High-resolution Positron Emission Tomography Scanner Research Articles

Towards Quantitative Image Reconstruction Using Monte-Carlo Simulations in Multi-Wire Proportional Chamber-Based Small Animal PET

The quadHIDAC is a dedicated high resolution small animal PET scanner based on multi-wire proportional chamber detectors. It provides very high spatial resolution, good sensitivity, and a large field-of-view allowing the examination of more than one animal in a single scan or a whole body scan of larger species in a single bed position. Excellent image quality has been obtained through list-mode-based EM reconstruction using resolution recovery. However, quantitative results on local uptake are still missing due to both (1) lack of energy discrimination and (2) inaccurate characterization of random events recorded by the scanner. In this work we describe how quantification can be achieved through the use of an appropriate Monte Carlo simulation of the quadHIDAC. The complex structure of the quadHIDAC has been completely implemented in a Geant4 simulation. Point sources, line sources, cylindrical phantoms, and voxelized image data have been successfully simulated and compared to real measurements. The magnitude and spatial distribution of scattered and random events could be quantitatively characterized for the different phantom geometries. The simulation provides access to information on single hit distributions resulting in appropriate randoms corrections in image reconstruction. Both randoms and scatter correction is demonstrated to improve quantification. Their accuracy and performance was tested on simulated and measured data. Using simulation-based correction techniques for quantitative image reconstruction, multi-wire proportional chamber-based PET technology may be attractive for future high resolution PET scanners.

A Monte Carlo investigation of the spatial resolution performance of a small-animal PET scanner designed for mouse brain imaging studies

Our laboratory has developed PET detectors with depth-encoding accuracy of ∼2 mm based on finely pixelated crystals with a tapered geometry, readout at both ends with position-sensitive avalanche photodiodes (PSAPDs). These detectors are currently being used in our laboratory to build a one-ring high resolution PET scanner for mouse brain imaging studies. Due to the inactive areas around the PSAPDs, large gaps exist between the detector modules which can degrade the image spatial resolution obtained using analytical reconstruction with filtered backprojection (FBP). In this work, the Geant4-based GATE Monte Carlo package was used to assist in determining whether gantry rotation was necessary and to assess the expected spatial resolution of the system. The following factors were investigated: rotating vs. static gantry modes with and without compensation of missing data using the discrete cosine transform (DCT) method, two levels of depth-encoding, and positron annihilation effects for 18F. Our results indicate that while the static scanner produces poor quality FBP images with streak and ring artifacts, the image quality was greatly improved after compensation of missing data. The simulation indicates that the expected FWHM system spatial resolution is 0.70 ± 0.05 mm, which approaches the predicted limit of 0.5 mm FWHM due to positron range, photon non-colinearity and physical detector element size effects. We conclude that excellent reconstructed resolution without gantry rotation is possible even using FBP if the gaps are appropriately handled and that this design can approach the resolution limits set by positron annihilation physics.

Cerebral blood flow and glucose metabolism in healthy volunteers measured using a high-resolution PET scanner

BackgroundPositron emission tomography (PET) allows for the measurement of cerebral blood flow (CBF; based on [15O]H2O) and cerebral metabolic rate of glucose utilization (CMRglu; based on [18 F]-2-fluoro-2-deoxy-d-glucose ([18 F]FDG)). By using kinetic modeling, quantitative CBF and CMRglu values can be obtained. However, hardware limitations led to the development of semiquantitive calculation schemes which are still widely used. In this paper, the analysis of CMRglu and CBF scans, acquired on a current state-of-the-art PET brain scanner, is presented. In particular, the correspondence between nonlinear as well as linearized methods for the determination of CBF and CMRglu is investigated. As a further step towards widespread clinical applicability, the use of an image-derived input function (IDIF) is investigated.MethodsThirteen healthy male volunteers were included in this study. Each subject had one scanning session in the fasting state, consisting of a dynamic [15O]H2O scan and a dynamic [18 F]FDG PET scan, acquired at a high-resolution research tomograph. Time-activity curves (TACs) were generated for automatically delineated and for manually drawn gray matter (GM) and white matter regions. Input functions were derived using on-line arterial blood sampling (blood sampler derived input function (BSIF)). Additionally, the possibility of using carotid artery IDIFs was investigated. Data were analyzed using nonlinear regression (NLR) of regional TACs and parametric methods.ResultsAfter quality control, 9 CMRglu and 11 CBF scans were available for analysis. Average GM CMRglu values were 0.33 ± 0.04 μmol/cm3 per minute, and average CBF values were 0.43 ± 0.09 mL/cm3 per minute. Good correlation between NLR and parametric CMRglu measurements was obtained as well as between NLR and parametric CBF values. For CMRglu Patlak linearization, BSIF and IDIF derived results were similar. The use of an IDIF, however, did not provide reliable CBF estimates.ConclusionNonlinear regression analysis, allowing for the derivation of regional CBF and CMRglu values, can be applied to data acquired with high-spatial resolution current state-of-the-art PET brain scanners. Linearized models, applied to the voxel level, resulted in comparable values. CMRglu measurements do not require invasive arterial sampling to define the input function.Trial registrationClinicalTrials.gov NCT00626080

The AX-PET experiment: A demonstrator for an axial Positron Emission Tomograph

AX-PET stands for a new geometrical concept for a high resolution and high sensitivity PET scanner, based on an axial arrangement of long scintillating crystals in the tomograph, for a parallax free PET detector. Two identical AX-PET modules – consisting of matrices of LYSO crystals interleaved with WLS strips – have been built. They form the AX-PET Demonstrator, which has been extensively characterized and successfully used for the reconstruction of images of several phantoms. In this paper we report on the current status of the project, with emphasis on the most relevant results achieved both in terms of detector characterization and image reconstruction. We also discuss the recent preliminary results obtained with the digital SiPM from Philips (dSiPM), which are currently being tested as a possible alternative photodetector for AX-PET. With their very good intrinsic time resolution, dSiPM could add Time of Flight capability to the AX-PET concept.

Abstract SY13-03: Molecular imaging for advanced practice in oncology

Abstract Positron Emission Tomography (PET) with 2-flouro-2-D-oxyglucose (FDG) has been the poster child for MI and several million studies are performed for oncology indications in the US alone. FDG takes advantage of the Warburg effect, which is the aerobic glycolysis that is a common feature of many malignant tumors. The incorporation of high resolution CT into the same gantry with a high resolution PET scanner, has given a further boost to PET imaging of tumors and in fact, PET CT is the most rapidly growing clinical imaging modality in the US today. Tumors for which staging, monitoring treatment response are common place include, Lung, Lymphoma, Thyroid, head and neck, melanoma, colorectal cancers. But MI with PET/CT is potentially much more than FDG PET imaging, and several 100 tracers for specific molecular imaging have been developed in the last decade. Examples include amino acid tracers, like F-18 FACBC, nucleoside analogs, like F-18 FLT, and Na 124I to imaging iodide metabolism, Androgen receptor imaging (AR) with F-18 FDHT, and Estrogen receptor imaging with F-18 FES. In addition to small molecules, positron emitting tracers like 124I-, 68 Ga and 89 Zr are widely used for radiolabeling of antibodies and peptides, opening the entire universe of ligand receptor binding for human tumors. Radiolabeled drugs are being developed and examples include F-18 desatinib, a src family tyrosine kinase inhibitor and 124I-PUH71, a heat-shock protein 90 inhibitor. These radiolabeled drugs should facilitate the study of intratumoral pharmacology of human cancers. In addition radiolabeled nanoparticles are being developed and promise specialized targeting properties, and to serve as carriers for drugs to improve therapeutic index. In summary, MI with PET is rapidly evolving as a major frontier for development of the knowledge of tumor biology and pharmacology needed to optimize treatment of the individual oncology patient. References Schoder H, Grimm J and Larson SM: Molecular Imaging Section 6 in DeVita VT Lawrence TS and Rosenberg SA: Cancer Principles and Practice of Oncology 8th Edition Volume 1 p 746 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY13-03. doi:1538-7445.AM2012-SY13-03

Scatter Correction for Positron Emission Mammography using an Estimation of Trues Method Approach

ClearPEM is a high resolution PET scanner dedicated to breast imaging that offers good lesion detectability and localization. To obtain quantitative images, corrections need to be applied to the acquired data, but since there are no transmission sources available, only emission data can be used. In this paper we present the application of a method for scatter correction - Estimation of Trues Method (ETM) - to data acquired with the ClearPEM scanner. This approach is based on the energy of the detected photons and can be implemented in the image domain. Also, it is applicable in cases where a large amount of activity exists outside the field of view and does not require transmission information. ETM is being validated with real data from acquisitions with gelatin phantoms, showing improvements in image contrast and thus potentially increasing the detectability of lesions.

Characterization of a high resolution and high sensitivity pre-clinical PET scanner with 3D event reconstruction

COMPET is a preclinical PET scanner aiming towards a high sensitivity, a high resolution and MRI compatibility by implementing a novel detector geometry. In this approach, long scintillating LYSO crystals are used to absorb the γ-rays. To determine the point of interaction (POI) between γ-ray and crystal, the light exiting the crystals on one of the long sides is collected with wavelength shifters (WLS) perpendicularly arranged to the crystals. This concept has two main advantages: (1) The parallax error is reduced to a minimum and is equal for the whole field of view (FOV). (2) The POI and its energy deposit is known in all three dimension with a high resolution, allowing for the reconstruction of Compton scattered γ-rays. Point (1) leads to a uniform point source resolution (PSR) distribution over the whole FOV, and also allows to place the detector close to the object being imaged. Both points (1) and (2) lead to an increased sensitivity and allow for both high resolution and sensitivity at the same time, while keeping a low number of readout channels.In total, COMPET incorporates 1080 readout channels (600 crystals, 480 WLS). It has an axial FOV of 80mm and adjustable bore opening between 30mm and 80mm. It consists of four modules with five layers each. Simulations show a PSR of below 1mm in the transaxial plane and a sensitivity of up to 16% in the center of the FOV. The readout is based on time over threshold signals, sampled with an FPGA, which allows for the measurement of high event rates at the order of mega-counts per seconds. Its compact design and compatibility to high magnetic fields will allow to use it as an insert for an already existing MRI scanner.A first semi-layer with 12 WLS and 10 LYSO crystal was built and connected to the COMPET readout system. Coincidence data between this module and a tagger crystal using a small Ge-68 and a 60MBq F-18 source was taken.

Performance comparison of Si-PM-based block detectors with different pixel sizes for an ultrahigh-resolution small-animal PET system

The silicon photomultiplier (Si-PM) is a promising photodetector for a high-resolution PET scanner due to its small size, high gain and lower sensitivity to magnetic fields. There are several commercially available Si-PM arrays with different pixel sizes and fill factors, and these parameters can affect the performance of a PET block detector read out by these devices. We compared the performance of block detectors using 4 × 4 Si-PM arrays with 25 µm (Hamamatsu S11064-025P) and 50 µm (S11064-050P) pixels combined with the same 15 × 15 matrix LGSO block made of 0.7 × 0.7 × 6 mm3 scintillator pixels. Evaluated characteristics include photopeak linearity, energy resolution and positioning performance. Although the photopeak linearity and energy resolution are slightly better for the Si-PM with 25 µm pixels, the position performance measured by the separation of the position histogram is significantly better for the Si-PM with 50 µm pixels. We conclude that using the Si-PM with 50 µm pixels will provide a better solution for the development of ultrahigh-resolution PET systems.

Optimised Motion Tracking for Positron Emission Tomography Studies of Brain Function in Awake Rats

Positron emission tomography (PET) is a non-invasive molecular imaging technique using positron-emitting radioisotopes to study functional processes within the body. High resolution PET scanners designed for imaging rodents and non-human primates are now commonplace in preclinical research. Brain imaging in this context, with motion compensation, can potentially enhance the usefulness of PET by avoiding confounds due to anaesthetic drugs and enabling freely moving animals to be imaged during normal and evoked behaviours. Due to the frequent and rapid motion exhibited by alert, awake animals, optimal motion correction requires frequently sampled pose information and precise synchronisation of these data with events in the PET coincidence data stream. Motion measurements should also be as accurate as possible to avoid degrading the excellent spatial resolution provided by state-of-the-art scanners. Here we describe and validate methods for optimised motion tracking suited to the correction of motion in awake rats. A hardware based synchronisation approach is used to achieve temporal alignment of tracker and scanner data to within 10 ms. We explored the impact of motion tracker synchronisation error, pose sampling rate, rate of motion, and marker size on motion correction accuracy. With accurate synchronisation (<100 ms error), a sampling rate of >20 Hz, and a small head marker suitable for awake animal studies, excellent motion correction results were obtained in phantom studies with a variety of continuous motion patterns, including realistic rat motion (<5% bias in mean concentration). Feasibility of the approach was also demonstrated in an awake rat study. We conclude that motion tracking parameters needed for effective motion correction in preclinical brain imaging of awake rats are achievable in the laboratory setting. This could broaden the scope of animal experiments currently possible with PET.

The reliability of proton-nuclear interaction cross-section data to predict proton-induced PET images in proton therapy

In vivo PET range verification relies on the comparison of measured and simulated activity distributions. The accuracy of the simulated distribution depends on the accuracy of the Monte Carlo code, which is in turn dependent on the accuracy of the available cross-section data for β+ isotope production. We have explored different cross-section data available in the literature for the main reaction channels (16O(p,pn)15O, 12C(p,pn)11C and 16O(p,3p3n)11C) contributing to the production of β+ isotopes by proton beams in patients. Available experimental and theoretical values were implemented in the simulation and compared with measured PET images obtained with a high-resolution PET scanner. Each reaction channel was studied independently. A phantom with three different materials was built, two of them with high carbon or oxygen concentration and a third one with average soft tissue composition. Monoenergetic and SOBP field irradiations of the phantom were accomplished and measured PET images were compared with simulation results. Different cross-section values for the tissue-equivalent material lead to range differences below 1 mm when a 5 min scan time was employed and close to 5 mm differences for a 30 min scan time with 15 min delay between irradiation and scan (a typical off-line protocol). The results presented here emphasize the need of more accurate measurement of the cross-section values of the reaction channels contributing to the production of PET isotopes by proton beams before this in vivo range verification method can achieve mm accuracy.

DOI‐based reconstruction algorithms for a compact breast PET scanner

The authors discuss the design and evaluate the performance of combined event estimation and image reconstruction algorithms designed for a proposed high-resolution rectangular breast PET scanner (PETX). The PETX scanner will be capable of measuring the depth of interaction by utilizing detector modules composed of depth-of-interaction microcrystal element (dMiCE) crystal pairs. This design allows a unique combination of event estimation and fast projection methods. The authors implemented a Monte Carlo simulator to model the PETX system using only true coincident events. The performance of the dMiCE crystal pairs was determined experimentally over a range of depths of interaction. This distribution was used to simulate the noisy dMiCE detector signals and to estimate the line of response for each decay. Three different statistical methods were implemented to determine photon event positioning. Images were reconstructed from these line of response estimators with the exact planogram frequency distance rebinning algorithm, which is an exact analytical reconstruction algorithm for planar systems. Reconstructed images were analyzed with contrast, noise, and spatial resolution metrics. The authors' simulations demonstrate the ability for the PETX system to produce quantitatively accurate images from true coincident events with a contrast recovery coefficient of greater than 0.8 for 5 mm spheres at the axial center of the scanner and a spatial resolution (FWHM) of 3 mm throughout most of the imaging field of view. The authors' proposed positioning and reconstruction algorithms for the PETX system show the potential for creating high-quality, high-resolution, and quantitatively accurate images within a clinically feasible reconstruction time.

COMPET – high resolution and high sensitivity PET scanner with novel readout concept: Setup and simulations

Abstract COMPET is a MRI compatible preclinical PET scanner aiming towards a high sensitivity and a high point source resolution (PSR) by implementing a novel block detector geometry. Layers of matrices consisting of long LYSO crystals and wavelength shifter (WLS) fibers are used to determine the point of interaction (POI) of the γ ‐ray within the LYSO crystal. This reduces the parallax error to a minimum and allows for a high PSR and a high sensitivity, while keeping a low number of readout channels. Simulations show that the detector achieves a PSR below 1 mm in the transaxial plane and a sensitivity of up to 16%.

Improving the singles rate method for modeling accidental coincidences in high-resolution PET

Random coincidences (‘randoms’) are one of the main sources of image degradation in PET imaging. In order to correct for this effect, an accurate method to estimate the contribution of random events is necessary. This aspect becomes especially relevant for high-resolution PET scanners where the highest image quality is sought and accurate quantitative analysis is undertaken. One common approach to estimate randoms is the so-called singles rate method (SR) widely used because of its good statistical properties. SR is based on the measurement of the singles rate in each detector element. However, recent studies suggest that SR systematically overestimates the correct random rate. This overestimation can be particularly marked for low energy thresholds, below 250 keV used in some applications and could entail a significant image degradation. In this work, we investigate the performance of SR as a function of the activity, geometry of the source and energy acceptance window used. We also investigate the performance of an alternative method, which we call ‘singles trues’ (ST) that improves SR by properly modeling the presence of true coincidences in the sample. Nevertheless, in any real data acquisition the knowledge of which singles are members of a true coincidence is lost. Therefore, we propose an iterative method, STi, that provides an estimation based on ST but which only requires the knowledge of measurable quantities: prompts and singles. Due to inter-crystal scatter, for wide energy windows ST only partially corrects SR overestimations. While SR deviations are in the range 86–300% (depending on the source geometry), the ST deviations are systematically smaller and contained in the range 4–60%. STi fails to reproduce the ST results, although for not too high activities the deviation with respect to ST is only a few percent. For conventional energy windows, i.e. those without inter-crystal scatter, the ST method corrects the SR overestimations, and deviations from the true random rate are of the order of 1% or less. In addition, in the case of conventional energy window STi results reproduce ST results and therefore the former can be used to obtain the true random rate.

POD14 Amyloid PET using 18F-AV-45 in Alzheimer's disease and frontotemporal dementia: first UK results

Introduction18F-AV-45 (Florbetapir F-18) is a novel 18F-labelled positron emission tomography (PET) tracer for in vivo imaging of cerebral amyloid deposition. Here we present preliminary results for differentiation between Alzheimer's disease...

Optimization of a partially segmented block detector for MR-compatible small animal PET

Abstract In recent years, there has been an increasing interest in the magnetic resonance (MR)-compatible positron emission tomography (PET) scanners for both clinical and preclinical practice. The aim of this study was to design a novel PET detector module using a segmented block crystal readout with an array of multi-pixel photon counters (MPPCs). A 16.5×16.5×10.0 mm3 LSO block was segmented into an 11×11 array, and reflective material was used to fill in the cuts to optically isolate the elements. The block was attached to a 4×4 MPPC array (Hamamatsu S11064) of 3.0×3.0 mm2 detectors to give a total effective area of 144 mm2. To visualize all the individual detector elements in this 11×11 detector module, the depth of the cuts was optimized by DETECT2000 simulations. The depth of the cuts determines the spread of scintillation light onto the MPPC array. The accuracy of positioning was evaluated by varying the depth of the cuts from 0.0 to 10.0 mm in steps of 0.5 mm. A spatial resolution of 1.5 mm was achieved using the optimized partially segmented block detector. The simulation results of this study can be used effectively as a guide for parameter optimization for the development of a partially segmented block detector for high-resolution MR-compatible PET scanners.

Gap-filling methods for 3D PlanTIS data

The range of positron emitters and their labeled compounds have led to high-resolution PET scanners becoming widely used, not only in clinical and pre-clinical studies but also in plant studies. A high-resolution PET scanner, plant tomographic imaging system (PlanTIS), was designed to study metabolic and physiological functions of plants noninvasively. The gantry of the PlanTIS scanner has detector-free regions. Even when the gantry of the PlanTIS is rotated during the scan, these regions result in missing sinogram bins in the acquired data. Missing data need to be estimated prior to the analytical image reconstructions in order to avoid artifacts in the final reconstructed images. In this study, we propose three gap-filling methods for estimation of the unique gaps existing in the 3D PlanTIS sinogram data. The 3D sinogram data were gap-filled either by linear interpolation in the transaxial planes or by the bicubic interpolation method (proposed for the ECAT high-resolution research tomograph) in the transradial planes or by the inpainting method in the transangular planes. Each gap-filling method independently compensates for slices in one of three orthogonal sinogram planes (transaxial, transradial and transangular planes). A 3D numerical Shepp–Logan phantom and the NEMA image quality phantom were used to evaluate the methods. The gap-filled sinograms were reconstructed using the analytical 3D reprojection (3DRP) method. The NEMA phantom sinograms were also reconstructed by the iterative reconstruction method, ordered subsets maximum a posteriori one step late (OSMAPOSL), to compare the results of gap filling followed by 3DRP with the results of OSMAPOSL reconstruction without gap filling. The three methods were evaluated quantitatively (by mean square error and coefficients of variation) over the selected regions of the 3D numerical Shepp–Logan phantom at eight different Poisson noise levels. Moreover, the NEMA phantom scan data were used in visual assessments of the methods. We observed that all methods improved the reconstructed images both quantitatively and visually. Therefore, the proposed gap-filling methods followed by the analytical 3DRP are alternative for the reconstructions of not only the 3D PlanTIS data, but also other PET scanner data of the ClearPET family.

Isochronous Assessment of Cardiac Metabolism and Function in Mice Using Hybrid PET/MRI

Recently, integrated small-animal PET/MRI prototypes that provide isochronous and coregistered datasets of morphology and function through the simultaneous acquisition of PET and MRI data have been developed. However, the need for MRI compatibility can constrain the technical design of the PET components and may lead to a lower sensitivity and lower spatial and temporal resolutions. The aim of this study was to evaluate the suitability of a prototype preclinical PET/MRI system for the simultaneous assessment of cardiac metabolism and function in mice. A stand-alone high-resolution small-animal PET scanner using the same evaluation protocols was used as a reference. Simultaneous PET/MR images of an infarct mouse model (21 animals plus 3 controls) were acquired. The imaging performance of the MRI-compatible PET insert was evaluated with respect to count sensitivity; myocardium-to-background contrast; suitability for the analysis of global left ventricular function; and uptake difference in scar, border-zone, and remote regions. The radiotracer (18)F-FDG was used to acquire cardiac gated PET data, applying retrospective coincidence sorting. The PET insert data were coregistered to the MR images by determination of the appropriate transformation matrix. An optimal registration of PET and MR images from the integrated system was achieved, and the reconstructed images showed a good visual correspondence in infarct areas between PET and MRI data. As expected, the PET insert showed a poorer performance with respect to counting rate and myocardium-to-background ratio than did the high-resolution PET. Assessment of left ventricular volumes was possible with the current PET/MRI prototype. A good correlation was found between PET and MRI (R > 0.95). Local PET uptake was successfully determined for different tissue, and a differentiation among remote, border-zone, and scar tissue was possible. However, the uptake difference for the PET/MRI prototype was lower than that for the high-resolution stand-alone PET system. A hybrid PET/MRI prototype was successfully used to assess cardiac parameters in an infarct mouse model, although performance was reduced when compared with a high-resolution animal PET scanner. Future technical improvements are expected to result in comparable performance while providing higher registration accuracy.

A Movable Phantom Design for Quantitative Evaluation of Motion Correction Studies on High Resolution PET Scanners

Head movements during brain imaging using high resolution positron emission tomography (PET) impair the image quality which, along with the improvement of the spatial resolution of PET scanners, in general, raises the importance of motion correction. Here, we present a new design for an automatic, movable, mechanical PET phantom to simulate patients' head movements while being scanned. This can be used for evaluating motion correction methods. A low-cost phantom controlled by a rotary stage motor was built and tested for axial rotations of 1°-10° with the multiple acquisition frame method. The phantom is able to perform stepwise and continuous axial rotations with submillimeter accuracy, and the movements are repeatable. The scans were acquired on the high resolution research tomograph dedicated brain scanner. The scans were reconstructed with the new 3-D ordered subset expectation maximization algorithm with modeling of the point spread function (3DOSEM-PSF), and they were corrected for motions based on external tracking information using the Polaris Vicra real-time stereo motion-tracking system. The new automatic, movable phantom has a robust design and is a potential quality assessment tool for the development and evaluation of future motion correction methods.

Design and initial performance of PlanTIS: a high-resolution positron emission tomograph for plants

Positron emitters such as 11C, 13N and 18F and their labelled compounds are widely used in clinical diagnosis and animal studies, but can also be used to study metabolic and physiological functions in plants dynamically and in vivo. A very particular tracer molecule is 11CO2 since it can be applied to a leaf as a gas. We have developed a Plant Tomographic Imaging System (PlanTIS), a high-resolution PET scanner for plant studies. Detectors, front-end electronics and data acquisition architecture of the scanner are based on the ClearPET™ system. The detectors consist of LSO and LuYAP crystals in phoswich configuration which are coupled to position-sensitive photomultiplier tubes. Signals are continuously sampled by free running ADCs, and data are stored in a list mode format. The detectors are arranged in a horizontal plane to allow the plants to be measured in the natural upright position. Two groups of four detector modules stand face-to-face and rotate around the field-of-view. This special system geometry requires dedicated image reconstruction and normalization procedures. We present the initial performance of the detector system and first phantom and plant measurements.

Imaging of Proliferation in Hepatocellular Carcinoma with the In Vivo Marker 18F-Fluorothymidine

We determined the ability of PET with the thymidine analog 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) to detect hepatocellular carcinoma (HCC). In this pilot study, (18)F-FLT PET was performed in 18 untreated patients with clinically suspected HCC. Routine diagnostic procedures included ultrasound, MRI, or contrast-enhanced spiral CT of the upper gastrointestinal tract in all patients. At 45-60 min after the intravenous injection of approximately 270-340 MBq of (18)F-FLT, emission and transmission scanning was performed with a high-resolution PET scanner. Tracer uptake in the tumor and surrounding liver tissue was evaluated semiquantitatively by calculation of mean and maximum standardized uptake values (SUVs). Results were correlated with those of the conventional imaging methods. A total of 13 of 18 tumors (sensitivity, 72%; 95% confidence interval [CI], 47%-90%) showed focal (18)F-FLT uptake higher than surrounding liver activity and were detectable as hot lesions. Five tumors were characterized as photopenic lesions or contained a mixture of hot and cold lesions exhibiting a comparable or lower (18)F-FLT uptake than the surrounding liver tissue. When all lesions were considered, the mean (18)F-FLT SUV was 7.8 (range, 2.5-11.1), and the maximum (18)F-FLT SUV was 9.3 (range, 2.9-14.3). Histology and clinical follow-up revealed HCC in 16 patients and cholangiocarcinoma in 2 patients. In the subgroup of HCC, the sensitivity for tumor detection was 69% (11/16; 95% CI, 41%-89%). Correlation analysis demonstrated a significant positive relationship between the proliferation marker MIB-1 and the mean SUV (r = 0.66, P = 0.02). Survival analysis (Cox proportional hazards regression) for initial (18)F-FLT uptake (mean and maximum SUVs) revealed increased hazard ratios (mean SUV, 1.20; maximum SUV, 1.12), but because of the small number of events, these results were not statistically significant. In this pilot study, HCC tumors showed a mixed uptake pattern for the in vivo proliferation marker (18)F-FLT. A total of 69% of the HCC lesions showed (18)F-FLT uptake higher than that of the surrounding liver tissue, whereas the remaining lesions were photopenic or contained a mixture of hot and cold lesions. High initial (18)F-FLT uptake seems to be associated with reduced overall survival and could be an important prognostic factor if this tendency can be confirmed in a larger prospective trial.