Advances in animal PET scanners.

Nowadays, a growing number of research groups shows a great interest for the application of PET and SPECT techniques to the development of new drugs. Preliminary studies on small animals require high performance dedicated scanners with a higher spatial resolution and sensitivity than those of clinical systems. In this paper the potential applications of such innovative instruments are shown together with a brief review of the dedicated PET and SPECT tomographs developed worldwide. Most of the scanners have been built as research prototypes. Only two are commercially available: micro-PET(R), designed and developed at UCLA, Los Angeles as a research prototype, and now produced and distributed by Concorde Microsystems Inc. (USA) and HIDAC PET produced by Oxford Positron Systems Ltd. (UK). Also in Italy, a high performance tomograph, YAP-(S) PET able to perform both PET and SPECT studies, has been developed at the University of Ferrara. The technical characteristics and performance of this scanner are described. Tomographs with combined imaging techniques, such as PET/CT or SPECT/CT, are now under study in various international research centers. The advantages of this new generation of animal scanners will be briefly outlined.     

Semiautomated analysis of small-animal PET data.

The objective of the work reported here was to develop and test automated methods to calculate biodistribution of PET tracers using small-animal PET images. METHODS: After developing software that uses visually distinguishable organs and other landmarks on a scan to semiautomatically coregister a digital mouse phantom with a small-animal PET scan, we elastically transformed the phantom to conform to those landmarks in 9 simulated scans and in 18 actual PET scans acquired of 9 mice. Tracer concentrations were automatically calculated in 22 regions of interest (ROIs) reflecting the whole body and 21 individual organs. To assess the accuracy of this approach, we compared the software-measured activities in the ROIs of simulated PET scans with the known activities, and we compared the software-measured activities in the ROIs of real PET scans both with manually established ROI activities in original scan data and with actual radioactivity content in immediately harvested tissues of imaged animals. RESULTS: PET/atlas coregistrations were successfully generated with minimal end-user input, allowing rapid quantification of 22 separate tissue ROIs. The simulated scan analysis found the method to be robust with respect to the overall size and shape of individual animal scans, with average activity values for all organs tested falling within the range of 98% +/- 3% of the organ activity measured in the unstretched phantom scan. Standardized uptake values (SUVs) measured from actual PET scans using this semiautomated method correlated reasonably well with radioactivity content measured in harvested organs (median r = 0.94) and compared favorably with conventional SUV correlations with harvested organ data (median r = 0.825). CONCLUSION: A semiautomated analytic approach involving coregistration of scan-derived images with atlas-type images can be used in small-animal whole-body radiotracer studies to estimate radioactivity concentrations in organs. This approach is rapid and less labor intensive than are traditional methods, without diminishing overall accuracy. Such techniques have the possibility of saving time, effort, and the number of animals needed for such assessments.     

Design considerations for PET scanners.

In 2-D PET scanners employing septa, scattered radiation is reduced by the septa, placing less importance on good energy resolution. Additionally, the reduced sensitivity in 2-D limits the maximum countrates encountered in clinical FDG studies. In contrast, 3-D PET scanners rely on good energy resolution to reduce the scattered radiation and also must deal with countrates, which are typically 5 times higher than in 2-D mode. To achieve good energy resolution, 3 factors must be considered: 1) choice of a scintillator with good intrinsic energy resolution, 2) choice of a crystal dimension which transmits a uniform amount of light to the PMT in order to avoid light loss along the length of the crystal and 3) choice of a crystal-to-PMT coupling which collects a uniform amount of light from all crystals. As PET scanners are being designed using new, faster scintillators for 3-D imaging, the appropriate trade-off between energy resolution and countrate capability must be found to give the best overall system performance. An example of a fully 3-D PET scanner is the Allegro (ADAC Laboratories), which uses GSO as the detector material. Given the right choice of material and design parameters, good quality, high contrast images can be obtained in 3-D in a relatively short time.     

Quantitation of small-animal (124)I activity distributions using a clinical PET/CT scanner.

Time-dependent PET imaging can be an important tool in the assessment of radiotracer performance in murine models. We have performed a quantitative analysis of PET images of (124)I, acquired on a clinical PET system using a small-animal phantom. We then compared the recovered activity concentrations with the known activity concentration in the phantom spheres. The recovery coefficients found from the phantom data were applied to in vivo (124)I anti-HER2/neu C6.5 diabody PET data and compared with necropsy biodistribution data from the same tumor-bearing immunodeficient mouse. METHODS: The small-animal phantom consisted of a 4 x 8 cm water-filled acrylic cylinder with hollow spheres filled with water ranging in volume from 0.0625 to 1.0 mL and activity concentration of 27 +/- 2 kBq/mL. The background activity concentrations varied from 0 to 0.05 to 0.10 of the spheres. Data were acquired at 0, 5, and 10 cm from the scanner longitudinal axis. Recovery coefficients were theoretically calculated for spheres of different volume, background-to-target concentrations, and distance from the scanner's longitudinal axis. The theoretic recovery coefficients were applied to the maximum sphere activity concentration measured from the PET images, thus obtaining a recovered activity concentration to be compared with the known activity concentration of the spheres. RESULTS: The mean recovered activity concentration for the phantom spheres was 25 +/- 2 kBq/mL. The (124)I diabody PET image of a mouse with a tumor xenograft was then analyzed using the techniques described. The tumor percentage injected dose per gram estimated from the murine PET image (4.8 +/- 0.4) compared well with those obtained from necropsy studies (5.1). CONCLUSION: This study indicates the feasibility of performing quantitative imaging on murine (124)I antibody fragment PET images using a large-bore clinical scanner, which enables high-throughput studies to evaluate the performance of PET tracers in a timely and cost-effective manner by imaging multiple animals simultaneously. Tracers deemed promising by this screening method can then be further evaluated using traditional necropsy studies. Our group is currently conducting time-dependent (124)I diabody PET and necropsy comparative studies with larger numbers of mice.     

From PET detectors to PET scanners

This review describes the properties of available and emerging radiation detector and read-out technologies and discusses how they may affect PET scanner performance. After a general introduction, there is a section in which the physical properties of several different detector scintillators are compared. This is followed by a discussion of recent advances in read-out electronics. Finally, the physical performance of the several commercial PET scanners is summarized.     

Noninvasive measurement of cardiovascular function in mice with high-temporal-resolution small-animal PET.

The aim of this study was to explore the feasibility of determining parameters of cardiovascular function in mice noninvasively by high-temporal-resolution imaging with a dedicated small-animal PET system. METHODS: Twenty-five anesthetized mice (28.8 +/- 4.6 g) were injected via an intravenous catheter with a 30-microL bolus of (18)F-FDG (8-44 MBq). The first 9 s of data were reconstructed into 30 frames of 0.3 s using filtered backprojection. The time-activity curve derived from a left ventricle volume of interest was corrected for tracer recirculation and partial volume. Cardiac output was calculated by the Stewart-Hamilton method, in which cardiac output is total injected activity divided by the area under the left ventricle time-activity curve. Cardiac output divided by body weight was defined as cardiac index; cardiac output divided by heart rate yielded the stroke volume. In 5 mice, measurements were repeated 2-4 times to assess reproducibility. In 4 mice, the hemodynamic response to dobutamine was examined by measuring heart rate, cardiac output, and stroke volume. RESULTS: The cardiac output averaged 20.4 +/- 3.4 mL/min; in the repeated measurements, the parameter displayed a mean percentage SD per mouse of 10% +/- 6%. The cardiac index averaged 0.73 +/- 0.19 mL/min/g and the stroke volume 45.0 +/- 6.9 microL, and both correlated with heart rate (r = 0.53, P = 0.007, and r = 0.49, P = 0.01, respectively). During dobutamine stress, heart rate increased from 423 +/- 50 to 603 +/- 30 beats/min (P = 0.002) and cardiac output increased from 18.5 +/- 1.9 to 32.0 +/- 4.2 mL/min (P = 0.008). CONCLUSION: Parameters of cardiovascular function can be measured in mice noninvasively by radionuclide angiography using high-temporal-resolution small-animal PET. Measured values of cardiac output and stroke volume are reproducible and comparable to those obtained with MRI. The approach permits the monitoring of changes in cardiovascular function in response to pharmacologic intervention.     

Performance evaluation of the 32-module quadHIDAC small-animal PET scanner.

The 32-module quadHIDAC is a commercial, high-resolution animal PET scanner, based on gas multiwire proportional chambers. METHODS: Several scanner parameters that characterize the performance of the system were evaluated in this study, such as spatial resolution, absolute sensitivity, scatter, and count rate performance. The spatial resolution has been determined with filtered back-projected images of a point source. A line source, a mouse phantom, and a rat phantom have been used to characterize the count rate performance. The scatter fraction and photon absorption have been measured with a mouse scatter phantom. The absolute sensitivity has been determined using a line source with aluminum shields of different thickness. RESULTS: Spatial resolution (full width at half maximum) offers values of 1.08, 1.08, and 1.04 mm in the radial, tangential, and axial directions, respectively. The maximum count rate is 370 kcps for a line source of 19 MBq activity. Registration of scattered coincidences is caused primarily by photons scattering in the large coincidence detectors. For a mouse-sized object, only 5% of the measured coincidences scatter inside the animal, whereas 32% of the coincidences scatter inside the detectors. Photon attenuation within a mouse phantom was 22%. After scatter corrections, the absolute sensitivity of the system is 15.2 cps/kBq for a point source and 13.7 cps/kBq for a 7.8-cm-long line source. The peak noise equivalent count rates are 67 kcps@209 kBq/mL for the mouse phantom and 52 kcps@96 kBq/mL for the rat phantom. Finally, a comparison has been made with the microPET R4, a commercial scintillation crystal-based PET camera. CONCLUSION: The results confirm that the quadHIDAC PET scanner, with its large cylindric field of view (165-mm diameter, 280-mm axial length), is particularly suitable for imaging small animals such as mice or rats.     

18F-Fallypride的自动化合成与小动物PET显像

目的 研究高效、简单的自动化合成多巴胺D2受体显像剂(S)-(-)-N-(1-烯丙基吡咯烷-2-氨基甲基)-5-(3-18F)-2,3-二甲氧基苯甲酰胺(18F-Fallypride)的方法,并用小动物PET观察其在小鼠活体内的生物分布.方法 采用国产氟标记多功能模块控制整个过程,18F-在乙腈溶液中与前体(s)-(-)-N-(1-烯丙基吡咯烷-2-氨基甲基)-5-(3-磺酰基)-2,3-二甲氧基苯甲酰胺(OTSF)直接反应生成18F-Fallypride,混合物装柱,产品被C18柱吸附,用水冲洗柱,用少量乙醇淋出,加生理盐水稀释.ICR小鼠给药后经小动物PET活体显像.结果 18F-Fallypride放化产率为40.7%(已校正),合成时间为40 min,无需高效液相色谱(HPLC)法分离,放化纯＞95%.注射18F-Fallypride后ICR小鼠经小动物PET显像,脑内纹状体区域摄取最高,且双侧放射性浓聚对称,清除较慢.结论 18F-Fallypride自动化合成速度快,效率高.18F-Fallypride适于多巴胺D2受体显像.     

Multimodality imaging of tumor xenografts and metastases in mice with combined small-animal PET, small-animal CT, and bioluminescence imaging.

Recent developments have established molecular imaging of mouse models with small-animal PET and bioluminescence imaging (BLI) as an important tool in cancer research. One of the disadvantages of these imaging modalities is the lack of anatomic information. We combined small-animal PET and BLI technology with small-animal CT to obtain fusion images with both molecular and anatomic information. METHODS: We used small-animal PET/CT and BLI to detect xenografts of different cell lines and metastases of a melanoma cell line (A375M-3F) that had been transduced with a lentiviral vector containing a trimodality imaging reporter gene encoding a fusion protein with Renilla luciferase, monomeric red fluorescent protein, and a mutant herpes simplex virus type 1 thymidine kinase. RESULTS: Validation studies in mouse xenograft models showed a good coregistration of images from both PET and CT. Melanoma metastases were detected by 18F-FDG PET, 9-[4-(18)F-fluoro-3-(hydroxymethyl)butyl]guanine (18F-FHBG) PET, CT, and BLI and confirmed by ex vivo assays of Renilla luciferase and mutant thymidine kinase expression. 18F-FHBG PET/CT allowed detection and localization of lesions that were not seen on CT because of poor contrast resolution and were not seen on 18F-FDG PET because of higher background uptake relative to 18F-FHBG. CONCLUSION: The combination of 18F-FHBG PET, small-animal CT, and BLI allows a sensitive and improved quantification of tumor burden in mice. This technique is potentially useful for the study of the biologic determinants of metastasis and for the evaluation of novel cancer treatments.     

Multicenter comparison of calibration and cross calibration of PET scanners.

The purpose of this study was to compare the calibration of PET scanners and their cross calibration to peripheral devices in a multicenter study. METHODS: Twenty-three dedicated PET scanners were investigated, applying standardized protocols. To ensure exact determination of the activity used, dose calibrators were checked using (68)Ge standards. RESULTS: Nine of 19 and 11 of 20 scanners displayed an error of <5% in 3-dimensional and 2-dimensional acquisition modes, respectively. Four and 5 scanners displayed an error of 10% in 3-dimensional and 2-dimensional modes, respectively. All other scanners yielded errors of 5% to <10%. Because of hardware and software problems, the measurements performed on 1 scanner could not be adequately analyzed. CONCLUSION: An investigation of calibration is mandatory. Especially for quantitative analyses in clinical multicenter trials, identification of potentially miscalibrated scanners is necessary.     

Performance evaluation of the GE healthcare eXplore VISTA dual-ring small-animal PET scanner.

We evaluated the performance characteristics of the eXplore VISTA dual-ring small-animal PET scanner, a stationary, ring-type, depth-of-interaction (DOI) correcting system designed to simultaneously maximize sensitivity, resolution, and resolution uniformity over a field of view sufficient to image rodent-sized animals. METHODS: We measured the intrinsic spatial resolution response of the VISTA detector modules, spatial and volume resolution throughout a representative portion of the field of view, and imaged several common resolution phantoms to provide a qualitative picture of resolution performance. We obtained an axial sensitivity profile and measured central point source sensitivity, scatter fractions and noise equivalent count (NEC) rates for rat- and mouse-sized objects using different energy windows, and count rate linearity. In addition, we measured the energy and timing resolution of both of the crystal layers (cerium-doped gadolinium orthosilicate and cerium-doped lutetium-yttrium orthosilicate) that give VISTA machines a DOI compensation capability. We examined the effectiveness of this DOI compensation by comparing spatial resolution measurements with and without the DOI correction enabled. Finally, several animal studies were included to illustrate system performance in the field. RESULTS: Spatial and volume resolutions averaged approximately 1.4 mm and 2.9 mm(3), respectively (with 3-dimensional Fourier rebinning and 2-dimensional filtered backprojection image reconstructions and an energy window of 250-700 keV), along the central axis of the scanner, and the spatial resolution was better than 1.7 mm and 2.1 mm at 1 and 2 cm off the central axis, respectively. Central point source sensitivity measured approximately 4% with peak NEC rates of 126.8 kcps at 455 kBq/mL and 77.1 kcps at 141 kBq/mL for mouse- and rat-sized uniform, cylindric phantoms, respectively. The radial spatial resolution at 2.8 cm off axis with DOI compensation was 2.5 mm but degraded (by 56%) to 3.9 mm without DOI compensation (as would be the case with a geometrically identical scanner without DOI correction capability). CONCLUSION: These results indicate that the VISTA small-animal PET scanner is well suited to imaging rodent-sized animals. The combination of high spatial resolution, resolution uniformity, sensitivity, and count rate performance, made possible in part by the novel use of phoswich detector modules, confers significant technical advantages over machines with similar geometry but without DOI correction capability.     

Assessment of myocardial metabolism in diabetic rats using small-animal PET: a feasibility study.

This feasibility study was undertaken to determine whether kinetic modeling in conjunction with small-animal PET could noninvasively quantify alterations in myocardial perfusion and substrate metabolism in rats. METHODS: All small-animal PET was performed on either of 2 tomographs. Myocardial blood flow and substrate metabolism were measured in 10 male Zucker diabetic fatty rats (ZDF, fa/fa) and 10 lean littermates (Lean, Fa/+) using (15)O-water, 1-(11)C-glucose, 1-(11)C-acetate, and 1-(11)C-palmitate. Animals were 12.0 +/- 1.4-wk old. RESULTS: Consistent with a type 2 diabetic phenotype, the ZDF animals showed higher plasma hemoglobin A(1c), insulin, glucose, and free fatty acid (FFA) levels than their lean controls. Myocardial glucose uptake (mL/g/min) was not significantly different between the 2 groups. However, higher glucose plasma levels in the ZDF rats resulted in higher myocardial glucose utilization (nmol/g/min) (Lean, 629 +/- 785, vs. ZDF, 1,737 +/- 1,406; P = 0.06). Similarly, myocardial FFA uptake (mL/g/min) was not significantly different between the 2 groups, (Lean, 0.51 +/- 28, vs. ZDF, 0.72 +/- 0.19; P = not significant) However, due to higher FFA plasma levels, utilization and oxidation (nmol/g/min) were significantly higher in the ZDF group (Lean, 519 +/- 462, vs. ZDF, 1,623 +/- 712, P < .001; and Lean, 453 +/- 478, vs. ZDF, 1,636 +/- 730, P < .01). CONCLUSION: Noninvasive measurements of myocardial substrate metabolism in ZDF rats using small-animal PET are consistent with the expected early metabolic abnormalities that occur in this well-characterized model of type 2 diabetes mellitus. Thus, small-animal PET demonstrates significant promise in providing a means to link the myocardial metabolic abnormalities that occur in rat of disease with the human condition.     

Investigation of single, random, and true counts from natural radioactivity in LSO-based clinical PET

OBJECTIVE: Lutetium oxyorthosilicate (LSO) contains natural radioactivity that emits beta particles and three gamma photons simultaneously. These beta particles and gamma photons increase the single and random rates in a positron emission tomography (PET) system while a beta particle and gamma photon produced in the same decay of Lu-176 and detected by another detector can be beta-gamma coincidence true events. The purpose of this work is to measure the single, random, and true count rates due to the natural radioactivity in LSO and determine the optimum lower energy threshold level for an energy window in an LSO-based clinical PET. METHODS: First, we measured the energy spectra of these beta particles and gamma photons in LSO using a single crystal to obtain the basic data. Then, we measured single, random, and true count rates of an LSO-based clinical PET from the natural radioactivity as a function of the lower energy threshold. RESULTS: In the PET, single and random count rates due to the natural background activity were gradually decreased as the lower energy threshold level increased. The true count rates due to the beta-gamma coincidence were more than 10 kcps below a lower energy threshold of 250 keV. However, these true count rates due to the natural radioactivity in LSO can be decreased to less than 1 kcps at a lower energy threshold level set at more than 350 keV. CONCLUSION: With these considerations, in an LSO-based clinical PET, a lower energy threshold level set at above 350 keV is recommended.     

PET performance measurements for an LSO-based combined PET/CT scanner using the National Electrical Manufacturers Association NU 2-2001 standard.

Results of performance measurements for a lutetium oxyorthosilicate (LSO)-based PET/CT scanner using new National Electrical Manufacturers Association (NEMA) NU 2-2001 standards are reported. METHODS: Performance measurements following the NU 2-2001 standards were performed on an LSO-based PET/CT scanner. In addition, issues associated with the application of the NEMA standard to LSO-based tomographs in the presence of intrinsic radiation are discussed. RESULTS: We report on some difficulties experienced in following the suggested NEMA measurement techniques and describe alternative approaches. Measurements with the new standard (as compared with NU-1994) incorporate the effects of activity outside the scanner and facilitate measurements of the entire axial field of view. Realistic clinical conditions are also simulated in image quality measurements of a torso phantom. CONCLUSION: We find that, with appropriate modifications, NU 2-2001 can be successfully applied to LSO-based scanners.     

Performance evaluation of a high-sensitivity large-aperture small-animal PET scanner: ClairvivoPET

OBJECTIVE: In this study, we evaluated the performance of a newly commercialized small-animal positron emission tomography (PET) scanner, ClairvivoPET, which provides significant advantages in spatial resolution, sensitivity, and quantitative accuracy. METHODS: This scanner consists of depth of interaction detector modules with a large axial extent of 151 mm and an external (137)Cs source for attenuation correction. Physical performances, resolution, sensitivity, scatter fraction (SF), counting rate including noise equivalent count (NEC) rate, quantitative accuracy versus activity strength, and transmission accuracy, were measured and evaluated. Animal studies were also performed. RESULTS: Transaxial spatial resolution, measured with a capillary tube, was 1.54 mm at the center and 2.93 mm at a radial offset of 40 mm. The absolute sensitivity was 8.2% at the center, and SFs for mouse-and rat-sized phantoms were 10.7% and 24.2%, respectively. Peak NEC rates for mouse-and rat-sized uniform cylindrical phantoms were 328 kcps at 173 kBq/ml and 119 kcps at 49 kBq/ml, respectively. The quantitative stability of emission counts against activity strength was within 2% over 5 half-lives, ranging from 0.6 MBq to 30 MBq. Transmission measurement based on segmented attenuation correction allowed 6-min and 10-min scans for mouse-and rat-sized cylindrical phantoms, respectively. Rat imaging injected with (18)F-NaF resulted in visibility of fine bone structures, and mouse imaging injected with (18)F-D-fluoromethyl tyrosine demonstrated the feasibility of using this system to obtain simultaneous time activity curves from separate regions, such as for the heart and tumors. CONCLUSIONS: ClairvivoPET is well suited to quantitative imaging even with short scan times, and will provide a number of advantages in new drug development and for kinetic measurement in molecular imaging.     

In vivo quantitation of glucose metabolism in mice using small-animal PET and a microfluidic device.

The challenge of sampling blood from small animals has hampered the realization of quantitative small-animal PET. Difficulties associated with the conventional blood-sampling procedure need to be overcome to facilitate the full use of this technique in mice. METHODS: We developed an automated blood-sampling device on an integrated microfluidic platform to withdraw small blood samples from mice. We demonstrate the feasibility of performing quantitative small-animal PET studies using (18)F-FDG and input functions derived from the blood samples taken by the new device. (18)F-FDG kinetics in the mouse brain and myocardial tissues were analyzed. RESULTS: The studies showed that small ( approximately 220 nL) blood samples can be taken accurately in volume and precisely in time from the mouse without direct user intervention. The total blood loss in the animal was <0.5% of the body weight, and radiation exposure to the investigators was minimized. Good model fittings to the brain and the myocardial tissue time-activity curves were obtained when the input functions were derived from the 18 serial blood samples. The R(2) values of the curve fittings are >0.90 using a (18)F-FDG 3-compartment model and >0.99 for Patlak analysis. The (18)F-FDG rate constants K(1)(*), k(2)(*), k(3)(*), and k(4)(*), obtained for the 4 mouse brains, were comparable. The cerebral glucose metabolic rates obtained from 4 normoglycemic mice were 21.5 +/- 4.3 mumol/min/100 g (mean +/- SD) under the influence of 1.5% isoflurane. By generating the whole-body parametric images of K(FDG)(*) (mL/min/g), the uptake constant of (18)F-FDG, we obtained similar pixel values as those obtained from the conventional regional analysis using tissue time-activity curves. CONCLUSION: With an automated microfluidic blood-sampling device, our studies showed that quantitative small-animal PET can be performed in mice routinely, reliably, and safely in a small-animal PET facility.     

Comparison of 2-dimensional and 3-dimensional acquisition for 18F-FDG PET oncology studies performed on an LSO-based scanner.

Three-dimensional (3D) PET acquisition has the potential to reduce image noise but the advantage of 3D PET for studies outside the brain has not been well established. To compare the performance of 2-dimensional (2D) and 3D acquisition for whole-body (18)F-FDG applications, a series of patient studies were performed using a lutetium oxyorthosilicate (LSO)-based tomograph. METHODS: Comparative 2D and 3D images were acquired for 27 oncology patients using an LSO-based tomograph. Data acquisition (350-650 keV, 6 ns) started 99 +/- 12 min (mean +/- SD) after injection of 624 +/- 76 MBq (18)F-FDG. Bias caused by tracer redistribution and decay was eliminated by acquiring dynamic data over a single-bed position using a protocol that alternated between septa-in and septa-out modes (2D, 3D, 2D, 3D, 2D, 3D). Frames were combined to form 8 statistically independent sinograms: four 2D replicates (105 s) and four 3D replicates (90 s). The different frame durations in 2D and 3D compensated for the different number of overlapping bed positions required for an 85-cm whole-body study. Images were reconstructed with either 2D or fully 3D ordered-subsets expectation maximization (2 iterations and 8 subsets; 2D 6-mm gaussian, 3D 5- and 6-mm gaussian). Image target-to-background ratio was assessed by dividing the lesion maximum by the mean within a neighboring background region. Image noise was assessed by applying background regions of interest to the replicate images and calculating the within-patient coefficient of variation. RESULTS: The difference in target-to-background ratio between the 2D and 3D images, when they were filtered with 6-mm and 5-mm gaussian filters, respectively, was not highly statistically significant (P = 0.16). The mean ratio of 3D to 2D image values was 0.94 with 95% limits of agreement of 0.63-1.41. The within-patient coefficients of variation for the 2D and 3D images were 13% +/- 15% and 9% +/- 10%, respectively (P = 0.0005). CONCLUSION: Under conditions of matched target to-to-background ratios, the 3D mode was found to produce images with significantly less variability than the 2D mode. These data provide support for the use of 3D acquisition with LSO detectors to reduce scan times in whole-body (18)F-FDG applications.     

Microliter-ordered automatic blood sampling system for fully quantitative analysis of small-animal PET

Annals of Nuclear Medicine - The objective of the present study was to develop a fully automated blood sampling system for kinetic analysis in mice positron emission tomography (PET) studies....     

Spillover and partial-volume correction for image-derived input functions for small-animal 18F-FDG PET studies.

We present and validate a method to obtain an input function from dynamic image data and 0 or 1 blood sample for small-animal 18F-FDG PET studies. The method accounts for spillover and partial-volume effects via a physiologic model to yield a model-corrected input function (MCIF). METHODS: Image-derived input functions (IDIFs) from heart ventricles and myocardial time-activity curves were obtained from 14 Sprague-Dawley rats and 17 C57BL/6 mice. Each MCIF was expressed as a mathematic equation with 7 parameters, which were estimated simultaneously with the myocardial model parameters by fitting the IDIFs and myocardium curves to a dual-output compartment model. Zero or 1 late blood sample was used in the simultaneous estimation. MCIF was validated by comparison with input measured from blood samples. Validation included computing errors in the areas under the curves (AUCs) and in the 18F-FDG influx constant Ki in 3 types of tissue. RESULTS: For the rat data, the AUC error was 5.3% +/- 19.0% in the 0-sample MCIF and -2.3% +/- 14.8% in the 1-sample MCIF. When the MCIF was used to calculate the Ki of the myocardium, brain, and muscle, the overall errors were -6.3% +/- 27.0% in the 0-sample method (correlation coefficient r = 0.967) and 3.1% +/- 20.6% in the 1-sample method (r = 0.970). The t test failed to detect a significant difference (P > 0.05) in the Ki estimates from both the 0-sample and the 1-sample MCIF. For the mouse data, AUC errors were 4.3% +/- 25.5% in the 0-sample MCIF and -1.7% +/- 20.9% in the 1-sample MCIF. Ki errors averaged -8.0% +/- 27.6% for the 0-sample method (r = 0.955) and -2.8% +/- 22.7% for the 1-sample method (r = 0.971). The t test detected significant differences in the brain and muscle in the Ki for the 0-sample method but no significant differences with the 1-sample method. In both rat and mouse, 0-sample and 1-sample MCIFs both showed at least a 10-fold reduction in AUC and Ki errors compared with uncorrected IDIFs. CONCLUSION: MCIF provides a reliable, noninvasive estimate of the input function that can be used to accurately quantify the glucose metabolic rate in small-animal 18F-FDG PET studies.