3D Volumetric Reconstruction for Light-Field SPECT

Preclinical research on single-photon emission computed tomography (SPECT) imaging is now well acknowledged for its critical role. It is fundamental for functional imaging and is a well-researched area of nuclear medicine emission tomography. Numerous efforts were made to provide an optimized SPECT collimator and detector design. However, these approaches suffer from limited sensitivity and resolution, demanding an efficient reconstruction algorithm development. Moreover, due to the image deterioration induced by the non-stationary collimator-detector response and the single-photon emitting nature of SPECT, it is difficult to quantify the 3D radiopharmaceutical distribution within the patient quantitatively. This dissertation's primary incentive is to design and develop a complete computational framework for the newly proposed L-SPECT scan procedure from the image acquisition to the image reconstruction. Using this framework, I solve several challenging problems related to implementing a dedicated novel 3D L-SPECT image reconstruction algorithm. In particular, a volumetric reconstruction algorithm for L-SPECT system is developed by considering the system configurations. Also, an in-depth analysis of the SPECT imaging system based on the light field concept using the micro pinhole range collimator is presented in this thesis. Moreover, I evaluate the performance of the developed reconstruction algorithms under various imaging circumstances in terms of image quality, computational complexity, and resolution. A Monte Carlo simulation environment for L-SPECT was developed by modelling the properties of the SPECT imaging setup. By examining the existing limitations in the proposed L-SPECT, an improved collimator-detector geometry for the micro-pinhole arrays was introduced in this thesis as one of the main contributions. The modular L-SPECT with the detector heads in a partial ring geometry achieved higher sensitivity and resolution than the planer L-SPECT. The modular L-SPECT was further improved by shifting the centre of the scanning detectors to eliminate the artifacts in the reconstructed images. A dedicated reconstruction algorithm for the modular L-SPECT was developed as proof of concept. In SPECT reconstruction, identification of uncertainty information would help to enhance and mitigate the limitations of the existing reconstruction algorithms. The critical contribution of this thesis is manifested in the development of an image reconstruction algorithm based on Bayesian probabilistic programming for SPECT and L-SPECT. A NUTS based MCMC algorithm is used for probabilistic programming-based reconstruction. The uncertainty associated with the radiation measurement is identified as a distribution from the posterior samples generated using the MCMC algorithm. The performance of the NUTS algorithm improved by using reverse-mode automatic differentiation and distributed programming. The automatic differentiation variational inference-based SPECT reconstruction algorithm is developed to reduce the computational cost in NUTS based reconstruction and uncertainty analysis. Further in this thesis, the L-SPECT simulations are calibrated by comparing with GATE simulations, which are the gold standard in this field. The projection results of MATLAB based simulations are comparable with GATE simulations. The system performance for the proposed different configurations was investigated and contrasted against the existing SPECT modalities and systems, such as LEHR and Inveon SPECT, respectively. The performance analysis of the L-SPECT revealed the system is able to achieve improved sensitivity and better field of view compared to the existing systems. The essential characteristics of this L-SPECT system based on the reconstructed images were assessed with pinhole radii of 0.1 mm and 0.05 mm. In addition, the system sensitivity, spatial resolution, and image quality are appraised from the 3D reconstructed images. The maximum achieved system’s sensitivity was 1000 Cps/Bbq using arrays with a pinhole radius of 0.1 mm at 1 mm pitch, while the highest resolution was obtained using arrays with 0.05 mm pinhole and 3 mm pitch. The designed L-SPECT with different configurations and the developed 3D reconstruction algorithms yielded superior image quality compared with LEHR reconstructions

Organ-Dedicated Molecular Imaging Systems

[EN] In this review, we will cover both clinical and technical aspects of the advantages and disadvantages of organ specific (dedicated) molecular imaging (MI) systems, namely positron emission tomography (PET) and single photon emission computed tomography, including gamma cameras. This review will start with the introduction to the organ-dedicated MI systems. Thereafter, we will describe the differences and their advantages/disadvantages when compared with the standard large size scanners. We will review time evolution of dedicated systems, from first attempts to current scanners, and the ones that ended in clinical use. We will review later the state of the art of these systems for different organs, namely: breast, brain, heart, and prostate. We will also present the advantages offered by these systems as a function of the special application or field, such as in surgery, therapy assistance and assessment, etc. Their technological evolution will be introduced for each organ-based imager. Some of the advantages of dedicated devices are: higher sensitivity by placing the detectors closer to the organ, improved spatial resolution, better image contrast recovery (by reducing the noise from other organs), and also lower cost. Designing a complete ring-shaped dedicated PET scanner is sometimes difficult and limited angle tomography systems are preferable as they have more flexibility in placing the detectors around the body/organ. Examples of these geometries will be presented for breast, prostate and heart imaging. Recently achievable excellent time of flight capabilities below 300-ps full width at half of the maximum reduce significantly the impact of missing angles on the reconstructed images.This work was supported in part by the European Research Council through the European Union's Horizon 2020 Research and Innovation Program under Grant 695536, in part by the EU through the FP7 Program under Grant 603002, and in part by the Spanish Ministerio de Economia, Industria y Competitividad through PROSPET (DTS15/00152) funded by the Ministerio de Economia y Competitividad under Grant TEC2016-79884-C2-1-R.González Martínez, AJ.; Sánchez, F.; Benlloch Baviera, JM. (2018). Organ-Dedicated Molecular Imaging Systems. IEEE Transactions on Radiation and Plasma Medical Sciences. 2(5):388-403. https://doi.org/10.1109/TRPMS.2018.2846745S3884032

Development of clinical simultaneous SPECT/MRI

There is increasing clinical use of combined positron emission tomography (PET) and magnetic resonance imaging (MRI) but to date there has been no clinical system developed capable of simultaneous single photon emission computed tomography (SPECT) and MRI. There has been development of preclinical systems, but there are several challenges faced by researchers who are developing a clinical prototype including the need for the system to be compact and stationary with MRI-compatible components. The limited work in this area is described with specific reference to the Integrated SPECT/MRI for Enhanced stratification in Radio-chemo Therapy (INSERT) project, which is at an advanced stage of developing a clinical prototype. Issues of SPECT/MRI compatibility are outlined and the clinical appeal of such a system is discussed, especially in the management of brain tumour treatment

Design and Evaluation of a Novel Lens-Based SPECT System Based on Laue Lens Gamma Diffraction: GEANT4/GAMOS Monte Carlo Study

Abstract While improvements in SPECT imaging techniques constitute a significant advance in biomedical science and cancer diagnosis, their limited spatial resolution has hindered their application to small animal research and early tumour detection. Using recent breakthroughs established by the high-energy astrophysics community, focusing X-ray optics provides a method to overcome the paradigm of low resolution and presents the possibility of imaging small objects with sub-millimetre resolution. This thesis aims to tackle the constraints associated with the current SPECT imaging designs by exploiting the notion of focusing high energy photons through Laue lens diffraction and developing a means of performing gamma rays imaging that would not rely on parallel or pinhole collimators. The gradual development of the novel system is discussed, starting from the single, modular, and multi-Laue lens-based SPECT. A customized 3D reconstruction algorithm was developed to reconstruct an accurate 3D radioactivity distribution from focused projections. A plug-in implementing the Laue diffraction concept was developed and used to model gamma rays focusing in the GEANT4 toolkit. The plug-in will be incorporated into GEANT4 upon final approval from its developers. The single lens-based, modular lens-based and multi lens-based SPECT models detected one hit per 42 source photons (sensitivity of 790 ⁄), three hits per 42 source photons (sensitivity of 2,373 ⁄), and one hit per 20 source photons (sensitivity of 1,670 ⁄), respectively. Based on the generated 3D reconstructed images, the achievable spatial resolution was found to be 0.1 full width at half maximum (FWHM). The proposed design’s performance parameters were compared against the existing SIEMENS parallel LEHR and multi-pinhole (5-MWB-1.0) Inveon SPECT. The achievable spatial resolution is decoupled from the sensitivity of the system, which is in stark contrast with the existing collimators that suffer from the resolution-sensitivity trade-off and are limited to a resolution of 2 . The proposed system allows discrimination between adjacent volumes as small as 0.113 , which is substantially smaller than what can be imaged by any existing SPECT or PET system. The proposed design could lay the foundation for a new SPECT imaging technology akin to a combination of tomosynthesis and lightfield imaging

The clinical utilities of multi-pinhole single photon emission computed tomography

Single photon emission computed tomography (SPECT) is an important imaging modality for various applications in nuclear medicine. The use of multi-pinhole (MPH) collimators can provide superior resolution-sensitivity trade-off when imaging small field-of-view compared to conventional parallel-hole and fan-beam collimators. Besides the very successful application in small animal imaging, there has been a resurgence of the use of MPH collimators for clinical cardiac and brain studies, as well as other small field-of-view applications. This article reviews the basic principles of MPH collimators and introduces currently available and proposed clinical MPH SPECT systems

Inclusion of quasi-vertex views in a brain-dedicated multi-pinhole SPECT system for improved imaging performance

With brain-dedicated multi-detector systems employing pinhole apertures the usage of detectors facing the top of the patient\u27s head (i.e., quasi-vertex views) can provide the advantage of additional viewing from close to the brain for improved detector coverage. In this paper, we report the results of simulation and reconstruction studies to investigate the impact of the quasi-vertex views on the imaging performance of AdaptiSPECT-C, a brain-dedicated stationary SPECT system under development. In this design, both primary and scatter photons from regions located inferior to the brain can contribute to SPECT projections acquired by the quasi-vertex views, and thus degrade AdaptiSPECT-C imaging performance. In this work, we determined the proportion, origin, and nature (i.e., primary, scatter, and multiple-scatter) of counts emitted from structures within the head and throughout the body contributing to projections from the different AdaptiSPECT-C detector rings, as well as from a true vertex view detector. We simulated phantoms used to assess different aspects of image quality (i.e., uniform sphere and Derenzo), as well as anthropomorphic phantoms with multiple count levels emulating clinical(123)I activity distributions (i.e., DaTscan and perfusion). We determined that attenuation and scatter in the patient\u27s body greatly diminish the probability of the photons emitted outside the volume of interest reaching to detectors and being recorded within the 15% photopeak energy window. In addition, we demonstrated that the inclusion of the residual of such counts in the system acquisition does not degrade visual interpretation or quantitative analysis. The addition of the quasi-vertex detectors increases volumetric sensitivity, angular sampling, and spatial resolution leading to significant enhancement in image quality, especially in the striato-thalamic and superior regions of the brain. Besides, the use of quasi-vertex detectors improves the recovery of clinically relevant metrics such as the striatal binding ratio and mean activity in selected cerebral structures

A versatile imaging system for in vivo small animal research

In vivo small animal imaging has become an essential technique for molecular biology studies. However, requirements of spatial resolution, sensitivity and image quality are quite challenging for the development of small-animal imaging systems. The capabilities of the system are also significant for carrying out small animal imaging in a wide range of biological studies. The goal of this dissertation is to develop a high-performance imaging system that can readily meet a wide range of requirements for a variety of small animal imaging applications. Several achievements have been made in order to fulfill this goal.;To supplement our system for parallel-hole single photon emission computed tomography (SPECT) based upon a 110 mm diameter circular detector, we have developed novel compact gamma cameras suitable for imaging an entire mouse. These gamma cameras facilitate multi-head (\u3e2) parallel-hole SPECT with the mouse in close proximity to the detector face in order to preserve spatial resolution. Each compact gamma cameras incorporates pixellated Nal(Tl) scintillators and a pair of Hamamatsu H8500 position sensitive photomultiplier tubes (PSPMTs). Two types of copper-beryllium parallel-hole collimators have been designed. These provide high-sensitivity imaging of I-125 or excellent spatial resolution over a range of object-detector distances. Both phantom and animal studies have demonstrated that these gamma cameras perform well for planar scintigraphy and parallel-hole SPECT of mice.;To further address the resolution limitations in parallel-hole SPECT and the sensitivity and limited field of view of single-pinhole SPECT, we have developed novel multipinhole helical SPECT based upon a 110 mm diameter circular detector equipped with a pixellated Nal(Tl) scintillator array. A brass collimator has been designed and produced containing five 1 mm diameter pinholes. Results obtained in SPECT studies of various phantoms show an enlarged field of view, very good resolution and improved sensitivity using this new imaging technique.;These studies in small-animal imaging have been applied to in vivo biological studies related to human health issues including studies of the thyroid and breast cancer. A re-evaluation study of potassium iodide blocking efficiency in radioiodine uptake in mice suggests that the FDA-recommended human dose of stable potassium iodide may not be sufficient to effectively protect the thyroid from radioiodine contamination. Another recent study has demonstrated that multipinhole helical SPECT can resolve the fine structure of the mouse thyroid using a relatively low dose (200 muCi). Another preclinical study has focused on breast tumor imaging using a compact gamma camera and an endogenous reporter gene. In that ongoing study, mammary tumors are imaged at different stages. Preliminary results indicate different functional patterns in the uptake of radiotracers and their potential relationship with other tumor parameters such as tumor size.;In summary, we have developed a versatile imaging system suitable for in vivo small animal research as evidenced by a variety of applications. The modular construction of this system will allow expansion and further development as new needs and new opportunities arise

Gamma-ray imaging detector for small animal research

A novel radiation imaging technology for in vivo molecular imaging in small mammals is described. The goal of this project is to develop a new type of imaging detector system suitable for real-time in vivo probe imaging studies in small animals. This technology takes advantage of the gamma-ray and x-ray emission properties of the radioisotope iodine 125 (125I) which is employed as the label for molecular probes. The radioisotope 125I is a gamma-ray emitting radioisotope that can be commercially obtained already attached to biomedically interesting molecules to be used as tracers for biomedical and molecular biology research.;The isotope 125I decays via electron capture consequently emitting a 35 keV gamma-ray followed by the near coincident emission of several 27--32 keV Kalpha and Kbeta shell x-rays. Because of these phenomena, a coincidence condition can be set to detect 125I thus enabling the reduction of any background radiation that could contaminate the image. The detector system is based on an array of CsI(Na) crystal scintillators coupled to a 125 mm diameter position sensitive photomultiplier tube. An additional standard 125 mm diameter photomultiplier tube coupled to a NaI(Tl) scintillator acts as the coincident detector. to achieve high resolution images the detector system utilizes a custom-built copper laminate high resolution collimator. The 125I detector system can achieve a spatial resolution of less than 2 mm FWHM for an object at a distance of 1.5 cm from the collimator. The measured total detector sensitivity while using the copper collimator was 68 cpm/muCi.;Results of in vivo mouse imaging studies of the biodistribution of iodine, melatonin, and a neurotransmitter analog (RTI-55) are presented. Many studies in molecular biology deal with following the expression and regulation of a gene at different stages of an organism\u27s development or under different physiological conditions. This detector system makes it possible for laboratories without access to standard nuclear medicine radiopharmaceuticals to perform in vivo imaging research on small a mammals using a whole range of 125I labeled markers that are obtainable from commercial sources

Reconstruction Algorithms for Novel Joint Imaging Techniques in PET

Positron emission tomography (PET) is an important functional in vivo imaging modality with many clinical applications. Its enormously wide range of applications has made both research and industry combine it with other imaging modalities such as X-ray computed tomography (CT) or magnetic resonance imaging (MRI). The general purpose of this work is to study two cases in PET where the goal is to perform image reconstruction jointly on two data types. The first case is the Beta-Gamma image reconstruction. Positron emitting isotopes, such as 11C, 13N, and 18F, can be used to label molecules, and tracers, such as 11CO2, are delivered to plants to study their biological processes, particularly metabolism and photosynthesis, which may contribute to the development of plants that have higher yield of crops and biomass. Measurements and resulting images from PET scanners are not quantitative in young plant structures or in plant leaves due to low positron annihilation in thin objects. To address this problem we have designed, assembled, modeled, and tested a nuclear imaging system (Simultaneous Beta-Gamma Imager). The imager can simultaneously detect positrons (β+) and coincidence-gamma rays (γ). The imaging system employs two planar detectors; one is a regular gamma detector which has a LYSO crystal array, and the other is a phoswich detector which has an additional BC-404 plastic scintillator for beta detection. A forward model for positrons is proposed along with a joint image reconstruction formulation to utilize the beta and coincidence-gamma measurements for estimating radioactivity distribution in plant leaves. The joint reconstruction algorithm first reconstructs the beta and gamma images independently to estimate the thickness component of the beta forward model, and then jointly estimates the radioactivity distribution in the object. We have validated the physics model and the reconstruction framework through a phantom imaging study and imaging a tomato leaf that has absorbed 11CO2. The results demonstrate that the simultaneously acquired beta and coincidence-gamma data, combined with our proposed joint reconstruction algorithm, improved the quantitative accuracy of estimating radioactivity distribution in thin objects such as leaves. We used the Structural Similarity (SSIM) index for comparing the leaf images from the Simultaneous Beta-Gamma Imager with the ground truth image. The jointly reconstructed images yield SSIM indices of 0.69 and 0.63, whereas the separately reconstructed beta alone and gamma alone images had indices of 0.33 and 0.52, respectively. The second case is the virtual-pinhole PET technology, which has shown that higher resolution and contrast recovery can be gained by adding a high resolution PET insert with smaller crystals to a conventional PET scanner. Such enhancements are obtained when the insert is placed in proximity of the region of interest (ROI) and in coincidence with the conventional PET scanner. Intuitively, the insert may be positioned within the scanner\u27s axial field-of-view (FOV) and radially closer to the ROI than the scanner\u27s ring. One of the complicating factors of this design is the insert\u27s blocking the scanner\u27s lines-of-response (LORs). Such data may be compensated through attenuation and scatter correction in image reconstruction. However, a potential solution is to place the insert outside of the scanner\u27s axial FOV and to move the body to be in proximity of the insert. We call this imaging strategy the surveillance mode. As the main focus of this work, we have developed an image reconstruction framework for the surveillance mode imaging. The preliminary results show improvement in spatial resolution and contrast recovery. Any improvement in contrast recovery should result in enhancement in tumor detectability, which will be of high clinical significance