Rob Kreuger

VECTor: A Preclinical Imaging System for Simultaneous Submillimeter SPECT and PET

Today, PET and SPECT tracers cannot be imaged simultaneously at high resolutions but require 2 separate imaging systems. This paper introduces a Versatile Emission Computed Tomography system (VECTor) for radionuclides that enables simultaneous submillimeter imaging of single-photon and positron-emitting radiolabeled molecules. Methods: γ-photons produced both by electron–positron annihilation and by single-photon emitters are projected onto the same detectors by means of a novel cylindric high-energy collimator containing 162 narrow pinholes that are grouped in clusters. This collimator is placed in an existing SPECT system (U-SPECT-II) with 3 large-field-of-view γ-detectors. From the acquired projections, PET and SPECT images are obtained using statistical image reconstruction that corrects for energy-dependent system blurring. Results: For PET tracers, the tomographic resolution obtained with a Jaszczak hot rod phantom was less than 0.8 mm, and 0.5-mm resolution images of SPECT tracers were acquired simultaneously. SPECT images were barely degraded by the simultaneous presence of a PET tracer, even when the activity concentration of the PET tracer exceeded that of the SPECT tracer by up to a factor of 2.5. Furthermore, we simultaneously acquired fully registered 3- and 4-dimensional multiple functional images from living mice that, in the past, could be obtained only sequentially. Conclusion: High-resolution complementary information about tissue function contained in SPECT and PET tracer distributions can now be obtained simultaneously using a fully integrated imaging device. These combined unique capabilities pave the way for new perspectives in imaging the biologic systems of rodents.

An enhanced high-resolution EMCCD-based gamma camera using SiPM side detection

Electron-multiplying charge-coupled devices (EMCCDs) coupled to scintillation crystals can be used for high-resolution imaging of gamma rays in scintillation counting mode. However, the detection of false events as a result of EMCCD noise deteriorates the spatial and energy resolution of these gamma cameras and creates a detrimental background in the reconstructed image. In order to improve the performance of an EMCCD-based gamma camera with a monolithic scintillation crystal, arrays of silicon photon-multipliers (SiPMs) can be mounted on the sides of the crystal to detect escaping scintillation photons, which are otherwise neglected. This will provide a priori knowledge about the correct number and energies of gamma interactions that are to be detected in each CCD frame. This information can be used as an additional detection criterion, e.g. for the rejection of otherwise falsely detected events. The method was tested using a gamma camera based on a back-illuminated EMCCD, coupled to a 3 mm thick continuous CsI:Tl crystal. Twelve SiPMs have been mounted on the sides of the CsI:Tl crystal. When the information of the SiPMs is used to select scintillation events in the EMCCD image, the background level for (99m)Tc is reduced by a factor of 2. Furthermore, the SiPMs enable detection of (125)I scintillations. A hybrid SiPM-/EMCCD-based gamma camera thus offers great potential for applications such as in vivo imaging of gamma emitters.

U-SPECT-BioFluo: an integrated radionuclide, bioluminescence, and fluorescence imaging platform

BackgroundIn vivo bioluminescence, fluorescence, and single-photon emission computed tomography (SPECT) imaging provide complementary information about biological processes. However, to date these signatures are evaluated separately on individual preclinical systems. In this paper, we introduce a fully integrated bioluminescence-fluorescence-SPECT platform. Next to an optimization in logistics and image fusion, this integration can help improve understanding of the optical imaging (OI) results.MethodsAn OI module was developed for a preclinical SPECT system (U-SPECT, MILabs, Utrecht, the Netherlands). The applicability of the module for bioluminescence and fluorescence imaging was evaluated in both a phantom and in an in vivo setting using mice implanted with a 4 T1-luc + tumor. A combination of a fluorescent dye and radioactive moiety was used to directly relate the optical images of the module to the SPECT findings. Bioluminescence imaging (BLI) was compared to the localization of the fluorescence signal in the tumors.ResultsBoth the phantom and in vivo mouse studies showed that superficial fluorescence signals could be imaged accurately. The SPECT and bioluminescence images could be used to place the fluorescence findings in perspective, e.g. by showing tracer accumulation in non-target organs such as the liver and kidneys (SPECT) and giving a semi-quantitative read-out for tumor spread (bioluminescence).ConclusionsWe developed a fully integrated multimodal platform that provides complementary registered imaging of bioluminescent, fluorescent, and SPECT signatures in a single scanning session with a single dose of anesthesia. In our view, integration of these modalities helps to improve data interpretation of optical findings in relation to radionuclide images.

Multiplexed Eighty Channel PMT List-Mode Data Acquisition System for 27–511 keV Gamma Ray Imaging

We have developed an 80-channel readout system for gamma cameras which acquires PMT signals and stores them in list-mode format on a computer. The system combines low noise and a large signal range to handle PMT signals from a wide range of SPECT and PET tracers simultaneously (27 to 511 keV). All channels of the read-out system have a gated integrator to determine the charge per event. Each 16 channels are multiplexed to a 12-bit 40 MS/s pipelined ADCs. Using multiplexing only 5 ADCs are needed which share a commercial USB 2.0 interface board to send the event data to the computer. The signal input range is up to 120 pC with a noise level of 57 fC. The integral non-linearity is better than 1% for all channels, while the channel response has a gain non-uniformity less than 2.4% for the different channels. The crosstalk between channels is better than 64 dB. The dead time is 2.5 μs, including a 760 ns integration period. The system can handle a sustained event rate of 155 kcps on the USB 2.0 bus. Connected to a clinical gamma camera we show that the isotopes 125I (27-35 keV), 99mTc (140.5 keV) and 22Na (511 keV) can all be imaged without electronic adjustments thus enabling, for instance, simultaneous pinhole PET/SPECT. With this PMT list-mode acquisition system, advanced offline event positioning and energy estimation with e.g. maximum likelihood methods are enabled.

SiPM side detectors for performance enhancements of an EMCCD-based gamma camera

To achieve ultra-high spatial resolution gamma ray imaging, the use of charge-coupled devices (CCDs) has become of great interest. However, these detectors still suffer from performances degradations due to their high intrinsic noise level. In our developped electron-multiplying CCD based gamma camera, we have introduced the use of solid state photomultipliers in side detection of a continuous crystal to improve the signal-to-background ratio and energy resolution. The so-called silicon photomultipliers (SiPMs) are individually read-out to measure the previously lost optical photons escaping through the crystal sides to give an a-priori evaluation of the energy and position of the γ-rays interactions to a statistical algorithm for EM-CCD image analysis. In this work, we show the results obtained using 12 SiPMs optically coupled to a 3 mm thick CsI:Tl crystal where the prelocated events are reconstructed using a maximum likelihood algorithm. This algorithm uses Look-Up Tables (LUTs) evaluated by Monte-Carlo simulations to retrieve the interaction positions via the individual SiPMs signals. The spatial resolution obtained with this process is evaluated at 0.8 mm using a 200 µm pinhole collimator with a 99mTc source. The energy resolution is then measured at 19% for the 140 keV γ-rays emission.

Novel light-guide-PMT geometries to reduce dead edges of a scintillation camera

Anger cameras based on monolithic NaI scintillators read out by an array of PMTs are predominant in planar gamma imaging and SPECT. However, position estimation of gamma interactions is usually severely degraded near the edges of the scintillator which can be extremely undesirable for applications like breast imaging. Here we propose a relatively cost-effective solution based on the use of scintillators with absorptive edges with an unconventional light-guide-PMT layout employing a maximum likelihood positioning algorithm. The basic design on which we aim to improve consists of a monolithic NaI(Tl) scintillator read out by 3 × 5 square PMTs (conventional layout, CL) that could be suitable for molecular breast imaging. To better detect gamma interactions near the crystals critical edge, we tried different set-ups: we replaced the 5 large PMTs near the edge by 11 smaller PMTs (small-sensor layout, SSL); we emulated rectangular PMTs along the critical edge by inserting a row of 5 rectangular light-guides that direct the light toward square PMTs placed behind (shifted layout, SL); we inserted rectangular light-guides alternatingly, such that the PMTs are in an interlocking pattern (alternating shifted layout, ASL). The performance of our designs was tested with Monte Carlo simulations. Results showed that SSL, SL, and ASL gave better spatial resolution near the critical edge than CL (3.4, 3.6, and 4.1 mm near the edge compared with 5.3 mm for CL), and thus resulted in a larger usable detector area. To conclude, for applications where small dead edges are crucial, our designs may be cost-effective solutions.