TOWARDS FURTHER OPTIMIZATION OF RECONSTRUCTION METHODS FOR DUAL-RADIONUCLIDE MYOCARDIAL PERFUSION SPECT

Coronary artery disease (CAD) is the most prevalent type of heart disease and a leading cause of death both in the United States and worldwide. Myocardial perfusion SPECT (MPS) is a well-established and widely-used non-invasive imaging technique to diagnose CAD. MPS images the distribution of radioactive perfusion agent in the myocardium to assess the myocardial perfusion status at rest and stress state and allow diagnosis of CAD and allow differentiation of CAD and previous myocardial infarctions. The overall goal of this dissertation was to optimize the image reconstruction methods for MPS by patient-specific optimization of two advanced iterative reconstruction methods based on simulations of realistic patients population modeling existing hardware and previously optimized dual-isotope simultaneous-acquisition imaging protocols. After optimization, the two algorithms were compared to determine the optimal reconstruction methods for MPS. First, we developed a model observer strategy to evaluate image quality and allow optimization of the reconstruction methods using a population of phantoms modeling the variability seen in human populations. The Hotelling Observer (HO) is widely used to evaluate image quality, often in conjunction with anthropomorphic channels to model human observer performance. However, applying the HO to non- multivariate-normally (MVN) distributed, such as the output from a channel model applied to images with variable signals and background, is not optimal. In this work, we proposed a novel model observer strategy to evaluate the image quality of such data. First, the entire data ensemble is divided into sub-ensembles that are exactly or approximately MVN and homoscedastic. Next, the Linear Discriminant (LD) is applied to estimate test statistics for each sub-ensemble, and a single area under the receiver operating characteristics curve (AUC) is calculated using the pooled test statistics from all the sub-ensembles. The AUC serves as the figure of merit for performance on the defect detection task. The proposed multi-template LD was compared to other model observer strategies and was shown to be a practical, theoretically justified, and produced higher AUC values for non-MVN data such as that arising from the clinically-realistic SKS task used in the remainder of this work. We then optimized two regularized statistical reconstruction algorithms. One is the widely used post-filtered ordered subsets-expectation maximization (OS-EM) algorithm. The other is a maximum a posteriori (MAP) algorithm with dual-tracer prior (DTMAP) that was proposed for dual-isotope MPS study and was expected to outperform the post-filtered OS-EM algorithm. Of importance, we proposed to investigate patient-specific optimization of the reconstruction parameters. To accomplish this, the phantom population was divided into three anatomy groups based on metrics that expected to affect image noise and resolution and thus the optimal reconstruction parameters. In particular, these metrics were the distance from the center of the heart to the face of the collimator, which is directly related to image resolution, heart size, and counts from the myocardium, which is expected to determine image noise. Reconstruction parameters were optimized for each of these groups using the proposed model observer strategy. Parameters for the rest and stress images were optimized separately, and the parameters that achieve the highest AUC were deemed optimal. The results showed that the proposed group-wise optimization method offered slightly better task performance than using a single set of parameters for all the phantoms. For DTMAP, we also applied the group-wise optimization approach. The extra challenges for DTMAP optimization are that it has three parameters to be optimized simultaneously, and it is substantially more computationally expensive than OS-EM. Thus, we adopted optimization strategies to reduce the size of the parameter search space. In particular, we searched in two parameter ranges expected to give result in good image quality. We also reduced the computation burden by exploiting limiting behavior of the penalty function to reduce the number of parameters that need to be optimized. Despite this effort, the optimized DTMAP had poorer task performance compared to the optimized OS-EM algorithm. As a result, we studied the limitations of the DTMAP algorithm and suggest reasons of its worse performance for the task investigated. The results of this study indicate that there is benefit from patient-specific optimization. The methods and optimal patient-specific parameters may be applicable to clinical MPS studies. In addition, the model observer strategy and the group-wise optimization approach may also be applicable both to future work in MPS and to other relevant fields

Task-based Optimization of Administered Activity for Pediatric Renal SPECT Imaging

Like any real-world problem, the design of an imaging system always requires tradeoffs. For medical imaging modalities using ionization radiation, a major tradeoff is between diagnostic image quality (IQ) and risk to the patient from absorbed dose (AD). In nuclear medicine, reducing the AD requires reducing the administered activity (AA). Lower AA to the patient can reduce risk and adverse effects, but can also result in reduced diagnostic image quality. Thus, ultimately, it is desirable to use the lowest AA that gives sufficient image quality for accurate clinical diagnosis. In this dissertation, we proposed and developed tools for a general framework for optimizing RD with task-based assessment of IQ. Here, IQ is defined as an objective measure of the user performing the diagnostic task that the images were acquired to answer. To investigate IQ as a function of renal defect detectability, we have developed a projection image database modeling imaging of 99mTc-DMSA, a renal function agent. The database uses a highly-realistic population of pediatric phantoms with anatomical and body morphological variations. Using the developed projection image database, we have explored patient factors that affect IQ and are currently in the process of determining relationships between IQ and AA in terms of these found factors. Our data have shown that factors that are more local to the target organ may be more robust than weight for estimating the AA needed to provide a constant IQ across a population of patients. In the case of renal imaging, we have discovered that girth is more robust than weight (currently used in clinical practice) in predicting AA needed to provide a desired IQ. In addition to exploring the patient factors, we also did some work on improving the task simulating capability for anthropomorphic model observer. We proposed a deep learning-based anthropomorphic model observer to fully and efficiently (in terms of both training data and computational cost) model the clinical 3D detection task using multi-slice, multi-orientation image sets. The proposed model observer is important and could be readily adapted to model human observer performance on detection tasks for other imaging modalities such as PET, CT or MRI

Deep Learning for Task-Based Image Quality Assessment in Medical Imaging

It has been advocated to use objective measures of image quality (IQ) for assessing and optimizing medical imaging systems. Objective measures of IQ quantify the performance of an observer at a specific diagnostic task. Binary signal detection tasks and joint signal detection and localization (detection-localization) tasks are commonly considered in medical imaging. When optimizing imaging systems for binary signal detection tasks, the performance of the Bayesian Ideal Observer (IO) has been advocated for use as a figure-of-merit (FOM). The IO maximizes the observer performance that is summarized by the receiver operating characteristic (ROC) curve. When signal detection-localization tasks are considered, the IO that implements a modified generalized likelihood ratio test (MGLRT) maximizes the observer performance as measured by the localization ROC (LROC) curve. However, computation of the IO test statistic generally is analytically intractable. To address this difficulty, sampling-based methods that employ Markov-Chain Monte Carlo (MCMC) techniques have been proposed. However, current applications of MCMC methods have been limited to relatively simple stochastic object models (SOMs). When the IO is difficult or intractable to compute, the optimal linear observer, known as the Hotelling Observer (HO), can be employed to evaluate objective measures of IQ. Although computation of the HO is easier than that of the IO, it can still be challenging or even intractable because a potentially large covariance matrix needs to be estimated and subsequently inverted. In the first part of the dissertation, we introduce supervised learning-based methods for approximating the IO and the HO for binary signal detection tasks. The use of convolutional neural networks (CNNs) to approximate the IO and the use of single layer neural networks (SLNNs) to directly estimate the Hotelling template without computing and inverting covariance matrices are demonstrated. In the second part, a supervised learning method that employs CNNs to approximate the IO for signal detection-localization tasks is presented. This method represents a deep-learning-based implementation of a MGLRT that defines the IO decision strategy for signal detection-localization tasks. When evaluating observer performance for assessing and optimizing imaging systems by use of objective measures of IQ, all sources of variability in the measured image data should be accounted for. One important source of variability that can significantly affect observer performance is the variation in the ensemble of objects to-be-imaged. To describe this variability, a SOM can be established. A SOM is a generative model that can produce an ensemble of simulated objects with prescribed statistical properties. In order to establish a realistic SOM, it is desirable to use experimental data. Generative adversarial networks (GANs) hold great potential for establishing SOMs. However, images produced by imaging systems are affected by the measurement noise and a potential reconstruction process. Therefore, GANs that are trained by use of these images cannot represent SOMs because they are not established to learn object variability alone. An augmented GAN architecture named AmbientGAN that includes a measurement operator was proposed to address this issue. However, AmbientGANs cannot be immediately implemented with advanced GAN training strategies such as progressive growing of GANs (ProGANs). Therefore, the ability of AmbientGANs to establish realistic and sophisticated SOMs is limited. In the third part of this dissertation, we propose a novel deep learning method named progressively growing AmbientGANs (ProAmGANs) that incorporates the advanced progressive growing training procedure and therefore enables the AmbientGAN to be applied to realistically sized medical image data. Stylized numerical studies involving a variety of object ensembles with common medical imaging modalities are presented. Finally, a novel sampling-based method named MCMC-GAN is developed to approximate the IO. This method applies MCMC algorithms to SOMs that are established by use of GAN techniques. Because the implementation of GANs is general and not limited to specific images, our proposed method can be implemented with sophisticated object models and therefore extends the domain of applicability of the MCMC techniques. Numerical studies involving clinical brain positron emission tomography (PET) images and brain magnetic resonance (MR) images are presented

Objective Assessment of Image Quality: Extension of Numerical Observer Models to Multidimensional Medical Imaging Studies

Encompassing with fields on engineering and medical image quality, this dissertation proposes a novel framework for diagnostic performance evaluation based on objective image-quality assessment, an important step in the development of new imaging devices, acquisitions, or image-processing techniques being used for clinicians and researchers. The objective of this dissertation is to develop computational modeling tools that allow comprehensive evaluation of task-based assessment including clinical interpretation of images regardless of image dimensionality. Because of advances in the development of medical imaging devices, several techniques have improved image quality where the format domain of the outcome images becomes multidimensional (e.g., 3D+time or 4D). To evaluate the performance of new imaging devices or to optimize various design parameters and algorithms, the quality measurement should be performed using an appropriate image-quality figure-of-merit (FOM). Classical FOM such as bias and variance, or mean-square error, have been broadly used in the past. Unfortunately, they do not reflect the fact that the average performance of the principal agent in medical decision-making is frequently a human observer, nor are they aware of the specific diagnostic task. The standard goal for image quality assessment is a task-based approach in which one evaluates human observer performance of a specified diagnostic task (e.g. detection of the presence of lesions). However, having a human observer performs the tasks is costly and time-consuming. To facilitate practical task-based assessment of image quality, a numerical observer is required as a surrogate for human observers. Previously, numerical observers for the detection task have been studied both in research and industry; however, little research effort has been devoted toward development of one utilized for multidimensional imaging studies (e.g., 4D). Limiting the numerical observer tools that accommodate all information embedded in a series of images, the performance assessment of a particular new technique that generates multidimensional data is complex and limited. Consequently, key questions remain unanswered about how much the image quality improved using these new multidimensional images on a specific clinical task. To address this gap, this dissertation proposes a new numerical-observer methodology to assess the improvement achieved from newly developed imaging technologies. This numerical observer approach can be generalized to exploit pertinent statistical information in multidimensional images and accurately predict the performance of a human observer over the complexity of the image domains. Part I of this dissertation aims to develop a numerical observer that accommodates multidimensional images to process correlated signal components and appropriately incorporate them into an absolute FOM. Part II of this dissertation aims to apply the model developed in Part I to selected clinical applications with multidimensional images including: 1) respiratory-gated positron emission tomography (PET) in lung cancer (3D+t), 2) kinetic parametric PET in head-and-neck cancer (3D+k), and 3) spectral computed tomography (CT) in atherosclerotic plaque (3D+e). The author compares the task-based performance of the proposed approach to that of conventional methods, evaluated based on a broadly-used signal-known-exactly /background-known-exactly paradigm, which is in the context of the specified properties of a target object (e.g., a lesion) on highly realistic and clinical backgrounds. A realistic target object is generated with specific properties and applied to a set of images to create pathological scenarios for the performance evaluation, e.g., lesions in the lungs or plaques in the artery. The regions of interest (ROIs) of the target objects are formed over an ensemble of data measurements under identical conditions and evaluated for the inclusion of useful information from different complex domains (i.e., 3D+t, 3D+k, 3D+e). This work provides an image-quality assessment metric with no dimensional limitation that could help substantially improve assessment of performance achieved from new developments in imaging that make use of high dimensional data