F.J. Beekman

System Calibration and Statistical Image Reconstruction for Ultra-High Resolution Stationary Pinhole SPECT

For multipinhole single-photon emission computed tomography (SPECT), iterative reconstruction algorithms are preferred over analytical methods, because of the often complex multipinhole geometries and the ability of iterative algorithms to compensate for effects like spatially variant sensitivity and resolution. Ideally, such compensation methods are based on accurate knowledge of the position-dependent point spread functions (PSFs) specifying the response of the detectors to a point source at every position in the instrument. This paper describes a method for model-based generation of complete PSF lookup tables from a limited number of point-source measurements for stationary SPECT systems and its application to a submillimeter resolution stationary small-animal SPECT system containing 75 pinholes (U-SPECT-I). The method is based on the generalization over the entire object to be reconstructed, of a small number of properties of point-source responses which are obtained at a limited number of measurement positions. The full shape of measured point-source responses can almost be preserved in newly created PSF tables. We show that these PSFs can be used to obtain high-resolution SPECT reconstructions: the reconstructed resolutions judged by rod visibility in a micro-Derenzo phantom are 0.45 mm with 0.6-mm pinholes and below 0.35 mm with 0.3-mm pinholes. In addition, we show that different approximations, such as truncating the PSF kernel, with significant reduction of reconstruction time, can still lead to acceptable reconstructions.

Photon-counting gamma camera based on an electron-multiplying CCD

We have developed a compact ultra-high-resolution gamma camera (UGC), based on an electron-multiplying charge-coupled device (EMCCD) coupled to a columnar CsI(Tl) scintillator. The EMCCD is suitable for photon-counting gamma-camera imaging, since it has an extremely low readout noise, even at high frame rates (<1 electron/pixel at 50 images/s or 11 Mpixel/s). The high frame rate prevents overlapping of scintillation events and reduces the accumulation of dark current noise. In this paper, we describe the drive- and readout electronics of the EMCCD, the image processing hardware and software, and the first ultra-high-resolution gamma-ray images obtained with the UGC. A digital signal processor (DSP) facilitates real-time frame analysis, comprising photon counting and energy discrimination, and reduces the data stream from 162 kB per frame to 8 B per detected scintillation event (i.e., for a typical application in multipinhole single photon emission computed tomography (SPECT) a data reduction from 28 GB/h by a factor of 20 000 to 1.4 MB/h). Such a reduced data stream is needed for applications that require the use of a large number of gamma cameras simultaneously. The image processing hardware that we describe allows the images from the EMCCD to be processed in real-time, at a rate of 50 images per second. First gamma-camera images with a spatial resolution as good as 60 /spl mu/m full-width of half-maximum (FWHM) are shown. The prototype UGC allows for photon counting without the need for an image intensifier and has energy discriminating capabilities.

An efficient simulator for pinhole imaging of PET isotopes

Today, small-animal multi-pinhole single photon emission computed tomography (SPECT) can reach sub-half-millimeter image resolution. Recently we have shown that dedicated multi-pinhole collimators can also image PET tracers at sub-mm level. Simulations play a vital role in the design and optimization of such collimators. Here we propose and validate an efficient simulator that models the whole imaging chain from emitted positron to detector signal. This analytical simulator for pinhole positron emission computed tomography (ASPECT) combines analytical models for pinhole and detector response with Monte Carlo (MC)-generated kernels for positron range. Accuracy of ASPECT was validated by means of a MC simulator (MCS) that uses a kernel-based step for detector response with an angle-dependent detector kernel based on experiments. Digital phantom simulations with ASPECT and MCS converge to almost identical images. However, ASPECT converges to an equal image noise level three to four orders of magnitude faster than MCS. We conclude that ASPECT could serve as a practical tool in collimator design and iterative image reconstruction for novel multi-pinhole PET.

3-D Rat Brain Phantom for High-Resolution Molecular Imaging

With the steadily improving resolution of novel small-animal single photon emission computed tomography (SPECT) and positron emission tomography devices, highly detailed phantoms are required for testing and optimizing these systems. We present a three-dimensional (3-D) digital and physical phantom pair to represent, e.g., cerebral blood flow, glucose metabolism, or neuroreceptor binding in small regions of the rat brain. The anatomical structures are based on digital photographs of the uncut part of a rat brain cryosection block. The photographs have been segmented into ventricles and gray and white matter and have been stacked afterwards. In the resulting voxelized digital phantom, tracer concentration in gray and white matter can be scaled independently. This is of relevance since, e.g., cerebral blood flow or metabolism are much higher in gray than in white matter. The physical phantom is based on the digital phantom and has been manufactured out of hardened polymer using rapid prototyping, a process in which complicated 3-D objects can be built up layer by layer. X-ray computed tomography and high-resolution SPECT images of the physical phantom are compared with the digital phantom. The detailed physical phantom can be filled bubble-free. Excellent correspondence is shown between details in the digital and physical phantom. Therefore, this newly developed brain phantom will enable the optimization of high-resolution imaging for recovery of complex shaped molecular distributions.

System calibration and statistical image reconstruction for sub-mm stationary pinhole SPECT

Iterative SPECT reconstruction requires position-dependent point spread functions (PSFs) specifying the response of the detectors to a point source at every position in the instrument. To obtain accurately reconstructed images, the PSFs should incorporate all important effects of photon transport and imaging geometry. The PSFs can be measured directly, but measuring in each voxel of the object space can be impractical for sub-mm-resolution instruments. This study describes a method for generating complete PSF lookup tables from a limited number of point source measurements for a stationary small-animal SPECT system with 75 pinholes (U-SPECT-I, J. Nucl. Med., 2005, pp. 1194-1200). The method is based on modeling the shape of the PSFs, measured at a limited number of positions. Subsequently the model parameters are generalized to estimate and shape PSFs at missing positions. The method enables us to obtain 0.45 mm reconstructed resolution with 0.6 mm pinholes and 0.35 mm resolution with 0.3 mm pinholes with a SPECT system which has 3.2 mm intrinsic detector resolution

Accurate measurements of the rise and decay times of fast scintillators with solid state photon counters

In this work we present a measurement setup for the determination of scintillation pulse shapes of fast scintillators. It is based on a time-correlated single photon counting approach that utilizes correlation between 511 keV annihilation photons to produce start and stop signals in two, separate crystals. The measurement is potentially cost effective and simple to set up while maintaining an excellent timing resolution of 120 ps. Apart from these advantages this method probes the entire volume of the crystal under investigation rather than a thin layer at the surface. Here, we present a proof-of-concept and first results for the time constants of LYSO.

Penetration, Scatter and Sensitivity in Channel Micro-Pinholes for SPECT: A Monte Carlo Investigation

Channel-edge pinhole designs have been proposed in order to reduce the penetration of gamma rays through the edge of the pinhole aperture. A characterization of penetration and scatter in the pinhole aperture metal can be used in the design of small animal SPECT collimators or for model based corrections during micro-SPECT image reconstruction. In this study the penetration and scatter contributions of micro-pinholes were compared for Tc-99m, I-123, and I-125 for knife-edges and channel-edges. To this end, Geant 4 Monte Carlo simulations of 0.3 mm and 0.5 mm diameter apertures with acceptance angles ranging from 20 to 60 degrees were performed. At perpendicular incidence of the photons, channel pinholes had lower penetration and scatter fractions than did knife-edge pinholes. This advantage disappeared at higher angles of incidence. In addition, the total sensitivity decreased substantially with increasing channel height. Planar projection images of a grid of spheres showed that channel-edge pinholes resulted in a slightly higher spatial resolution than knife-edge pinholes with an equal diameter, when combined with a high-resolution detector. However, the channel-edge pinholes sensitivity and Contrast Inverse Coefficient of Variation were lower than the knife edge pinholes at the edges of the detector. We conclude that channel pinholes can result in lower imaging performance when used with non-perpendicular incidence photons because of loss of sensitivity

EMCCD-based photon-counting mini gamma camera with a spatial resolution < 100 /spl mu/m

Compact gamma cameras with high intrinsic spatial resolution and photon counting capabilities are very desirable for several applications in astronomy, biology and medicine. Here we present a novel photon-counting gamma camera that is based on an Electron-multiplying CCD (EMCCD). Effectively, the EMCCD has sub-electron read out noise, even at 50 frames per second. This high frame rate allows for analyzing individual scintillation events with respect to energy and position. In our camera, the EMCCD is Peltier cooled and a fiber optic taper with a CsI(Tl) columnar crystal layer are mounted on it. By cooling the CCD to -30 degC, dark current noise is negligible. Intrinsic resolution was determined using a line shaped gamma beam, and was better than 100 microns FWHM for both Co-57 and I-125. We conclude that EMCCDs combined with columnar crystals allow for constructing extremely high-resolution photon counting gamma cameras, which are suitable for pinhole SPECT

Electronics for a photon-counting gamma camera based on an electron-multiplying CCD

We have developed a compact ultra-high resolution gamma camera (UGC), based on an Electron-multiplying CCD (EMCCD). The EMCCD can be used for photon-counting gamma-camera imaging, since it has an extremely low readout noise even at high readout rates (>1 electron/pixel at 50 images/s or 11.1 Mpixel/s). The high frame rate facilitates the analysis of individual non-overlapping scintillation events with minimal accumulation of dark current noise. In this article we describe the drive- and readout electronics of the EMCCD, and the image processing hardware and software. A digital signal processor (DSP) facilitates realtime frame analysis, comprising photon counting and energy discrimination, and reduces the data stream from 162 kB per frame to eight bytes per detected scintillation event (i.e. for a typical application in multi-pinhole SPECT a data reduction from 28 GByte/hour by a factor of 20,000 to 1.4 MByte/hour). Such a reduced data stream is needed for applications that require the use of a large number of gamma cameras simultaneously. The image processing hardware that we describe allows the images from the EMCCD to be processed in real-time, at a rate of 50 images per second. First gamma camera images with a spatial resolution better than 150 micrometers full width of half maximum (FWHM) are shown

U-SPECT-I: a stationary molecular imaging system for small animals with 0.1 micro-litre resolution

A novel SPECT system, U-SPECT-I, was designed and constructed at Utrecht University for the ultra high-resolution imaging of small laboratory animals. The goal was to devise a system with superb resolution and sensitivity that could be used for the imaging of murine organs. Methods: In the center of a triple detector SPECT system, a cylindrical collimator is placed containing 75 gold micro-pinhole apertures. The detectors are divided into sub-cameras, by taking care of that each pinhole projects on a limited area. Radiation shielding prevents overlapping of the projections. The resulting mini pinhole cameras focus to the center of the field-of-view (FOV). The pinholes are arranged in 5 rings of 44 mm diameter. The high number of focusing cameras result in an excellent sensitivity for a small field-of-view that contains a mouse heart, brain, part of the spine or a tumor. SPECT images are reconstructed using Maximum Likelihood Expectation Maximization (ML-EM) Resolution recovery is performed during reconstruction using measured and interpolated point spread function tables. Results: The peak absolute sensitivity measured with a point source is 0.22 % and remains higher than 0.12 % in the central 12 mm of the central plane. Images of a resolution phantom clearly show 0.5 mm capillaries separated by 0.5 mm. A sufficient number of different projection angles for reconstructing images of mouse organs can be readily acquired without any detector or collimator movement. Images of a mouse spine show Tc-99m-hydroxy-methylene diphosfate uptake down to the level of parts of vertebral processes. Bone uptake of the tracer is clearly separated from tiny structures like the (inter-)vertebral foramen. Myocardial perfusion in the left and right ventricular wall, and in structures as small as papillary muscles can be observed in Tc-99m tetrofosmin images. Conclusions: This is the first SPECT scanner to use a highly focused multiple gold micro-pinhole collimation, dedicated to the imaging of mouse organs, at a higher resolution than can be reached with state-of-the-art small animal PET. The combination of imaging characteristics of this prototype system (resolution and sensitivity) opens up new possibilities for the study of animal models. It allows differentiation between the uptake of various structures of about one micro-liter. The system can be transformed from clinical triple detector SPECT system to the U-SPECT-I setup within ten minutes. This means that our new animal imaging set-up is both flexible and cost-effective.