Transaxial Field Of View Research Articles

Early Prediction of Radiation Response of Brain Metastases with [ 18F]-ML-10: A Novel Molecular PET Imaging Agent for Apoptosis

A. M. Allen, A. Shirvan, E. Mishani, A. Steinmetz, A. Reshef, I. Ziv, E. Fenig Davidoff Center, Petach Tikva, Israel, Aposense LTD, Petach Tikva, Israel, Hadassah Medical School, Jerusalem, Israel, Aposense LTD., Petach Tikva, Israel, Aposense, Petach Tikva, Israel Purpose/Objective(s): Radiographic response to radiation therapy often lags 4-6 weeks behind the biological effect. The [F]ML-10 is a novel PET tracer that has been shown in preclinical models to effectively image an early apoptotic response to radiation therapy. We sought to test this imaging technique in a prospective study of patients undergoing WBRT for brain metastasis. Materials/Methods: Patients with brain metastasis were enrolled into a prospective Phase II trial of [F]-ML-10-PET scanning before and after WBRT. The study was approved by the Helsinki commission of the Rabin Medical Center. Enrollment was limited to patients with lesions .1.5 cm in diameter on pretreatment MRI scans. All patients received 30 Gy in 10 daily fractions following CT simulation and treatment planning. Prior to RT, each patient underwent [F]-ML-10-PET scan on GE Discovery STE scanner, with a 15.7 cm axial and 70 cm transaxial field of view (FOV). The PET voxel intensities (Bq/cm) were normalized to the superior sagittal sinus and were recorded. Following 9-10 fractions of radiation patients underwent a second [F]-ML-10 PET scan. Six to 8 weeks following the completion of therapy patients underwent a follow-up MRI scan to measure the change in tumor size. All PET and MRI scans were coregistered using a Normalized Mutual Information algorithm (version 2.9 build 2 by PMOD Technologies Ltd). A voxel based analysis was carried out to determine the change in PET voxel intensity in the target lesions from initial to follow-up PET scans (DPET) using a homegrown program written with MATLAB (version 7.4.0 by MathWorks). Response was assessed by MRI, based on the percentage of change in tumor size. The percent of ‘‘changed’’ voxels for each lesion was calculated and tested for correlation with the change in the anatomical size according to MRI.

Multisphere phantom and analysis algorithm for PET image quality assessment

PET image quality measurements of lesion detectability frequently use a small, radioactive sphere in a larger phantom. The typical analysis of a small single sphere in background has several shortcomings as a measure for detectability and quantitation: the measurement has low statistical power; the region of interest (ROI) is susceptible to large pixel-to-pixel fluctuations; only a single point in the axial and transaxial field of view is analyzed; background noise measurements in regions away from the signal sphere may bias the detectability measurement and user-placed ROIs can cause inconsistent measurements. For a more robust measurement and repeatable analysis of small lesion detectability in PET images, a multisphere phantom and analysis algorithm were developed. The multisphere phantom consists of a collection of 50 1.0-cm spheres, mounting rods and a gridded plate. A PET/CT study is presented where 29 spheres with a 4:1 sphere-to-background radioactivity ratio were acquired for multiple frame durations and reconstructed. An analysis algorithm was implemented and applied to the acquired PET/CT that detects the contrast-enhanced spheres in a CT, places ROIs on the spheres and their respective proximal background, applies the ROIs to the PET and performs quantitation. Results are presented that show the impact of increasing number of signal spheres and of different background ROI placement methods on the image quality measurement. Increasing the number of spheres reduced the variability in the image quality measurements, but only up to a point, beyond which increasing the number of spheres did not considerably reduce the variability. A phantom with numerous spherical inserts increases several measurement aspects: the flexibility of sphere placement during setup, the number of radioactivity concentrations that can be used during a single study and the statistical power of measurements. Additionally, an automated algorithm that localizes spheres, places ROIs and performs quantitation will increase reliability and reproducibility of image quality assessment, in addition to simplifying the analysis.

Effects of system geometry and other physical factors on photon sensitivity of high-resolution positron emission tomography

We are studying two new detector technologies that directly measure the three-dimensional coordinates of 511 keV photon interactions for high-resolution positron emission tomography (PET) systems designed for small animal and breast imaging. These detectors are based on (1) lutetium oxyorthosilicate (LSO) scintillation crystal arrays coupled to position-sensitive avalanche photodiodes (PSAPD) and (2) cadmium zinc telluride (CZT). The detectors have excellent measured 511 keV photon energy resolutions (⩽12% FWHM for LSO-PSAPD and ⩽3% for CZT) and good coincidence time resolutions (2 ns FWHM for LSO-PSAPD and 8 ns for CZT). The goal is to incorporate the detectors into systems that will achieve 1 mm3 spatial resolution (∼1 mm3, uniform throughout the field of view (FOV)), with excellent contrast resolution as well. In order to realize 1 mm3 spatial resolution with high signal-to-noise ratio (SNR), it is necessary to significantly boost coincidence photon detection efficiency (referred to as photon sensitivity). To facilitate high photon sensitivity in the proposed PET system designs, the detector arrays are oriented ‘edge-on’ with respect to incoming 511 keV annihilation photons and arranged to form a compact FOV with detectors very close to, or in contact with, the subject tissues. In this paper, we used Monte Carlo simulation to study various factors that limit the photon sensitivity of a high-resolution PET system dedicated to small animal imaging. To optimize the photon sensitivity, we studied several possible system geometries for a fixed 8 cm transaxial and 8 cm axial FOV. We found that using rectangular-shaped detectors arranged into a cylindrical geometry does not yield the best photon sensitivity. This is due to the fact that forming rectangular-shaped detectors into a ring produces significant wedge-shaped inter-module gaps, through which Compton-scattered photons in the detector can escape. This effect limits the center point source photon sensitivity to <6% for a cylindrical system with rectangular-shaped blocks, 8 cm diameter and 8 cm axial FOV, and a 350–650 keV energy window setting. On the other hand, if the proposed rectangular-shaped detectors are arranged into an 8 × 8 × 8 cm3 FOV box configuration (four detector panels), there are only four inter-module gaps and the favorable distribution of these gaps yields >8% photon sensitivity for the LSO-PSAPD box configuration and >15% for CZT box geometry, using a 350–650 keV energy window setting. These simulation results compare well with analytical estimations. The trend is different for a clinical whole-body PET system that uses conventional LSO-PMT block detectors with larger crystal elements. Simulations predict roughly the same sensitivity for both box and cylindrical detector configurations. This results from the fact that a large system diameter (>80 cm) results in relatively small inter-module gaps in clinical whole-body PET. In addition, the relatively large block detectors (typically >5 × 5 cm2 cross-sectional area) and large crystals (>4 × 4 × 20 mm3) enable a higher fraction of detector scatter photons to be absorbed compared to a small animal system. However, if the four detector sides (panels) of a box-shaped system geometry are configured to move with respect to each other, to better fit the transaxial FOV to the actual size of the object to be imaged, a significant increase in photon sensitivity is possible. Simulation results predict a 60–100% relative increase of photon sensitivity for the proposed small animal PET box configurations and >60% increase for a clinical whole-body system geometry. Thus, simulation results indicate that for a PET system built from rectangular-shaped detector modules, arranging them into a box-shaped system geometry may help us to significantly boost photon sensitivity for both small animal and clinical PET systems.

Monte Carlo based performance assessment of different animal PET architectures using pixellated CZT detectors

The majority of present position emission tomography (PET) animal systems are based on the coupling of high-density scintillators and light detectors. A disadvantage of these detector configurations is the compromise between image resolution, sensitivity and energy resolution. In addition, current combined imaging devices are based on simply placing back-to-back and in axial alignment different apparatus without any significant level of software or hardware integration. The use of semiconductor CdZnTe (CZT) detectors is a promising alternative to scintillators for gamma-ray imaging systems. At the same time CZT detectors have the potential properties necessary for the construction of a truly integrated imaging device (PET/SPECT/CT). The aims of this study was to assess the performance of different small animal PET scanner architectures based on CZT pixellated detectors and compare their performance with that of state of the art existing PET animal scanners. Different scanner architectures were modelled using GATE (Geant4 Application for Tomographic Emission). Particular scanner design characteristics included an overall cylindrical scanner format of 8 and 24 cm in axial and transaxial field of view, respectively, and a temporal coincidence window of 8 ns. Different individual detector modules were investigated, considering pixel pitch down to 0.625 mm and detector thickness from 1 to 5 mm. Modified NEMA NU2-2001 protocols were used in order to simulate performance based on mouse, rat and monkey imaging conditions. These protocols allowed us to directly compare the performance of the proposed geometries with the latest generation of current small animal systems. Results attained demonstrate the potential for higher NECR with CZT based scanners in comparison to scintillator based animal systems.

Design and development of an MR-compatible PET scanner for imaging small animals

A single-slice magnetic resonance (MR) compatible positron emission tomography (PET) system with a transaxial field of view /spl sim/6 cm has been designed and is currently under construction. It will consist of four concentric rings of lutetium oxyorthosilicate (LSO) scintillation crystals, each coupled to one of eight multi-channel photomultiplier tubes (PMTs) via 3.5 m optical fibers. The annulus containing the crystals has an outside diameter of 12 cm and is placed within the MR field of view whilst the PMTs are located outside the main magnetic field. A highly reproducible method that optimizes the amount of scintillation light that reaches the PMTs has been established. Two small sections of the scanner, each containing 4 by 4 crystal arrays, demonstrated good flood position histograms with all sixteen channels clearly identifiable. The light loss through a fiber of length of 3.25 m was approximately 70%. The spatial resolution of the two arrays in coincidence was measured at 1.6 mm full-width half-maximum (FWHM), and the temporal resolution of one array in coincidence with a single LSO crystal was measured to be 10.9 ns. The design incorporates a novel technique for improving sampling at the center of the field of view within the scanner. The concentric rings are offset with respect to one another by one quarter of the crystal width between layers resulting in significantly improved sampling. The results indicate that the PET scanner will have a performance comparable with that of current small animal systems and it will be used to investigate the utility and potential applications of combining PET and MR in small animals.

A high-throughput whole-body PET scanner using flat panel PS-PMTs

A new positron emission tomography (PET) scanner for whole-body studies has been developed. The scanner has 720 block detectors, each of which consists of a flat panel position-sensitive photomultiplier and a 16/spl times/8 BGO crystal array. The detector system is composed of 12 layers of block detector rings stacked axially, and each ring consists of a circular array of 60 block detectors. Since each block detector ring contains eight crystal rings, the total number of detector rings is 96 and the axial field of view (FOV) is 685 mm, which is sufficient to measure a whole-body with two steps of scan. The detector ring diameter is 1 020 mm and the transaxial FOV is 600 mm in diameter. Coarse slice septa are placed between the block detector rings, which are effective to reduce scattered coincidence events while keeping a high detection sensitivity. Parallel 16 personal computers are used for the data acquisition and processing to deal with a large amount of event data. The acquired data in 3-D manner are converted to 2-D data set with Fourier rebinning algorithm and reconstructed with a fast iterative algorithm "DRAMA". The reconstructed images for the whole body are obtained within 5 min after the scan. By using the coarse septa, the scatter fraction measured with NEMA NU2-2001 standard was 31.4% whose value was significantly lower than that of 3-D PET without septa. The system sensitivity was 9.72 cps/kBq, and the peak counts of the noise equivalent count rate used with direct random-subtraction was 113.6 kcps at 10.5 kBq/ml.

Optimization and performance evaluation of the microPET II scanner for in vivo small-animal imaging

MicroPET II is a newly developed PET (positron emission tomography) scanner designed for high-resolution imaging of small animals. It consists of 17 640 LSO crystals each measuring 0.975 × 0.975 × 12.5 mm3, which are arranged in 42 contiguous rings, with 420 crystals per ring. The scanner has an axial field of view (FOV) of 4.9 cm and a transaxial FOV of 8.5 cm. The purpose of this study was to carefully evaluate the performance of the system and to optimize settings for in vivo mouse and rat imaging studies. The volumetric image resolution was found to depend strongly on the reconstruction algorithm employed and averaged 1.1 mm (1.4 µl) across the central 3 cm of the transaxial FOV when using a statistical reconstruction algorithm with accurate system modelling. The sensitivity, scatter fraction and noise-equivalent count (NEC) rate for mouse- and rat-sized phantoms were measured for different energy and timing windows. Mouse imaging was optimized with a wide open energy window (150–750 keV) and a 10 ns timing window, leading to a sensitivity of 3.3% at the centre of the FOV and a peak NEC rate of 235 000 cps for a total activity of 80 MBq (2.2 mCi) in the phantom. Rat imaging, due to the higher scatter fraction, and the activity that lies outside of the field of view, achieved a maximum NEC rate of 24 600 cps for a total activity of 80 MBq (2.2 mCi) in the phantom, with an energy window of 250–750 keV and a 6 ns timing window. The sensitivity at the centre of the FOV for these settings is 2.1%. This work demonstrates that different scanner settings are necessary to optimize the NEC count rate for different-sized animals and different injected doses. Finally, phantom and in vivo animal studies are presented to demonstrate the capabilities of microPET II for small-animal imaging studies.

A new high-resolution PET scanner dedicated to brain research

A high-resolution positron emission tomography (PET) scanner dedicated to brain studies has been developed and its physical performance was evaluated. The block detector consists of a new compact position-sensitive photomultiplier tube (PS-PMT, Hamamatsu R7600-C12) and an 8/spl times/4 bismuth germanate (BGO) array. The size of each crystal is 2.8 mm/spl times/6.55 mm/spl times/30 mm. The system has a total of 11 520 crystals arranged in 24 detector rings 508 mm in diameter (480 per ring). The field of view (FOV) is 330 mm in diameter/spl times/163 mm, which is sufficient to measure the entire human brain. The diameter of the scanner's opening is equal to the transaxial FOV (330 mm). The system can be operated in three-dimensional (3-D) data acquisition mode, when the slice septa are retracted. The mechanical motions of the gantry and bed are specially designed to measure the patient in various postures; lying, sitting, and even standing postures. The spatial resolution of 2.9 mm in both the transaxial and axial directions is obtained at the center of the FOV. The total system sensitivity is 6.4 kc/s/kBq/ml in two-dimensional (2-D) mode, with a 20-cm-diameter cylindrical phantom. The imaging capabilities of the scanner were studied with the Hoffman brain phantom and with a normal volunteer.

Randoms simulation for dual head coincidence imaging of cylindrically symmetric source distributions

High detector singles rates in Dual Head Coincidence Imaging (DHCI) produce significant randoms fractions in the acquired data. Although some DHCI systems provide a means to estimate randoms, randoms correction is not routinely performed in DHCI. We simulate random coincidence data from cylindrically symmetric objects in a DHCI system with 51-cm/spl times/37-cm detectors of 9.5-mm thick NaI(TI) spaced 63 cm apart. The randoms are normalized as if they were true events and reconstructed using 3D reprojection. The reconstructed normalized random coincidences are broadly distributed throughout the field of view (FOV). Axially, they peak toward the center of activity; they have a transaxial structure that is weakly object-dependent. Transaxial randoms image profiles of cylindrically symmetric objects have an offset at the transaxial FOV edge and a broad peak toward the FOV center. Centered spheres and cylinders can produce cold lines along the axis of rotation, whereas flood sources create randoms distributions that peak along the axis of rotation. A Monte Carlo investigation of the bias and variance that randoms contribute to images of a 20-cm cylinder acquired for 20 minutes at a singles rate of 400 photopeak kcps per detector is described. Without attenuation correction, randoms contribute an average bias equal to 9.2% of the mean true+scatter image intensities over the cylinder. Attenuation correction without randoms subtraction amplifies this error. Randoms subtraction with attenuation correction does not significantly boost the image noise for the 20-cm cylinder.

Performance study of a 3D small animal PET scanner based on BaF 2 crystals and a photo sensitive wire chamber

A 3D small animal PET scanner, designed and built at the University of Brussel, has been operational since the beginning of 1996. The scanner has a transaxial field of view (FOV) of 110 mm and an axial FOV of 52 mm. The absolute sensitivity is around 35,000 coincidences s −1 MBq −1 for a point source at the center of the scanner and the time resolution is 29 ns FWHM. To measure the achievable spatial resolution, a thin 22Na source was scanned at various distances from the scanner axis. The resolution in a reconstructed image for a source close to the center is 3.0 mm FWHM. This figure can be improved at the expense of the sensitivity by lowering the voltage on the anodes in the wire chamber. Finally, to assess the overall image quality, scans were made of a cylindrical phantom with holes of varying diameter.

Three-dimensional performance of a small-diameter positron emission tomograph

Recently, the initial 2D physical characterization of a small-diameter positron emission tomograph, designed specifically for scanning of small laboratory animals, was reported. The physical characteristics of the tomograph operating in 3D mode have now been measured and compared to those obtained in 2D mode. In 3D, the transaxial resolution was measured as full width at half maximum (FWHM) and full width at tenth maximum (FWTM) at the centre of the transaxial field of view (FOV). These values degraded to (tangential) and (radial) FWHM and (tangential) and (radial) FWTM, respectively, at a radial distance of 40 mm from the centre of the transaxial FOV. The axial resolution was measured as FWHM and FWTM at the centre of the transaxial FOV, increasing to FWHM and FWTM at a radial distance of 40 mm from the centre of the transaxial FOV. These resolutions are similar to those obtained for the tomograph operating in 2D mode. The sensitivity of the tomograph operating in 3D was at 250 - 850 keV compared to in 2D at the same energy thresholds. In this energy window the noise equivalent count rate peaked at , compared to in 2D. A scatter fraction of 30.2% at 250 - 850 keV was measured for a line source centred in a 60 mm diameter water filled phantom in 3D, compared to 31.0% in 2D for the same scanning geometry and energy thresholds. A comparison was made between 2D and 3D kinetic analyses for a group of five anaesthetized rats scanned using [] SCH 23390, a marker of dopamine receptors. The integrity of the results was maintained between 2D and 3D data sets, though in 3D there was a significant reduction in the standard error of the fitted parameter. The results demonstrate that, with regard to sensitivity, there are significant gains in the physical performance of this tomograph when operating in 3D compared to 2D mode and that the quantification of PET studies of small animals using the 3D data reflects this.

Digital coincidence detection: a scanning VLSI implementation

The authors have implemented a modular digital coincidence detection circuit in VLSI, which drastically reduces the size and increases the performance of the coincidence detection logic required in a PET (positron emission tomography) scanner. Important acquisition features contained within this integrated solution include: (1) prompt and delayed processing channels for each event-pair, with programmable coincidence time windows; (2) event time difference mode, which allows for a fast and accurate system timing calibration algorithm; (3) programmable axial event acceptance, which provides acquisition flexibility from conventional 2-D through fully 3-D sinogram sets; and (4) programmable transaxial field of view, which provides an electronic collimator to ignore event-pairs outside of the desired field of view. The modularity of the design allows it to be used on various system geometries. >