiving 10 or 12 Gy TBI. Our results indicate that the strain and age of mice, and even purchasing company (especially outbred), should be matched over experimental groups in TBI experiment. Based on our results, 8-week-old male ICR mice from B company subjected to 12 Gy of TBI showed LD70/30 and suitable as a mouse model for further development of new drug using the ideal total-body irradiation model.

Effect of Harderian adenectomy on the statistical analyses of mouse brain imaging using positron emission tomography

Positron emission tomography (PET) using 2-deoxy-2-[18F] fluoro-D-glucose (FDG) as a radioactive tracer is a useful technique for in vivo brain imaging. However, the anatomical and physiological features of the Harderian gland limit the use of FDG-PET imaging in the mouse brain. The gland shows strong FDG uptake, which in turn results in distorted PET images of the frontal brain region. The purpose of this study was to determine if a simple surgical procedure to remove the Harderian gland prior to PET imaging of mouse brains could reduce or eliminate FDG uptake. Measurement of FDG uptake in unilaterally adenectomized mice showed that the radioactive signal emitted from the intact Harderian gland distorts frontal brain region images. Spatial parametric measurement analysis demonstrated that the presence of the Harderian gland could prevent accurate assessment of brain PET imaging. Bilateral Harderian adenectomy efficiently eliminated unwanted radioactive signal spillover into the frontal brain region beginning on postoperative Day 10. Harderian adenectomy did not cause any post-operative complications during the experimental period. These findings demonstrate the benefits of performing a Harderian adenectomy prior to PET imaging of mouse brains.

Quantitative Assessment Technology of Small Animal Myocardial Infarction PET Image Using Gaussian Mixture Model / 의학물리

Nuclear medicine images (SPECT, PET) were widely used tool for assessment of myocardial viability and perfusion. However it had difficult to define accurate myocardial infarct region. The purpose of this study was to investigate methodological approach for automatic measurement of rat myocardial infarct size using polar map with adaptive threshold. Rat myocardial infarction model was induced by ligation of the left circumflex artery. PET images were obtained after intravenous injection of 37 MBq 18F-FDG. After 60 min uptake, each animal was scanned for 20 min with ECG gating. PET data were reconstructed using ordered subset expectation maximization (OSEM) 2D. To automatically make the myocardial contour and generate polar map, we used QGS software (Cedars-Sinai Medical Center). The reference infarct size was defined by infarction area percentage of the total left myocardium using TTC staining. We used three threshold methods (predefined threshold, Otsu and Multi Gaussian mixture model; MGMM). Predefined threshold method was commonly used in other studies. We applied threshold value form 10% to 90% in step of 10%. Otsu algorithm calculated threshold with the maximum between class variance. MGMM method estimated the distribution of image intensity using multiple Gaussian mixture models (MGMM2, em leader MGMM5) and calculated adaptive threshold. The infarct size in polar map was calculated as the percentage of lower threshold area in polar map from the total polar map area. The measured infarct size using different threshold methods was evaluated by comparison with reference infarct size. The mean difference between with polar map defect size by predefined thresholds (20%, 30%, and 40%) and reference infarct size were 7.04+/-3.44%, 3.87+/-2.09% and 2.15+/-2.07%, respectively. Otsu verse reference infarct size was 3.56+/-4.16%. MGMM methods verse reference infarct size was 2.29+/-1.94%. The predefined threshold (30%) showed the smallest mean difference with reference infarct size. However, MGMM was more accurate than predefined threshold in under 10% reference infarct size case (MGMM: 0.006%, predefined threshold: 0.59%). In this study, we was to evaluate myocardial infarct size in polar map using multiple Gaussian mixture model. MGMM method was provide adaptive threshold in each subject and will be a useful for automatic measurement of infarct size.

Estimation of Internal Motion for Quantitative Improvement of Lung Tumor in Small Animal / 의학물리

The purpose of this study was to estimate internal motion using molecular sieve for quantitative improvement of lung tumor and to localize lung tumor in the small animal PET image by evaluated data. Internal motion has been demonstrated in small animal lung region by molecular sieve contained radioactive substance. Molecular sieve for internal lung motion target was contained approximately 37 kBq Cu-64. The small animal PET images were obtained from Siemens Inveon scanner using external trigger system (BioVet). SD-Rat PET images were obtained at 60 min post injection of FDG 37 MBq/0.2 mL via tail vein for 20 min. Each line of response in the list-mode data was converted to sinogram gated frames (2~16 bin) by trigger signal obtained from BioVet. The sinogram data was reconstructed using OSEM 2D with 4 iterations. PET images were evaluated with count, SNR, FWHM from ROI drawn in the target region for quantitative tumor analysis. The size of molecular sieve motion target was 1.59x2.50 mm. The reference motion target FWHM of vertical and horizontal was 2.91 mm and 1.43 mm, respectively. The vertical FWHM of static, 4 bin and 8 bin was 3.90 mm, 3.74 mm, and 3.16 mm, respectively. The horizontal FWHM of static, 4 bin and 8 bin was 2.21 mm, 2.06 mm, and 1.60 mm, respectively. Count of static, 4 bin, 8 bin, 12 bin and 16 bin was 4.10, 4.83, 5.59, 5.38, and 5.31, respectively. The SNR of static, 4 bin, 8 bin, 12 bin and 16 bin was 4.18, 4.05, 4.22, 3.89, and 3.58, respectively. The FWHM were improved in accordance with gate number increase. The count and SNR were not proportionately improve with gate number, but shown the highest value in specific bin number. We measured the optimal gate number what minimize the SNR loss and gain improved count when imaging lung tumor in small animal. The internal motion estimation provide localized tumor image and will be a useful method for organ motion prediction modeling without external motion monitoring system.

Performance Measurement of Siemens Inveon PET Scanner for Small Animal Imaging / 의학물리

Inveon PET is a recently developed preclinical PET system for small animal. This study was conducted to measure the performance of Inveon PET as recommended by the NEMA NU 4-2008. We measured the spatial resolution, the sensitivity, the scatter fraction and the NECR using a F-18 source. A 3.432 ns coincidence window was used. A 1 mm3 sized F-18 point source was used for the measurement of spatial resolution within an energy window of 350~625 keV. PET acquisition was performed to obtain the spatial resolution from the center to the 5 cm offset toward the edge of the transverse FOV. Sensitivity, scatter fraction, and NECR were measured within an energy window of 350~750 keV. For measuring the sensitivity, a F-18 line source (length: 12.7 cm) was used with concentric 5 aluminum tubes. For the acquisition of the scatter fraction and the NECR, two NEMA scatter phantoms (rat: 50 mm in diameter, 150 mm in length; mouse: 25 mm in diameter, 70 mm in length) were used and the data for 14 half-lives (25.6 hr) was obtained using the F-18 line source (rat: 316 MBq, mouse: 206 MBq). The spatial resolution of the F-18 point source was 1.53, 1.50 and 2.33 mm in the radial, tangential and axial directions, respectively. The volumetric resolution was 5.43 mm3 in the center. The absolute sensitivity was 6.61%. The peak NECR was 486 kcps @121 MBq (rat phantom), and 1056 kcps @128 MBq (mouse phantom). The values of the scatter fraction were 20.59% and 7.93% in the rat and mouse phantoms, respectively. The performances of the Inveon animal PET scanner were measured in this study. This scanner will be useful for animal imaging.

mage-Based Assessment and Clinical Significance of Absorbed Radiation Dose to Tumor in Repeated High-Dose (131)I Anti-CD20 Monoclonal Antibody (Rituximab) Radioimmunotherapy for Non-Hodgkin's Lymphoma / 핵의학분자영상

PURPOSE: We assessed the absorbed dose to the tumor (Dosetumor) by using pretreatment FDG-PET and whole-body (WB) planar images in repeated radioimmunotherapy (RIT) with 131I rituximab for NHL. MATERIALS AND METHODS: Patients with NHL (n=4) were administered a therapeutic dose of (131)I rituximab. Serial WB planar images after RIT were acquired and overlaid to the coronal maximum intensity projection (MIP) PET image before RIT. On registered MIP PET and WB planar images, 2D-ROIs were drawn on the region of tumor (n=7) and left medial thigh as background, and Dosetumor was calculated. The correlation between Dosetumor and the CT-based tumor volume change after RIT was analyzed. The differences of Dosetumor and the tumor volume change according to the number of RIT were also assessed. RESULTS: The values of absorbed dose were 397.7+/-646.2cGy (53.0~2853.0cGy). The values of CT-based tumor volume were 11.3+/-9.1 cc (2.9~34.2cc), and the % changes of tumor volume before and after RIT were -29.8+/-44.3% (-100.0%~+42.5%), respectively. Dosetumor and the tumor volume change did not show the linear relationship (p>0.05). Dosetumor and the tumor volume change did not correlate with the number of repeated administration (p>0.05). CONCLUSION: We could determine the position and contour of viable tumor by MIP PET image. And, registration of PET and gamma camera images was possible to estimate the quantitative values of absorbed dose to tumor.

Bone Mineral Density Measurement of Rats Using Dual-energy X-ray Absorptiometry: Precision of In Vivo Measurements for Various Skeletal Sites with or without Repositioning / 핵의학분자영상

PURPOSE: Bone mineral density (BMD) measurements need to be precise enough to be capable of detecting small changes in bone mass of rats. Using a regular dual-energy X-ray absorptiometry (DXA), we measured many BMD of various skeletal sites in rats to examine precision of DXA in relation to the repositioning on the bones of rats. MATERIALS AND METHODS: Using DXA and small animal software, scans were performed 4 times in all 12 male rats without repositioning (Group 1a). Another four scans for 6 of 12 rats were done with repositioning between scans (Group 2). Customized regions of interest (ROIs), encapsulate the right hind limb, L1-4, skull and pelvic bones were drawn at each measurement. The precision of the measurements was evaluated by measuring the coefficient of variation (CV) of four measurements of BMD at each skeletal site of all rats with or without repositioning. Significance of differences between group 1b (six rats out of group 1a, which were come under group 2) and group2 were evaluated with Wilcoxon Signed Rank Sum Test. RESULTS: CVs obtained at different skeletal sites of all measurements in Group 1b and 2. It was 3.51+/-1.20, 2.62+/-1.20 for the hindlimb (p=0.173), 3.83+/-2.02, 4.59+/-2.02 for L1-4 (p=0.600), 3.73+/-1.87, 1.53+/-0.89 for skull (p=0.046), and 2.92+/-0.60, 1.45+/-0.60 for pelvic bones (p=0.075). CONCLUSION: Our study demonstrates that the DXA technique has the precision necessary when used to assess BMD for various skeletal sites in rats regardless of repositioning.

Small Animal 18FFDG PET Imaging for Tumor Model Study / 핵의학분자영상

PET allows non-invasive, quantitative and repetitive imaging of biological function in living animals. Small animal PET imaging with [18F]FDG has been successfully applied to investigation of metabolism, receptor-ligand interactions, gene expression, adoptive cell therapy and somatic gene therapy. Experimental condition of animal handling impacts on the biodistribution of [18F]FDG in small animal study. The small animal PET and CT images were registered using the hardware fiducial markers and small animal contour point. Tumor imaging in small animal with small animal [18F]FDG PET should be considered fasting, warming, and isoflurane anesthesia level. Registered imaging with small animal PET and CT image could be useful for the detection of tumor. Small animal experimental condition of animal handling and registration method will be of most importance for small lesion detection of metastases tumor model.

Motion Correction in PET/CT Images / 핵의학분자영상

PET/CT fused image with anatomical and functional information have improved medical diagnosis and interpretation. This fusion has resulted in more precise localization and characterization of sites of radio-tracer uptake. However, a motion during whole-body imaging has been recognized as a source of image quality degradation and reduced the quantitative accuracy of PET/CT study. The respiratory motion problem is more challenging in combined PET/CT imaging. In combined PET/CT, CT is used to localize tumors and to correct for attenuation in the PET images. An accurate spatial registration of PET and CT image sets is a prerequisite for accurate diagnosis and SUV measurement. Correcting for the spatial mismatch caused by motion represents a particular challenge for the requisite registration accuracy as a result of differences in PET/CT image. This paper provides a brief summary of the materials and methods involved in multiple investigations of the correction for respiratory motion in PET/CT imaging, with the goal of improving image quality and quantitative accuracy.

Imaging of Lung Metastasis Tumor Mouse Model using 18FFDG Small Animal PET and CT / 핵의학분자영상

PURPOSE: The purpose of this study is to image metastaic lung melanoma model with optimal pre-conditions for animal handling by using [18F]FDG small animal PET and clinical CT. MATERIALS AND METHODS: The pre-conditions for lung region tumor imaging were 16-22 h fasting and warming temperature at 30 degrees C. Small animal PET image was obtained at 60 min postinjection of 7.4 MBq [18F]FDG and compared pattern of [18F]FDG uptake and glucose standard uptake value (SUVG) of lung region between Ketamine/Xylazine (Ke/Xy) and Isoflurane (Iso) anesthetized group in normal mice. Metastasis tumor mouse model to lung was established by intravenous injection of B16-F10 cells in C57BL/6 mice. In lung metastasis tumor model, [18F]FDG image was obtained and fused with anatomical clinical CT image. RESULTS: Average blood glucose concentration in normal mice were 128.0+/-23.87 and 86.0+/-21.65 mg/dL in Ke/Xy group and Iso group, respectively. Ke/Xy group showed 1.5 fold higher blood glucose concentration than Iso group. Lung to Background ratio (L/B) in SUVG image was 8.6+/-0.48 and 12.1+/-0.63 in Ke/Xy group and Iso group, respectively. In tumor detection in lung region, [18F]FDG image of Iso group was better than that of Ke/Xy group, because of high L/B ratio. Metastatic tumor location in [18F]FDG small animal PET image was confirmed by fusion image using clinical CT. CONCLUSION: Tumor imaging in small animal lung region with [18F]FDG small animal PET should be considered pre-conditions which fasting, warming and an anesthesia during [18F]FDG uptake. Fused imaging with small animal PET and CT image could be useful for the detection of metastatic tumor in lung region.

Quantitative Comparisons between CT and 68Ge Transmission Attenuation Corrected 18F-FDG PET Images: Measured Attenuation Correction vs. Segmented Attenuation Correction / 핵의학분자영상

PURPOSE: It was reported that CT-based measured attenuation correction (CT-MAC) produced radioactivity concentration values significantly higher than 68Ge-based segmented attenuation correction (Ge-SAC) in PET images. However, it was unknown whether the radioactivity concentration difference resulted from different sources (CT vs. Ge) or types (MAC vs. SAC) of attenuation correction (AC). We evaluated the influences of the source and type of AC on the radioactivity concentration differences between reconstructed PET images in normal subjects and patients. MATERIAL AND METHODS: Five normal subjects and 35 patients with a known or suspected cancer underwent 18F-FDG PET/CT. In each subject, attenuation corrected PET images using OSEM algorithm (28 subsets, 2 iterations) were reconstructed by 4 methods: CT-MAC, CT-SAC, Ge-MAC, and Ge-SAC. The physiological uptake in normal subjects and pathological uptake in patients were quantitatively compared between the PET images according to the source and type of AC. RESULTS: The SUVs of physiological uptake measured in CT-MAC PET images were significantly higher than other 3 differently corrected PET images. Maximum SUVs of the 145 foci with abnormal FDG uptake in CT-MAC images were significantly highest among 4 differently corrected PET images with a difference of 2.4% to 5.1% (p<0.001). The SUVs of pathological uptake in Ge-MAC images were significantly higher than those in CT-SAC and Ge-MAC PET images (p<0.001). CONCLUSION: Quantitative radioactivity values were highest in CT-MAC PET images. The adoption of MAC may make a more contribution than the adoption of CT attenuation map to such differences.

Quantification of Myocardial Blood flow using Dynamic N-13 Ammonia PET and factor Analysis / 대한핵의학회잡지

PURPOSE: We evaluated the feasibility of extracting pure left ventricular blood pool and myocardial time-activity curves (TACs) and of generating factor images from human dynamic N-13 ammonia PET using factor analysis. The myocardial blood flow (MBF) estimates obtained with factor analysis were compared with those obtained with the user drawn region-of-interest (ROI) method. MATERIALS AND METHODS: Stress and rest N-13 ammonia cardiac PET imaging was acquired for 23 min in 5 patients with coronary artery disease using GE Advance tomograph. Factor analysis generated physiological TACs and factor images using the normalized TACs from each dixel. Four steps were involved in this algorithm: (a) data preprocessing; (b) principal component analysis; (c) oblique rotation with positivity constraints; (d) factor image computation. Area under curves and MBF estimated using the two compartment N-13 ammonia model were used to validate the accuracy of the factor analysis generated physiological TACs. The MBF estimated by factor analysis was compared to the values estimated by using the ROI method. RESULTS: MBF values obtained by factor analysis were linearly correlated with MBF obtained by the ROI method (slope=0.84, r=0.91). Left ventricular blood pool TACs obtained by the two methods agreed well (Area under curve ratio: 1.02 (0~1 min), 0.98 (0~2 min), 0.86 (1~2 min)). CONCLUSION:: The RESULTS of this study demonstrates that MBF can be measured accurately and noninvasively with dynamic N-13 ammonia PET imaging and factor analysis. This method is simple and accurate, and can measure MBF without blood sampling, ROI definition or spillover correction. KW: N-13 ammonia, PET, Myocardial blood flow, Factor analysis