Performance evaluation of the Philips MOSAIC small animal PET scanner

Purpose In this study an evaluation of the performance of the Philips MOSAIC small animal PET scanner is presented, with special emphasis on the ability of the system to provide quantitatively accurate PET images. Methods The performance evaluation was structured according to NEMA-like procedures. Results The transaxial spatial resolution of the system (radial component) ranged between 2.7 mm FWHM at the centre and 3.2 mm FWHM at a radial offset of 45 mm from the centre. The axial spatial resolution of the system ranged between 3.4 mm FWHM at the centre and 5.8 mm FWHM at a radial offset of 45 mm from the centre. The scatter fraction was determined for a mouse- as well as for a rat-sized phantom, and the values obtained were 9.6% and 16.8%, respectively. For the mouse phantom, the maximum count rate measured was 560 kcps at 93 MBq; the maximum NEC rate equalled 308 kcps at 1.7 MBq/ml. For the rat phantom, these values were 400 kcps at 100 MBq and 129 kcps at 0.24 MBq/ml, respectively. The sensitivity of the system was derived to be 0.65%. An energy window between 410 and 665 keV was used in all experiments. Conclusion The MOSAIC system exhibits moderate spatial resolution and sensitivity values, but good NEC performance. In combination with its relatively large field of view, the system allows for high-throughput whole-body imaging of mice and rats. The accurate measurement of relative changes in radiotracer distributions is feasible.     

Hybrid image and blood sampling input function for quantification of small animal dynamic PET data

We describe and validate a hybrid image and blood sampling (HIBS) method to derive the input function for quantification of microPET mice data. The HIBS algorithm derives the peak of the input function from the image, which is corrected for recovery, while the tail is derived from 5 to 6 optimally placed blood sampling points. A Bezier interpolation algorithm is used to link the rightmost image peak data point to the leftmost blood sampling point. To assess the performance of HIBS, 4 mice underwent 60-min microPET imaging sessions following a 0.40–0.50-mCi bolus administration of ¹⁸FDG. In total, 21 blood samples (blood-sampled plasma time–activity curve, bsPTAC) were obtained throughout the imaging session to compare against the proposed HIBS method. MicroPET images were reconstructed using filtered back projection with a zoom of 2.75 on the heart. Volumetric regions of interest (ROIs) were composed by drawing circular ROIs 3 pixels in diameter on 3–4 transverse planes of the left ventricle. Performance was characterized by kinetic simulations in terms of bias in parameter estimates when bsPTAC and HIBS are used as input functions. The peak of the bsPTAC curve was distorted in comparison to the HIBS-derived curve due to temporal limitations and delay in blood sampling, which affected the rates of bidirectional exchange between plasma and tissue. The results highlight limitations in using bsPTAC. The HIBS method, however, yields consistent results, and thus, is a substitute for bsPTAC.     

Multi-tracer small animal PET imaging of the tumour response to the novel pan-Erb-B inhibitor CI-1033

Purpose This study was designed as “proof of concept” for a drug development model utilising multi-tracer serial small animal PET imaging to characterise tumour responses to molecularly targeted therapy. Methods Mice bearing subcutaneous A431 human squamous carcinoma xenografts (n=6–8) were treated with the pan-Erb-B inhibitor CI-1033 or vehicle and imaged serially (days 0, 3 and 6 or 7) with [¹⁸F]fluorodeoxyglucose, [¹⁸F]fluoro-L-thymidine, [¹⁸F]fluoro-azoazomycinarabinoside or [¹⁸F]fluoromisonidazole. Separate cohorts (n=3) were treated identically and tumours were assessed ex vivo for markers of glucose metabolism, proliferation and hypoxia. Results During the study period, mean uptake of all PET tracers generally increased for control tumours compared to baseline. In contrast, tracer uptake into CI-1033-treated tumours decreased by 20–60% during treatment. Expression of the glucose transporter Glut-1 and cell cycle markers was unchanged or increased in control tumours and generally decreased with CI-1033 treatment, compared to baseline. Thymidine kinase activity was reduced in all tumours compared to baseline at day 3 but was sevenfold higher in control versus CI-1033-treated tumours by day 6 of treatment. Uptake of the hypoxia marker pimonidazole was stable in control tumours but was severely reduced following 7 days of CI-1033 treatment. Conclusion CI-1033 treatment significantly affects tumour metabolism, proliferation and hypoxia as determined by PET. The PET findings correlated well with ex vivo biomarkers for each of the cellular processes studied. These results confirm the utility of small animal PET for evaluation of the effectiveness of molecularly targeted therapies and simultaneously definition of specific cellular processes involved in the therapeutic response. The first two authors contributed equally to the results presented in this report.     

Dynamic <Superscript>18</Superscript>F-fluoride small animal PET to noninvasively assess renal function in rats

Purpose

Renal function can be quantified by both laboratory and scintigraphic methods. In the case of small animal diagnostics, scintigraphic image-based methods are ideal since they can assess split renal function, work noninvasively, and can be repeated. The aim of this study is to validate a ¹⁸F-PET-based method to quantify renal function in rats.

Materials and methods

Fluoride clearance was calculated from a dynamic whole body listmode acquisition of 60 min length in a small animal PET scanner following an i.v. injection of 15 MBq ¹⁸F-fluoride. Volumes of interest (VOIs) were placed in the left ventricle and the bladder as well as traced around the kidney contours. The respective time–activity curves (TAC) were calculated. The renal ¹⁸F-clearance was calculated by the ratio of the total renal excreted activity (bladder VOI) and the integral of the blood TAC. PET-derived renal function was validated by intraindividual measurements of creatinine clearance (n?=?23), urea clearance (n?=?23), and tubular excretion rate (TER-MAG3). The split renal function was derived from the injection of the clinically available radionuclide ^99mTc-mercaptotriglycine by blood sampling and planar renography (n?=?8).

Results

In all animals studied, PET revealed high-quality TACs. PET-derived renal fluoride clearance was linearly correlated with intraindividual laboratory measures (PET vs. creatinine: r?=?0.78; PET vs. urea: r?=?0.73; PET vs. TER-MAG3: r?=?0.73). Split function was comparable (¹⁸F-PET vs. MAG3-renography: r?=?0.98). PET-derived measures were highly reproducible.

Conclusions

¹⁸F-PET is able to noninvasively assess renal function in rats and provides a significant potential for serial studies in different experimental scenarios.

     

Improving the quality of small animal brain pinhole SPECT imaging by Bayesian reconstruction

The possibility of using existing hardware makes pinhole single-photon emission computed tomography (SPECT) attractive when pursuing the ultra-high resolution required for small animal brain imaging. Unfortunately, the poor sensitivity and the heavy weight of the collimator hamper the use of pinhole SPECT in animal studies by generating noisy and misaligned projections. To improve the image quality we have developed a new Bayesian reconstruction method, pinhole median root prior (PH-MRP), which prevents the excessive noise accumulation from the projections to the reconstructed image. The PH-MRP algorithm was used to reconstruct data acquired with our small animal rotating device, which was designed to reduce the rotation orbit misalignments. Phantom experiments were performed to test the device and compare the PH-MRP with the conventional Feldkamp-Davis-Kress (FDK) and pinhole ordered subsets maximum likelihood expectation maximisation (PH-OSEM) reconstruction algorithms. The feasibility of the system for small animal brain imaging was studied with Han-Wistar rats injected with ¹²³I-epidepride and ^99mTc-hydroxy methylene diphosphonate. Considering all the experiments, no shape distortions due to orbit misalignments were encountered and remarkable improvements in noise characteristics and also in overall image quality were observed when the PH-MRP was applied instead of the FDK or PH-OSEM. In addition, the proposed methods utilise existing hardware and require only a certain amount of construction and programming work, making them easy to implement.     

Current status and future perspectives of in vivo small animal imaging using radiolabeled nanoparticles

Small animal molecular imaging is a rapidly expanding efficient tool to study biological processes non-invasively. The use of radiolabeled tracers provides non-destructive, imaging information, allowing time related phenomena to be repeatedly studied in a single animal. In the last decade there has been an enormous progress in related technologies and a number of dedicated imaging systems overcome the limitations that the size of small animal possesses. On the other hand, nanoparticles (NPs) gain increased interest, due to their unique properties, which make them perfect candidates for biological applications. Over the past 5 years the two fields seem to cross more and more often; radiolabeled NPs have been assessed in numerous pre-clinical studies that range from oncology, till HIV treatment. In this article the current status in the tools, applications and trends of radiolabeled NPs reviewed.     

Techniques necessary for multiple tracer quantitative small-animal imaging studies

INTRODUCTION: An increasing number and variety of studies on rodent models are being conducted using small-animal positron emission tomography scanners. We aimed to determine if animal handling techniques could be developed to perform routine animal imaging in a timely and efficient manner and with minimal effect on animal physiology. These techniques need to be reproducible in the same animal while maintaining hemodynamic and physiological stability. METHODS: The necessary techniques include (a) the use of inhalant anesthesia, (b) arterial and venous cannulation for multiple tracer administrations and blood sampling, (c) development of small-volume analytic columns and techniques and (d) measurement of the physiological environment during the imaging session. RESULTS: We provide an example of a cardiac imaging study using four radiotracers (15O-water, 1-[11C]-acetate, 1-[11C]-palmitate and 1-[11C]-glucose) injected into normal rats. Plasma substrates, CO2 production and total metabolites were measured. The animals remained anesthetized over the entire imaging session, and their physiological state was maintained. CONCLUSION: The intrastudy stability of the physiological measurements and substrate levels and interstudy reproducibility of the measurements are reported.     

In vivo structural imaging of the rat brain with a 3-T clinical human scanner

PURPOSE: To examine the feasibility of using product acquisition software on a 3-T human MRI system to acquire high-resolution structural brain images in the rat. MATERIALS AND METHODS: Three sets of dual spin-echo, high-resolution (0.234 x 0.234 mm in-plane, 0.5 mm thick) images covering the entire rat brain were collected and averaged in 66 min. The images had sufficient signal-to-noise ratio (SNR) and resolution for visual identification and manual outlining of exemplary structures, including the lateral ventricles and dorsal and ventral portions of the hippocampus. Further, the data were adequate for unsupervised, automated segmentation, permitting quantification of the dorsolateral ventricles. The images compared favorably with those collected on a 7-T system. RESULTS: Interrater reliabilities (intraclass correlations) of manual ventricular scoring were greater than 0.97, and manual vs. automated correlations were 0.97. The variability of lateral ventricular size across animals was substantially higher than that of the hippocampus. CONCLUSION: The large variability of some brain structures that can exist across even a highly selected strain of rats can readily be detected with the use of human 3-T systems for the study of small animals.     

FDG small animal PET permits early detection of malignant cells in a xenograft murine model

Purpose The administration of new anticancer drugs in animal models is the first step from in vitro to in vivo pre-clinical protocols. At this stage it is crucial to ensure that cells are in the logarithmic phase of growth and to avoid vascular impairment, which can cause inhomogeneous distribution of the drug within the tumour and thus lead to bias in the final analysis of efficacy. In subcutaneous xenograft murine models, positivity for cancer is visually recognisable 2–3 weeks after inoculation, when a certain amount of necrosis is usually already present. The aim of this study was to evaluate the accuracy of FDG small animal PET for the early detection of malignant masses in a xenograft murine model of human rhabdomyosarcoma. A second goal was to analyse the metabolic behaviour of this xenograft tumour over time. Methods We studied 23 nude mice, in which 7 × 10⁶ rhabdomyosarcoma cells (RH-30 cell line) were injected in the dorsal subcutaneous tissues. Each animal underwent four FDG PET scans (GE, eXplore Vista DR) under gas anaesthesia. The animals were studied 2, 5, 14 and 20 days after inoculation. We administered 20 MBq of FDG via the tail vein. Uptake time was 60 min, and acquisition time, 20 min. Images were reconstructed with OSEM 2D iterative reconstruction and the target to background ratio (TBR) was calculated for each tumour. Normal subcutaneous tissue had a TBR of 0.3. Necrosis was diagnosed when one or more cold areas were present within the mass. All the animals were sacrificed and histology was available to verify PET results. PET results were concordant with the findings of necropsy and histology in all cases. Results The incidence of the tumour was 69.6% (16/23 animals); seven animals did not develop a malignant mass. Ten of the 23 animals had a positive PET scan 2 days after inoculation. Nine of these ten animals developed a tumour; the remaining animal became negative, at the third scan. The positive predictive value of the early PET scan was 90% (9/10 animals) while the negative predictive value was 46% (6/13 animals). In the whole group of animals, mean TBR increased scan by scan. There was a statistically significant difference in TBR between 2 and 20 days after inoculation. Necrosis was present at the second scan in two animals, at the third scan in six animals and at the fourth scan in 11 animals. Conclusion The high positive predictive value of FDG PET 2 days after inoculation means that an animal with a first positive scan has a very high likelihood of developing a mass and can be treated at an early stage with an experimental drug. Animals negative at this point in time will never develop a mass or will eventually do so at a late phase. As 2 of the 16 (12.5%) positive animals had necrosis at the second scan, indicating a vascular mismatch, it may be argued that animals should be treated 2 days after inoculation to guarantee homogeneous vascularisation (thereby ensuring a good drug supply within the tumour) in all subjects.     

Design and characterization of an economical 192Ir hemi-brain small animal irradiator

Abstract

Purpose: To describe the design and dosimetric characterization of a simple and economical small animal irradiator.

Materials and methods: A high dose rate (HDR) ¹⁹²Ir brachytherapy source from a commercially available afterloader was used with a 1.3 cm thick tungsten collimator to provide sharp beam penumbra suitable for hemi-brain irradiation of mice. The unit was equipped with continuous gas anesthesia to allow robust animal immobilization. Dosimetric characterization of the device was performed with Gafchromic film measurements.

Results: The tungsten collimator provided a sharp penumbra suitable for hemi-brain irradiation, and dose rates on the order of 200 cGy/minute were achieved. The sharpness of the penumbra attainable with this device compares favorably to those measured experimentally for 6 MV photons, and 6 and 20 MeV electron beams from a linear accelerator, and was comparable to those measured for a 300 kVp orthovoltage beam and a Monte Carlo simulated 90 MeV proton beam.

Conclusions: Due to its simplicity and low cost, the apparatus described is an attractive alternative for small animal irradiation experiments requiring steep dose gradients.     

Evaluation of the quantitative capability of a high-resolution positron emission tomography scanner for small animal imaging

OBJECTIVE: The quantitative capability of a positron emission tomography scanner for small animal imaging was evaluated in this study. METHODS: The microPET P4 (Concorde Microsystems, Knoxville, TN) scanner's capability for dynamic imaging and corrections for radioactive decay, dead time, and attenuation were evaluated. Rat brain and heart studies with and without attenuation correction were compared. A calibration approach to convert the data to nanocuries per milliliter was implemented. Calibration factors were determined using calibration phantoms of 2 sizes with and without attenuation correction. Quantitation was validated using the MiniPhantom (Data Spectrum, Chapel Hill, NC) with hot features (5:1 ratio) of different sizes (4, 6.4, 8, 13, and 16 mm). RESULTS: The microPET P4 scanner's ability to acquire dynamic studies and to correct for decay, dead time, and attenuation was demonstrated. The microPET P4 scanner provided accurate quantitation to within 6% for features larger than 10 mm. Sixty percent of object contrast was retained for features as small as 4 mm. CONCLUSIONS: The microPET P4 scanner can provide accurate quantitation.     

Use of a compact pixellated gamma camera for small animal pinhole SPECT imaging

OBJECTIVES: Pinhole SPECT which permits in vivo high resolution 3D imaging of physiological functions in small animals facilitates objective assessment of pharmaceutical development and regenerative therapy in pre-clinical trials. For handiness and mobility, the miniature size of the SPECT system is useful. We developed a small animal SPECT system based on a compact high-resolution gamma camera fitted to a pinhole collimator and an object-rotating unit. This study was aimed at evaluating the basic performance of the detection system and the feasibility of small animal SPECT imaging. METHODS: The gamma camera consists of a 22 x 22 pixellated scintillator array of 1.8 mm x 1.8 mm x 5 mm NaI(Tl crystals with 0.2-mm gap between the crystals coupled to a 2" flat panel position-sensitive photomultiplier tube (Hamamatsu H8500) with 64 channels. The active imaging region of the camera was 43.8 mm x 43.8 mm. Data acquisition is controlled by a personal computer (Microsoft Windows) through the camera controller. Projection data over 360 degrees for SPECT images are obtained by synchronizing with the rotating unit. The knife-edge pinhole collimators made of tungsten are attached on the camera and have 0.5-mm and 1.0-mm apertures. The basic performance of the detection system was evaluated with 99mTc and 201Tl solutions. Energy resolution, system spatial resolution and linearity of count rate were measured. Rat myocardial perfusion SPECT scans were sequentially performed following intravenous injection of 201TlCl. Projection data were reconstructed using a previously validated pinhole 3D-OSEM method. RESULTS: The energy resolution at 140 keV was 14.8% using a point source. The system spatial resolutions were 2.8-mm FWHM and 2.5-mm FWHM for 99mTc and 201Tl line sources, respectively, at 30-mm source distance (magnification factor of 1.3) using a 1.0-mm pinhole. The linearity between the activity and count rate was good up to 10 kcps. In a rat study, the left ventricular walls were clearly visible in all scans. CONCLUSIONS: We developed a compact SPECT system using compact gamma camera for small animals and evaluated basic physical performances. The present system may be of use for quantitation of biological functions such as myocardial blood flow in small animals.     

High resolution SPECT imaging for visualization of intratumoral heterogeneity using a SPECT/CT scanner dedicated for small animal imaging

Objectives

Tumor interiors are never homogeneous and in vivo visualization of intratumoral heterogeneity would be an innovation that contributes to improved cancer therapy. But, conventional nuclear medicine tests have failed to visualize heterogeneity in vivo because of limited spatial resolution. Recently developed single photon emission computed tomographic (SPECT) scanners dedicated for small animal imaging are of interest due to their excellent spatial resolution of <1?mm, but few studies have focused on the evaluation of intratumoral heterogeneity. We investigated the optimal conditions related to high resolution imaging of heterogeneous tumor interiors using a small animal SPECT scanner.

Methods

The conditions related to SPECT/CT visualization of heterogeneous tumor interiors were investigated using phantoms with ¹¹¹In and simulations of actual small animal imaging. The optimal conditions obtained were validated by in vivo imaging of sarcoma 180-bearing mice.

Results

Larger number of counts must be obtained within limited acquisition time to visualize tumor heterogeneity in vivo in animal imaging, compared to cases that simply detect tumors. At an acquisition time of 30?min, better image quality was obtained with pinhole apertures diameter of 1.4?mm than of 1.0?mm. The obtained best spatial resolution was 1.3?mm, it was acceptable for our purpose, though a little worse than the best possible performance of the scanner (1.0?mm). Additionally, the reconstruction parameters, such as noise suppression, voxel size, and iteration/subset number, needed to be optimized under the limited conditions and were different from those found under the ideal condition. The minimal radioactivity concentration for visualization of heterogeneous tumor interiors was estimated to be as high as 0.2?C0.5?MBq/mL. Liposomes containing ¹¹¹In met this requirement and were administered to tumor-bearing mice. SPECT imaging successfully showed heterogeneous ¹¹¹In distribution within the tumors in vivo with good spatial resolution. A threshold of 0.2?MBq/g for clear visualization of tumor heterogeneity was validated. Autoradiograms obtained ex vivo of excised tumors confirmed that the in vivo SPECT images accurately depicted the heterogeneous intratumoral accumulation of liposomes.

Conclusion

Intratumoral heterogeneity was successfully visualized under the optimized conditions using a SPECT/CT scanner.     

基于小动物精准放疗平台构建Wistar大鼠急性放射性食管炎动物模型

目的 基于小动物精准放疗平台(SARRP)建立Wistar大鼠急性放射性食管炎体内模型。方法 将36只Wistar大鼠按照随机数表法分为对照组、40、60和75 Gy组,每组9只。基于SARRP结合照射前磁共振图像(MRI)勾画大鼠食管靶区并制定计划,每次分别照射0、8、12和15 Gy,连续照射5 d,观察大鼠体重、进食量、食管病理和磁共振图像改变。结果 75 Gy组大鼠在照后第6天体重最先出现明显降低(P<0.05),照后第9天各照射组大鼠食管较对照组增粗(F=14.20,P<0.05)。照后第9天HE染色显示,40 Gy组放射性食管炎形成率为4/5,60 Gy 组食管炎形成率为5/5,且以轻度食管炎为主,75 Gy组食管炎形成率为5/5,其中3/5表现为重度。照后第9天各组大鼠病理损伤评分[M(Q₁, Q₃)]为0、1.0(0.5, 2.5)、1.0(1.0, 2.5)和4.0(1.5, 6.0),75 Gy组与对照组相比,差异有统计学意义(H=12.69,P<0.05)。动态监测颈部MRI图像后发现,照后第9天时各照射组大鼠食管信号增强变宽。结论 本实验基于小动物精准放疗平台结合MRI成功建立大鼠的急性放射性食管炎动物模型,75 Gy是最佳照射剂量,且第9天是最佳观察时间点。     

PET imaging of apoptosis with <Superscript>64</Superscript>Cu-labeled streptavidin following pretargeting of phosphatidylserine with biotinylated annexin-V

Purpose In vivo detection of apoptosis is a diagnostic tool with potential clinical applications in cardiology and oncology. Radiolabeled annexin-V (anxV) is an ideal probe for in vivo apoptosis detection owing to its strong affinity for phosphatidylserine (PS), the molecular flag on the surface of apoptotic cells. Most clinical studies performed to visualize apoptosis have used ^99mTc-anxV; however, its poor distribution profile often compromises image quality. In this study, tumor apoptosis after therapy was visualized by positron emission tomography (PET) using ⁶⁴Cu-labeled streptavidin (SAv), following pre-targeting of apoptotic cells with biotinylated anxV. Methods Apoptosis was induced in tumor-bearing mice by photodynamic therapy (PDT) using phthalocyanine dyes as photosensitizers, and red light. After PDT, mice were injected i.v. with biotinylated anxV, followed 2 h later by an avidin chase, and after another 2 h with ⁶⁴Cu-DOTA-biotin-SAv. PET images were subsequently recorded up to 13 h after PDT. Results PET images delineated apoptosis in treated tumors as early as 30 min after ⁶⁴Cu-DOTA-biotin-SAv administration, with tumor-to-background ratios reaching a maximum at 3 h post-injection, i.e., 7 h post-PDT. Omitting the administration of biotinylated anxV or the avidin chase failed to provide a clear PET image, confirming that all three steps are essential for adequate visualization of apoptosis. Furthermore, differences in action mechanisms between photosensitizers that target tumor cells directly or via initial vascular stasis were clearly recognized through differences in tracer uptake patterns detecting early or delayed apoptosis. Conclusion This study demonstrates the efficacy of a three-step ⁶⁴Cu pretargeting procedure for PET imaging of apoptosis. Our data also confirm the usefulness of small animal PET to evaluate cancer treatment protocols.     

计算机自动定量诊断脑萎缩的初步研究

目的研究正常人群脑容积随年龄及性别的变化规律,提出计算机定量诊断脑萎缩的客观标准。方法利用最新提出的脑容积计算机自动定量算法,测量了脑萎缩组487例(男,310例,女,177例)和正常组1901例(男,993例,女,908例)的颅腔容积、脑容积和脑实质分数(BPF),并通过多项式曲线拟合技术,研究正常人BPF随年龄变化的函数关系。结果正常组颅腔容积为(1271322±128699)mm3,脑容积为(1211725±122077)mm3,BPF为(95.3471±2.3453)%;脑萎缩组颅腔容积为(1276900±125180)mm3,脑容积为(1203400±117760)mm3,BPF为(91.8115±2.3035)%。两组之间的颅腔容积和脑容积差异无统计学意义(P>0.05),而BPF差异具有统计学意义(P<0.001);BPF定量与年龄之间的二次多项式函数关系P(x)=-0.0008x2+0.0193x+96.9999能够较为准确表达正常人BPF随年龄变化的函数关系,其95%可信区间下限为y=-0.0008x2+0.0184x+95.1090。结论BPF与年龄之间函数关系的95%可信区间下限,可作为计算机自动定量诊断脑萎缩的客观标准。     

Successful high-resolution animal positron emission tomography of human Ewing tumours and their metastases in a murine xenograft model

Purpose As primary osseous metastasis is the main adverse prognostic factor in patients with Ewing tumours, a NOD/scid mouse model for human Ewing tumour metastases has been established to examine the mechanisms of metastasis. The aim of this study was to evaluate the feasibility of diagnostic molecular imaging by small animal PET in this mouse model. Methods Human Ewing tumour cells were transplanted into immune-deficient NOD/scid mice via s.c injection (n=17) or i.v. injection (n=17). The animals (mean weight 23.2 g) were studied 2–7 weeks after transplantation using a submillimetre resolution animal PET scanner. To assess glucose utilisation and bone metabolism, mice were scanned after intravenous injection of 9.6 MBq (mean) 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FDG) or 9.4 MBq (mean) [¹⁸F]fluoride. Whole-body PET images were analysed visually and semi-quantitatively [%ID/g, tumour to non-tumour ratio (T/NT)]. Foci of pathological uptake were identified with respect to the physiological organ uptake in corresponding regions. Results Subcutaneously transplanted Ewing tumours demonstrated a moderately increased glucose uptake (median %ID/g 2.5; median T/NT 2.2). After i.v. transplantation, the pattern of metastasis was similar to that in patients with metastases in lung, bone and soft tissue. These metastases showed an increased FDG uptake (median %ID/g 3.6; median T/NT 2.7). Osseous metastases were additionally visible on [¹⁸F]fluoride PET by virtue of decreased [¹⁸F]fluoride uptake (osteolysis; median %ID/g 8.4; median T/NT 0.59). Metastases were confirmed immunohistologically. Conclusion Diagnostic molecular imaging of Ewing tumours and their small metastases in an in vivo NOD/scid mouse model is feasible using a submillimetre resolution PET scanner.     

Determination of tumour hypoxia with the PET tracer [<Superscript>18</Superscript>F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model

Purpose The 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a 2-nitroimidazole derivative which undergoes bioreductive activation under hypoxic conditions. Using the PET tracer [¹⁸F]EF3 in mice, tumour-to-muscle ratios ranging from 1.3 to 3.5 were observed. This study investigated the impact of various interventions aimed at increasing [¹⁸F]EF3 elimination, thus potentially increasing the tumour-to-noise ratio in mice, by increasing the renal filtration rate (spironolactone, furosemide), decreasing tubular re-absorption (metronidazole, ornidazole, amino acid solution) or stimulating gastro-intestinal elimination (phenobarbital). Methods C3H mice were injected i.v. with an average of 12.95 MBq of [¹⁸F]EF3. Drugs were injected i.v. 15 min before the tracer or daily 4 days prior to the experiment (phenobarbital). Anaesthetised mice were imaged from 30 to 300 min with a dedicated animal PET (Mosaic, Philips). Regions of interest were delineated around the tumour, bladder, heart, liver and leg muscle. Radioactivity was expressed as a percentage of injected activity per gram of tissue. Results Ornidazole decreased the urinary excretion and increased the liver uptake of [¹⁸F]EF3, but without causing any changes in the other organs. Phenobarbital significantly increased the liver concentration and decreased radioactivity in blood and muscle without affecting the tracer uptake in tumour. Consequently, a small but non-significant increase in tumour-to-noise ratio was observed. Although some effects were observed with other drugs, they did not modify the tumour-to-noise ratio. Conclusion Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation.     

MR扩散张量成像对脑肿瘤的初步应用研究

目的 :评价MR扩散张量成像在脑肿瘤中的应用价值。方法 :搜集经手术及病理证实的脑膜瘤和星形细胞瘤病例共 3 3例 ,行常规MRI、扩散张量成像 (DTI)检查。构建各向异性分数 (FA)图 ,并测量肿瘤及周围白质的FA值。结果 :正常白质纤维在FA图上表现为高信号。在肿瘤存在时 ,周围白质纤维可表现为受推压移位或浸润破坏 ,破坏后FA值降低 ,表现为低信号。这些表现在常规MRI上均未清楚显示。结论 :DTI可清楚显示肿瘤与周围白质纤维的解剖关系 ,指导临床制订手术方案。     

Influence of some instrumental parameters on the determination of quantitative data using the PET scanner PC4096-15WB

In order to evaluate the influence of physical and instrumental limitations of the PET technique on metabolic data, various parameters have been tested. The measurements were done with a whole body PET scanner PC4096-15WB. The dependence on the transaxial resolution of reconstruction filter cut off frequency _c was investigated. The high resolution (4.8 mm atr=0) in the field of view) and the low scatter fraction (<5%) of this system yields a higher grey/white matter ratio (3.8:1) than that found with older scanners (2:1). The use of a rotating pin source allows transmission scans to be performed after tracer administration with an error of less than 5%.This article was presented at the 1st EEC workshop on accuracy determination in PET, January 19-20th. 1989 Pisa, Italy (COMAC-BME Concerted Project Characterization and Standardization of PET Instrumentation)