Noise-aware Dynamic Image Denoising and Positron Range Correction for Rubidium-82 Cardiac PET Imaging via Self-supervision

Rb-82 is a radioactive isotope widely used for cardiac PET imaging. Despite numerous benefits of 82-Rb, there are several factors that limits its image quality and quantitative accuracy. First, the short half-life of 82-Rb results in noisy dynamic frames. Low signal-to-noise ratio would result in inaccurate and biased image quantification. Noisy dynamic frames also lead to highly noisy parametric images. The noise levels also vary substantially in different dynamic frames due to radiotracer decay and short half-life. Existing denoising methods are not applicable for this task due to the lack of paired training inputs/labels and inability to generalize across varying noise levels. Second, 82-Rb emits high-energy positrons. Compared with other tracers such as 18-F, 82-Rb travels a longer distance before annihilation, which negatively affect image spatial resolution. Here, the goal of this study is to propose a self-supervised method for simultaneous (1) noise-aware dynamic image denoising and (2) positron range correction for 82-Rb cardiac PET imaging. Tested on a series of PET scans from a cohort of normal volunteers, the proposed method produced images with superior visual quality. To demonstrate the improvement in image quantification, we compared image-derived input functions (IDIFs) with arterial input functions (AIFs) from continuous arterial blood samples. The IDIF derived from the proposed method led to lower AUC differences, decreasing from 11.09% to 7.58% on average, compared to the original dynamic frames. The proposed method also improved the quantification of myocardium blood flow (MBF), as validated against 15-O-water scans, with mean MBF differences decreased from 0.43 to 0.09, compared to the original dynamic frames. We also conducted a generalizability experiment on 37 patient scans obtained from a different country using a different scanner.

TAI-GAN: A Temporally and Anatomically Informed Generative Adversarial Network for early-to-late frame conversion in dynamic cardiac PET inter-frame motion correction

Inter-frame motion in dynamic cardiac positron emission tomography (PET) using rubidium-82 (82-Rb) myocardial perfusion imaging impacts myocardial blood flow (MBF) quantification and the diagnosis accuracy of coronary artery diseases. However, the high cross-frame distribution variation due to rapid tracer kinetics poses a considerable challenge for inter-frame motion correction, especially for early frames where intensity-based image registration techniques often fail. To address this issue, we propose a novel method called Temporally and Anatomically Informed Generative Adversarial Network (TAI-GAN) that utilizes an all-to-one mapping to convert early frames into those with tracer distribution similar to the last reference frame. The TAI-GAN consists of a feature-wise linear modulation layer that encodes channel-wise parameters generated from temporal information and rough cardiac segmentation masks with local shifts that serve as anatomical information. Our proposed method was evaluated on a clinical 82-Rb PET dataset, and the results show that our TAI-GAN can produce converted early frames with high image quality, comparable to the real reference frames. After TAI-GAN conversion, the motion estimation accuracy and subsequent myocardial blood flow (MBF) quantification with both conventional and deep learning-based motion correction methods were improved compared to using the original frames.

Dual-Domain Coarse-to-Fine Progressive Estimation Network for Simultaneous Denoising, Limited-View Reconstruction, and Attenuation Correction of Cardiac SPECT

Single-Photon Emission Computed Tomography (SPECT) is widely applied for the diagnosis of coronary artery diseases. Low-dose (LD) SPECT aims to minimize radiation exposure but leads to increased image noise. Limited-view (LV) SPECT, such as the latest GE MyoSPECT ES system, enables accelerated scanning and reduces hardware expenses but degrades reconstruction accuracy. Additionally, Computed Tomography (CT) is commonly used to derive attenuation maps ($\mu$-maps) for attenuation correction (AC) of cardiac SPECT, but it will introduce additional radiation exposure and SPECT-CT misalignments. Although various methods have been developed to solely focus on LD denoising, LV reconstruction, or CT-free AC in SPECT, the solution for simultaneously addressing these tasks remains challenging and under-explored. Furthermore, it is essential to explore the potential of fusing cross-domain and cross-modality information across these interrelated tasks to further enhance the accuracy of each task. Thus, we propose a Dual-Domain Coarse-to-Fine Progressive Network (DuDoCFNet), a multi-task learning method for simultaneous LD denoising, LV reconstruction, and CT-free $\mu$-map generation of cardiac SPECT. Paired dual-domain networks in DuDoCFNet are cascaded using a multi-layer fusion mechanism for cross-domain and cross-modality feature fusion. Two-stage progressive learning strategies are applied in both projection and image domains to achieve coarse-to-fine estimations of SPECT projections and CT-derived $\mu$-maps. Our experiments demonstrate DuDoCFNet's superior accuracy in estimating projections, generating $\mu$-maps, and AC reconstructions compared to existing single- or multi-task learning methods, under various iterations and LD levels. The source code of this work is available at https://github.com/XiongchaoChen/DuDoCFNet-MultiTask.

An Adaptive Correspondence Scoring Framework for Unsupervised Image Registration of Medical Images

We propose an adaptive training scheme for unsupervised medical image registration. Existing methods rely on image reconstruction as the primary supervision signal. However, nuisance variables (e.g. noise and covisibility) often cause the loss of correspondence between medical images, violating the Lambertian assumption in physical waves (e.g. ultrasound) and consistent imaging acquisition. As the unsupervised learning scheme relies on intensity constancy to establish correspondence between images for reconstruction, this introduces spurious error residuals that are not modeled by the typical training objective. To mitigate this, we propose an adaptive framework that re-weights the error residuals with a correspondence scoring map during training, preventing the parametric displacement estimator from drifting away due to noisy gradients, which leads to performance degradations. To illustrate the versatility and effectiveness of our method, we tested our framework on three representative registration architectures across three medical image datasets along with other baselines. Our proposed adaptive framework consistently outperforms other methods both quantitatively and qualitatively. Paired t-tests show that our improvements are statistically significant. The code will be publicly available at \url{https://voldemort108x.github.io/AdaCS/}.

Heteroscedastic Uncertainty Estimation for Probabilistic Unsupervised Registration of Noisy Medical Images

This paper proposes a heteroscedastic uncertainty estimation framework for unsupervised medical image registration. Existing methods rely on objectives (e.g. mean-squared error) that assume a uniform noise level across the image, disregarding the heteroscedastic and input-dependent characteristics of noise distribution in real-world medical images. This further introduces noisy gradients due to undesired penalization on outliers, causing unnatural deformation and performance degradation. To mitigate this, we propose an adaptive weighting scheme with a relative $\gamma$-exponentiated signal-to-noise ratio (SNR) for the displacement estimator after modeling the heteroscedastic noise using a separate variance estimator to prevent the model from being driven away by spurious gradients from error residuals, leading to more accurate displacement estimation. To illustrate the versatility and effectiveness of the proposed method, we tested our framework on two representative registration architectures across three medical image datasets. Our proposed framework consistently outperforms other baselines both quantitatively and qualitatively while also providing accurate and sensible uncertainty measures. Paired t-tests show that our improvements in registration accuracy are statistically significant. The code will be publicly available at \url{https://voldemort108x.github.io/hetero_uncertainty/}.

TAI-GAN: Temporally and Anatomically Informed GAN for early-to-late frame conversion in dynamic cardiac PET motion correction

The rapid tracer kinetics of rubidium-82 ($^{82}$Rb) and high variation of cross-frame distribution in dynamic cardiac positron emission tomography (PET) raise significant challenges for inter-frame motion correction, particularly for the early frames where conventional intensity-based image registration techniques are not applicable. Alternatively, a promising approach utilizes generative methods to handle the tracer distribution changes to assist existing registration methods. To improve frame-wise registration and parametric quantification, we propose a Temporally and Anatomically Informed Generative Adversarial Network (TAI-GAN) to transform the early frames into the late reference frame using an all-to-one mapping. Specifically, a feature-wise linear modulation layer encodes channel-wise parameters generated from temporal tracer kinetics information, and rough cardiac segmentations with local shifts serve as the anatomical information. We validated our proposed method on a clinical $^{82}$Rb PET dataset and found that our TAI-GAN can produce converted early frames with high image quality, comparable to the real reference frames. After TAI-GAN conversion, motion estimation accuracy and clinical myocardial blood flow (MBF) quantification were improved compared to using the original frames. Our code is published at https://github.com/gxq1998/TAI-GAN.

Joint Denoising and Few-angle Reconstruction for Low-dose Cardiac SPECT Using a Dual-domain Iterative Network with Adaptive Data Consistency

Myocardial perfusion imaging (MPI) by single-photon emission computed tomography (SPECT) is widely applied for the diagnosis of cardiovascular diseases. Reducing the dose of the injected tracer is essential for lowering the patient's radiation exposure, but it will lead to increased image noise. Additionally, the latest dedicated cardiac SPECT scanners typically acquire projections in fewer angles using fewer detectors to reduce hardware expenses, potentially resulting in lower reconstruction accuracy. To overcome these challenges, we propose a dual-domain iterative network for end-to-end joint denoising and reconstruction from low-dose and few-angle projections of cardiac SPECT. The image-domain network provides a prior estimate for the projection-domain networks. The projection-domain primary and auxiliary modules are interconnected for progressive denoising and few-angle reconstruction. Adaptive Data Consistency (ADC) modules improve prediction accuracy by efficiently fusing the outputs of the primary and auxiliary modules. Experiments using clinical MPI data show that our proposed method outperforms existing image-, projection-, and dual-domain techniques, producing more accurate projections and reconstructions. Ablation studies confirm the significance of the image-domain prior estimate and ADC modules in enhancing network performance.

Cross-domain Iterative Network for Simultaneous Denoising, Limited-angle Reconstruction, and Attenuation Correction of Low-dose Cardiac SPECT

Single-Photon Emission Computed Tomography (SPECT) is widely applied for the diagnosis of ischemic heart diseases. Low-dose (LD) SPECT aims to minimize radiation exposure but leads to increased image noise. Limited-angle (LA) SPECT enables faster scanning and reduced hardware costs but results in lower reconstruction accuracy. Additionally, computed tomography (CT)-derived attenuation maps ($\mu$-maps) are commonly used for SPECT attenuation correction (AC), but it will cause extra radiation exposure and SPECT-CT misalignments. In addition, the majority of SPECT scanners in the market are not hybrid SPECT/CT scanners. Although various deep learning methods have been introduced to separately address these limitations, the solution for simultaneously addressing these challenges still remains highly under-explored and challenging. To this end, we propose a Cross-domain Iterative Network (CDI-Net) for simultaneous denoising, LA reconstruction, and CT-free AC in cardiac SPECT. In CDI-Net, paired projection- and image-domain networks are end-to-end connected to fuse the emission and anatomical information across domains and iterations. Adaptive Weight Recalibrators (AWR) adjust the multi-channel input features to enhance prediction accuracy. Our experiments using clinical data showed that CDI-Net produced more accurate $\mu$-maps, projections, and reconstructions compared to existing approaches that addressed each task separately. Ablation studies demonstrated the significance of cross-domain and cross-iteration connections, as well as AWR, in improving the reconstruction performance.

Segmentation-free PVC for Cardiac SPECT using a Densely-connected Multi-dimensional Dynamic Network

In nuclear imaging, limited resolution causes partial volume effects (PVEs) that affect image sharpness and quantitative accuracy. Partial volume correction (PVC) methods incorporating high-resolution anatomical information from CT or MRI have been demonstrated to be effective. However, such anatomical-guided methods typically require tedious image registration and segmentation steps. Accurately segmented organ templates are also hard to obtain, particularly in cardiac SPECT imaging, due to the lack of hybrid SPECT/CT scanners with high-end CT and associated motion artifacts. Slight mis-registration/mis-segmentation would result in severe degradation in image quality after PVC. In this work, we develop a deep-learning-based method for fast cardiac SPECT PVC without anatomical information and associated organ segmentation. The proposed network involves a densely-connected multi-dimensional dynamic mechanism, allowing the convolutional kernels to be adapted based on the input images, even after the network is fully trained. Intramyocardial blood volume (IMBV) is introduced as an additional clinical-relevant loss function for network optimization. The proposed network demonstrated promising performance on 28 canine studies acquired on a GE Discovery NM/CT 570c dedicated cardiac SPECT scanner with a 64-slice CT using Technetium-99m-labeled red blood cells. This work showed that the proposed network with densely-connected dynamic mechanism produced superior results compared with the same network without such mechanism. Results also showed that the proposed network without anatomical information could produce images with statistically comparable IMBV measurements to the images generated by anatomical-guided PVC methods, which could be helpful in clinical translation.

Dual-Branch Squeeze-Fusion-Excitation Module for Cross-Modality Registration of Cardiac SPECT and CT

Single-photon emission computed tomography (SPECT) is a widely applied imaging approach for diagnosis of coronary artery diseases. Attenuation maps (u-maps) derived from computed tomography (CT) are utilized for attenuation correction (AC) to improve diagnostic accuracy of cardiac SPECT. However, SPECT and CT are obtained sequentially in clinical practice, which potentially induces misregistration between the two scans. Convolutional neural networks (CNN) are powerful tools for medical image registration. Previous CNN-based methods for cross-modality registration either directly concatenated two input modalities as an early feature fusion or extracted image features using two separate CNN modules for a late fusion. These methods do not fully extract or fuse the cross-modality information. Besides, deep-learning-based rigid registration of cardiac SPECT and CT-derived u-maps has not been investigated before. In this paper, we propose a Dual-Branch Squeeze-Fusion-Excitation (DuSFE) module for the registration of cardiac SPECT and CT-derived u-maps. DuSFE fuses the knowledge from multiple modalities to recalibrate both channel-wise and spatial features for each modality. DuSFE can be embedded at multiple convolutional layers to enable feature fusion at different spatial dimensions. Our studies using clinical data demonstrated that a network embedded with DuSFE generated substantial lower registration errors and therefore more accurate AC SPECT images than previous methods.