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

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

Accurate molecular imaging of small animals taking into account animal models, handling, anaesthesia, quality control and imaging system performance

Small-animal imaging has become an important technique for the development of new radiotracers, drugs and therapies. Many laboratories have now a combination of different small-animal imaging systems, which are being used by biologists, pharmacists, medical doctors and physicists. The aim of this paper is to give an overview of the important factors in the design of a small animal, nuclear medicine and imaging experiment. Different experts summarize one specific aspect important for a good design of a small-animal experiment

An extension to artifact-free projection overlaps

Purpose: In multipinhole single photon emission computed tomography, the overlapping of projections has been used to increase sensitivity. Avoiding artifacts in the reconstructed image associated with projection overlaps (multiplexing) is a critical issue. In our previous report, two types of artifactfree projection overlaps, i.e., projection overlaps that do not lead to artifacts in the reconstructed image, were formally defined and proved, and were validated via simulations. In this work, a new proposition is introduced to extend the previously defined type-II artifact-free projection overlaps so that a broader range of artifact-free overlaps is accommodated. One practical purpose of the new extension is to design a baffle window multipinhole system with artifact-free projection overlaps. Methods: First, the extended type-II artifact-free overlap was theoretically defined and proved. The new proposition accommodates the situation where the extended type-II artifact-free projection overlaps can be produced with incorrectly reconstructed portions in the reconstructed image. Next, to validate the theory, the extended-type-II artifact-free overlaps were employed in designing the multiplexing multipinhole spiral orbit imaging systems with a baffle window. Numerical validations were performed via simulations, where the corresponding 1-pinhole nonmultiplexing reconstruction results were used as the benchmark for artifact-free reconstructions. The mean square error (MSE) was the metric used for comparisons of noise-free reconstructed images. Noisy reconstructions were also performed as part of the validations.Results: Simulation results show that for noise-free reconstructions, the MSEs of the reconstructed images of the artifact-free multiplexing systems are very similar to those of the corresponding 1-pinhole systems. No artifacts were observed in the reconstructed images. Therefore, the testing results for artifact-free multiplexing systems designed using the extended type-II artifact-free overlaps numerically validated the developed theory. Conclusions: First, the extension itself is of theoretical importance because it broadens the selection range for optimizing multiplexing multipinhole designs. Second, the extension has an immediate application: using a baffle window to design a special spiral orbit multipinhole imaging system with projection overlaps in the orbit axial direction. Such an artifact-free baffle window design makes it possible for us to image any axial portion of interest of a long object with projection overlaps to increase sensitivity

Targeting murine heart and brain: visualisation conditions for multi-pinhole SPECT with 99mTc- and 123I-labelled probes

The study serves to optimise conditions for multi-pinhole SPECT small animal imaging of (123)I- and (99m)Tc-labelled radiopharmaceuticals with different distributions in murine heart and brain and to investigate detection and dose range thresholds for verification of differences in tracer uptake.A Triad 88/Trionix system with three 6-pinhole collimators was used for investigation of dose requirements for imaging of the dopamine D(2) receptor ligand [(123)I]IBZM and the cerebral perfusion tracer [(99m)Tc]HMPAO (1.2-0.4 MBq/g body weight) in healthy mice. The fatty acid [(123)I]IPPA (0.94 +/- 0.05 MBq/g body weight) and the perfusion tracer [(99m)Tc]sestamibi (3.8 +/- 0.45 MBq/g body weight) were applied to cardiomyopathic mice overexpressing the prostaglandin EP(3) receptor.In vivo imaging and in vitro data revealed 45 kBq total cerebral uptake and 201 kBq cardiac uptake as thresholds for visualisation of striatal [(123)I]IBZM and of cardiac [(99m)Tc]sestamibi using 100 and 150 s acquisition time, respectively. Alterations of maximal cerebral uptake of [(123)I]IBZM by >20% (116 kBq) were verified with the prerequisite of 50% striatal of total uptake. The labelling with [(99m)Tc]sestamibi revealed a 30% lower uptake in cardiomyopathic hearts compared to wild types. [(123)I]IPPA uptake could be visualised at activity doses of 0.8 MBq/g body weight.Multi-pinhole SPECT enables detection of alterations of the cerebral uptake of (123)I- and (99m)Tc-labelled tracers in an appropriate dose range in murine models targeting physiological processes in brain and heart. The thresholds of detection for differences in the tracer uptake determined under the conditions of our experiments well reflect distinctions in molar activity and uptake characteristics of the tracers

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

The Performance of MLEM for Dynamic Imaging From Simulated Few-View, Multi-Pinhole SPECT

Stationary small-animal SPECT systems are being developed for rapid dynamic imaging from limited angular views. This work quantified, through simulations, the performance of Maximum Likelihood Expectation Maximization (MLEM) for reconstructing a time-activity curve (TAC) with uptake duration of a few seconds from a stationary, three-camera multi-pinhole SPECT system. The study also quantified the benefits of a heuristic method of initializing the reconstruction with a prior image reconstructed from a conventional number of views, for example from data acquired during the late-study portion of the dynamic TAC. We refer to MLEM reconstruction initialized by a prior-image initial guess (IG) as MLEMig. The effect of the prior-image initial guess on the depiction of contrast between two regions of a static phantom was quantified over a range of angular sampling schemes. A TAC was modeled from the experimentally measured uptake of 99mTc-hexamethylpropyleneamine oxime (HMPAO) in the rat lung. The resulting time series of simulated images was quantitatively analyzed with respect to the accuracy of the estimated exponential washin and washout parameters. In both static and dynamic phantom studies, the prior-image initial guess improved the spatial depiction of the phantom, for example improved definition of the cylinder boundaries and more accurate quantification of relative contrast between cylinders. For example in the dynamic study, there was ~ 50% error in relative contrast for MLEM reconstructions compared to ~ 25-30% error for MLEMig. In the static phantom study, the benefits of the initial guess decreased as the number of views increased. The prior-image initial guess introduced an additive offset in the reconstructed dynamic images, likely due to biases introduced by the prior image. MLEM initialized with a uniform initial guess yielded images that faithfully reproduced the time dependence of the simulated TAC; there were no s- atistically significant differences in the mean exponential washin/washout parameters estimated from MLEM reconstructions compared to the true values. Washout parameters estimated from MLEMig reconstructions did not differ significantly from the true values, however the estimated washin parameter differed significantly from the true value in some cases. Overall, MLEM reconstruction from few views and a uniform initial guess accurately quantified the time dependance of the TAC while introducing errors in the spatial depiction of the object. Initializing the reconstruction with a late-study initial guess improved spatial accuracy while decreasing temporal accuracy in some cases