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Medical imaging systems are commonly assessed and optimized by the use of objective measures of image quality (IQ). The performance of the ideal observer (IO) acting on imaging measurements has long been advocated as a figure-of-merit to guide the optimization of imaging systems. For computed imaging systems, the performance of the IO acting on imaging measurements also sets an upper bound on task-performance that no image reconstruction method can transcend. As such, estimation of IO performance can provide valuable guidance when designing under-sampled data-acquisition techniques by enabling the identification of designs that will not permit the reconstruction of diagnostically inappropriate images for a specified task - no matter how advanced the reconstruction method is or how plausible the reconstructed images appear. The need for such analysis is urgent because of the substantial increase of medical device submissions on deep learning-based image reconstruction methods and the fact that they may produce clean images disguising the potential loss of diagnostic information when data is aggressively under-sampled. Recently, convolutional neural network (CNN) approximated IOs (CNN-IOs) was investigated for estimating the performance of data space IOs to establish task-based performance bounds for image reconstruction, under an X-ray computed tomographic (CT) context. In this work, the application of such data space CNN-IO analysis to multi-coil magnetic resonance imaging (MRI) systems has been explored. This study utilized stylized multi-coil sensitivity encoding (SENSE) MRI systems and deep-generated stochastic brain models to demonstrate the approach. Signal-known-statistically and background-known-statistically (SKS/BKS) binary signal detection tasks were selected to study the impact of different acceleration factors on the data space IO performance., Comment: 4 pages

In certain three-dimensional (3D) applications of photoacoustic computed tomography (PACT), including \textit{in vivo} breast imaging, hemispherical measurement apertures that enclose the object within their convex hull are employed for data acquisition. Data acquired with such measurement geometries are referred to as \textit{half-scan} data, as only half of a complete spherical measurement aperture is employed. Although previous studies have demonstrated that half-scan data can uniquely and stably reconstruct the sought-after object, no closed-form reconstruction formula for use with half-scan data has been reported. To address this, a semi-analytic reconstruction method in the form of filtered backprojection (FBP), referred to as the half-scan FBP method, is developed in this work. Because the explicit form of the filtering operation in the half-scan FBP method is not currently known, a learning-based method is proposed to approximate it. The proposed method is systematically investigated by use of virtual imaging studies of 3D breast PACT that employ ensembles of numerical breast phantoms and a physics-based model of the data acquisition process. The method is subsequently applied to experimental data acquired in an \textit{in vivo} breast PACT study. The results confirm that the half-scan FBP method can accurately reconstruct 3D images from half-scan data. Importantly, because the sought-after inverse mapping is well-posed, the reconstruction method remains accurate even when applied to data that differ considerably from those employed to learn the filtering operation.

Quantitative photoacoustic computed tomography (qPACT) is an emerging medical imaging modality that carries the promise of high-contrast, fine-resolution imaging of clinically relevant quantities like hemoglobin concentration and blood-oxygen saturation. However, qPACT image reconstruction is governed by a multiphysics, partial differential equation (PDE) based inverse problem that is highly non-linear and severely ill-posed. Compounding the difficulty of the problem is the lack of established design standards for qPACT imaging systems, as there is currently a proliferation of qPACT system designs for various applications and it is unknown which ones are optimal or how to best modify the systems under various design constraints. This work introduces a novel computational approach for the optimal experimental design (OED) of qPACT imaging systems based on the Bayesian Cram\'er-Rao bound (CRB). Our approach incorporates several techniques to address challenges associated with forming the bound in the infinite-dimensional function space setting of qPACT, including priors with trace-class covariance operators and the use of the variational adjoint method to compute derivatives of the log-likelihood function needed in the bound computation. The resulting Bayesian CRB based design metric is computationally efficient and independent of the choice of estimator used to solve the inverse problem. The efficacy of the bound in guiding experimental design was demonstrated in a numerical study of qPACT design schemes under a stylized two-dimensional imaging geometry. To the best of our knowledge, this is the first work to propose Bayesian CRB based design for systems governed by PDEs.

Computational wave imaging (CWI) extracts hidden structure and physical properties of a volume of material by analyzing wave signals that traverse that volume. Applications include seismic exploration of the Earth's subsurface, acoustic imaging and non-destructive testing in material science, and ultrasound computed tomography in medicine. Current approaches for solving CWI problems can be divided into two categories: those rooted in traditional physics, and those based on deep learning. Physics-based methods stand out for their ability to provide high-resolution and quantitatively accurate estimates of acoustic properties within the medium. However, they can be computationally intensive and are susceptible to ill-posedness and nonconvexity typical of CWI problems. Machine learning-based computational methods have recently emerged, offering a different perspective to address these challenges. Diverse scientific communities have independently pursued the integration of deep learning in CWI. This review delves into how contemporary scientific machine-learning (ML) techniques, and deep neural networks in particular, have been harnessed to tackle CWI problems. We present a structured framework that consolidates existing research spanning multiple domains, including computational imaging, wave physics, and data science. This study concludes with important lessons learned from existing ML-based methods and identifies technical hurdles and emerging trends through a systematic analysis of the extensive literature on this topic., Comment: 29 pages, 11 figures

In photoacoustic computed tomography (PACT) the accurate estimation of the initial pressure (IP) distribution generally requires knowledge of the object's heterogeneous speed-of-sound (SOS) distribution. Although hybrid imagers that combine ultrasound tomography with PACT have been proposed, in many current applications of PACT the SOS distribution remains unknown. Joint reconstruction (JR) of the IP and SOS distributions from PACT measurement data alone can address this issue. However, this joint estimation problem is ill-posed and corresponds to a non-convex optimization problem. While certain regularization strategies have been deployed, stabilizing the JR problem to yield accurate estimates of the IP and SOS distributions has remained an open challenge. To address this, the presented numerical studies explore the effectiveness of easy to implement canonical object constraints for stabilizing the JR problem. The considered constraints include support, bound, and total variation constraints, which are incorporated into an optimization-based method for JR. Computer-simulation studies that employ anatomically realistic numerical breast phantoms are conducted to evaluate the impact of these object constraints on JR accuracy. Additionally, the impact of certain data inconsistencies, such as caused by measurement noise and physics modeling mismatches, on the effectiveness of the object constraints is investigated. The results demonstrate, for the first time, that the incorporation of canonical object constraints in an optimization-based image reconstruction method holds significant potential for mitigating the ill-posed nature of the PACT JR problem.

The objective of this work is to showcase the ortho-positronium lifetime as a probe for soft-tissue characterization. We employed positron annihilation lifetime spectroscopy to experimentally measure the three components of the positron annihilation lifetime para-positronium (p-Ps), positron, and ortho-positronium (o-Ps) for three types of porcine, non-fixated soft tissues ex vivo: adipose, hepatic, and muscle.Then, we benchmarked our measurements with X-ray phase-contrast imaging, which is the current state-of-the-art for soft-tissue analysis. We found that the o-Ps lifetime in adipose tissues (2.54+/-0.12) ns was approximately 20\% longer than in hepatic (2.04+/-0.09 ns) and muscle (2.03+/-0.12 ns) tissues .In addition, the separation between the measurements for adipose tissue and the other tissues was better from o-Ps lifetime measurement than from X-ray phase-contrast imaging. This experimental study proved that the o-Ps lifetime is a viable non-invasive probe for characterizing and classifying the different soft tissues. Specifically, o-Ps lifetime as a soft-tissue characterization probe had a strong sensitivity to the lipid content that can be potentially implemented in commercial positron emission tomography scanners that feature list-mode data acquisition.

Wide-field calcium imaging (WFCI) that records neural calcium dynamics allows for identification of functional brain networks (FBNs) in mice that express genetically encoded calcium indicators. Estimating FBNs from WFCI data is commonly achieved by use of seed-based correlation (SBC) analysis and independent component analysis (ICA). These two methods are conceptually distinct and each possesses limitations. Recent success of unsupervised representation learning in neuroimage analysis motivates the investigation of such methods to identify FBNs. In this work, a novel approach referred as LSTM-AER, is proposed in which a long short-term memory (LSTM) autoencoder (AE) is employed to learn spatial-temporal latent embeddings from WFCI data, followed by an ordinary least square regression (R) to estimate FBNs. The goal of this study is to elucidate and illustrate, qualitatively and quantitatively, the FBNs identified by use of the LSTM-AER method and compare them to those from traditional SBC and ICA. It was observed that spatial FBN maps produced from LSTM-AER resembled those derived by SBC and ICA while better accounting for intra-subject variation, data from a single hemisphere, shorter epoch lengths and tunable number of latent components. The results demonstrate the potential of unsupervised deep learning-based approaches to identifying and mapping FBNs.

Purpose: Quantitative phase imaging (QPI) is a label-free technique that provides high-contrast images of tissues and cells without the use of chemicals or dyes. Accurate semantic segmentation of cells in QPI is essential for various biomedical applications. While DM-based segmentation has demonstrated promising results, the requirement for multiple sampling steps reduces efficiency. This study aims to enhance DM-based segmentation by introducing prior-guided content information into the starting noise, thereby minimizing inefficiencies associated with multiple sampling. Approach: A prior-guided mechanism is introduced into DM-based segmentation, replacing randomly sampled starting noise with noise informed by content information. This mechanism utilizes another trained DM and DDIM inversion to incorporate content information from the to-be-segmented images into the starting noise. An evaluation method is also proposed to assess the quality of the starting noise, considering both content and distribution information. Results: Extensive experiments on various QPI datasets for cell segmentation showed that the proposed method achieved superior performance in DM-based segmentation with only a single sampling. Ablation studies and visual analysis further highlighted the significance of content priors in DM-based segmentation. Conclusion: The proposed method effectively leverages prior content information to improve DM-based segmentation, providing accurate results while reducing the need for multiple samplings. The findings emphasize the importance of integrating content priors into DM-based segmentation methods for optimal performance.

The findings of the 2023 AAPM Grand Challenge on Deep Generative Modeling for Learning Medical Image Statistics are reported in this Special Report. The goal of this challenge was to promote the development of deep generative models (DGMs) for medical imaging and to emphasize the need for their domain-relevant assessment via the analysis of relevant image statistics. As part of this Grand Challenge, a training dataset was developed based on 3D anthropomorphic breast phantoms from the VICTRE virtual imaging toolbox. A two-stage evaluation procedure consisting of a preliminary check for memorization and image quality (based on the Frechet Inception distance (FID)), and a second stage evaluating the reproducibility of image statistics corresponding to domain-relevant radiomic features was developed. A summary measure was employed to rank the submissions. Additional analyses of submissions was performed to assess DGM performance specific to individual feature families, and to identify various artifacts. 58 submissions from 12 unique users were received for this Challenge. The top-ranked submission employed a conditional latent diffusion model, whereas the joint runners-up employed a generative adversarial network, followed by another network for image superresolution. We observed that the overall ranking of the top 9 submissions according to our evaluation method (i) did not match the FID-based ranking, and (ii) differed with respect to individual feature families. Another important finding from our additional analyses was that different DGMs demonstrated similar kinds of artifacts. This Grand Challenge highlighted the need for domain-specific evaluation to further DGM design as well as deployment. It also demonstrated that the specification of a DGM may differ depending on its intended use.

Accurate spatiotemporal image reconstruction methods are needed for a wide range of biomedical research areas but face challenges due to data incompleteness and computational burden. Data incompleteness arises from the undersampling often required to increase frame rates, while computational burden emerges due to the memory footprint of high-resolution images with three spatial dimensions and extended time horizons. Neural fields (NFs), an emerging class of neural networks that act as continuous representations of spatiotemporal objects, have previously been introduced to solve these dynamic imaging problems by reframing image reconstruction as a problem of estimating network parameters. Neural fields can address the twin challenges of data incompleteness and computational burden by exploiting underlying redundancies in these spatiotemporal objects. This work proposes ProxNF, a novel neural field training approach for spatiotemporal image reconstruction leveraging proximal splitting methods to separate computations involving the imaging operator from updates of the network parameters. Specifically, ProxNF evaluates the (subsampled) gradient of the data-fidelity term in the image domain and uses a fully supervised learning approach to update the neural field parameters. This method is demonstrated in two numerical phantom studies and an in-vivo application to tumor perfusion imaging in small animal models using dynamic contrast-enhanced photoacoustic computed tomography (DCE PACT)., Comment: 16 pages, 12 figures

The spherical Radon transform (SRT) is an integral transform that maps a function to its integrals over concentric spherical shells centered at specified sensor locations. It has several imaging applications, including synthetic aperture radar and photoacoustic computed tomography. However, computation of the SRT can be expensive. Efficient implementation of SRT on general purpose graphic processing units (GPGPUs) often utilizes non-matched implementation of the adjoint operator, leading to inconsistent gradients in optimization-based image reconstruction methods. This work details an efficient implementation of the SRT and its adjoint for the case of a cylindrical measurement aperture. Exploiting symmetry of the cylindrical geometry, the SRT can then be expressed as the composition of two circular Radon transforms (CRT). Utilizing this formulation then allows for an efficient implementation of the SRT as a discrete-to-discrete operator utilizing sparse matrix representation., Comment: 4 pages

Ultrasound computed tomography (USCT) quantifies acoustic tissue properties such as the speed-of-sound (SOS). Although full-waveform inversion (FWI) is an effective method for accurate SOS reconstruction, it can be computationally challenging for large-scale problems. Deep learning-based image-to-image learned reconstruction (IILR) methods can offer computationally efficient alternatives. This study investigates the impact of the chosen input modalities on IILR methods for high-resolution SOS reconstruction in USCT. The selected modalities are traveltime tomography (TT) and reflection tomography (RT), which produce a low-resolution SOS map and a reflectivity map, respectively. These modalities have been chosen for their lower computational cost relative to FWI and their capacity to provide complementary information: TT offers a direct SOS measure, while RT reveals tissue boundary information. Systematic analyses were facilitated by employing a virtual USCT imaging system with anatomically realistic numerical breast phantoms. Within this testbed, a supervised convolutional neural network (CNN) was trained to map dual-channel (TT and RT images) to a high-resolution SOS map. Single-input CNNs were trained separately using inputs from each modality alone (TT or RT) for comparison. The accuracy of the methods was systematically assessed using normalized root mean squared error (NRMSE), structural similarity index measure (SSIM), and peak signal-to-noise ratio (PSNR). For tumor detection performance, receiver operating characteristic analysis was employed. The dual-channel IILR method was also tested on clinical human breast data. Ensemble average of the NRMSE, SSIM, and PSNR evaluated on this clinical dataset were 0.2355, 0.8845, and 28.33 dB, respectively., Comment: Associated SPIE proceeding: Jeong, Gangwon, et al. "A deep-learning-based image reconstruction method for USCT that employs multimodality inputs." Medical Imaging 2023: Ultrasonic Imaging and Tomography. Vol. 12470. SPIE, 2023

Significance: Endoscopic screening for esophageal cancer may enable early cancer diagnosis and treatment. While optical microendoscopic technology has shown promise in improving specificity, the limited field of view (<1 mm) significantly reduces the ability to survey large areas efficiently in esophageal cancer screening. Aim: To improve the efficiency of endoscopic screening, we proposed a novel end-expandable endoscopic optical fiber probe for larger field of visualization and employed a deep learning-based image super-resolution (DL-SR) method to overcome the issue of limited sampling capability. Approach: To demonstrate feasibility of the end-expandable optical fiber probe, DL-SR was applied on simulated low-resolution (LR) microendoscopic images to generate super-resolved (SR) ones. Varying the degradation model of image data acquisition, we identified the optimal parameters for optical fiber probe prototyping. The proposed screening method was validated with a human pathology reading study. Results: For various degradation parameters considered, the DL-SR method demonstrated different levels of improvement of traditional measures of image quality. The endoscopist interpretations of the SR images were comparable to those performed on the high-resolution ones. Conclusions: This work suggests avenues for development of DL-SR-enabled end-expandable optical fiber probes to improve high-yield esophageal cancer screening.

Significance: Dynamic photoacoustic computed tomography (PACT) is a valuable technique for monitoring physiological processes. However, current dynamic PACT techniques are often limited to 2D spatial imaging. While volumetric PACT imagers are commercially available, these systems typically employ a rotating gantry in which the tomographic data are sequentially acquired. Because the object varies during the data-acquisition process, the sequential data-acquisition poses challenges to image reconstruction associated with data incompleteness. The proposed method is highly significant in that it will address these challenges and enable volumetric dynamic PACT imaging with existing imagers. Aim: The aim of this study is to develop a spatiotemporal image reconstruction (STIR) method for dynamic PACT that can be applied to commercially available volumetric PACT imagers that employ a sequential scanning strategy. The proposed method aims to overcome the challenges caused by the limited number of tomographic measurements acquired per frame. Approach: A low-rank matrix estimation-based STIR method (LRME-STIR) is proposed to enable dynamic volumetric PACT. The LRME-STIR method leverages the spatiotemporal redundancies to accurately reconstruct a 4D spatiotemporal image. Results: The numerical studies substantiate the LRME-STIR method's efficacy in reconstructing 4D dynamic images from measurements acquired with a rotating gantry. The experimental study demonstrates the method's ability to faithfully recover the flow of a contrast agent at a frame rate of 0.1 s even when only a single tomographic measurement per frame is available. Conclusions: The LRME-STIR method offers a promising solution to the challenges faced by enabling 4D dynamic imaging using commercially available volumetric imagers. By enabling accurate 4D reconstruction, this method has the potential to advance preclinical research.

Diffusion models have emerged as a popular family of deep generative models (DGMs). In the literature, it has been claimed that one class of diffusion models -- denoising diffusion probabilistic models (DDPMs) -- demonstrate superior image synthesis performance as compared to generative adversarial networks (GANs). To date, these claims have been evaluated using either ensemble-based methods designed for natural images, or conventional measures of image quality such as structural similarity. However, there remains an important need to understand the extent to which DDPMs can reliably learn medical imaging domain-relevant information, which is referred to as `spatial context' in this work. To address this, a systematic assessment of the ability of DDPMs to learn spatial context relevant to medical imaging applications is reported for the first time. A key aspect of the studies is the use of stochastic context models (SCMs) to produce training data. In this way, the ability of the DDPMs to reliably reproduce spatial context can be quantitatively assessed by use of post-hoc image analyses. Error-rates in DDPM-generated ensembles are reported, and compared to those corresponding to a modern GAN. The studies reveal new and important insights regarding the capacity of DDPMs to learn spatial context. Notably, the results demonstrate that DDPMs hold significant capacity for generating contextually correct images that are `interpolated' between training samples, which may benefit data-augmentation tasks in ways that GANs cannot., Comment: This paper is under consideration at IEEE TMI

Generative models have gained popularity for their potential applications in imaging science, such as image reconstruction, posterior sampling and data sharing. Flow-based generative models are particularly attractive due to their ability to tractably provide exact density estimates along with fast, inexpensive and diverse samples. Training such models, however, requires a large, high quality dataset of objects. In applications such as computed imaging, it is often difficult to acquire such data due to requirements such as long acquisition time or high radiation dose, while acquiring noisy or partially observed measurements of these objects is more feasible. In this work, we propose AmbientFlow, a framework for learning flow-based generative models directly from noisy and incomplete data. Using variational Bayesian methods, a novel framework for establishing flow-based generative models from noisy, incomplete data is proposed. Extensive numerical studies demonstrate the effectiveness of AmbientFlow in learning the object distribution. The utility of AmbientFlow in a downstream inference task of image reconstruction is demonstrated., Comment: Accepted to Transactions on Machine Learning Research (TMLR). OpenReview: https://openreview.net/forum?id=txpYITR8oa

Ultrasound computed tomography (USCT) is an emerging imaging modality that holds great promise for breast imaging. Full-waveform inversion (FWI)-based image reconstruction methods incorporate accurate wave physics to produce high spatial resolution quantitative images of speed of sound or other acoustic properties of the breast tissues from USCT measurement data. However, the high computational cost of FWI reconstruction represents a significant burden for its widespread application in a clinical setting. The research reported here investigates the use of a convolutional neural network (CNN) to learn a mapping from USCT waveform data to speed of sound estimates. The CNN was trained using a supervised approach with a task-informed loss function aiming at preserving features of the image that are relevant to the detection of lesions. A large set of anatomically and physiologically realistic numerical breast phantoms (NBPs) and corresponding simulated USCT measurements was employed during training. Once trained, the CNN can perform real-time FWI image reconstruction from USCT waveform data. The performance of the proposed method was assessed and compared against FWI using a hold-out sample of 41 NBPs and corresponding USCT data. Accuracy was measured using relative mean square error (RMSE), structural self-similarity index measure (SSIM), and lesion detection performance (DICE score). This numerical experiment demonstrates that a supervised learning model can achieve accuracy comparable to FWI in terms of RMSE and SSIM, and better performance in terms of task performance, while significantly reducing computational time., Comment: 13 pages, 12 figures

Phantoms are test objects used for initial testing and optimization of medical imaging techniques, but these rarely capture the complex properties of the tissue. Here we introduce super phantoms, that surpass standard phantoms being able to replicate complex anatomic and functional imaging properties of tissues and organs. These super phantoms can be computer models, inanimate physical objects, or ex-vivo organs. Testing on these super phantoms, will enable iterative improvements well before in-vivo studies, fostering innovation. We illustrate super phantom examples, address development challenges, and envision centralized facilities supporting multiple institutions in applying these models for medical advancements., Comment: 12 pages, 2 figures. Accepted for publication in Commun. Engg

Automated semantic segmentation of cell nuclei in microscopic images is crucial for disease diagnosis and tissue microenvironment analysis. Nonetheless, this task presents challenges due to the complexity and heterogeneity of cells. While supervised deep learning methods are promising, they necessitate large annotated datasets that are time-consuming and error-prone to acquire. Semi-supervised approaches could provide feasible alternatives to this issue. However, the limited annotated data may lead to subpar performance of semi-supervised methods, regardless of the abundance of unlabeled data. In this paper, we introduce a novel unsupervised pre-training-based semi-supervised framework for cell-nuclei segmentation. Our framework is comprised of three main components. Firstly, we pretrain a diffusion model on a large-scale unlabeled dataset. The diffusion model's explicit modeling capability facilitates the learning of semantic feature representation from the unlabeled data. Secondly, we achieve semantic feature aggregation using a transformer-based decoder, where the pretrained diffusion model acts as the feature extractor, enabling us to fully utilize the small amount of labeled data. Finally, we implement a collaborative learning framework between the diffusion-based segmentation model and a supervised segmentation model to further enhance segmentation performance. Experiments were conducted on four publicly available datasets to demonstrate significant improvements compared to competitive semi-supervised segmentation methods and supervised baselines. A series of out-of-distribution tests further confirmed the generality of our framework. Furthermore, thorough ablation experiments and visual analysis confirmed the superiority of our proposed method.

We present a novel method that integrates subspace modeling with an adaptive generative image prior for high-dimensional MR image reconstruction. The subspace model imposes an explicit low-dimensional representation of the high-dimensional images, while the generative image prior serves as a spatial constraint on the "contrast-weighted" images or the spatial coefficients of the subspace model. A formulation was introduced to synergize these two components with complimentary regularization such as joint sparsity. A special pretraining plus subject-specific network adaptation strategy was proposed to construct an accurate generative-model-based representation for images with varying contrasts, validated by experimental data. An iterative algorithm was introduced to jointly update the subspace coefficients and the multiresolution latent space of the generative image model that leveraged a recently developed intermediate layer optimization technique for network inversion. We evaluated the utility of the proposed method in two high-dimensional imaging applications: accelerated MR parameter mapping and high-resolution MRSI. Improved performance over state-of-the-art subspace-based methods was demonstrated in both cases. Our work demonstrated the potential of integrating data-driven and adaptive generative models with low-dimensional representation for high-dimensional imaging problems.

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., Comment: Submitted to IEEE Transactions on Medical Imaging

Interpretability is highly desired for deep neural network-based classifiers, especially when addressing high-stake decisions in medical imaging. Commonly used post-hoc interpretability methods have the limitation that they can produce plausible but different interpretations of a given model, leading to ambiguity about which one to choose. To address this problem, a novel decision-theory-inspired approach is investigated to establish a self-interpretable model, given a pre-trained deep binary black-box medical image classifier. This approach involves utilizing a self-interpretable encoder-decoder model in conjunction with a single-layer fully connected network with unity weights. The model is trained to estimate the test statistic of the given trained black-box deep binary classifier to maintain a similar accuracy. The decoder output image, referred to as an equivalency map, is an image that represents a transformed version of the to-be-classified image that, when processed by the fixed fully connected layer, produces the same test statistic value as the original classifier. The equivalency map provides a visualization of the transformed image features that directly contribute to the test statistic value and, moreover, permits quantification of their relative contributions. Unlike the traditional post-hoc interpretability methods, the proposed method is self-interpretable, quantitative. Detailed quantitative and qualitative analyses have been performed with three different medical image binary classification tasks.

Ultrasound computed tomography (USCT) is an emerging medical imaging modality that holds great promise for improving human health. Full-waveform inversion (FWI)-based image reconstruction methods account for the relevant wave physics to produce high spatial resolution images of the acoustic properties of the breast tissues. A practical USCT design employs a circular ring-array comprised of elevation-focused ultrasonic transducers, and volumentric imaging is achieved by translating the ring-array orthogonally to the imaging plane. In commonly deployed slice-by-slice (SBS) reconstruction approaches, the three-dimensional (3D) volume is reconstructed by stacking together two-dimensional (2D) images reconstructed for each position of the ring-array. A limitation of the SBS reconstruction approach is that it does not account for 3D wave propagation physics and the focusing properties of the transducers, which can result in significant image artifacts and inaccuracies. To perform 3D image reconstruction when elevation-focused transducers are employed, a numerical description of the focusing properties of the transducers should be included in the forward model. To address this, a 3D computational model of an elevation-focused transducer is developed to enable 3D FWI-based reconstruction methods to be deployed in ring-array-based USCT. The focusing is achieved by applying a spatially varying temporal delay to the ultrasound pulse (emitter mode) and recorded signal (receiver mode). The proposed numerical transducer model is quantitatively validated and employed in computer-simulation studies that demonstrate its use in image reconstruction for ring-array USCT

A variety of deep neural network (DNN)-based image denoising methods have been proposed for use with medical images. These methods are typically trained by minimizing loss functions that quantify a distance between the denoised image, or a transformed version of it, and the defined target image (e.g., a noise-free or low-noise image). They have demonstrated high performance in terms of traditional image quality metrics such as root mean square error (RMSE), structural similarity index measure (SSIM), or peak signal-to-noise ratio (PSNR). However, it has been reported recently that such denoising methods may not always improve objective measures of image quality. In this work, a task-informed DNN-based image denoising method was established and systematically evaluated. A transfer learning approach was employed, in which the DNN is first pre-trained by use of a conventional (non-task-informed) loss function and subsequently fine-tuned by use of the hybrid loss that includes a task-component. The task-component was designed to measure the performance of a numerical observer (NO) on a signal detection task. The impact of network depth and constraining the fine-tuning to specific layers of the DNN was explored. The task-informed training method was investigated in a stylized low-dose X-ray computed tomography (CT) denoising study for which binary signal detection tasks under signal-known-statistically (SKS) with background-known-statistically (BKS) conditions were considered. The impact of changing the specified task at inference time to be different from that employed for model training, a phenomenon we refer to as "task-shift", was also investigated. The presented results indicate that the task-informed training method can improve observer performance while providing control over the trade off between traditional and task-based measures of image quality.

Quantitative phase retrieval (QPR) in propagation-based x-ray phase contrast imaging of heterogeneous and structurally complicated objects is challenging under laboratory conditions due to partial spatial coherence and polychromaticity. A learning-based method (LBM) provides a non-linear approach to this problem while not being constrained by restrictive assumptions about object properties and beam coherence. In this work, a LBM was assessed for its applicability under practical scenarios by evaluating its robustness and generalizability under typical experimental variations. Towards this end, an end-to-end LBM was employed for QPR under laboratory conditions and its robustness was investigated across various system and object conditions. The robustness of the method was tested via varying propagation distances and its generalizability with respect to object structure and experimental data was also tested. Although the LBM was stable under the studied variations, its successful deployment was found to be affected by choices pertaining to data pre-processing, network training considerations and system modeling. To our knowledge, we demonstrated for the first time, the potential applicability of an end-to-end learning-based quantitative phase retrieval method, trained on simulated data, to experimental propagation-based x-ray phase contrast measurements acquired under laboratory conditions. We considered conditions of polychromaticity, partial spatial coherence, and high noise levels, typical to laboratory conditions. This work further explored the robustness of this method to practical variations in propagation distances and object structure with the goal of assessing its potential for experimental use. Such an exploration of any LBM (irrespective of its network architecture) before practical deployment provides an understanding of its potential behavior under experimental settings., Comment: Under review as a journal submission. Early version with partial results has been accepted for poster presentation at SPIE-MI 2023

Dynamic imaging is essential for analyzing various biological systems and behaviors but faces two main challenges: data incompleteness and computational burden. For many imaging systems, high frame rates and short acquisition times require severe undersampling, which leads to data incompleteness. Multiple images may then be compatible with the data, thus requiring special techniques (regularization) to ensure the uniqueness of the reconstruction. Computational and memory requirements are particularly burdensome for three-dimensional dynamic imaging applications requiring high resolution in both space and time. Exploiting redundancies in the object's spatiotemporal features is key to addressing both challenges. This contribution investigates neural fields, or implicit neural representations, to model the sought-after dynamic object. Neural fields are a particular class of neural networks that represent the dynamic object as a continuous function of space and time, thus avoiding the burden of storing a full resolution image at each time frame. Neural field representation thus reduces the image reconstruction problem to estimating the network parameters via a nonlinear optimization problem (training). Once trained, the neural field can be evaluated at arbitrary locations in space and time, allowing for high-resolution rendering of the object. Key advantages of the proposed approach are that neural fields automatically learn and exploit redundancies in the sought-after object to both regularize the reconstruction and significantly reduce memory storage requirements. The feasibility of the proposed framework is illustrated with an application to dynamic image reconstruction from severely undersampled circular Radon transform data., Comment: 13 pages, 10 figures

In recent years, generative adversarial networks (GANs) have gained tremendous popularity for potential applications in medical imaging, such as medical image synthesis, restoration, reconstruction, translation, as well as objective image quality assessment. Despite the impressive progress in generating high-resolution, perceptually realistic images, it is not clear if modern GANs reliably learn the statistics that are meaningful to a downstream medical imaging application. In this work, the ability of a state-of-the-art GAN to learn the statistics of canonical stochastic image models (SIMs) that are relevant to objective assessment of image quality is investigated. It is shown that although the employed GAN successfully learned several basic first- and second-order statistics of the specific medical SIMs under consideration and generated images with high perceptual quality, it failed to correctly learn several per-image statistics pertinent to the these SIMs, highlighting the urgent need to assess medical image GANs in terms of objective measures of image quality.

Modern generative models, such as generative adversarial networks (GANs), hold tremendous promise for several areas of medical imaging, such as unconditional medical image synthesis, image restoration, reconstruction and translation, and optimization of imaging systems. However, procedures for establishing stochastic image models (SIMs) using GANs remain generic and do not address specific issues relevant to medical imaging. In this work, canonical SIMs that simulate realistic vessels in angiography images are employed to evaluate procedures for establishing SIMs using GANs. The GAN-based SIM is compared to the canonical SIM based on its ability to reproduce those statistics that are meaningful to the particular medically realistic SIM considered. It is shown that evaluating GANs using classical metrics and medically relevant metrics may lead to different conclusions about the fidelity of the trained GANs. This work highlights the need for the development of objective metrics for evaluating GANs., Comment: Published in SPIE Medical Imaging 2022: Image Perception, Observer Performance, and Technology Assessment

Generative adversarial networks (GANs) have been widely investigated for many potential applications in medical imaging. DatasetGAN is a recently proposed framework based on modern GANs that can synthesize high-quality segmented images while requiring only a small set of annotated training images. The synthesized annotated images could be potentially employed for many medical imaging applications, where images with segmentation information are required. However, to the best of our knowledge, there are no published studies focusing on its applications to medical imaging. In this work, preliminary studies were conducted to investigate the utility of DatasetGAN in medical imaging. Three improvements were proposed to the original DatasetGAN framework, considering the unique characteristics of medical images. The synthesized segmented images by DatasetGAN were visually evaluated. The trained DatasetGAN was further analyzed by evaluating the performance of a pre-defined image segmentation technique, which was trained by the use of the synthesized datasets. The effectiveness, concerns, and potential usage of DatasetGAN were discussed.

Computed medical imaging systems require a computational reconstruction procedure for image formation. In order to recover a useful estimate of the object to-be-imaged when the recorded measurements are incomplete, prior knowledge about the nature of object must be utilized. In order to improve the conditioning of an ill-posed imaging inverse problem, deep learning approaches are being actively investigated for better representing object priors and constraints. This work proposes to use a style-based generative adversarial network (StyleGAN) to constrain an image reconstruction problem in the case where additional information in the form of a prior image of the sought-after object is available. An optimization problem is formulated in the intermediate latent-space of a StyleGAN, that is disentangled with respect to meaningful image attributes or "styles", such as the contrast used in magnetic resonance imaging (MRI). Discrepancy between the sought-after and prior images is measured in the disentangled latent-space, and is used to regularize the inverse problem in the form of constraints on specific styles of the disentangled latent-space. A stylized numerical study inspired by MR imaging is designed, where the sought-after and the prior image are structurally similar, but belong to different contrast mechanisms. The presented numerical studies demonstrate the superiority of the proposed approach as compared to classical approaches in the form of traditional metrics.

Tomographic imaging is in general an ill-posed inverse problem. Typically, a single regularized image estimate of the sought-after object is obtained from tomographic measurements. However, there may be multiple objects that are all consistent with the same measurement data. The ability to generate such alternate solutions is important because it may enable new assessments of imaging systems. In principle, this can be achieved by means of posterior sampling methods. In recent years, deep neural networks have been employed for posterior sampling with promising results. However, such methods are not yet for use with large-scale tomographic imaging applications. On the other hand, empirical sampling methods may be computationally feasible for large-scale imaging systems and enable uncertainty quantification for practical applications. Empirical sampling involves solving a regularized inverse problem within a stochastic optimization framework to obtain alternate data-consistent solutions. In this work, a new empirical sampling method is proposed that computes multiple solutions of a tomographic inverse problem that are consistent with the same acquired measurement data. The method operates by repeatedly solving an optimization problem in the latent space of a style-based generative adversarial network (StyleGAN), and was inspired by the Photo Upsampling via Latent Space Exploration (PULSE) method that was developed for super-resolution tasks. The proposed method is demonstrated and analyzed via numerical studies that involve two stylized tomographic imaging modalities. These studies establish the ability of the method to perform efficient empirical sampling and uncertainty quantification., Comment: Submitted to IEEE Transactions on Medical Imaging