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.

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.

Small Animal PET Imaging with 124IFIAU for Herpes Simplex Virus Type 1 Thymidine Kinase Gene Expression in a Hepatoma Model / 핵의학분자영상

PURPOSE: The HSV1-tk gene has been extensively studied as a type of reporter gene. In hepatocellular carcinoma (HCC), only a small proportion of patients are eligible for surgical resection and there is limitation in palliative options. Therefore, there is a need for the develoopement of new treatment modalities and gene therapy is a leading candidate. In the present study, we investigated the usefulness of substrate, 2'-fluoro-2'-deoxy-1-beta-D-arabino-furanosyl-5-[124/125I]iodo- uracil ([124/125I]FIAU) as a non-invasive imaging agent for HSV1-tk gene therapy in hepatoma model using small animal PET. MATERIAL AND METHODS: With the Morris hepatoma MCA cell line and MCA-tk cell line which was transduced with the HSV1-tk gene, in vitro uptake and correlation study between [125I]FIAU uptake according to increasing numeric count of percentage of MCA-tk cell were performed. The biodistribution data and small animal PET images with [124I]FIAU were obtained with Balb/c-nude mice bearing both MCA and MCA-tk tumors. RESULTS: Specific accumulation of [125I]FIAU was observed in MCA-tk cells but uptake was low in MCA cells. Uptake in MCA-tk cells was 15 times higher than that of MCA cells at 480 min. [125I]FIAU uptake was linearly correlated (R2=0.964, p=0.01) with increasing percentage of MCA-tk numeric cell count. Biodistribution results showed that [125I]FIAU was mainly excreted via the renal system in the early phase. Ratios of MCA-tk tumor to blood acting were 10, 41, and 641 at 1 h, 4 h, and 24 h post-injection, respectively. The maximum ratio of MCA-tk to MCA tumor was 192.7 at 24 h. Ratios of MCA-tk tumor to liver were 13.8, 66.8, and 588.3 at 1 h, 4 h, and 24 h, respectively. On small aninal PET, [124I]FIAU accumulated in substantial higher levels in MCA-tk tumor and liver than MCA tumor. CONCLUSION: FIAU shows selective accumulation to HSV1-tk expressing hepatoma cell tumors with minimal uptake in normal liver. Therefore, radiolabelled FIAU is expected to be a useful substrate for non-invasive imaging of HSV1-tk gene therapy and therapeutic response monitoring of HCC.

Development of Position Encoding Circuit for a Multi-Anode Position Sensitive Photomultiplier Tube / 핵의학분자영상

PURPOSE: The goal of this paper is to present the design and performance of a position encoding circuit for 16 x 16 array of position sensitive multi-anode photomultiplier tube for small animal PET scanners. This circuit which reduces the number of readout channels from 256 to 4 channels is based on a charge division method utilizing a resistor array. MATERIALS AND METHODS: The position encoding circuit was simulated with PSpice before fabrication. The position encoding circuit reads out the signals from H9500 flat panel PMTs (Hamamatsu Photonics K.K., Japan) on which 1.5 x 1.5 x 7.0 mm3 L0.9GSO (Lu1.8Gd0.2SiO5:Ce) crystals were mounted. For coincidence detection, two different PET modules were used. One PET module consisted of a 29 x 29 L0.9GSO crystal layer, and the other PET module two 28 x 28 and 29 x 29 L0.9GSO crystal layers which have relative offsets by half a crystal pitch in x- and y-directions. The crystal mapping algorithm was also developed to identify crystals. RESULTS: Each crystal was clearly visible in flood images. The crystal identification capability was enhanced further by changing the values of resistors near the edge of the resistor array. Energy resolutions of individual crystal were about 11.6%(SD 1.6). The flood images were segmented well with the proposed crystal mapping algorithm. CONCLUSION: The position encoding circuit resulted in a clear separation of crystals and sufficient energy resolutions with H9500 flat-panel PMT and L0.9GSO crystals. This circuit is good enough for use in small animal PET scanners.

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.

Effects of Attenuation and Scatter Corrections in Cat Brain PET Images Using microPET R4 Scanner / 핵의학분자영상

PURPOSE: The aim of this study was to examine the effects of attenuation correction (AC) and scatter correction (SC) on the quantification of PET count rates. MATERIALS AND METHODS: To assess the effects of AC and SC, 18F-FDG PET images of phantom and cat brain were acquired using microPET R4 scanner. Thirty-minute transmission images using 68Ge source and emission images after injection of FDG were acquired. PET images were reconstructed using 2D OSEM. AC and SC were applied. Regional count rates were measured using ROIs drawn on cerebral cortex including frontal, parietal, and latral temporal lobes and deep gray matter including head of caudate nucleus, putamen and thalamus for pre- and post-AC and SC images. The count rates were then normalized with the injected dose per body weight. To assess the effects of AC, count ratio of "deep gray matter/cerebral cortex" was calculated. To assess the effects of SC, ROIs were also drawn on the gray matter (GM) and white matter (WM), and contrast between them ((GM-WM)/GM) was measured. RESULTS: After the AC, count ratio of "deep gray matter/cerebral cortex" was increased by 17+/-7%. After the SC, contrast was also increased by 12+/-3%. CONCLUSION: Relative count of deep gray matter and contrast between gray and white matters were increased after AC and SC, suggesting that the AC would be critical for the quantitative analysis of cat brain PET data.

Development of a Small Animal Positron Emission Tomography Using Dual-Layer Phoswich Detector and Position Sensitive Photomultiplier Tube: Preliminary Results / 대한핵의학회잡지

PURPOSE: The purpose of this study was to develop a small animal PET using dual layer phoswich detector to minimize parallax error that degrades spatial resolution at the outer part of field-of-view (FOV). MATERIALS AND METHODS: A simulation tool GATE (Geant4 Application for Tomographic Emission) was used to derive optimal parameters of small PET, and PET was developed employing the parameters. Lutetium Oxyorthosilicate (LSO) and Lutetium-Yttrium Aluminate-Perovskite (LuYAP) was used to construct dual layer phoswitch crystal. 8 X 8 arrays of LSO and LuYAP pixels, 2 mm X 2 mm X 8 mm in size, were coupled to a 64-channel position sensitive photomultiplier tube. The system consisted of 16 detector modules arranged to one ring configuration (ring inner diameter 10 cm, FOV of 8 cm). The data from phoswich detector modules were fed into an ADC board in the data acquisition and preprocessing PC via sockets, decoder block, FPGA board, and bus board. These were linked to the master PC that stored the events data on hard disk. RESULTS: In a preliminary test of the system, reconstructed images were obtained by using a pair of detectors and sensitivity and spatial resolution were measured. Spatial resolution was 2.3 mm FWHM and sensitivity was 10.9 cps/micro Ci at the center of FOV. CONCLUSION: The radioactivity distribution patterns were accurately represented in sinograms and images obtained by PET with a pair of detectors. These preliminary results indicate that it is promising to develop a high performance small animal PET.

The application of small animal PET in drug development / 中国药理学通报

Small animal PET is a quantitative imaging technique that can noninvasive and dynamically image the distribution of positron-labeled radiopharmaceuticals in vivo,therefore representing a new means of providing information for drug development and evaluation.This article reviews the fundamental basis of PET imaging and their application in preclinical drug discovery and development.

Small animal PET and its application in medicine and drug development / 中国药理学通报

Small animal PET is a noninvasive molecular imaging technique, which provides an important bridge between experimental sciences and clinical sciences, and plays an unique role in medicine and drug development. Advantages and challenges, fundamentals, and development of small animal PET are reviewed and applications of small animal PET in medicine and drug development are discussed in this article.