This study has been performed to design the combination of the new ClearPET (ClearPET is a trademark of the Crystal Clear Collaboration), a small animal positron emission tomography (PET) system, with a micro-computed tomography (microCT) scanner. The properties of different microCT systems have been determined by simulations based on GEANT4. We will 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.

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 /spl gamma/-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.

Multi-Pinhole SPECT systems provide high-resolution and high-sensitivity imaging for small animal research. We currently perform SPECT imaging using commercial gamma cameras upgraded with multi-pinhole collimators. We have shown that for most tasks we are capable of achieving reconstructed spatial resolutions as low as 1.2 mm with average sensitivities up to 1600 cps/MBq. In an attempt to achieve better orientation in SPECT images we are equipping a compact commercial gamma camera with an X-ray CT system to create an integrated dual modality system. We are adding the CT system to our gantry to enhance the imaging capabilities of our SPECT system. Our gantry is equipped with a 3D translation stage that enables us to image objects that extend beyond the field of view in the axial direction by performing helical scan orbits. We are capable of performing such helical scan orbits for both modalities. We have designed a cost-effective CT add-on that provides additional anatomical information to the systems users. Specifically, the CT reconstructions aid in the acquisition and interpretation of the corresponding SPECT images.

We present a novel imaging technique based on two orthogonal multi-pinhole detectors. In contrary to conventional SPECT systems, where the detectors are rotated around the object, the detectors are kept stationary in T-SPECT mode while the object is moved through their field of view. Therefore, this new imaging method is called translatory SPECT or T-SPECT. The advantage of this system is a simplification of the whole imaging system in the sense that only the light object has to be moved instead of the heavy weighted detectors. Two commercial gamma cameras are equipped with multi-pinhole collimators to achieve higher sensitivity. As the pinhole axes are tilted in axial and transaxial direction, the object is seen from slightly different directions, even without rotation.

Within the Crystal Clear Collaboration a modular system for a small animal PET scanner (ClearPET(TM)) 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(TM) demonstrator is equipped with 10240 crystals on 80 PMTs. This paper presents an overview of the data acquisition system.

A scanning SQUID microscope based on high-temperature superconductor (HTS) dc-SQUIDs was developed. An extremely soft magnetic amorphous foil was used to guide the flux from room temperature samples to the liquid-nitrogen-cooled SQUID sensor and back. The flux guide passes through the pick-up loop of the HTS SQUID, providing an improved coupling of magnetic flux of the object to the SQUID. The device measures the z component (direction perpendicular to the sample surface) of the stray field of the sample, which is rastered with submicron precision in the x–y direction by a motorized computer-controlled scanning stage. A lateral resolution better than 10 µm, with a field resolution of about 0.6 nT Hz−1/2 was achieved for the determination of the position of the current carrying thin wires. The presence of the soft magnetic foil did not significantly increase the flux noise of the SQUID.

The ClearPET initiative is a project being undertaken by working groups of the Crystal Clear Collaboration (CCC). Its aim is to develop a second-generation high performance small animal positron emission tomograph. The ClearPET/spl trade/ camera is expected to provide both high sensitivity and high spatial resolution. It uses a phoswich arranging combining two types of lutetium-based scintillator materials: LSO and LuYAP:Ce. Based on the same detector modules different designs from each collaboration partner are realized for their associated medical institutes. Each dedicated version is expressed by the name ClearPET/spl trade/ plus an extension. The ClearPET/spl trade/ neuro scanner is a dedicated small animal scanner to allow measurements of signal transduction in non-human primates under physiological conditions. This scanner is build by working groups of the Research Center Julich (FZJ). The gantry allows rotation of the detector modules as well as tilting by 90 degrees to measure non-human primates in an upright sitting position. The opening diameter of the ring is variable between 130 mm and 300 mm, the axial detector length is 110 mm.

The ClearPET® scanners developed by the Crystal Clear Collaboration use multichannel PMTs as photodetectors with scintillator pixels coupled individually to each channel. In order to localize an event each channel anode is connected to a comparator that triggers when the anode signal exceeds a common predefined threshold. Two major difficulties here are crosstalk of light and the gain nonuniformity of the PMT channels. Crosstalk can generate false triggering in channels adjacent to the actual event. On the one hand this can be suppressed by sufficiently increasing the threshold, but on the other hand a threshold too high can already prevent valid events on the lower gain channels from being detected. Finally, both effects restrict the dynamic range of pulse heights that can be processed. The requirements to the dynamic range are not low as the ClearPET® scanners detect the depth of interaction by phoswich pixels consisting of LSO and Lu0.7Y0.3AP, two scintillators with different light yields. We will present a model to estimate the achievable dynamic range and show solutions to increase it.

UNLABELLEDAdenosine modulates brain activity through 4 G protein-coupled receptors, primarily adenosine A(1) receptors (A(1)ARs). A(1)ARs are heterogeneously distributed throughout the brain and participate in many physiologic processes-for example, the induction of sleep and feedback inhibition of excitatory neurotransmission. There is also evidence that A(1)ARs are involved in brain pathologies, including cerebral ischemia, epilepsy, and neurodegeneration. Therefore, measuring A(1)ARs in the living brain has been a long-standing goal. This report describes the preclinical evaluation of (18)F-8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine ((18)F-CPFPX), a novel A(1)AR PET ligand.METHODSCPFPX, a xanthine-based A(1)AR antagonist, was labeled with either (18)F or (3)H, maintaining identical chemical structures, and evaluated in rats as a putative radioligand for in vivo or in vitro imaging of brain A(1)ARs by quantitative receptor autoradiography and the combination of high-resolution small animal PET and MRI.RESULTS(3)H-CPFPX bound with nanomolar affinity (K(d), 4.4 nmol/L) to A(1)ARs and showed a distribution typical of cerebral A(1)ARs. In extensive in vitro competition studies, (3)H-CPFPX proved to be a highly selective and specific A(1)AR radioligand. Neither the nonxanthine-type adenosine A(2A) receptor antagonist ZM 241385 nor multiple cholinergic, serotoninergic, and glutamatergic receptor compounds competed for (3)H-CPFPX below the micromolar level. In vivo animal PET and ex vivo autoradiographic experiments measured radioactivity in discrete brain regions after intravenous injection of (18)F-CPFPX. (18)F-CPFPX had excellent in vivo stability and penetrated the blood-brain barrier immediately after injection due to its high lipophilicity. Brain uptake was rapid and particularly high in gray matter regions. Retention of (18)F-CPFPX was highest in the cerebellum, thalamus, and neocortex with evidence of saturable binding. Low binding potentials were found in the midbrain. In vivo displacement PET experiments with the A(1)AR antagonist 8-cyclopentyl-1,3-dipropylxanthine showed a 72% +/- 8% displacement of (18)F-CPFPX.CONCLUSION(18)F-CPFPX is a highly selective and specific ligand for A(1)ARs and a suitable radioligand for noninvasive PET imaging of A(1)ARs in the living brain. These studies also support the application of high-resolution animal PET as an effective in vivo imaging tool in the evaluation process of new radioligands.

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.

Adenosine modulates brain activity through 4 G protein- cou- pled receptors, primarily adenosine A1 receptors (A1ARs). A1ARs are heterogeneously distributed throughout the brain and par- ticipate in many physiologic processes—for example, the in- duction of sleep and feedback inhibition of excitatory neuro- transmission. There is also evidence that A1ARs are involved in brain pathologies, including cerebral ischemia, epilepsy, and neurodegeneration. Therefore, measuring A1ARs in the living brain has been a long-standing goal. This report describes the preclinical evaluation of 18F-8-cyclopentyl-3-(3-fluoropropyl)-1- propylxanthine (18F-CPFPX), a novel A1AR PET ligand. Meth- ods: CPFPX, a xanthine-based A1AR antagonist, was labeled with either 18 Fo r3H, maintaining identical chemical structures, and evaluated in rats as a putative radioligand for in vivo or in vitro imaging of brain A1ARs by quantitative receptor autora- diography and the combination of high-resolution small animal PET and MRI. Results: 3H-CPFPX bound with nanomolar affin- ity (Kd, 4.4 nmol/L) to A1ARs and showed a distribution typical of cerebral A1ARs. In extensive in vitro competition studies, 3H- CPFPX proved to be a highly selective and specific A1AR radio- ligand. Neither the nonxanthine-type adenosine A2A receptor antagonist ZM 241385 nor multiple cholinergic, serotoninergic, and glutamatergic receptor compounds competed for 3H- CPFPX below the micromolar level. In vivo animal PET and ex vivo autoradiographic experiments measured radioactivity in discrete brain regions after intravenous injection of 18F-CPFPX. 18F-CPFPX had excellent in vivo stability and penetrated the blood- brain barrier immediately after injection due to its high lipophilicity. Brain uptake was rapid and particularly high in gray matter regions. Retention of 18F-CPFPX was highest in the cerebellum, thalamus, and neocortex with evidence of saturable binding. Low binding potentials were found in the midbrain. In vivo displacement PET experiments with the A1AR antagonist 8-cyclopentyl-1,3-dipropylxanthine showed a 72% 8% dis- placement of 18F-CPFPX. Conclusion: 18F-CPFPX is a highly selective and specific ligand for A1ARs and a suitable radioli- gand for noninvasive PET imaging of A1ARs in the living brain. These studies also support the application of high-resolution animal PET as an effective in vivo imaging tool in the evaluation process of new radioligands.

We present our results on the development and characterization of a prototype of Hilbert spectrometer, which is intended to operate with pulsed far-infrared radiation. The new prototype consists of high-T/sub c/ Josephson detector in an optical cryostat, analog electronics with the bandwidth of 14 MHz, and a DSP-based data acquisition system, controlling spectroscopic measurements. The specially developed digital data acquisition system gives a possibility to operate in two regimes - with and without integration of the pulsed signal. The tests have been carried out using pulsed 94 GHz radiation with pulse duration of 200 ns and a pulse repetition rate of 1 MHz. A measuring time of 7 ms for a data set of 512 spectral points has been realized. It has been demonstrated, that in a broadband (/spl ap/10 MHz) regime of measurements without integration the developed spectrometer has a dynamic range of external signal power of 17 dB, which can be enhanced by using integration function.

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.