Unsupervised Generation of Pseudo Normal PET from MRI with Diffusion Model for Epileptic Focus Localization

[$^{18}$F]fluorodeoxyglucose (FDG) positron emission tomography (PET) has emerged as a crucial tool in identifying the epileptic focus, especially in cases where magnetic resonance imaging (MRI) diagnosis yields indeterminate results. FDG PET can provide the metabolic information of glucose and help identify abnormal areas that are not easily found through MRI. However, the effectiveness of FDG PET-based assessment and diagnosis depends on the selection of a healthy control group. The healthy control group typically consists of healthy individuals similar to epilepsy patients in terms of age, gender, and other aspects for providing normal FDG PET data, which will be used as a reference for enhancing the accuracy and reliability of the epilepsy diagnosis. However, significant challenges arise when a healthy PET control group is unattainable. Yaakub \emph{et al.} have previously introduced a Pix2PixGAN-based method for MRI to PET translation. This method used paired MRI and FDG PET scans from healthy individuals for training, and produced pseudo normal FDG PET images from patient MRIs that are subsequently used for lesion detection. However, this approach requires a large amount of high-quality, paired MRI and PET images from healthy control subjects, which may not always be available. In this study, we investigated unsupervised learning methods for unpaired MRI to PET translation for generating pseudo normal FDG PET for epileptic focus localization. Two deep learning methods, CycleGAN and SynDiff, were employed, and we found that diffusion-based method achieved improved performance in accurately localizing the epileptic focus.

Ambient-Pix2PixGAN for Translating Medical Images from Noisy Data

Image-to-image translation is a common task in computer vision and has been rapidly increasing the impact on the field of medical imaging. Deep learning-based methods that employ conditional generative adversarial networks (cGANs), such as Pix2PixGAN, have been extensively explored to perform image-to-image translation tasks. However, when noisy medical image data are considered, such methods cannot be directly applied to produce clean images. Recently, an augmented GAN architecture named AmbientGAN has been proposed that can be trained on noisy measurement data to synthesize high-quality clean medical images. Inspired by AmbientGAN, in this work, we propose a new cGAN architecture, Ambient-Pix2PixGAN, for performing medical image-to-image translation tasks by use of noisy measurement data. Numerical studies that consider MRI-to-PET translation are conducted. Both traditional image quality metrics and task-based image quality metrics are employed to assess the proposed Ambient-Pix2PixGAN. It is demonstrated that our proposed Ambient-Pix2PixGAN can be successfully trained on noisy measurement data to produce high-quality translated images in target imaging modality.

AmbientCycleGAN for Establishing Interpretable Stochastic Object Models Based on Mathematical Phantoms and Medical Imaging Measurements

Medical imaging systems that are designed for producing diagnostically informative images should be objectively assessed via task-based measures of image quality (IQ). Ideally, computation of task-based measures of IQ needs to account for all sources of randomness in the measurement data, including the variability in the ensemble of objects to be imaged. To address this need, stochastic object models (SOMs) that can generate an ensemble of synthesized objects or phantoms can be employed. Various mathematical SOMs or phantoms were developed that can interpretably synthesize objects, such as lumpy object models and parameterized torso phantoms. However, such SOMs that are purely mathematically defined may not be able to comprehensively capture realistic object variations. To establish realistic SOMs, it is desirable to use experimental data. An augmented generative adversarial network (GAN), AmbientGAN, was recently proposed for establishing SOMs from medical imaging measurements. However, it remains unclear to which extent the AmbientGAN-produced objects can be interpretably controlled. This work introduces a novel approach called AmbientCycleGAN that translates mathematical SOMs to realistic SOMs by use of noisy measurement data. Numerical studies that consider clustered lumpy background (CLB) models and real mammograms are conducted. It is demonstrated that our proposed method can stably establish SOMs based on mathematical models and noisy measurement data. Moreover, the ability of the proposed AmbientCycleGAN to interpretably control image features in the synthesized objects is investigated.

Ideal Observer Computation by Use of Markov-Chain Monte Carlo with Generative Adversarial Networks

Medical imaging systems are often evaluated and optimized via objective, or task-specific, measures of image quality (IQ) that quantify the performance of an observer on a specific clinically-relevant task. The performance of the Bayesian Ideal Observer (IO) sets an upper limit among all observers, numerical or human, and has been advocated for use as a figure-of-merit (FOM) for evaluating and optimizing medical imaging systems. However, the IO test statistic corresponds to the likelihood ratio that is intractable to compute in the majority of cases. A sampling-based method that employs Markov-Chain Monte Carlo (MCMC) techniques was previously proposed to estimate the IO performance. However, current applications of MCMC methods for IO approximation have been limited to a small number of situations where the considered distribution of to-be-imaged objects can be described by a relatively simple stochastic object model (SOM). As such, there remains an important need to extend the domain of applicability of MCMC methods to address a large variety of scenarios where IO-based assessments are needed but the associated SOMs have not been available. In this study, a novel MCMC method that employs a generative adversarial network (GAN)-based SOM, referred to as MCMC-GAN, is described and evaluated. The MCMC-GAN method was quantitatively validated by use of test-cases for which reference solutions were available. The results demonstrate that the MCMC-GAN method can extend the domain of applicability of MCMC methods for conducting IO analyses of medical imaging systems.

A deep Q-learning method for optimizing visual search strategies in backgrounds of dynamic noise

Humans process visual information with varying resolution (foveated visual system) and explore images by orienting through eye movements the high-resolution fovea to points of interest. The Bayesian ideal searcher (IS) that employs complete knowledge of task-relevant information optimizes eye movement strategy and achieves the optimal search performance. The IS can be employed as an important tool to evaluate the optimality of human eye movements, and potentially provide guidance to improve human observer visual search strategies. Najemnik and Geisler (2005) derived an IS for backgrounds of spatial 1/f noise. The corresponding template responses follow Gaussian distributions and the optimal search strategy can be analytically determined. However, the computation of the IS can be intractable when considering more realistic and complex backgrounds such as medical images. Modern reinforcement learning methods, successfully applied to obtain optimal policy for a variety of tasks, do not require complete knowledge of the background generating functions and can be potentially applied to anatomical backgrounds. An important first step is to validate the optimality of the reinforcement learning method. In this study, we investigate the ability of a reinforcement learning method that employs Q-network to approximate the IS. We demonstrate that the search strategy corresponding to the Q-network is consistent with the IS search strategy. The findings show the potential of the reinforcement learning with Q-network approach to estimate optimal eye movement planning with real anatomical backgrounds.

Supervised Learning-Enabled Ideal Observer Approximation for Joint Detection and Estimation Tasks

The ideal observer (IO) sets an upper performance limit among all observers and has been advocated for assessing and optimizing imaging systems. For general joint detection and estimation (detection-estimation) tasks, estimation ROC (EROC) analysis has been established for evaluating the performance of observers. However, in general, it is difficult to accurately approximate the IO that maximizes the area under the EROC curve. In this study, a hybrid method that employs machine learning is proposed to accomplish this. Specifically, a hybrid approach is developed that combines a multi-task convolutional neural network and a Markov-Chain Monte Carlo (MCMC) method in order to approximate the IO for detection-estimation tasks. In addition, a purely supervised learning-based sub-ideal observer is proposed. Computer-simulation studies are conducted to validate the proposed method, which include signal-known-statistically/background-known-exactly and signal-known-statistically/background-known-statistically tasks. The EROC curves produced by the proposed method are compared to those produced by the MCMC approach or analytical computation when feasible. The proposed method provides a new approach for approximating the IO and may advance the application of EROC analysis for optimizing imaging systems.

Learning stochastic object models from medical imaging measurements by use of advanced AmbientGANs

In order to objectively assess new medical imaging technologies via computer-simulations, it is important to account for all sources of variability that contribute to image data. One important source of variability that can significantly limit observer performance is associated with the variability in the ensemble of objects to-be-imaged. This source of variability can be described by stochastic object models (SOMs), which are generative models that can be employed to sample from a distribution of to-be-virtually-imaged objects. It is generally desirable to establish SOMs from experimental imaging measurements acquired by use of a well-characterized imaging system, but this task has remained challenging. Deep generative neural networks, such as generative adversarial networks (GANs) hold potential for such tasks. To establish SOMs from imaging measurements, an AmbientGAN has been proposed that augments a GAN with a measurement operator. However, the original AmbientGAN could not immediately benefit from modern training procedures and GAN architectures, which limited its ability to be applied to realistically sized medical image data. To circumvent this, in this work, a modified AmbientGAN training strategy is proposed that is suitable for modern progressive or multi-resolution training approaches such as employed in the Progressive Growing of GANs and Style-based GANs. AmbientGANs established by use of the proposed training procedure are systematically validated in a controlled way by use of computer-simulated measurement data corresponding to a stylized imaging system. Finally, emulated single-coil experimental magnetic resonance imaging data are employed to demonstrate the methods under less stylized conditions.

Assessing the Impact of Deep Neural Network-based Image Denoising on Binary Signal Detection Tasks

A variety of deep neural network (DNN)-based image denoising methods have been proposed for use with medical images. Traditional measures of image quality (IQ) have been employed to optimize and evaluate these methods. However, the objective evaluation of IQ for the DNN-based denoising methods remains largely lacking. In this work, we evaluate the performance of DNN-based denoising methods by use of task-based IQ measures. Specifically, binary signal detection tasks under signal-known-exactly (SKE) with background-known-statistically (BKS) conditions are considered. The performance of the ideal observer (IO) and common linear numerical observers are quantified and detection efficiencies are computed to assess the impact of the denoising operation on task performance. The numerical results indicate that, in the cases considered, the application of a denoising network can result in a loss of task-relevant information in the image. The impact of the depth of the denoising networks on task performance is also assessed. The presented results highlight the need for the objective evaluation of IQ for DNN-based denoising technologies and may suggest future avenues for improving their effectiveness in medical imaging applications.

Advancing the AmbientGAN for learning stochastic object models

Medical imaging systems are commonly assessed and optimized by use of objective-measures of image quality (IQ) that quantify the performance of an observer at specific tasks. Variation in the objects to-be-imaged is an important source of variability that can significantly limit observer performance. This object variability can be described by stochastic object models (SOMs). In order to establish SOMs that can accurately model realistic object variability, it is desirable to use experimental data. To achieve this, an augmented generative adversarial network (GAN) architecture called AmbientGAN has been developed and investigated. However, AmbientGANs cannot be immediately trained by use of advanced GAN training methods such as the progressive growing of GANs (ProGANs). Therefore, the ability of AmbientGANs to establish realistic object models is limited. To circumvent this, a progressively-growing AmbientGAN (ProAmGAN) has been proposed. However, ProAmGANs are designed for generating two-dimensional (2D) images while medical imaging modalities are commonly employed for imaging three-dimensional (3D) objects. Moreover, ProAmGANs that employ traditional generator architectures lack the ability to control specific image features such as fine-scale textures that are frequently considered when optimizing imaging systems. In this study, we address these limitations by proposing two advanced AmbientGAN architectures: 3D ProAmGANs and Style-AmbientGANs (StyAmGANs). Stylized numerical studies involving magnetic resonance (MR) imaging systems are conducted. The ability of 3D ProAmGANs to learn 3D SOMs from imaging measurements and the ability of StyAmGANs to control fine-scale textures of synthesized objects are demonstrated.

Approximating the Ideal Observer for joint signal detection and localization tasks by use of supervised learning methods

Medical imaging systems are commonly assessed and optimized by use of objective measures of image quality (IQ). The Ideal Observer (IO) performance has been advocated to provide a figure-of-merit for use in assessing and optimizing imaging systems because the IO sets an upper performance limit among all observers. When joint signal detection and localization tasks are considered, the IO that employs a modified generalized likelihood ratio test maximizes observer performance as characterized by the localization receiver operating characteristic (LROC) curve. Computations of likelihood ratios are analytically intractable in the majority of cases. Therefore, sampling-based methods that employ Markov-Chain Monte Carlo (MCMC) techniques have been developed to approximate the likelihood ratios. However, the applications of MCMC methods have been limited to relatively simple object models. Supervised learning-based methods that employ convolutional neural networks have been recently developed to approximate the IO for binary signal detection tasks. In this paper, the ability of supervised learning-based methods to approximate the IO for joint signal detection and localization tasks is explored. Both background-known-exactly and background-known-statistically signal detection and localization tasks are considered. The considered object models include a lumpy object model and a clustered lumpy model, and the considered measurement noise models include Laplacian noise, Gaussian noise, and mixed Poisson-Gaussian noise. The LROC curves produced by the supervised learning-based method are compared to those produced by the MCMC approach or analytical computation when feasible. The potential utility of the proposed method for computing objective measures of IQ for optimizing imaging system performance is explored.