Freek J. Beekman

U-SPECT-II : An Ultra-High-Resolution Device for Molecular Small-Animal Imaging

We present a new rodent SPECT system (U-SPECT-II) that enables molecular imaging of murine organs down to resolutions of less than half a millimeter and high-resolution total-body imaging. Methods: The U-SPECT-II is based on a triangular stationary detector set-up, an XYZ stage that moves the animal during scanning, and interchangeable cylindric collimators (each containing 75 pinhole apertures) for both mouse and rat imaging. A novel graphical user interface incorporating preselection of the field of view with the aid of optical images of the animal focuses the pinholes to the area of interest, thereby maximizing sensitivity for the task at hand. Images are obtained from list-mode data using statistical reconstruction that takes system blurring into account to increase resolution. Results: For 99mTc, resolutions determined with capillary phantoms were smaller than 0.35 and 0.45 mm using the mouse collimator with 0.35- and 0.6-mm pinholes, respectively, and less than 0.8 mm using the rat collimator with 1.0-mm pinholes. Peak geometric sensitivity is 0.07% and 0.18% for the mouse collimator with 0.35- and 0.6-mm pinholes, respectively, and 0.09% for the rat collimator. Resolution with 111In, compared with that with 99mTc, was barely degraded, and resolution with 125I was degraded by about 10%, with some additional distortion. In vivo, kidney, tumor, and bone images illustrated that U-SPECT-II could be used for novel applications in the study of dynamic biologic systems and radiopharmaceuticals at the suborgan level. Conclusion: Images and movies obtained with U-SPECT-II provide high-resolution radiomolecule visualization in rodents. Discrimination of molecule concentrations between adjacent volumes of about 0.04 μL in mice and 0.5 μL in rats with U-SPECT-II is readily possible.

Design and simulation of a high-resolution stationary SPECT system for small animals

Exciting new SPECT systems can be created by combining pinhole imaging with compact high-resolution gamma cameras. These new systems are able to solve the problem of the limited sensitivity-resolution trade-off that hampers contemporary small animal SPECT. The design presented here (U-SPECT-III) uses a set of detectors placed in a polygonal configuration and a cylindrical collimator that contains 135 pinholes arranged in nine rings. Each ring contains 15 gold pinhole apertures that focus on the centre of the cylinder. A non-overlapping projection is acquired via each pinhole. Consequently, when a mouse brain is placed in the central field-of-view, each voxel in the cerebrum can be observed via 130 to 135 different pinholes simultaneously. A method for high-resolution scintillation detection is described that eliminates the depth-of-interaction problem encountered with pinhole cameras, and is expected to provide intrinsic detector resolutions better than 150 microm. By means of simulations U-SPECT-III is compared to a simulated dual pinhole SPECT (DP-SPECT) system with a pixelated array consisting of 2.0 x 2.0 mm NaI crystals. Analytic calculations indicate that the proposed U-SPECT-III system yields an almost four times higher linear and about sixty times higher volumetric system resolution than DP-SPECT, when the systems are compared at matching system sensitivity. In addition, it should be possible to achieve a 15 up to 30 times higher sensitivity with U-SPECT-III when the systems are compared at equal resolution. Simulated images of a digital mouse-brain phantom show much more detail with U-SPECT-III than with DP-SPECT. In a resolution phantom, 0.3 mm diameter cold rods are clearly visible with U-SPECT-III, whereas with DP-SPECT the smallest visible rods are about 0.6-0.8 mm. Furthermore, with U-SPECT-III, the image deformations outside the central plane of reconstruction that hamper conventional pinhole SPECT are strongly suppressed. Simulation results indicate that future pinhole SPECT systems are likely to bring about significant improvements in radio-molecular imaging of small animals.

Efficient fully 3-D iterative SPECT reconstruction with Monte Carlo-based scatter compensation

Quantitative accuracy of single photon emission computed tomography (SPECT) images is highly dependent on the photon scatter model used for image reconstruction. Monte Carlo simulation (MCS) is the most general method for detailed modeling of scatter, but to date, fully three-dimensional (3-D) MCS-based statistical SPECT reconstruction approaches have not been realized, due to prohibitively long computation times and excessive computer memory requirements. MCS-based reconstruction has previously been restricted to two-dimensional approaches that are vastly inferior to fully 3-D reconstruction. Instead of MCS, scatter calculations based on simplified but less accurate models are sometimes incorporated in fully 3-D SPECT reconstruction algorithms. We developed a computationally efficient fully 3-D MCS-based reconstruction architecture by combining the following methods: 1) a dual matrix ordered subset (DM-OS) reconstruction algorithm to accelerate the reconstruction and avoid massive transition matrix precalculation and storage; 2) a stochastic photon transport calculation in MCS is combined with an analytic detector modeling step to reduce noise in the Monte Carlo (MC)-based reprojection after only a small number of photon histories have been tracked; and 3) the number of photon histories simulated is reduced by an order of magnitude in early iterations, or photon histories calculated in an early iteration are reused. For a 64/spl times/64/spl times/64 image array, the reconstruction time required for ten DM-OS iterations is approximately 30 min on a dual processor (AMD 1.4 GHz) PC, in which case the stochastic nature of MCS modeling is found to have a negligible effect on noise in reconstructions. Since MCS can calculate photon transport for any clinically used photon energy and patient attenuation distribution, the proposed methodology is expected to be useful for obtaining highly accurate quantitative SPECT images within clinically acceptable computation times.

Accelerated iterative transmission CT reconstruction using an ordered subsets convex algorithm

Iterative maximum likelihood (ML) transmission computed tomography algorithms have distinct advantages over Fourier-based reconstruction, but unfortunately require increased computation time. The convex algorithm is a relatively fast iterative ML algorithm but it is nevertheless too slow for many applications. Therefore, an acceleration of this algorithm by using ordered subsets of projections is proposed [ordered subsets convex algorithm (OSC)]. OSC applies the convex algorithm sequentially to subsets of projections, OSC was compared with the convex algorithm using simulated and physical thorax phantom data. Reconstructions were performed for OSC using eight and 16 subsets (eight and four projections/subset, respectively). Global errors, image noise, contrast recovery, and likelihood increase were calculated. Results show that OSC is faster than the convex algorithm, the amount of acceleration being approximately proportional to the number of subsets in OSC, and it causes only a slight increase of noise and global errors in the reconstructions. Images and image profiles of the reconstructions were in good agreement, In conclusion, OSC and the convex algorithm result in similar image quality but OSC is more than an order of magnitude faster.

Performance evaluation of A-SPECT: a high resolution desktop pinhole SPECT system for imaging small animals

Pinhole collimation of gamma rays to image distributions of radiolabeled tracers is considered promising for use in small animal imaging. The recent availability of transgenic mice, coupled with the development of /sup 125/I and /sup 99m/Tc labeled tracers, has allowed the study of a range of human disease models while creating demand for ultrahigh resolution imaging devices. We have developed a compact gamma camera that, in combination with pinhole collimation, allows for accessible, ultrahigh resolution in vivo single photon emission computed tomography (SPECT) imaging of small animals. The system is based on a pixilated array of NaI(Tl) crystals coupled to an array of position sensitive photomultiplier tubes. Interchangeable tungsten pinholes with diameters ranging from 0.5 to 3 mm are available, allowing the camera to be optimized for a variety of imaging situations. We use a three dimensional maximum likelihood expectation maximization algorithm to reconstruct the images. Our evaluation indicates that high quality, submillimeter spatial resolution images can be achieved in living mice. Reconstructed axial spatial resolution was measured to be 0.53, 0.74, and 0.96 mm full width at half maximum (FWHM) for rotation radii of 1, 2, and 3 cm, respectively, using the 0.5-mm pinhole. In this configuration, sensitivity is comparable to that of a high-resolution parallel hole collimator. SPECT images of hot- and cold-rod phantoms and a highly structured monkey brain phantom illustrate that high quality images can be obtained with the system. Images of living mice demonstrate the ability of the system to obtain high-resolution images in vivo. The effect of object size on the quantitative assessment of isotope distributions in an image was also studied.

A clinical perspective of accelerated statistical reconstruction

Although the potential benefits of maximum likelihood reconstruction have been recognised for many years, the technique has only recently found widespread popularity in clinical practice. Factors which have contributed to the wider acceptance include improved models for the emission process, better understanding of the properties of the algorithm and, not least, the practicality of application with the development of acceleration schemes and the improved speed of computers. The objective in this article is to present a framework for applying maximum likelihood reconstruction for a wide range of clinically based problems. The article draws particularly on the experience of the three authors in applying an acceleration scheme involving use of ordered subsets to a range of applications. The potential advantages of statistical reconstruction techniques include: (a) the ability to better model the emission and detection process, in order to make the reconstruction converge to a quantitative image, (b) the inclusion of a statistical noise model which results in better noise characteristics, and (c) the possibility to incorporate prior knowledge about the distribution being imaged. The great flexibility in adapting the reconstruction for a specific model results in these techniques having wide applicability to problems in clinical nuclear medicine.

Object shape dependent PSF model for SPECT imaging

An analytical expression for the point spread function (PSF) and the line spread function (LSF) of a parallel hole gamma camera is presented, for homogeneous media and for photons having mainly Compton interactions in the object. The PSF of scattered photons is described by convolving a zeroth-order modified Bessel function of the second kind with the unscattered PSF, which is approximated by a Gaussian. The complete PSF (scatter plus nonscatter) depends on the source distance (z) and depth (d) of the source in the object. For convex-shaped emitting objects, the dependence of the PSF on the object contour can be incorporated by a simple correction. Thus, a complete mathematical model of the imaging of an activity distribution in a homogeneous medium is obtained. The model has been evaluated for /sup 99m/Technetium line sources by using a LEAP collimator at various energy windows ( Delta E). It is shown that the model is valid to a high accuracy at Delta E=15%, for a large range of values of z and d. >

Accelerated simulation of cone beam X-ray scatter projections

Monte Carlo (MC) methods can accurately simulate scatter in X-ray imaging. However, when low noise scatter projections have to be simulated these MC simulations tend to be very time consuming. Rapid computation of scatter estimates is essential for several applications. The aim of the work presented in this paper is to speed up the estimation of noise-free scatter projections while maintaining their accuracy. Since X-ray scatter projections are often rather smooth, an approach is chosen whereby a short MC simulation is combined with a data fitting program that is robust to projection truncation and noise. This method allows us to estimate the smooth scatter projection rapidly. The speed-up and accuracy achieved by using the fitting algorithm were validated for the projection simulation of a small animal X-ray CT system. The acceleration that can be obtained over standard MC simulations is typically two orders of magnitude, depending on the accuracy required. The proposed approach may be useful for rapid simulation of patient and animal studies and for correction of the image-degrading effects of scatter in tomography.

Modelling the physics in the iterative reconstruction for transmission computed tomography

There is an increasing interest in iterative reconstruction (IR) as a key tool to improve quality and increase applicability of x-ray CT imaging. IR has the ability to significantly reduce patient dose; it provides the flexibility to reconstruct images from arbitrary x-ray system geometries and allows one to include detailed models of photon transport and detection physics to accurately correct for a wide variety of image degrading effects. This paper reviews discretization issues and modelling of finite spatial resolution, Compton scatter in the scanned object, data noise and the energy spectrum. The widespread implementation of IR with a highly accurate model-based correction, however, still requires significant effort. In addition, new hardware will provide new opportunities and challenges to improve CT with new modelling.

Monolithic scintillator PET detectors with intrinsic depth-of-interaction correction

We developed positron emission tomography (PET) detectors based on monolithic scintillation crystals and position-sensitive light sensors. Intrinsic depth-of-interaction (DOI) correction is achieved by deriving the entry points of annihilation photons on the front surface of the crystal from the light sensor signals. Here we characterize the next generation of these detectors, consisting of a 20 mm thick rectangular or trapezoidal LYSO:Ce crystal read out on the front and the back (double-sided readout, DSR) by Hamamatsu S8550SPL avalanche photodiode (APD) arrays optimized for DSR. The full width at half maximum (FWHM) of the detector point-spread function (PSF) obtained with a rectangular crystal at normal incidence equals approximately 1.05 mm at the detector centre, after correction for the approximately 0.9 mm diameter test beam of annihilation photons. Resolution losses of several tenths of a mm occur near the crystal edges. Furthermore, trapezoidal crystals perform almost equally well as rectangular ones, while improving system sensitivity. Due to the highly accurate DOI correction of all detectors, the spatial resolution remains essentially constant for angles of incidence of up to at least 30 degrees . Energy resolutions of approximately 11% FWHM are measured, with a fraction of events of up to 75% in the full-energy peak. The coincidence timing resolution is estimated to be 2.8 ns FWHM. The good spatial, energy and timing resolutions, together with the excellent DOI correction and high detection efficiency of our detectors, are expected to facilitate high and uniform PET system resolution.