Identifying Functional Brain Networks of Spatiotemporal Wide-Field Calcium Imaging Data via a Long Short-Term Memory Autoencoder

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.

Prior-guided Diffusion Model for Cell Segmentation in Quantitative Phase Imaging

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.

Report on the AAPM Grand Challenge on deep generative modeling for learning medical image statistics

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.

ProxNF: Neural Field Proximal Training for High-Resolution 4D Dynamic Image Reconstruction

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 and reduce acquisition times, while computational burden emerges due to the memory footprint of high-resolution images with three spatial dimensions and extended time horizons. Neural fields, 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 to 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 parameter. 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. By reducing the memory footprint and the computational cost of evaluating the imaging operator, the proposed ProxNF approach allows for reconstructing large, high-resolution spatiotemporal images. This method is demonstrated in two numerical studies involving virtual dynamic contrast-enhanced photoacoustic computed tomography imaging of an anatomically realistic dynamic numerical mouse phantom and a two-compartment model of tumor perfusion.

Technical Note: An Efficient Implementation of the Spherical Radon Transform with Cylindrical Apertures

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.

Attention-Based CNN-BiLSTM for Sleep State Classification of Spatiotemporal Wide-Field Calcium Imaging Data

Background: Wide-field calcium imaging (WFCI) with genetically encoded calcium indicators allows for spatiotemporal recordings of neuronal activity in mice. When applied to the study of sleep, WFCI data are manually scored into the sleep states of wakefulness, non-REM (NREM) and REM by use of adjunct EEG and EMG recordings. However, this process is time-consuming, invasive and often suffers from low inter- and intra-rater reliability. Therefore, an automated sleep state classification method that operates on spatiotemporal WFCI data is desired. New Method: A hybrid network architecture consisting of a convolutional neural network (CNN) to extract spatial features of image frames and a bidirectional long short-term memory network (BiLSTM) with attention mechanism to identify temporal dependencies among different time points was proposed to classify WFCI data into states of wakefulness, NREM and REM sleep. Results: Sleep states were classified with an accuracy of 84% and Cohen's kappa of 0.64. Gradient-weighted class activation maps revealed that the frontal region of the cortex carries more importance when classifying WFCI data into NREM sleep while posterior area contributes most to the identification of wakefulness. The attention scores indicated that the proposed network focuses on short- and long-range temporal dependency in a state-specific manner. Comparison with Existing Method: On a 3-hour WFCI recording, the CNN-BiLSTM achieved a kappa of 0.67, comparable to a kappa of 0.65 corresponding to the human EEG/EMG-based scoring. Conclusions: The CNN-BiLSTM effectively classifies sleep states from spatiotemporal WFCI data and will enable broader application of WFCI in sleep.

Investigating the Use of Traveltime and Reflection Tomography for Deep Learning-Based Sound-Speed Estimation in Ultrasound Computed Tomography

Ultrasound computed tomography (USCT) is actively being developed to quantify 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 are being investigated as scalable and 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 -- while low resolution -- SOS measure, while RT reveals tissue boundary information. Systematic analyses were facilitated by employing a stylized 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. Moreover, the CNN was fine-tuned using a weighted reconstruction loss that prioritized tumor regions to address tumor underrepresentation in the training dataset. To understand the benefits of employing dual-channel inputs, single-input CNNs were trained separately using inputs from each modality alone (TT or RT). The methods were assessed quantitatively using normalized root mean squared error and structural similarity index measure for reconstruction accuracy and receiver operating characteristic analysis to assess signal detection-based performance measures.

Deep learning-based image super-resolution of a novel end-expandable optical fiber probe for application in esophageal cancer diagnostics

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.

Spatiotemporal Image Reconstruction to Enable High-Frame Rate Dynamic Photoacoustic Tomography with Rotating-Gantry Volumetric Imagers

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.

Assessing the capacity of a denoising diffusion probabilistic model to reproduce spatial context

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.