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Bioluminescence imaging has been extensively applied to in vivo small animal imaging. Quantitative three-dimensional bioluminescent source information obtained by using bioluminescence tomography can directly and much more accurately reflect biological changes as opposed to planar bioluminescence imaging. Preliminary simulated and experimental reconstruction results demonstrate the feasibility and promise of bioluminescence tomography. However, the use of multiple approximations, particularly the diffusion approximation theory, affects the quality of in vivo small animal-based image reconstructions. In the development of new reconstruction algorithms, high-order approximation models of the radiative transfer equation and spectrally resolved data introduce new challenges to the reconstruction algorithm and speed. In this paper, an SP(3)-based (the third-order simplified spherical harmonics approximation) spectrally resolved reconstruction algorithm is proposed. The simple linear relationship between the unknown source distribution and the spectrally resolved data is established in this algorithm. A parallel version of this algorithm is realized, making BLT reconstruction feasible for the whole body of small animals especially for fine spatial domain discretization. In simulation validations, the proposed algorithm shows improved reconstruction quality compared with diffusion approximation-based methods when high absorption, superficial sources and detection modes are considered. In addition, comparisons between fine and coarse mesh-based BLT reconstructions show the effects of numerical errors in reconstruction image quality. Finally, BLT reconstructions using in vivo mouse experiments further demonstrate the potential and effectiveness of the SP(3)-based reconstruction algorithm.

PETbox is designed to be a low cost and easy to use bench top small animal PET scanner dedicated for high throughput quantitative pharmacokinetic and pharmacodynamic studies. To achieve this goal, the scanner is integrated with a complete animal management system that provides life support including reproducible positioning, temperature control, anesthesia, real-time monitoring of animal respiration and a pathogen barrier. This approach minimizes the overall cost and complexity of preclinical PET imaging and should enable non-imaging scientists to embrace the technology. The system uses two opposing detector heads, each one consisting of a pixilated BGO array coupled to two H8500 multi-channel photomultiplier tubes. The BGO crystals were segmented into 20 × 44 arrays with a pixel pitch of 2.2 mm and a total active area of 44 mm × 96.8 mm. Position and timing signals from the photomultiplier tube readout circuitry were connected to a field programmable gate array (FPGA) board with eight ADC channels, each running at 100MHz. Signal processing algorithms were developed for the FPGA to process received PET events and raw list-mode data were generated by the FPGA board and transferred to a host PC for storage. Basic system performance parameters were measured. The system has an average intrinsic spatial resolution of 1.72mm FWHM along detector long axis and 1.84mm FWHM along detector short axis. The coincidence timing resolution was measured to be 4.1ns FWHM. The average energy resolution of the crystals was 19.8% and the absolute sensitivity of the system was measured to be 3.8% at the center of the gantry. Initial imaging studies were also performed with live mice. A mouse tumor xenograft was imaged 1 hour after a 32uCi [18F]FDG injection for 20 minutes. 3D images were generated using a ML-EM method. Results demonstrate the capability and potential of the PETbox system for dedicated high throughput mouse studies such as biodistribution and organ uptake quantification.

PETbox, an integrated low-cost benchtop preclinical PET scanner dedicated to high throughput quantitative mouse studies is currently under development at the Crump Institute for Molecular Imaging, UCLA. The system employs two opposing flat panel BGO detector blocks on a static gantry and produces a limited number of projection angles around a central antero-posterior (AP) view. Iterative reconstruction based on a Maximum Likelihood and Expectation Maximization (ML-EM) algorithm was developed with incorporation of a probability matrix, which takes into account the detection probability and inter-crystal scattering. Point sources at different positions were simulated with the GATE software package and showed a peak sensitivity of 3.87% at a 150-650 keV energy window. When applying a sensitivity correction map, the image values of the reconstructed point sources at different positions are within a 5.3% standard deviation, indicating good quantification accuracy. The spatial resolution of point sources is largely uniform along the coronal direction across the field of view (FOV) with worse resolution along the direction orthogonal to the detector blocks, which is mainly due to the reduced spatial sampling in that direction. A voxelized digital mouse (Moby phantom) was also simulated and then iteratively reconstructed. Attenuation and non-uniform sensitivity corrections were applied. Quantification accuracy was evaluated with the reconstructed Moby data and two analytically simulated data sets. To a first approximation, reasonably good quantification accuracy was obtained for most important organs with the PETbox reconstructed image. This evaluation indicates that the integrated detector system design, reconstruction algorithm and attenuation correction work well, which is very important for quantitative pharmacokinetic and pharmacodynamic studies. In-vivo mouse studies were also acquired and reconstructed. The obtained images proved the capability of PETbox as a dedicated mouse scanner for both dynamic and static acquisitions.

PETBox is a new simplified bench top PET scanner dedicated for pre-clinical imaging of mice. It has only two facing detector heads in a static gantry. Using iterative methods, limited-angle reconstruction of 3D images is possible. The geometry of the PETBox is such that very oblique emission angles are detected traversing significant lengths of tissue, making attenuation correction necessary. To that effect, we have developed a method by which two orthogonal optical views are combined to create a 3-dimensional estimate of the subject. This estimate is used to produce attenuation correction data that significantly improve the quantitative accuracy of the reconstructed images. In this paper, we present the method and evaluate its accuracy.

The Inveon dedicated PET (DPET) scanner is the latest generation of preclinical PET systems devoted to high-resolution and high-sensitivity murine model imaging. In this study, we report on its performance based on the National Electrical Manufacturers Association (NEMA) NU-4 standards.The Inveon DPET consists of 64 lutetium oxyorthosilicate block detectors arranged in 4 contiguous rings, with a 16.1-cm ring diameter and a 12.7-cm axial length. Each detector block consists of a 20 x 20 lutetium oxyorthosilicate crystal array of 1.51 x 1.51 x 10.0 mm elements. The scintillation light is transmitted to position-sensitive photomultiplier tubes via optical light guides. Energy resolution, spatial resolution, sensitivity, scatter fraction, and counting-rate performance were evaluated. The NEMA NU-4 image-quality phantom and a healthy mouse injected with (18)F-FDG and (18)F(-) were scanned to evaluate the imaging capability of the Inveon DPET.The energy resolution at 511 keV was 14.6% on average for the entire system. In-plane radial and tangential resolutions reconstructed with Fourier rebinning and filtered backprojection algorithms were below 1.8-mm full width at half maximum (FWHM) at the center of the field of view. The radial and tangential resolution remained under 2.0 mm, and the axial resolution remained under 2.5-mm FWHM within the central 4-cm diameter of the field of view. The absolute sensitivity of the system was 9.3% for an energy window of 250-625 keV and a timing window of 3.432 ns. At a 350- to 625-keV energy window and a 3.432-ns timing window, the peak noise equivalent counting rate was 1,670 kcps at 130 MBq for the mouse-sized phantom and 590 kcps at 110 MBq for the rat-sized phantom. The scatter fractions at the same acquisition settings were 7.8% and 17.2% for the mouse- and rat-sized phantoms, respectively. The mouse image-quality phantom results demonstrate that for typical mouse acquisitions, the image quality correlates well with the measured performance parameters in terms of image uniformity, recovery coefficients, attenuation, and scatter corrections.The Inveon system, compared with previous generations of preclinical PET systems from the same manufacturer, shows significantly improved energy resolution, sensitivity, axial coverage, and counting-rate capabilities. The performance of the Inveon is suitable for successful murine model imaging experiments.

Two classes of bulk high-Z polymer composites were prepared, which exhibit scintillation properties for gamma-radiation detection.

Small animal PET imaging imposes high performance requirements on image resolution and system sensitivity. Scanners with larger solid angle, achieved by using smaller crystal ring diameter and longer axial field-of-view (FOV), have higher absolute sensitivity. The Inveon dedicated PET (DPET) system, the latest generation of commercial tomographs from Siemens Preclinical Solutions, Inc., is such a high sensitivity scanner. Its crystal ring diameter and axial extent is 16.1 cm and 12.7 cm respectively, which give a solid angle coverage of 62%. However, this geometry also accentuates inter-crystal penetration, especially in the axial direction and causes axial blurring. Axial and radial blurring recovery is crucial for high resolution small animal PET imaging. System response modeling in combination with iterative reconstruction algorithms like Maximum a posteriori reconstruction (MAP) can be used to recover the resolution loss. Blurring in both radial and axial directions were simulated in GATE with a planar strip of 18F source placed inside the Inveon scanner. Detector response for each possible line of response (LOR) was calculated and can be incorporated into iterative reconstruction algorithms. As the entrance ring difference (δ) increased, the recorded coincidences tended to shift to a larger ring difference. As the entrance radial offset (u) increased, the recorded coincidences tended to shift to a smaller radial offset. The blurring effect got larger as δ and/or u increased. A real 18F plane source printed on carbon paper was also imaged and compared with the simulation data as a validation. The coincidence counts recorded for each ring difference showed a very good agreement between simulation and experiment except for very large oblique angles. This discrepancy should be improved with the inclusion of the scanner end shields in future simulations.

The development of a prototype dual-modality optical and PET (OPET) small animal imaging tomograph is underway in the Crump Institute for Molecular Imaging at the University of California Los Angeles. OPET consists of a single ring of six detector modules with a diameter of 3.5 cm. Each detector has an 8times8 array of optically isolated BGO scintillators which are coupled to multichannel photomultiplier tubes and open on the front end. The system operates in either PET or optical mode and reconstructs the data sets as 3D tomograms. The detectors are capable of detecting both annihilation events (511 keV) from PET tracers as well as single photon events (SPEs) (2-3 eV) from bioluminescence. Detector channels are readout using a custom multiplex readout scheme and then filtered in analog circuitry using either a gamma-ray or SPE specific filter. Shaped pulses are sent to a digital signal processing (DSP) unit for event processing. The DSP unit has 100 MHz analog-to-digital converters on the front-end which send digitized samples to field programmable gate arrays which are programmed via user configurable algorithms to process PET coincidence events or bioluminescence SPEs. Information determined using DSP includes: event timing, energy determination-discrimination, position determination-lookup, and coincidence processing. Coincidence or SPE events are recorded to an external disk and minimal post processing is required prior to image reconstruction. Initial imaging results from a phantom filled with 18FDG solution and an optical pattern placed on the front end of a detector module in the vicinity of a SPE source are shown.

In Bioluminescence Tomography (BLT), a priori information is necessary to obtain unique BLT reconstruction. When using the explored a priori information, such as complex heterogeneous model and multispectral measurements, the reconstruction speed especially in whole-body small animal molecular imaging becomes slow. Because of the flexibility of the finite element method (FEM), reconstruction algorithms based on it are extensively developed. Fully 3D BLT reconstruction though is challenging. Although the computer hardware technology is rapidly developed, BLT reconstruction time becomes long, even impossible in a single PC when fine discretization is used to obtain the desirable spatial resolution. In this paper, a fully parallel 3D finite element reconstruction algorithm is proposed for spectrally-resolved BLT reconstruction. In this algorithm, anatomical information and multispectral measurements can be easily used to improve BLT reconstruction. Specifically, for parallelization, the reconstruction domain is partitioned into several subdomains corresponding to the number of nodes of the cluster. Establishment of a parallel linear relationship between the measured data and the unknown source distribution and optimization is performed to improve the reconstruction speed. In a numerical reconstruction, the effectiveness and potential is verified with a large-volume homogeneous phantom.

Whole-body optical molecular imaging is rapidly developing for preclinical research. It is essential and necessary to develop novel simulation methods of light propagation for optical imaging, especially when a priori knowledge, large-volume domain and wide-range optical properties need to be considered in the reconstruction algorithm. In this paper, we develop a three dimensional parallel adaptive finite element method with simplified spherical harmonics (SP N ) approximation to simulate photon propagation in large-volume heterogeneous tissues. Simulation speed is significantly improved by a posteriori parallel adaptive mesh refinement and dynamic mesh repartitioning. Compared with the diffusion equation, SP N method shows improved performance and the necessity of high-order approximation in heterogeneous domains. Optimal solver selection and time-costing analysis in real mouse geometry further improve the performance of the proposed algorithm.

This work proposes a novel method for quantitative imaging of radioactivity on microfluidic chips by using visible light emission from Cerenkov radiation. Cerenkov radiation is generated when charged particles travel through an optically transparent material with a velocity greater than that of light in that material. It has been observed at UCLA that microfluidic chips used for 18F-related radio-synthesis studies have shown unidentified visible light emissions. In this study, the origin of the light was investigated and its feasibility as a quantitative imaging source was tested.

Dual-energy x-ray computed tomography (DECT) has proved its potential in eliminating beam-hardening artifacts from reconstructed images. The method typically involves two successive scans with different x-ray tube voltage settings. This work proposes a new approach to dual-energy through x-ray beam filtration that requires only one scan and a single tube voltage setting.

Preclinical small animal imaging is an important tool at the disposition of biological researchers. While the range of studies performed by non-invasive preclinical imaging is greatly varied, high sensitivity is of key importance in any biological experiment with molecular imaging probes. The technologies that are used to achieve high system sensitivity mostly focus on the use of large solid angles and dense scintillator materials. In this work, we investigate and discuss different preclinical Positron Emission Tomography system designs and the effects of these designs on the overall sensitivity. We focus our investigations in hypothetical system geometries and scintillator materials and perform Monte Carlo simulations. The results indicate that preclinical PET systems based on detector materials that have minimal intrinsic background and higher effective atomic number, might offer performance advantages for situations where the weakest signal possible needs to be detected.

Reporter genes can provide a way of noninvasively assessing gene activity in vivo. However, current reporter gene strategies may be limited by the immunogenicity of foreign reporter proteins, endogenous expression, or unwanted biological activity. We have developed a reporter gene based on carcinoembryonic antigen (CEA), a human protein with limited normal tissue expression.To construct a CEA reporter gene for PET, a CEA minigene (N-A3) was fused to the extracellular and transmembrane domains of the human Fc gamma RIIb receptor. The NA3-Fc gamma RIIb recombinant gene, driven by a CMV promoter, was transfected in Jurkat (human T cell leukemia) cells. Expression was analyzed by flow cytometry, immunohistochemistry (IHC), and microPET imaging.Flow cytometry identified Jurkat clones stably expressing NA3-Fc gamma RIIb at low, medium, and high levels. High and medium NA3-Fc gamma RIIb expression could also be detected by Western blot. Reporter gene positive and negative Jurkat cells were used to establish xenografts in athymic mice. IHC showed staining of the tumor with high reporter gene expression; medium and low N-A3 expression was not detected. MicroPET imaging, using an anti-CEA (124)I-labeled single-chain Fv-Fc antibody fragment, demonstrated that only high N-A3 expression could be detected. Specific accumulation of activity was visualized at the N-A3 positive tumor as early as 4 h. MicroPET image quantitation showed tumor activity of 1.8 +/- 0.2, 15.2 +/- 1.3, and 4.6 +/- 1.2 percent injected dose per gram (%ID/g) at 4, 20, and 48 h, respectively. Biodistribution at 48 h demonstrated tumor uptake of 4.8 +/- 0.8%ID/g.The CEA N-A3 minigene has the potential to be used as a reporter gene for imaging cells in vivo.

It is unusual for a relatively mature field such as nuclear medicine to see an innovation akin to a new imaging modality. Although in its preliminary stages, the work by Tai et al. ( [1][1] ) on pages [471–479][2] of this issue of The Journal of Nuclear Medicine describes a novel concept that

A BGO based small animal PET scanner dedicated for imaging small rodent was simulated by GATE. The virtual PET scanner had the same ring diameter, axial field of view (FOV) and crystal arrangement as the LSO based Siemens Inveon PET system, but was simulated with varied crystal lengths. The simulated system sensitivity was 11.6%, 19.3% and 25.5% for 10, 15 and 20 mm BGO at an energy window of 250-750 keV. The spatial resolution was measured at radial offsets of 0, 15 and 28 mm from the center of the FOV for the three crystal thicknesses. The FWHM in the radial and tangential directions was below 2.5 mm and 1.8 mm respectively for all three crystal thicknesses, up to a 30 mm diameter FOV. Scatter fraction and count rate performance were measured using a line source inserted in a water cylinder 70 mm long and 25 mm diameter for the 20 mm BGO system. The maximum NECR was 0.99 Mcps at 24 MBq and the phantom scatter fraction was 4.5% with an energy window of 250-750 keV and a timing window of 12 ns. The BGO based PET scanner was compared with the Inveon and the microPET Focus 220 systems. With the same crystal thickness, the BGO scanner had higher system sensitivity than the LSO and further improvement in sensitivity can be achieved by using thicker crystals without sacrificing much spatial resolution. Both radial and tangential resolutions were comparable to the LSO based systems. At the evaluated energy window of 250-750 keV, the phantom scatter fraction was similar to the Inveon system, while the crystal scatter fraction was about 10% lower. The maximum NECR was lower than Inveon and was achieved at a lower activity level. Simulation of the BGO PET scanner proved the design concept of a high sensitivity small animal PET scanner, with comparable spatial resolution, similar phantom scatter fraction, and acceptable count rate performance.

We have constructed a three-dimensional (3D) whole body mouse atlas from coregistered x-ray CT and cryosection data of a normal nude male mouse. High quality PET, x-ray CT and cryosection images were acquired post mortem from a single mouse placed in a stereotactic frame with fiducial markers visible in all three modalities. The image data were coregistered to a common coordinate system using the fiducials and resampled to an isotropic 0.1 mm voxel size. Using interactive editing tools we segmented and labelled whole brain, cerebrum, cerebellum, olfactory bulbs, striatum, medulla, masseter muscles, eyes, lachrymal glands, heart, lungs, liver, stomach, spleen, pancreas, adrenal glands, kidneys, testes, bladder, skeleton and skin surface. The final atlas consists of the 3D volume, in which the voxels are labelled to define the anatomical structures listed above, with coregistered PET, x-ray CT and cryosection images. To illustrate use of the atlas we include simulations of 3D bioluminescence and PET image reconstruction. Optical scatter and absorption values are assigned to each organ to simulate realistic photon transport within the animal for bioluminescence imaging. Similarly, 511 keV photon attenuation values are assigned to each structure in the atlas to simulate realistic photon attenuation in PET. The Digimouse atlas and data are available at http://neuroimage.usc.edu/Digimouse.html.

A new device has been developed that allows imaging of charged particle emitting probes in a microfluidic circuit using a position sensitive avalanche photodiode (PSAPD). Microfluidic chips are an emerging technology that have been used in applications such as the synthesis of new molecular probes and incubation of live cell cultures in microfluidic chambers. This new device works by direct contact of the PSAPD detector with the substrate layer of a microfluidic chip and provides 2- dimensional images of the distribution of beta emitting probes over time. The spatial resolution of the PSAPD detector for beta particle imaging was evaluated with 18F line sources. The FWHM was measured to be 0.4 mm at the center of the field of view. The sensitivity of the device for 18F beta particle detection was evaluated as a function of substrate thickness between the source and detector surface. One of the applications of this new detector system is for the imaging of live cell cultures in a microfluidic environment. Preliminary images have also been acquired showing the uptake of [18F]fluorodeoxyglucose ([18F]FDG) probes in live cells incubated in a microfluidic chamber. Images of [18F]FDG uptake were acquired with less than 200 incubated cells over a period of 3 days. An increase in cellular [18F]FDG uptake was also observed by increasing the time period between cell feeding and [18F]FDG incubation in the cell chamber.

Spatial resolution and noise are strongly related properties and therefore meaningful evaluations of imaging systems and reconstruction algorithms should always include estimates of both. We have evaluated the performance of a statistical maximum a posteriori probability (MAP) reconstruction algorithm in terms of contrast recovery and signal to noise ratio (SNR) in comparison to filtered-backprojection (FBP) on a microPET Focus220 scanner. Printed 18F point sources sitting on uniform backgrounds were used as contrast recovery phantoms to evaluate the MAP and FBP performance. With this inkjet printed source method, the contrast recovery phantom was created with well controlled contrast levels and no finite boundaries were introduced between signal and background. The activities and contrast levels we used in our experiment were close to tumor uptakes and tumor to background contrasts in realistic mouse scans. Contrast evaluation demonstrated that at any given noise level, MAP reconstruction performance was better than FBP. To evaluate the effects of scatter in the two image reconstruction algorithms, analytical scatter correction was applied on a small animal mouse phantom containing water and air filled cavities and then reconstructed with both FBP and MAP algorithm. Residual activity in non-radioactive regions after scatter correction was proved to be similar for MAP and FBP reconstructions.

Microfluidic chips are an emerging technology that facilitates the study of molecular processes in nano-liter levels in a finely controlled manner. A prototype imaging system capable of detecting and quantifying very small amounts of beta particles in a microfluidic chip, utilizing a scintillator, an optical lens, and a charge coupled device (CCD), was developed and proof of concept was previously demonstrated [1]. In this study, we optimized the system design parameters, such as CCD binning and types of scintillators, and evaluated the system performance for spatial resolution and minimum detectable activity. Pixel binning of the CCD during readout process improved the signal-to-noise ratio with no spatial resolution degradation in beta particle imaging of 18F, up to a binning of 3times3 in our study, which was equivalent to 44 mum times 44 mum pixels in an object plane with a magnification of 0.5. The full width at half maximum (FWHM) of line sources with a finite width of 115 mum were measured to be 493 mum with a plastic scintillator and 289 mum with a CsI(Tl) scintillator. The minimum detectable activities were measured to be 360 pCi/mm2 with a plastic scintillator and 40 pCi/mm2 with a CsI(Tl) scintillator for a 5-min acquisition.

The development of a prototype dual-modality optical and PET (OPET) small animal imaging tomograph is underway in the Crump Institute for Molecular Imaging at the University of California Los Angeles. OPET consists of a single ring of six detector modules with a diameter of 3.5 cm. Each detector has an 8 times 8 array of optically isolated BGO scintillators which are coupled to multichannel photomultiplier tubes and open on the front end. The system operates in either PET or optical mode and reconstructs the data sets as 3D tomograms. The detectors are capable of detecting both annihilation events (511 keV) from PET tracers as well as single photon events (SPEs) (2-3 eV) from bioluminescence. Detector channels are readout using a custom multiplex readout scheme and then filtered in analog circuitry using either a gamma-ray or SPE specific filter. Shaped pulses are sent to a digital signal processing (DSP) unit for event processing. The DSP unit has 100 MHz analog-to-digital converters on the front-end which send digitized samples to field programmable gate arrays which are programmed via user configurable algorithms to process PET coincidence events or bioluminescence SPEs. Information determined using DSP includes: event timing, energy determination-discrimination, position determination-lookup, and coincidence processing. Coincidence or SPE events are recorded to an external disk and minimal post processing is required prior to image reconstruction. Initial results from a two-detector version of OPET are shown for a PET phantom image reconstruction as well as for an optical mode acquisition. Projection images of an optical pattern placed on the front end of the detector module in the vicinity of a SPE source and positron emitting source are shown. Current work includes assembly of the full ring system and tomographic reconstruction of an optical source.

Novel molecular imaging applications increasingly involve studies where very low amount of activity is present. This operation point can be challenging in terms of image quality especially when the intrinsic detector activity from scintillators such as LSO is considered. LSO crystals contain 176Lu which emits beta- particles followed by gamma photons, resulting in the detection of true and random events. This background activity has been shown to contribute a significant percentage of the total detected true events, when a very weak activity distribution is imaged. This can affect the weakest signal that can be detected by an LSO PET scanner which determines its "detection limit" and is evaluated by the parameter of minimum detectable activity or MDA. A series of acquisitions was performed in order to study the effect of the energy window to the intrinsic true and randoms rate. The experiments were also simulated with GATE, and the results were validated by comparing them with the experiment. Four square regions each with a unique signal to background activity concentration ratio were used. The background activity level was held constant between the different regions, while the activity of the point sources varied in 4 selected levels. The signal to background ratio was calculated separately for each region. The energy spectrum of the intrinsic background activity and its contribution to the total energy spectrum both for singles and coincidences was estimated through the GATE simulation. We histogrammed both the measured and simulated data on various time frames, which we reconstructed using the filtered backprojection algorithm. Every image was quantified based on the Currie equation in order to associate an MDA value for each of the 4 point sources as a function of the frame length. In the case of the microPET Focus 220 a total amount of 4nCi/mm3 can be reliably detected for frame lengths longer than 5 min and at regions where the signal to background activity concentration ratio is higher than 4. In the case of higher contrast regions detection can be achieved even for frame lengths down to 1 min.

Purpose: To examine the effect of different scintillator surface treatments (BGO crystals) on the fraction of scintillation photons that exit the crystal and reach the photodetector (SiPM). Methods: Positron Emission Tomography is based on the detection of light that exits scintillator crystals, after annihilation photons deposit energy inside these crystals. A considerable fraction of the scintillation light gets trapped or absorbed after going through multiple internal reflections on the interfaces surrounding the crystals. BGO scintillator crystals generate considerably less scintillation light than crystals made of LSO and its variants. Therefore, it is crucial that the small amount of light produced by BGO exits towards the light detector. The surface treatment of scintillator crystals is among the factors affecting the ability of scintillation light to reach the detectors. In this study, we analyze the effect of different crystal surface treatments on the fraction of scintillation light that is detected by the solid state photodetector (SiPM), once energy is deposited inside a BGO crystal. Simulations were performed by a Monte Carlo based software named GATE, and validated by measurements from individual BGO crystals coupled to Philips digital-SiPM sensor (DPC-3200). Results: The results showed an increment in light collection of about 4 percent when only the exit face of the BGO crystal, is unpolished; compared to when all the faces are polished. However, leaving several faces unpolished caused a reduction of at least 10 percent of light output when the interaction occurs as far from the exit face of the crystal as possible compared to when it occurs very close to the exit face. Conclusion: This work demonstrates the advantages on light collection from leaving unpolished the exit face of BGO crystals. The configuration with best light output will be used to obtain flood images from BGO crystal arrays coupled to SiPM sensors.

A new device is being developed that will allow imaging of the distribution of charged particles in microfluidic circuits, using position sensitive avalanche photodiodes (PSAPD). Microfluidic chips are an emerging technology that will facilitate the synthesis and study of new molecular imaging probes. These poly-dimethylsiloxane (PDMS) chips are low in cost to custom design and produce, and their development/prototyping cycles are relatively short. They can contain a variety of microcircuitry and microwells for manipulating nanoliter volumes of solutions. The new imaging device will be created by direct contact of a PSAPD detector with the fluidic layer of a PDMS chip and will provide 2-dimensional images of the distribution of beta emitting radiolabeled probes on the chip. Furthermore, the new device will also be capable of quantifying small amounts of these radiolabeled probes over time. The PSAPD will be used for the direct detection of positrons and other charged particles. Preliminary studies were performed in our laboratory to test the feasibility of detecting small amounts of radioactive positron emitting fluorodeoxyglucose (FDG) in a prototype device. Results have shown that sensitivities as low as 56 plusmn 0.1 pCi in a 4 mm2 ROI (14 pCi/mm2) and line pair spatial resolution of 0.5 mm can be achieved.

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.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.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).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.

The dual modality imaging system for small animal optical and positron emission tomography imaging (OPET) is currently being developed at the Crump Institute for Molecular Imaging. The OPET system is capable of detecting and simultaneously imaging both high-energy gamma-rays from PET tracers and single photons in the optical wavelength from bioluminescence. The PET performance characteristics for a two-detector prototype of the OPET system are described here. Each detector consists of an 8 /spl times/ 8 array of GSO crystals cut to different lengths providing a detector surface with a circular profile and a 3.4 cm ring diameter. The crystals were inserted into a laser-cut grid assembly constructed from 0.067 mm thick reflector film. Crystals were coupled to a 64-channel photomultiplier tube (PMT) and a charge-division readout circuit was implemented to decode the signals from the 64 outputs of the PMT into event location data. Flood images were taken to obtain look-up tables as well as energy spectra for each crystal. The timing resolution was determined to be 6.6 nsec. A 0.3 mm Na-22 point source was stepped across the field of view (FOV) and the intrinsic detector spatial resolution was 1.23 mm FWHM. The estimated peak absolute system sensitivity at the center of FOV for the two detector system was 0.33%. Data from a line phantom was acquired and reconstructed with an expectation maximization 3D reconstruction algorithm.

GEANT4 application for tomographic emission (GATE) is a toolkit for the simulation of full-fledged PET and SPECT systems. It allows the user to model realistic nuclear medicine experiments with an easy to use, yet powerful, scripting language. This paper describes a platform independent distributed computing approach for running GATE experiments on a cluster of computers in order to reduce the overall computing time by automatically generating fully resolved, non-parameterized macros accompanied with an on the fly generated cluster submit file. It was shown that GATE simulations with low data output rates such as low sensitivity SPECT simulations with voxelized phantoms scale very well and that an optimum can be derived for simulations that generate high data output rates, such as non-voxelized, high sensitivity small animal PET experiments

The purpose of the study was to calculate dynamic internal dose distributions from FDG-PET imaging procedures using a realistic mouse phantom and the Monte Carlo method. A realistic mouse phantom was used for simulations and consisted of a matrix with a voxel size of (400 /spl mu/m)/sup 3/ and tissue compositions taken from human counterparts. The GATE software was used to perform all simulations. Dose calculations were performed using discretized, image-based FDG biodistributions from dynamic acquisitions. For each biodistribution - considered constant for some time interval - dose in the phantom was calculated by tracking a sufficient number (10/sup 8/) of primary emitted particles (e+). Dose values were then scaled to take into account radioactive decay and dose integration with time. Dose averages for most organs were between 5 and 15 mGy per MBq of injected activity, with a whole body dose average of 11 mGy/MBq. The heart received about 75 mGy/MBq and for the unvoided bladder scenario, the dose to the bladder wall ranged from 100 to 1000 mGy/MBq, with an average close to 500 mGy/MBq. For a study using 200 /spl mu/Cl of injected tracer, this would translate into 550 and 3600 mGy delivered to the heart and bladder wall, respectively. The biological response and its eventual effect on investigations is unknown although the bladder wall is usually not considered a target tissue. Voiding the bladder at least partially can reduce the total absorbed dose by half.

Due to its long radiological half life, 124I can be used for investigation of lengthy biological processes. However, it is not an ideal PET isotope because it has poor positron yield and half of the positrons are emitted in cascade with 603 keV gammas. This decay spectrum results in coincidences between gammas and annihilation photons (dirty coincidences) leading to both inaccurate quantitation and overall reduction in the image quality. It has been shown that noise equivalent counts (NEC) have a direct link to signal to noise ratio of the reconstructed images. The purpose of this work was to investigate the effect of varying the energy window of the digitizer on the NEC measured from the non-pure positron emitter 124I and hence, on the image quality. Simulations were performed using the GATE software for a 1.32 cm radius cylinder filled with 300 muCi of 124I placed at the center of field of view. We report that by windowing in on the upper energy window of the data acquisition from a symmetric 50% (255-766 keV) energy window, to an asymmetric 255-600 keV one, it is possible to preferentially reduce the dirty coincidences with minor sensitivity changes. These findings will be verified with experimental data, and will lead to optimizing the data acquisition chain for 124I imaging performance

The purpose of this work was to calculate radiation dose and its organ distribution in a realistic mouse phantom from micro-computed tomography (microCT) imaging protocols. CT dose was calculated using GATE and a voxelized, realistic phantom. The x-ray photon energy spectra used in simulations were precalculated with GATE and validated against previously published data. The number of photons required per simulated experiments was determined by direct exposure measurements. Simulated experiments were performed for three types of beams and two types of mouse beds. Dose-volume histograms and dose percentiles were calculated for each organ. For a typical microCT screening examination with a reconstruction voxel size of 200 μm, the average whole body dose varied from 80 mGy (at 80 kVp) to 160 mGy (at 50 kVp), showing a strong dependence on beam hardness. The average dose to the bone marrow is close to the soft tissue average. However, due to dose nonuniformity and higher radiation sensitivity, 5% of the marrow would receive an effective dose about four times higher than the average. If CT is performed longitudinally, a significant radiation dose can be given. The total absorbed radiation dose is a function of milliamperes-second, beam hardness, and desired image quality (resolution, noise and contrast). To reduce dose, it would be advisable to use the hardest beam possible while maintaining an acceptable contrast in the image.

A new device is being developed that will allow imaging of the distribution of charged particles in microfluidic circuits, using a scintillator, a lens and a charge coupled device (CCD). Microfluidic chips are an emerging technology that will facilitate the study of molecular processes in pico-liter levels in a finely controlled manner. The ability to quantify low amounts of radioactivity in a microfluidic chip will provide researchers with a platform to investigate molecular processes in a controlled in-vitro environment. The new detector system consists of a plastic scintillator, a C-mount compact lens, and a Sony ICX285AL interline-transfer CCD cooled with a Peltier device. A microfluidic chip filled with fluoro-deoxy-glucose (FDG) solution was coupled to a plastic scintillator and the set up was placed inside a light-tight box for imaging. Preliminary studies were performed to test the feasibility of using the scintillator-based CCD detector system for this application. The CCD performance parameters were characterized by the photon transfer curve. The camera gain constant and read-out noise were measured to be 0.746 e-/ADU (analog-to-digital unit) and 8 e-, respectively. The dark current was also investigated with different temperatures and binning factors. The spatial resolution was measured and line pairs of FDG in a microfluidic chip were discernable down to a 0.5 mm separation. The system was able to quantify the activity level reliably down to 5 nCi/mm2.

The traditional method for estimating system matrices consists of simulating a number of annihilation events at each voxel position such that some error measured is minimized. However, axial sensitivity decreases as we move away from the center of the FOV and the number of detected coincidences is substantially smaller at the edge of the scanner than at the center. Therefore, the statistical error in computing should be increasingly larger for voxels at the edge of the image. To remedy in part this problem, we propose to estimate the system matrix using a number of events inversely proportional to plane sensitivity and compare its performance against the traditional approach by computing simple Figures-of-Merit. We simulate a noise cylinder phantom, a point-source phantom and a contrast phantom to measure noise, image resolution and contrast recovery, respectively, by image plane. Images are reconstructed using a ML-EM algorithm with system matrices built with the two methods. Simulation results show that noise is more uniform across the entire FOV when the matrix is estimated as proposed than when the traditional approach is used. Contrast recovery and resolution are not greatly improved.

A set of over 20 dynamic mouse FDG microPET images has been collected experimentally at UCLA and is made available to the public on the Internet. Accompanying each dynamic image set also is the radioactivity measurements of multiple sequential blood samples taken during the study. The data are expected to be useful for investigators who want to know more about the characteristics of dynamic mouse FDG microPET images before doing their own experiments, and will be especially useful for those who are interested in developing image-based methods for deriving blood activity curves from dynamic mouse microPET images.

Noninvasive imaging of molecular events and interactions in living small animal models has gained increasing importance in preclinical research. Two of the imaging modalities available for this research with potential for translation to the clinic are dedicated small animal positron emission tomography and single-photon emission computed tomography. This brief review introduces the fundamental principles behind these imaging technologies and instrumentation, and discusses the limitations in terms of their spatial resolution and sensitivity. In addition, it provides a perspective regarding the research and commercial development of these systems and presents examples of biological applications. Finally, it discusses the major challenges facing these technologies, advantages and limitations with respect to other technologies, and some future prospects.

Biological research in recent years has generated significant interest for in vivo small animal imaging technologies. 3D small animal X-ray computed tomography (CT) provides anatomical images with high spatial resolution and good bone-to-soft tissue contrast. Radiation doses to the subject can be significant when soft tissue contrast and high-resolution images are desired. We have used the MCNP Monte Carlo simulation, and calibrated thermoluminescent dosimeters (TLD's), in combination with high resolution X-ray spectra obtained with a cadmium zinc telluride (CZT) detector, to calculate the depth dependent dose in 3D high resolution X-ray CT. Three spectra (30 kVp with 0.25 mm of aluminum filtration, 40 kVp with 0.50 mm Al, and 50 kVp with 1.00 mm Al) were chosen as representative of soft, medium, and hard beams. MCNP was used to simulate the dose from these X-ray spectra incident upon a cylindrical mouse-sized phantom (2.54/spl times/6.1cm). The same phantom was also constructed from solid lucite material with thermo-luminescent dosimeters (TLD's) placed at the positions where we sampled the dose with MCNP. The maximum and minimum dose observed in this study is 19.7 /spl plusmn/ 1.7 cGy from the soft beam measured nearest the surface, and 5.2 /spl plusmn/ 0.1 cGy from the hard beam measured furthest from the source, for a typical data acquisition with 196 angles.

OPET is a combined optical and positron emission tomography (PET) scanner for small animal imaging, whose geometry presents several challenges for PET image reconstruction. The most important are the effects of depth-of-interaction, inter-crystal gaps, and angular sampling. Although these effects can be ameliorated through gantry rotations, the results are sub-optimal when reconstructing with filtered-back projection (FBP), because the system geometry is not modeled accurately. In this work, we present a study estimating the system model of the PET side of OPET with GATE, the Geant4 Application for PET and SPECT simulations, and the use of the model in iterative image reconstruction. At each image position, a 1 MBq voxel source irradiating isotropically in 3D was simulated. Coincidences were recorded for 10 seconds and the detected counts normalized and used as entries in the system matrix. Four transaxial and one axial image symmetries were exploited to reduce the number of simulations, but no assumptions were made on the model being axial or angularly independent. Resolution experiments were conducted by simulating a point source in warm background at various radial positions and images were reconstructed with the maximum likelihood expectation maximization (MLEM) algorithm. The simulations demonstrate that the use of the system model together with a statistical reconstruction produces images with improved and more uniform resolution across the field-of-view over FBP images.

Small animal anatomical imaging with x-ray computed tomography (CT) in cone-beam geometry suffers from inaccuracies in the measured attenuation coefficient due to the acceptance of scattered radiation. This work seeks to estimate the magnitude and effect of scatter in a commercial cone-beam microCT scanner in both projections and reconstructed images. The scatter-to-primary ratio (SPR) is estimated from projections using the beam stop method and from simulation. We also make initial attempts to quantitate the amount of inaccuracy in the measured image values under different scatter environments by reducing our 3D cone-beam geometry into a 2D fan-beam system. The extrapolated and simulated SPR (~0.3 for a mouse-sized object) for this microCT scanner indicates that the magnitude of scatter is not as high as in a prototype clinical cone-beam system. From the imaging studies, the resulting attenuation coefficients for the high scatter environment are about 10% lower than those for a low scatter environment. Further investigation is needed to determine the magnitude of errors caused by scatter and beam hardening separately because physical measurements suffer from compounding beam hardening effects. Simulations of the tomographic process are planned to individually evaluate the contribution of each of these effects

In this study, we evaluated the temporal resolution of a new microPET system in mice. We then applied the high resolution capability for determining the cardiovascular transit time which is an important physiological parameter in the study of animal models of cardiovascular disease. Two groups of mice, group 1 (n=12) with high body weight and group 2 (n=10) with low body weight, were studied. Each mouse was injected with a 18F-deoxyglucose (FDG; 40-50 /spl mu/L; 8-48 MBq) bolus and a list mode PET acquisition was started. MicroCT was performed for attenuation correction. We histogrammed the first 9 seconds of the list mode data into frames of 0.2 s-0.5 s duration. After the images were reconstructed and attenuation corrected, the ROIs were assigned to the following structures: vena cava, right and left ventricle blood pool (RV&LV), left lung and aorta. A time activity curve (VAC) of each ROI was generated. To correct for the recirculation, the end of each TAC was approximated by an exponential decay curve. The transit time (TT) was then calculated as the difference of the mean arrival times of the bolus in RV and LV. Short time frames of 0.3 s proved to be the best in terms of reducing noise and at the same being able to follow the rapid physiological processes. The peaks of the TACs showed good separation in various structures if the time spread of the bolus in the vena cava measured as full width of half maximum (FWHM) was shorter than 2 s. Group 1 had significantly (p

Attenuation correction is one of the important corrections required for quantitative positron emission tomography (PET). This work will compare the quantitative accuracy of attenuation correction using a simple global scale factor with traditional transmission-based methods acquired either with a small animal PET or a small animal x-ray computed tomography (CT) scanner. Two phantoms (one mouse-sized and one rat-sized) and two animal subjects (one mouse and one rat) were scanned in CTI Concorde Microsystem's MicroPET(R) Focus(TM) for emission and transmission data and in ImTek's MicroCAT(TM) II for transmission data. PET emission image values were calibrated against a scintillation well counter. Results indicate that the scale factor method of attenuation correction places the average measured activity concentration about the expected value, without correcting for the cupping artefact from attenuation. Noise analysis in the phantom studies with the PET-based method shows that noise in the transmission data increases the noise in the corrected emission data. The CT-based method was accurate and delivered low-noise images suitable for both PET data correction and PET tracer localization.

Antibody fragments are recognized as promising vehicles for delivery of imaging and therapeutic agents to tumor sites in vivo. The serum persistence of IgG1 and fragments with intact Fc region is controlled by the protective neonatal Fc receptor (FcRn) receptor. To modulate the half-life of engineered antibodies, we have mutated the Fc-FcRn binding site of chimeric anti–carcinoembryonic antigen (CEA) antibodies produced in a single-chain Fv-Fc format. The anti-CEA T84.66 single-chain Fv-Fc format wild-type and five mutants (I253A, H310A, H435Q, H435R, and H310A/H435Q, Kabat numbering system) expressed well in mammalian cell culture. After purification and characterization, effective in vitro antigen binding was shown by competition ELISA. Biodistribution studies in BALB/c mice using 125I- and 131I-labeled fragments revealed blood clearance rates from slowest to fastest as follows: wild-type > H435R > H435Q > I253A > H310A > H310A/H435Q. The terminal half-lives of the mutants ranged from 83.4 to 7.96 hours, whereas that of the wild-type was ∼12 days. Additionally, 124I-labeled wild-type, H435Q, I253A, H310A, and H310A/H435Q variants were evaluated in LS174T xenografted athymic mice by small animal positron emission tomography imaging, revealing localization to the CEA-positive xenografts. The slow clearing wild-type and H435Q constructs required longer to localize to the tumor and clear from the circulation. The I253A and H310A fragments showed intermediate behavior, whereas the H310A/H435Q variant quickly localized to the tumor site, rapidly cleared from the animal circulation and produced clear images. Thus, attenuating the Fc-FcRn interaction provides a way of controlling the antibody fragment serum half-life without compromising expression and tumor targeting.

Image-derived input functions (EDIF) are desirable for quantifying biological functions in mouse microPET studies. Due to difficulties in taking many blood samples from each mouse, conventional IDIF validation method of comparing blood samples with IDIF in a single animal is not applicable. A new approach that requires statistical testing on data of multiple animals has been conceived and investigated for IDIF validation. In this study, we evaluate and compare the power of 5 common statistical tests-Chi-square, sign test, signed-ranks, runs test, serial correlation-with the new approach for their ability to detect errors in IDIF. Computer simulation was used to simulate mouse FDG kinetics (60 min) and error-containing IDIF of various conditions. Deviations of IDIF from blood samples were examined with the 5 statistical tests. Results show that sign test, runs test and serial correlation do not have comparable power as the other two tests. The signed-ranks test generally had high statistical power, but was unable to detect errors that are random among animals or studies. Chi-square test could detect error in IDIF that was variable from study to study, but required accurate knowledge of noise variance. Combining signed-ranks test with Chi-square test is overall most sensitive for validation of IDIF.

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed. ispartof: Physics in medicine and biology vol:49 issue:19 pages:4543-4561 ispartof: location:England status: published

The design of an imaging system capable of detecting both high-energy /spl gamma/-rays and optical wavelength photons is underway at the UCLA Crump Institute for Molecular Imaging. This system, which we call optical PET (OPET), will be capable of noninvasively and repeatedly imaging small animal models in vivo for the presence of PET and optical signals. In this study, we describe the physical principles behind the operation of the OPET imaging system and discuss the design concept for one of the detector modules. Additionally, we demonstrate the operation of an initial prototype detector module for simultaneous detection and imaging of annihilation radiation and single optical photons emanating from separate sources. These results indicate that the construction of an imaging system based on this detector technology is feasible.

Imaging with Positron Emission Tomography (PET) requires compensation for attenuation of the annihilation photons in subject tissues. Although the magnitude of this correction for small subjects is significantly smaller than for humans, it Is important for a quantitatively accurate representation of the tracer distribution. Attenuation correction (AC) has been implemented on the Concorde microPET/spl reg/ P4 scanner using a Ge-68 point source (PS) that spirals through the field of view under computer control. Transmission (TX) scans of a rat-sized phantom were acquired with this PS and this tomograph by varying acquisition parameters including: acquisition mode (coincidence vs. singles), energy window, coincidence timing window, PS radius, PS activity, and acquisition time. We also evaluated the quality of post-injection TX images. Transmission data were processed by reconstruction of the log of the attenuation sinograms with 3D filtered backprojection. The attenuation coefficient images were subsequently analyzed with regions of interest in the uniform region of the phantom. Despite a significant amount of scatter contribution, singles data acquisition was found to have the best signal-to-noise ratio (SNR). We found that using higher PS activity or smaller PS radius resulted in a dramatic improvement in the SNR. A combination of both could lead to short acquisition times appropriate for TX imaging in a high throughput imaging facility. Attenuation correction sinograms were created by forward projecting through a smoothed TX image, in which the water-equivalent tissues were scaled to the appropriate /spl mu/-values. Noise levels in the corrected and uncorrected emission images indicate that no significant noise was introduced from the correction. A rat was imaged postinjection in the heart region. Singles TX images were used to create AC sinograms after emission contamination subtraction using a mock scan. The results are encouraging and demonstrate the feasibility of using PET TX images in AC.

Purpose Image-derived input functions are desirable for quantifying biological functions in dynamic mouse micro positron emission tomography (PET) studies, but the input function so derived needs to be validated. Conventional validation using serial blood samples is difficult in mice. We introduced the theoretical basis and used computer simulations to show the capability of a new approach that requires only a small number of blood samples per mouse but uses multiple animals. Procedures 2-Deoxy-2-[ 18 F]fluoro-D-glucose (FDG) kinetics (60 minutes) were simulated for 10 to 20 animals with three to six blood samples available per animal. Various amounts/types of noise/errors in the blood measurements were assumed, and different amounts/types of errors were added to the true input function to simulate image-derived input function. Deviations between blood samples and the derived input function were examined by statistical techniques to evaluate the capability of the approach for detecting the simulated errors in the derived input function. Results For a total of 60 blood samples and a 10% measurement noise, a 5% contaminating error in image-derived input function can be detected with a statistical power of ∼0.9 and with a 95% confidence. The power of the approach is directly related to the error magnitude in the image-derived input function, and is related to the total number of blood samples taken, but is inversely related to the measurement noise of the blood samples. Conclusion The new validation approach is expected to be useful for validating input functions derived with image-based methods in dynamic mouse microPET studies.

This chapter describes PET systems for imaging of small animals. It also discusses the opportunities for bringing together high-resolution PET imaging systems with the techniques of modern molecular biology, functional genomics, and drug development. Important factors considered in the design of dedicated small animal PET scanners are identified and the geometry and performance of several first-generation systems are reviewed. This chapter also describes newer small animal PET systems that are under development. Last section illustrates some of the early applications of PET for studying small laboratory animals and identifies the challenges, opportunities, and ultimate limitations in applying PET to small animal imaging. The role of PET in modern biology has yet to be defined, but, if some of the challenges identified in this chapter can be overcome, then it is likely to play a significant role in the study of animal models of disease.

MAP (maximum a posteriori) reconstructions of transmission images produce more accurate ACFs (attenuation correction factors) than smoothed division of blank and transmission scans and analytical methods. Also, for highly specific tracers, transmission images can provide useful anatomical cues for use in localizing structures and image coregistration. The resolution of MAP images reconstructed with a spatially invariant smoothing prior is known to be nonuniform. Spatially variant smoothing parameters are used to achieve uniform resolution throughout the transmission image. We also investigate the relationship between resolution and the global smoothing parameter through computer simulations. The resulting calibration curve can be used to select the smoothing parameter to achieve a desired spatial resolution. The tractability and feasibility of our method is demonstrated through an application to phantom transmission data collected using a Concorde P4 microPET system.