Determination of optimal collimation parameters for a rotating slat collimator system: a system matrix method using ML-EM.

Nowadays, Single Photon imaging has become an essential part of molecular imaging and nuclear medicine. Whether to establish a diagnosis or in the therapeutic monitoring, this modality presents performance that continues to improve. For over 50 years, several collimators have been proposed. Mainly governed by collimation parameters, the resolution-sensitivity trade-off is the factor determining the collimator the most suitable for an intended study. One alternative to the common approaches is the rotating slat collimator (RSC). In the present study, we are aiming at developing a preclinical system equipped with a RSC dedicated to mice and rats imaging, which requires both high sensitivity and spatial resolution. We investigated the resolution-sensitivity trade-offs obtained by varying different collimation parameters: (i) the slats height (H), and (ii) the gap between two consecutive slats (g), considering different intrinsic spatial resolutions. One system matrix was generated for each set of collimation parameters (H,g). Spatial resolutions, Signal-to-Noise Ratio (SNR) and sensitivity obtained for all the set of collimation parameters (H,g) were measured in the 2D projections reconstructed with ML-EM. According to our results, 20 mm high slats and a 1 mm gap were chosen as a good RSC candidate for a preclinical detection module. This collimator will ensure a sensitivity greater than 0.2% and a system spatial resolution below 1 mm, considering an intrinsic spatial resolution below 0.8 mm.

Small Animal In Vivo X-Ray Tomosynthesis: Anatomical Relevance of the Reconstructed Images.

Whole body X-ray micro-Digital Tomosynthesis (micro-DT) for small animal imaging is introduced in this work. Such a system allows to deal with geometrical constraints that do not allow to use a micro-CT system as well as to reduce the radiological dose compared to a micro-CT scan. Data was simulated using the Digimouse anatomical model of the mouse with the designed system. An algebraic reconstruction algorithm regularized by Total Variation norm (TV) minimization was used to reconstruct images. Parameters for the reconstruction were optimized and the algorithm performance was evaluated quantitatively. High contrast tissues were subsequently segmented by thresholding the image. Quantitative analysis of the segmented domains indicates that a relevant anatomical information can possibly be extracted from micro-DT images. Indeed the Dice's coefficient values are greater than 0.8 for the segmented High Contrast Tissues compared to the phantom, which indicates an important overlap between the domains. The volume of the segmented tissues is over-estimated for the bones and skin-with 1.313 and 1.113 ratios of the estimated over reference volumes, respectively-and under-estimated in the case of the lungs with a 0.762 ratio. The mean point to surface distance is inferior to the voxel size of 400 µm, for the three segmented tissues. These results are very encouraging and let us consider micro-DT as an alternative to micro-CT to deal with geometrical constraints.

Quantitative proton imaging from multiple physics processes: a proof of concept.

Proton imaging is developed in order to improve the accuracy of charged particle therapy treatment planning. It makes it possible to directly map the relative stopping powers of the materials using the information on the energy loss of the protons. In order to reach a satisfactory spatial resolution in the reconstructed images, the position and direction of each particle is recorded upstream and downstream from the patient. As a consequence of individual proton detection, information on the transmission rate and scattering of the protons is available. Image reconstruction processes are proposed to make use of this information. A proton tomographic acquisition of an anthropomorphic head phantom was simulated. The transmission rate of the particles was used to reconstruct a map of the macroscopic cross section for nuclear interactions of the materials. A two-step iterative reconstruction process was implemented to reconstruct a map of the inverse scattering length of the materials using the scattering of the protons. Results indicate that, while the reconstruction processes should be optimized, it is possible to extract quantitative information from the transmission rate and scattering of the protons. This suggests that proton imaging could provide additional knowledge on the materials that may be of use to further improve treatment planning.

Assessment of a fast generated analytical matrix for rotating slat collimation iterative reconstruction: a possible method to optimize the collimation profile.

In SPECT imaging, improvement or deterioration of performance is mostly due to collimator design. Classical SPECT systems mainly use parallel hole or pinhole collimators. Rotating slat collimators (RSC) can be an interesting alternative to optimize the tradeoff between detection efficiency and spatial resolution. The present study was conducted using a RSC system for small animal imaging called CLiR. The CLiR system was used in planar mode only. In a previous study, planar 2D projections were reconstructed using the well-known filtered backprojection algorithm (FBP). In this paper, we investigated the use of the statistical reconstruction algorithm maximum likelihood expectation maximization (MLEM) to reconstruct 2D images with the CLiR system using a probability matrix calculated using an analytic approach. The primary objective was to propose a method to quickly generate a light system matrix, which facilitates its handling and storage, while providing accurate and reliable performance. Two other matrices were calculated using GATE Monte Carlo simulations to investigate the performance obtained using the matrix calculated analytically. The first matrix calculated using GATE took all the physics processes into account, where the second did not consider for the scattering, as the analytical matrix did not take this physics process into account either. 2D images were reconstructed using FBP and MLEM with the three different probability matrices. Both simulated and experimental data were used. A comparative study of these images was conducted using different metrics: the modulation transfert function, the signal-to-noise ratio and quantification measurement. All the results demonstrated the suitability of using a probability matrix calculated analytically. It provided similar results in terms of spatial resolution (about 0.6 mm with differences <5%), signal-to-noise ratio (differences <10%), or quality of image.

The impact of tracking system properties on the most likely path estimation in proton CT.

Proton CT nowadays aims at improving hadron therapy treatment planning by mapping the stopping power of materials. In order to optimize a spatial resolution of the reconstructed images, the most likely path (MLP) of each proton can be computed. We investigated the errors in the computation of this path due to the configuration of the system, i.e. the spatial resolution of the tracking planes, their material budget, and their positioning. A method for computing the uncertainty in the estimated paths for a given system was derived. The uncertainties upon the entrance and exit of the object were propagated analytically in the path computation. This procedure was then used to evaluate the impact of each parameter, and to compare different systems. We show that the intrinsic characteristics of the system generate an uncertainty in the positions and directions of the particles propagated during the MLP computation. The spatial resolution and material budget of the trackers in particular may affect the path estimation, and thus the spatial resolution of an image.

[Scintigraphic study of the lymphatic drainage of the anterior chamber of the mouse eye and its pathophysiological implications]. / Étude scintigraphique du drainage lymphatique de la chambre antérieure de l'œil de la souris et ses implications physiopathologiques.

For many years, the intraocular lymphatic system and particularly the drainage of the aqueous humor by this system have been considered non-existant. Our study is the first to demonstrate, in a dynamic in vivo fashion, the existence of lymphatic drainage in the mouse eye. This has become possible with lymphoscintigraphy with nano-molecules of rhenium sulphide, marked by technetium-99m and injected into the anterior chamber of the mouse eye. Readings were taken using an experimental gamma camera specially built for the small animal. The hypothesis of a "uveolymphatic" drainage pathway within the ciliary body, contributing to aqueous outflow, has recently been highlighted by new improvements in microbiology (discovery of lymphatic endothelial-specific markers) and imaging. This new pathway may lead to many prospects: the development of techniques for visualization and quantification of this in vivo lymphatic flow may help to increase our understanding of the physiopathology and perhaps treatment of chronic glaucoma as well as neoplastic conditions.

Proton computed tomography from multiple physics processes.

Proton CT (pCT) nowadays aims at improving hadron therapy treatment planning by mapping the relative stopping power (RSP) of materials with respect to water. The RSP depends mainly on the electron density of the materials. The main information used is the energy of the protons. However, during a pCT acquisition, the spatial and angular deviation of each particle is recorded and the information about its transmission is implicitly available. The potential use of those observables in order to get information about the materials is being investigated. Monte Carlo simulations of protons sent into homogeneous materials were performed, and the influence of the chemical composition on the outputs was studied. A pCT acquisition of a head phantom scan was simulated. Brain lesions with the same electron density but different concentrations of oxygen were used to evaluate the different observables. Tomographic images from the different physics processes were reconstructed using a filtered back-projection algorithm. Preliminary results indicate that information is present in the reconstructed images of transmission and angular deviation that may help differentiate tissues. However, the statistical uncertainty on these observables generates further challenge in order to obtain an optimal reconstruction and extract the most pertinent information.

Characterization of a rotating slat collimator system dedicated to small animal imaging.

Some current investigations based on small animal models are dedicated to functional cerebral imaging. They represent a fundamental tool to understand the mechanisms involved in neurodegenerative diseases. In the radiopharmaceutical development approach, the main challenge is to measure the radioactivity distribution in the brain of a subject with good temporal and spatial resolutions. Classical SPECT systems mainly use parallel hole or pinhole collimators. In this paper we investigate the use of a rotating slat collimator system for small animal brain imaging. The proposed prototype consists of a 64-channel multi-anode photomultiplier tube (H8804, Hamamatsu Corp.) coupled to a YAP:Ce crystal highly segmented into 32 strips of 0.575 × 18.4 × 10 mm(3). The parameters of the rotating slat collimator are optimized using GATE Monte Carlo simulations. The performance of the proposed prototype in terms of spatial resolution, detection efficiency and signal-to-noise ratio is compared to that obtained with a gamma camera equipped with a parallel hole collimator. Preliminary experimental results demonstrate that a spatial resolution of 1.54 mm can be achieved with a detection efficiency of 0.012% for a source located at 20 mm, corresponding to the position of the brain in the prototype field of view.

Design and Characteristics of a Multichannel Front-End ASIC Using Current-Mode CSA for Small-Animal PET Imaging.

This paper presents the design and characteristics of a front-end readout application-specific integrated circuit (ASIC) dedicated to a multichannel-plate photodetector coupled to LYSO scintillating crystals. In our configuration, the crystals are oriented in the axial direction readout on both sides by individual photodetector channels allowing the spatial resolution and the detection efficiency to be independent of each other. Both energy signals and timing triggers from the photodetectors are required to be read out by the front-end ASIC. A current-mode charge-sensitive amplifier is proposed for this application. This paper presents performance characteristics of a 10-channel prototype chip designed and fabricated in a 0.35-µm complementary metal-oxide semiconductor process. The main results of simulations and measurements are presented and discussed. The gain of the chip is 13.1 mV/pC while the peak time of a CR-RC pulse shaper is 280 ns. The signal-to-noise ratio is 39 dB and the rms noise is 300 µV/√(Hz). The nonlinearity is less than 3% and the crosstalk is about 0.2%. The power dissipation is less than 15 mW/channel. This prototype will be extended to a 64-channel circuit with integrated time-to-digital converter and analog-to-digital converter together for a high-sensitive small-animal positron emission tomography imaging system.

GATE: a simulation toolkit for PET and SPECT.

Monte Carlo simulation is an essential tool in emission tomography that can assist in the design of new medical imaging devices, the optimization of acquisition protocols and the development or assessment of image reconstruction algorithms and correction techniques. GATE, the Geant4 Application for Tomographic Emission, encapsulates the Geant4 libraries to achieve a modular, versatile, scripted simulation toolkit adapted to the field of nuclear medicine. In particular, GATE allows the description of time-dependent phenomena such as source or detector movement, and source decay kinetics. This feature makes it possible to simulate time curves under realistic acquisition conditions and to test dynamic reconstruction algorithms. This paper gives a detailed description of the design and development of GATE by the OpenGATE collaboration, whose continuing objective is to improve, document and validate GATE by simulating commercially available imaging systems for PET and SPECT. Large effort is also invested in the ability and the flexibility to model novel detection systems or systems still under design. A public release of GATE licensed under the GNU Lesser General Public License can be downloaded at http:/www-lphe.epfl.ch/GATE/. Two benchmarks developed for PET and SPECT to test the installation of GATE and to serve as a tutorial for the users are presented. Extensive validation of the GATE simulation platform has been started, comparing simulations and measurements on commercially available acquisition systems. References to those results are listed. The future prospects towards the gridification of GATE and its extension to other domains such as dosimetry are also discussed.

Fast fully 3-D image reconstruction in PET using planograms.

We present a method of performing fast and accurate three-dimensional (3-D) backprojection using only Fourier transform operations for line-integral data acquired by planar detector arrays in positron emission tomography. This approach is a 3-D extension of the two-dimensional (2-D) linogram technique of Edholm. By using a special choice of parameters to index a line of response (LOR) for a pair of planar detectors, rather than the conventional parameters used to index a LOR for a circular tomograph, all the LORs passing through a point in the field of view (FOV) lie on a 2-D plane in the four-dimensional (4-D) data space. Thus, backprojection of all the LORs passing through a point in the FOV corresponds to integration of a 2-D plane through the 4-D "planogram." The key step is that the integration along a set of parallel 2-D planes through the planogram, that is, backprojection of a plane of points, can be replaced by a 2-D section through the origin of the 4-D Fourier transform of the data. Backprojection can be performed as a sequence of Fourier transform operations, for faster implementation. In addition, we derive the central-section theorem for planogram format data, and also derive a reconstruction filter for both backprojection-filtering and filtered-backprojection reconstruction algorithms. With software-based Fourier transform calculations we provide preliminary comparisons of planogram backprojection to standard 3-D backprojection and demonstrate a reduction in computation time by a factor of approximately 15.