Doctor of Philosophy

dissertationSingle Photon Emission Computed Tomography (SPECT) myocardial perfusion imaging (MPI), a noninvasive and effective method for diagnosing coronary artery disease (CAD), is the most commonly performed SPECT procedure. Hence, it is not surprising that there is a tremendous market need for dedicated cardiac SPECT scanners. In this dissertation, a novel dedicated stationary cardiac SPECT system that using a segmented-parallel-hole collimator is investigated in detail. This stationary SPECT system can acquire true dynamic SPECT images and is inexpensive to build. A segmented-parallel-hole collimator was designed to fit the existing general-purpose SPECT cameras without any mechanical modifications of the scanner while providing higher detection sensitivity. With a segmented-parallel-hole collimator, each detector was segmented to seven sub-detector regions, providing seven projections simultaneously. Fourteen view-angles over 180 degree were obtained in total with two detectors positioned at 90 degree apart. The whole system was able to provide an approximate 34-fold gain in sensitivity over the conventional single-head SPECT system. The potential drawbacks of the stationary cardiac SPECT system are data truncation from small field of view (FOV) and limited number of view angles. A tailored maximum-likelihood expectation-maximization (ML-EM) algorithm was derived for reconstruction of truncated projections with few view angles. The artifacts caused by truncation and insufficient number of views were suppressed by reducing the image updating step sizes of the pixels outside the FOV. The performance of the tailored ML-EM algorithm was verified by computer simulations and phantom experiments. Compared with the conventional ML-EM algorithm, the tailored ML-EM algorithm successfully suppresses the streak artifacts outside the FOV and reduces the distortion inside the FOV. At 10 views, the tailored ML-EM algorithm has a much lower mean squared error (MSE) and higher relative contrast. In addition, special attention was given to handle the zero-valued projections in the image reconstruction. There are two categories of zero values in the projection data: one is outside the boundary of the object and the other is inside the object region, which is caused by count starvation. A positive weighting factor c was introduced to the ML-EM algorithm. By setting c>1 for zero values outside the projection, the boundary in the image is well preserved even at extremely low iterations. The black lines, caused by the zero values inside the object region, are completely removed by setting 0< c<1. Finally, the segmented-parallel-hole collimator was fabricated and calibrated using a point source. Closed-form explicit expressions for the slant angles and rotation radius were derived from the proposed system geometry. The geometric parameters were estimated independently or jointly. Monte Carlo simulations and real emission data were used to evaluate the proposed calibration method and the stationary cardiac system. The simulation results show that the difference between the estimated and the actual value is less than 0.1 degree for the slant angles and the 5 mm for the rotation radius, which is well below the detector's intrinsic resolution

Direct estimation of kinetic parametric images for dynamic PET.

Dynamic positron emission tomography (PET) can monitor spatiotemporal distribution of radiotracer in vivo. The spatiotemporal information can be used to estimate parametric images of radiotracer kinetics that are of physiological and biochemical interests. Direct estimation of parametric images from raw projection data allows accurate noise modeling and has been shown to offer better image quality than conventional indirect methods, which reconstruct a sequence of PET images first and then perform tracer kinetic modeling pixel-by-pixel. Direct reconstruction of parametric images has gained increasing interests with the advances in computing hardware. Many direct reconstruction algorithms have been developed for different kinetic models. In this paper we review the recent progress in the development of direct reconstruction algorithms for parametric image estimation. Algorithms for linear and nonlinear kinetic models are described and their properties are discussed

SPECT Imaging of Pulmonary Blood Flow in a Rat

Small animal imaging is experiencing rapid development due to its importance in providing high-throughput phenotypic data for functional genomics studies. We have developed a single photon emission computed tomography (SPECT) system to image the pulmonary perfusion distribution in the rat. A standard gamma camera, equipped with a pinhole collimator, was used to acquire SPECT projection images at 40 sec/view of the rat thorax following injection of Tc99m labeled albumin that accumulated in the rat\u27s lungs. A voxel-driven, ordered-subset expectation maximization reconstruction was implemented. Following SPECT imaging, the rat was imaged using micro-CT with Feldkamp conebeam reconstruction. The two reconstructed image volumes were fused to provide a structure/function image of the rat thorax. Reconstruction accuracy and performance were evaluated using numerical simulations and actual imaging of an experimental phantom consisting of Tc99m filled chambers with known diameters and count rates. Full-width half-maximum diameter measurement errors decreased with increasing chamber diameter, ranging from \u3c 6% down to 0.1%. Errors in the ratio of count rate estimates between tubes were also diameter dependent but still relatively small. This preliminary study suggests that SPECT will be useful for imaging and quantifying the pulmonary blood flow distribution and the distribution of Tc99m labeled ligands in the lungs of small laboratory animals

Quantification of Bronchial Circulation Perfusion in Rats

The bronchial circulation is thought to be the primary blood supply for pulmonary carcinomas. Thus, we have developed a method for imaging and quantifying changes in perfusion in the rat lung due to development of the bronchial circulation. A dual-modality micro-CT/SPECT system was used to detect change in perfusion in two groups of rats: controls and those with a surgically occluded left pulmonary artery. Both groups were imaged following injections on separate days i) 2mCi of Tc99m labeled macroaggregated albumin (MAA) into the left carotid artery (IA) and ii) a similar injection into the femoral vein (IV). The IA injection resulted in Tc99m accumulation in capillaries of the systemic circulation including the bronchial circulation, whereas the IV resulted in Tc99m accumulation in the pulmonary capillaries. Ordered subset expectation maximization (OSEM) was used to reconstruct the SPECT image volumes and a Feldkamp algorithm was used to reconstruct the micro-CT image volumes. The micro-CT and SPECT volumes were registered, the SPECT image volume was segmented using the right and left lung boundaries defined from the micro-CT volume, and the ratio of IA radioactivity accumulation in the left lung to IV radioactivity accumulation in both lungs was used as a measure of left lung flow via the bronchial circulation. This ratio was ~0.02 for the untreated rats compared to the treated animals that had an increased flow ratio of ~0.21 40 days after left pulmonary artery occlusion. This increase in flow to the occluded left lung via the bronchial circulation suggests this will be a useful model for further investigating antiangiogenic treatments

Quantification of Bronchial Circulation Perfusion in Rats

The bronchial circulation is thought to be the primary blood supply for pulmonary carcinomas. Thus, we have developed a method for imaging and quantifying changes in perfusion in the rat lung due to development of the bronchial circulation. A dual-modality micro-CT/SPECT system was used to detect change in perfusion in two groups of rats: controls and those with a surgically occluded left pulmonary artery. Both groups were imaged following injections on separate days i) 2mCi of Tc99m labeled macroaggregated albumin (MAA) into the left carotid artery (IA) and ii) a similar injection into the femoral vein (IV). The IA injection resulted in Tc99m accumulation in capillaries of the systemic circulation including the bronchial circulation, whereas the IV resulted in Tc99m accumulation in the pulmonary capillaries. Ordered subset expectation maximization (OSEM) was used to reconstruct the SPECT image volumes and a Feldkamp algorithm was used to reconstruct the micro-CT image volumes. The micro-CT and SPECT volumes were registered, the SPECT image volume was segmented using the right and left lung boundaries defined from the micro-CT volume, and the ratio of IA radioactivity accumulation in the left lung to IV radioactivity accumulation in both lungs was used as a measure of left lung flow via the bronchial circulation. This ratio was ~0.02 for the untreated rats compared to the treated animals that had an increased flow ratio of ~0.21 40 days after left pulmonary artery occlusion. This increase in flow to the occluded left lung via the bronchial circulation suggests this will be a useful model for further investigating antiangiogenic treatments

Four-dimensional tomographic reconstruction by time domain decomposition

Since the beginnings of tomography, the requirement that the sample does not change during the acquisition of one tomographic rotation is unchanged. We derived and successfully implemented a tomographic reconstruction method which relaxes this decades-old requirement of static samples. In the presented method, dynamic tomographic data sets are decomposed in the temporal domain using basis functions and deploying an L1 regularization technique where the penalty factor is taken for spatial and temporal derivatives. We implemented the iterative algorithm for solving the regularization problem on modern GPU systems to demonstrate its practical use

Integrating Learning from Examples into the Search for Diagnostic Policies

This paper studies the problem of learning diagnostic policies from training examples. A diagnostic policy is a complete description of the decision-making actions of a diagnostician (i.e., tests followed by a diagnostic decision) for all possible combinations of test results. An optimal diagnostic policy is one that minimizes the expected total cost, which is the sum of measurement costs and misdiagnosis costs. In most diagnostic settings, there is a tradeoff between these two kinds of costs. This paper formalizes diagnostic decision making as a Markov Decision Process (MDP). The paper introduces a new family of systematic search algorithms based on the AO* algorithm to solve this MDP. To make AO* efficient, the paper describes an admissible heuristic that enables AO* to prune large parts of the search space. The paper also introduces several greedy algorithms including some improvements over previously-published methods. The paper then addresses the question of learning diagnostic policies from examples. When the probabilities of diseases and test results are computed from training data, there is a great danger of overfitting. To reduce overfitting, regularizers are integrated into the search algorithms. Finally, the paper compares the proposed methods on five benchmark diagnostic data sets. The studies show that in most cases the systematic search methods produce better diagnostic policies than the greedy methods. In addition, the studies show that for training sets of realistic size, the systematic search algorithms are practical on todays desktop computers