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The ClearPET project
(2004)
The Crystal Clear Collaboration has designed and is building a high-resolution small animal PET scanner. The design is based on the use of the Hamamatsu R7600-M64 multi-anode photomultiplier tube and a LSO/LuYAP phoswich matrix with one to one coupling between the crystals and the photo-detector. The complete system will have 80 PM tubes in four rings with an inner diameter of 137 mm and an axial field of view of 110 mm. The PM pulses are digitized by free-running ADCs and digital data processing determines the gamma energy, the phoswich layer and even the pulse arrival time. Single gamma interactions are recorded and coincidences are found by software. The gantry allows rotation of the detector modules around the field of view. Simulations, and measurements a 2×4 module test set-up predict a spatial resolution of 1.5 mm in the centre of the field of view and a sensitivity of 5.9% for a point source in the centre of the field of view.
The ClearPET™ project is proposed by working groups of the Crystal Clear Collaboration (CCC) to develop a 2nd generation high performance small animal positron emission tomograph (PET). High sensitivity and high spatial resolution is foreseen for the ClearPET™ camera by using a phoswich arrangement combining mixed lutetium yttrium aluminum perovskite (LuYAP:Ce) and lutetium oxyorthosilicate (LSO) scintillating crystals. Design optimizations for the first photomultiplier tube (PMT) based ClearPET camera are done with a Monte-Carlo simulation package implemented on GEANT3 (CERN, Geneva, Switzerland). A dual-head prototype has been built to test the frontend electronics and was used to validate the implementation of the GEANT3 simulation tool. Multiple simulations were performed following the experimental protocols to measure the intrinsic resolution and the sensitivity profile in axial and radial direction. Including a mean energy resolution of about 27.0% the simulated intrinsic resolution is about (1.41±0.11)mm compared to the measured of (1.48±0.06)mm. The simulated sensitivity profiles show a mean square deviation of 12.6% in axial direction and 3.6% in radial direction. Satisfactorily these results are representative for all designs and confirm the scanner geometry.
MultiChannel Photomultipliers (PM), like the R7600-00-M64 or R5900-00-M64 from Hamamatsu, are often chosen as photodetectors in high-resolution positron emission tomography (PET). A major problem of this PM is the nonuniform channel gain. In order to solve this problem, light attenuating masks were created. The aim of the masks is a homogenization of the output of all 64 channels using different hole sizes at the channel positions. The hole area, which is individually defined for the different channels, is inversely proportional to the channel gain. The measurements by inserting light attenuating masks improved a homogenization to a ratio of 1:1.2.
Within the Crystal Clear Collaboration a modular system for a small animal PET scanner (ClearPET™) has been developed. The modularity allows the assembly of scanners of different sizes and characteristics in order to fit the specific needs of the individual member institutions. Now a first demonstrator is being completed in Julich. The system performs depth of interaction detection by using a phoswich arrangement combining LSO and LuYAP scintillators which are coupled to multi-channel photomultipliers (PMTs). A free-running ADC digitizes the signal from the PMT and the complete scintillation pulses are sampled by an FPGA and sent with 20 MB/S to a PC for preprocessing. The pulse provides information about the gamma energy and the scintillator material which identifies the interaction layer. Furthermore, the exact pulse starting time is obtained from the sampled data. This is important as no hardware coincidence detection is implemented. All single events are recorded and coincidences are identified by software. An advantage of that is that the coincidence window and the dimensions of the field of view can be adjusted easily. The ClearPET™ demonstrator is equipped with 10240 crystals on 80 PMTs. This paper presents an overview of the data acquisition system.
A 2nd generation high performance small animal PET scanner, called ClearPET™, has been designed and a first prototype is built by working groups of the Crystal Clear Collaboration (CCC). In order to achieve high sensitivity and maintain good uniform spatial resolution over the field of view in high resolution PET systems, it is necessary to extract the depth of interaction (DOI) information and correct for spatial degradation. The design of the first ClearPET™ Demonstrator based on the use of the multi-anode photomultiplier tube (Hamamatsu R7600-M64) and a LSO/LuYAP phoswich matrix. The two crystal layers of 8*8 crystals (2*2*10 mm3) are stacked on each other and mounted without light guide as one to one on the PMT. A unit of four PMTs arranged in-line represents one of 20 sectors of the ring design. The opening diameter of the crystal ring is 137 mm, the axial detector length is 110 mm. The PMT pulses are digitized by free-running ADCs and digital data processing determines the gamma energy, the phoswich layer and even the pulse arrival time. Single gamma interactions are recorded and coincidences are found by software. The gantry allows rotation of the detector modules around the field of view. The measurements have been done using the first LSO/LuYAP detector cassettes.
This study has been performed to design the combination of the new ClearPET TM (ClearPET is a trademark of the Crystal Clear Collaboration), a small animal Positron Emission Tomography (PET) system, with a microComputed Tomography (microCT) scanner. The properties of different microCT systems have been determined by simulations based on GEANT4. We demonstrate the influence of the detector material and the X-ray spectrum on the obtained contrast. Four different detector materials (selenium, cadmium zinc telluride, cesium iodide and gadolinium oxysulfide) and two X-ray spectra (a molybdenum and a tungsten source) have been considered. The spectra have also been modified by aluminum filters of varying thickness. The contrast between different tissue types (water, air, brain, bone and fat) has been simulated by using a suitable phantom. The results indicate the possibility to improve the image contrast in microCT by an optimized combination of the X-ray source and detector material.
Pulse shape discrimination of LSO and LuYAP scintillators for depth of interaction detection in PET
(2003)
A feasible way to gain the depth of interaction information in a positron emission tomography scanner is the use of phoswich detectors. In general, the layer of interaction is identified from the pulse shape of the corresponding scintillator material. In this work, pulses from LSO and LuYAP crystals were investigated in order to find a practical method of distinguishing. It turned out that such a pulse processing could be kept simple because of an additional slow component in the light decay of the LuYAP pulse. At the same time, the short decay time guarantees that the major amount of the light output is still collected within a short pulse recording time.
Pulse shape discrimination of LSO and LuYAP scintillators for depth of interaction detection in PET
(2003)
A feasible way to gain the depth of interaction information in a PET scanner is the use of phoswich detectors. In general the layer of interaction is identified front the pulse shape of the corresponding scintillator material. In this work pulses from LSO and LuYAP crystals were investigated in order to find a practical method of distinguishing. It turned out that such a pulse processing could he kept simple due to an additional slow component in the light decay of the LuYAP pulse. At the same time the short decay time guarantees that the major amount of the light output is still collected within a short pulse recording time.
Within the Crystal Clear Collaboration (CCC), four centers are developing second generation high performance small animal positron emission tomography (PET) scanners for different kinds of animals and medical applications. The first prototypes are photomultiplier tube (PMT)-based systems including depth of interaction (DOI) detection by using a phoswich layer of lutetium oxyorthosilicate (LSO) and lutetium yttrium aluminum perovskite (LuYAP). The aim of these simulation studies is to optimize sensitivity and spatial resolution of given designs, which vary in fields of view (FOVs) caused by different detector configurations (ring/octagon) and sizes. For this purpose the simulation tool GEANT3 (CERN, Geneva, Switzerland) was used.
Within the Crystal Clear Collaboration four centres are developing 2nd generation high performance small animal PET scanners for different kinds of animals and medical applications. The first prototypes are PMT-based systems including depth of interaction (DOI) detection by using a phoswich layer of LSO and LuYAP. The aim of these simulation studies is to optimize sensitivity and spatial resolution of given designs, which vary in FOVs caused by different detector configurations (ring/octagon) and sizes. For this purpose the simulation tool GEANT3 (CERN) was used. The simulations have shown that all PMT designs with one-to-one coupling of crystals have a very nonlinear axial sensitivity profile. By shifting every other PMT 1/4 of a PMT length in axial direction the sampling of the FOVs became more homogeneous. At an energy threshold of 350keV the regression coefficient increases from 0.818 for the non-shifted to 0.993 for the shifted design. Simulations of a point source centred in the FOV (threshold: 350keV) resulted in sensitivities of 4.2% for a 4×20PMT (LSO/LuYAP a 10mm) and 3.8% for a 4×16PMT (LSO/LuYAP a 8mm) ring design. The 3D-MLEM reconstruction of a point source shows the enormous improvement of resolution using a crystal double layer with DOI (3.1mm at 40mm from CFOV) instead of a 20mm single layer (11.9mm).
Within the developments for the Crystal Clear small animal PET project (CLEARPET) a dual head PET system has been established. The basic principle is the early digitization of the detector pulses by free running ADCs. The determination of the γ-energy and also the coincidence detection is performed by data processing of the sampled pulses on the host computer. Therefore a time mark is attached to each pulse identifying the current cycle of the 40 MHz sampling clock. In order to refine the time resolution the pulse starting time is interpolated from the samples of the pulse rise. The detector heads consist of multichannel PMTs with a single LSO scintillator crystal coupled to each channel. For each PMT only one ADC is required. The position of an event is obtained separately from trigger signals generated for each single channel. An FPGA is utilized for pulse buffering, generation of the time mark and for the data transfer to the host via a fast I/O-interface.
We are developing an X-ray computed tomography (CT) system which will be combined with a high resolution animal PET system. This permits acquisition of both molecular and anatomical images in a single machine. In particular the CT will also be utilized for the quantification of the animal PET data by providing accurate data for attenuation correction. A first prototype has been built using a commercially available plane silicon diode detector. A cone-beam reconstruction provides the images using the Feldkamp algorithm. First measurements with this system have been performed on a mouse. It could be shown that the CT setup fulfils all demands for a high quality image of the skeleton of the mouse. It is also suited for soft tissue measurements. To improve contrast and resolution and to acquire the X-ray energy further development of the system, especially the use of semiconductor detectors and iterative reconstruction algorithms are planned.
Coincident events in two scintillator crystals coupled to photomultipliers (PMT) are detected by processing just the digital data of the recorded pulses. For this purpose the signals from both PMTs are continuously sampled by free-running ADCs at a sampling rate of 40 MHz. For each sampled pulse the starting time is determined by processing the pulse data. Even a fairly simple interpolating algorithm results in a FWHM of about 2 ns.
A small PET system has been built up with two multichannel photomultipliers, which are attached to a matrix of 64 single LSO crystals each. The signal from each multiplier is being sampled continuously by a 12 bit ADC at a sampling frequency of 40 MHz. In case of a scintillation pulse a subsequent FPGA sends the corresponding set of samples together with the channel information and a time mark to the host computer. The data transfer is performed with a rate of 20 MB/s. On the host all necessary information is extracted from the data. The pulse energy is determined, coincident events are detected and multiple hits within one matrix can be identified. In order to achieve a narrow time window the pulse starting time is refined further than the resolution of the time mark (=25 ns) would allow. This is possible by interpolating between the pulse samples. First data obtained from this system will be presented. The system is part of developments for a much larger system and has been created to study the feasibility and performance of the technique and the hardware architecture.
The optimization of light output and energy resolution of scintillators is of special interest for the development of high resolution and high sensitivity PET. The aim of this work is to obtain statistically reliable results concerning optimal surface treatment of scintillation crystals and the selection of reflector material. For this purpose, raw, mechanically polished and etched LSO crystals (size 2×2×10 mm3) were combined with various reflector materials (Teflon tape, Teflon matrix, BaSO4) and exposed to a 22Na source. In order to ensure the statistical reliability of the results, groups of 10 LSO crystals each were measured for all combinations of surface treatment and reflector material. Using no reflector material the light output increased up to 551±35% by mechanical polishing the surface compared to 100±5% for raw crystals. Etching the surface increased the light output to 441±29%. The untreated crystals had an energy resolution of 24.6±4.0%. By mechanical polishing the surface it was possible to achieve an energy resolution of 13.2±0.8%, by etching of 14.8±0.7%. In combination with BaSO4 as reflector material the maximum increase of light output has been established to 932±57% for mechanically polished and 895±61% for etched crystals. The combination with BaSO4 also caused the best improvement of the energy resolution up to 11.6±0.2% for mechanically polished and 12.2±0.3% for etched crystals. Relating to the light output there was no significant statistical difference between the two surface treatments in combination with BaSO4. In contrast to this, the statistical results of the energy resolution have shown the combination of mechanical polishing and BaSO4 as the optimum.
Pulses from a position-sensitive photomultiplier (PS-PMT) are recorded by free-running ADCs at a sampling rate of 40 MHz. A four-channel acquisition board has been developed which is equipped with four 12-bit ADCs connected to one field programmable gate array (FPGA). The FPGA manages data acquisition and the transfer to the host computer. It can also work as a digital trigger, so a separate hardware trigger can be omitted. The method of free-running sampling provides a maximum of information, besides the pulse charge and amplitude also pulse shape and starting time are contained in the sampled data. This information is crucial for many tasks such as distinguishing between different scintillator materials, determination of radiation type, pile-up recovery, coincidence detection or time-of-flight applications. The absence of an analog integrator allows very high count rates to be dealt with. Since this method is to be employed in positron emission tomography (PET), the position of an event is also important. The simultaneous readout of four channels allows localization by means of center-of-gravity weighting. First results from a test setup with LSO scintillators coupled to the PS-PMT are presented here
Pulses from a position-sensitive photomultiplier (PS-PMT) are recorded by free running ADCs at a sampling rate of 40 MHz. A four-channel acquisition-board has been developed which is equipped with four 12 bit-ADCs connected to one FPGA (field programmable gate array). The FPGA manages data acquisition and the transfer to the host computer. It can also work as a digital trigger, so a separate hardware-trigger can be omitted. The method of free running sampling provides a maximum of information, besides the pulse charge and amplitude also pulse shape and starting time are contained in the sampled data. These informations are crucial for many tasks such as distinguishing between different scintillator materials, determination of radiation type, pile-up recovery, coincidence detection or time-of-flight applications. The absence of an analog integrator allows coping with very high count rates. Since this method is going to be employed in positron emission tomography (PET), the position of an event is another important information. The simultaneous readout of four channels allows localization by means of center-of-gravity weighting. First results from a test setup with LSO-scintillators coupled to the PS-PMT are presented
A network of brain areas is expected to be involved in supporting the motion aftereffect. The most active components of this network were determined by means of an fMRI study of nine subjects exposed to a visual stimulus of moving bars producing the effect. Across the subjects, common areas were identified during various stages of the effect, as well as networks of areas specific to a single stage. In addition to the well-known motion-sensitive area MT the prefrontal brain areas BA44 and 47 and the cingulate gyrus, as well as posterior sites such as BA37 and BA40, were important components during the period of the motion aftereffect experience. They appear to be involved in control circuitry for selecting which of a number of processing styles is appropriate. The experimental fMRI results of the activation levels and their time courses for the various areas are explored. Correlation analysis shows that there are effectively two separate and weakly coupled networks involved in the total process. Implications of the results for awareness of the effect itself are briefly considered in the final discussion.
Single-photon emission tomography (SPET) with the amino acid analogue l-3-[123I]iodo-α-methyl tyrosine (IMT) is helpful in the diagnosis and monitoring of cerebral gliomas. Radiolabelled amino acids seem to reflect tumour infiltration more specifically than conventional methods like magnetic resonance imaging and computed tomography. Automatic tumour delineation based on maximal tumour uptake may cause an overestimation of mean tumour uptake and an underestimation of tumour extension in tumours with circumscribed peaks. The aim of this study was to develop a program for tumour delineation and calculation of mean tumour uptake which takes into account the mean background activity and is thus optimised to the problem of tumour definition in IMT SPET. Using the frequency distribution of pixel intensities of the tomograms a program was developed which automatically detects a reference brain region and draws an isocontour region around the tumour taking into account mean brain radioactivity. Tumour area and tumour/brain ratios were calculated. A three-compartment phantom was simulated to test the program. The program was applied to IMT SPET studies of 20 patients with cerebral gliomas and was compared to the results of manual analysis by three different investigators. Activity ratios and chamber extension of the phantom were correctly calculated by the automatic analysis. A method based on image maxima alone failed to determine chamber extension correctly. Manual region of interest analysis in patient studies resulted in a mean inter-observer standard deviation of 8.7%±6.1% (range 2.7%–25.0%). The mean value of the results of the manual analysis showed a significant correlation to the results of the automatic analysis (r = 0.91, P<0.0001 for the uptake ratio; r = 0.87, P<0.0001 for the tumour area). We conclude that the algorithm proposed simplifies the calculation of uptake ratios and may be used for observer-independent evaluation of IMT SPET studies. Three-dimensional tumour recognition and transfer to co-registered morphological images based on this program may be useful for the planning of surgical and radiation treatment.