Alzheimer's disease (AD) is the most prevalent form of dementia, and its early diagnosis is essential for slowing disease progression. Recent studies on multimodal neuroimaging fusion using MRI and PET have achieved promising results by integrating multi-scale complementary features. However, most existing approaches primarily emphasize cross-modal complementarity while overlooking the diagnostic importance of modality-specific features. In addition, the inherent distributional differences between modalities often lead to biased and noisy representations, degrading classification performance. To address these challenges, we propose a Collaborative Attention and Consistent-Guided Fusion framework for MRI and PET based AD diagnosis. The proposed model introduces a learnable parameter representation (LPR) block to compensate for missing modality information, followed by a shared encoder and modality-independent encoders to preserve both shared and specific representations. Furthermore, a consistency-guided mechanism is employed to explicitly align the latent distributions across modalities. Experimental results on the ADNI dataset demonstrate that our method achieves superior diagnostic performance compared with existing fusion strategies.

Fluorodeoxyglucose (FDG) PET to evaluate patients with epilepsy is one of the most common applications for simultaneous PET/MRI, given the need to image both brain structure and metabolism, but is suboptimal due to the radiation dose in this young population. Little work has been done synthesizing diagnostic quality PET images from MRI data or MRI data with ultralow-dose PET using advanced generative AI methods, such as diffusion models, with attention to clinical evaluations tailored for the epilepsy population. Here we compared the performance of diffusion- and non-diffusion-based deep learning models for the MRI-to-PET image translation task for epilepsy imaging using simultaneous PET/MRI in 52 subjects (40 train/2 validate/10 hold-out test). We tested three different models: 2 score-based generative diffusion models (SGM-Karras Diffusion [SGM-KD] and SGM-variance preserving [SGM-VP]) and a Transformer-Unet. We report results on standard image processing metrics as well as clinically relevant metrics, including congruency measures (Congruence Index and Congruency Mean Absolute Error) that assess hemispheric metabolic asymmetry, which is a key part of the clinical analysis of these images. The SGM-KD produced the best qualitative and quantitative results when synthesizing PET purely from T1w and T2 FLAIR images with the least mean absolute error in whole-brain specific uptake value ratio (SUVR) and highest intraclass correlation coefficient. When 1% low-dose PET images are included in the inputs, all models improve significantly and are interchangeable for quantitative performance and visual quality. In summary, SGMs hold great potential for pure MRI-to-PET translation, while all 3 model types can synthesize full-dose FDG-PET accurately using MRI and ultralow-dose PET.

Background and Objective. Research in the cross-modal medical image translation domain has been very productive over the past few years in tackling the scarce availability of large curated multimodality datasets with the promising performance of GAN-based architectures. However, only a few of these studies assessed task-based related performance of these synthetic data, especially for the training of deep models. Method. We design and compare different GAN-based frameworks for generating synthetic brain [18F]fluorodeoxyglucose (FDG) PET images from T1 weighted MRI data. We first perform standard qualitative and quantitative visual quality evaluation. Then, we explore further impact of using these fake PET data in the training of a deep unsupervised anomaly detection (UAD) model designed to detect subtle epilepsy lesions in T1 MRI and FDG PET images. We introduce novel diagnostic task-oriented quality metrics of the synthetic FDG PET data tailored to our unsupervised detection task, then use these fake data to train a use case UAD model combining a deep representation learning based on siamese autoencoders with a OC-SVM density support estimation model. This model is trained on normal subjects only and allows the detection of any variation from the pattern of the normal population. We compare the detection performance of models trained on 35 paired real MR T1 of normal subjects paired either on 35 true PET images or on 35 synthetic PET images generated from the best performing generative models. Performance analysis is conducted on 17 exams of epilepsy patients undergoing surgery. Results. The best performing GAN-based models allow generating realistic fake PET images of control subject with SSIM and PSNR values around 0.9 and 23.8, respectively and in distribution (ID) with regard to the true control dataset. The best UAD model trained on these synthetic normative PET data allows reaching 74% sensitivity. Conclusion. Our results confirm that GAN-based models are the best suited for MR T1 to FDG PET translation, outperforming transformer or diffusion models. We also demonstrate the diagnostic value of these synthetic data for the training of UAD models and evaluation on clinical exams of epilepsy patients. Our code and the normative image dataset are available.

Positron Emission Tomography (PET) imaging requires accurate attenuation correction (AC) to account for photon loss due to tissue density variations. In PET/MR systems, computed tomography (CT), which offers a straightforward estimation of AC is not available. This study presents a deep learning approach to generate synthetic CT (sCT) images directly from Time-of-Flight (TOF) non-attenuation corrected (NAC) PET images, enhancing AC for PET/MR. We first evaluated models pre-trained on large-scale natural image datasets for a CT-to-CT reconstruction task, finding that the pre-trained model outperformed those trained solely on medical datasets. The pre-trained model was then fine-tuned using an institutional dataset of 35 TOF NAC PET and CT volume pairs, achieving the lowest mean absolute error (MAE) of 74.49 HU and highest peak signal-to-noise ratio (PSNR) of 28.66 dB within the body contour region. Visual assessments demonstrated improved reconstruction of both bone and soft tissue structures from TOF NAC PET images. This work highlights the effectiveness of using pre-trained deep learning models for medical image translation tasks. Future work will assess the impact of sCT on PET attenuation correction and explore additional neural network architectures and datasets to further enhance performance and practical applications in PET imaging.

Generating positron emission tomography (PET) images from computed tomography (CT) scans via deep learning offers a promising pathway to reduce radiation exposure and costs associated with PET imaging, improving patient care and accessibility to functional imaging. Whole-body image translation presents challenges due to anatomical heterogeneity, often limiting generalized models. We propose a framework that segments whole-body CT images into four regions-head, trunk, arms, and legs-and uses district-specific Generative Adversarial Networks (GANs) for tailored CT-to-PET translation. Synthetic PET images from each region are stitched together to reconstruct the whole-body scan. Comparisons with a baseline non-segmented GAN and experiments with Pix2Pix and CycleGAN architectures tested paired and unpaired scenarios. Quantitative evaluations at district, whole-body, and lesion levels demonstrated significant improvements with our district-specific GANs. Pix2Pix yielded superior metrics, ensuring precise, high-quality image synthesis. By addressing anatomical heterogeneity, this approach achieves state-of-the-art results in whole-body CT-to-PET translation. This methodology supports healthcare Digital Twins by enabling accurate virtual PET scans from CT data, creating virtual imaging representations to monitor, predict, and optimize health outcomes.

Brain positron emission tomography (PET) imaging is broadly used in research and clinical routines to study, diagnose, and stage Alzheimer's disease (AD). However, its potential cannot be fully exploited yet due to the lack of portable motion correction solutions, especially in clinical settings. Head motion during data acquisition has indeed been shown to degrade image quality and induces tracer uptake quantification error. In this study, we demonstrate that it also biases machine learning-based AD classification. We start by proposing a binary classification algorithm solely based on PET images. We find that it reaches a high accuracy in classifying motion corrected images into cognitive normal or AD. We demonstrate that the classification accuracy substantially decreases when images lack motion correction, thereby limiting the algorithm's effectiveness and biasing image interpretation. We validate these findings in cohorts of 128 $^{11}$C-UCB-J and 173 $^{18}$F-FDG scans, two tracers highly relevant to the study of AD. Classification accuracies decreased by 10% and 5% on 20 $^{18}$F-FDG and 20 $^{11}$C-UCB-J testing cases, respectively. Our findings underscore the critical need for efficient motion correction methods to make the most of the diagnostic capabilities of PET-based machine learning.

Cross-modality translation between MRI and PET imaging is challenging due to the distinct mechanisms underlying these modalities. Blood-based biomarkers (BBBMs) are revolutionizing Alzheimer's disease (AD) detection by identifying patients and quantifying brain amyloid levels. However, the potential of BBBMs to enhance PET image synthesis remains unexplored. In this paper, we performed a thorough study on the effect of incorporating BBBM into deep generative models. By evaluating three widely used cross-modality translation models, we found that BBBMs integration consistently enhances the generative quality across all models. By visual inspection of the generated results, we observed that PET images generated by CycleGAN exhibit the best visual fidelity. Based on these findings, we propose Plasma-CycleGAN, a novel generative model based on CycleGAN, to synthesize PET images from MRI using BBBMs as conditions. This is the first approach to integrate BBBMs in conditional cross-modality translation between MRI and PET.

PET imaging is an invaluable tool in clinical settings as it captures the functional activity of both healthy anatomy and cancerous lesions. Developing automatic lesion segmentation methods for PET images is crucial since manual lesion segmentation is laborious and prone to inter- and intra-observer variability. We propose PET-Disentangler, a 3D disentanglement method that uses a 3D UNet-like encoder-decoder architecture to disentangle disease and normal healthy anatomical features with losses for segmentation, reconstruction, and healthy component plausibility. A critic network is used to encourage the healthy latent features to match the distribution of healthy samples and thus encourages these features to not contain any lesion-related features. Our quantitative results show that PET-Disentangler is less prone to incorrectly declaring healthy and high tracer uptake regions as cancerous lesions, since such uptake pattern would be assigned to the disentangled healthy component.

PET imaging is widely employed for observing biological metabolic activities within the human body. However, numerous benign conditions can cause increased uptake of radiopharmaceuticals, confounding differentiation from malignant tumors. Several studies have indicated that dual-time PET imaging holds promise in distinguishing between malignant and benign tumor processes. Nevertheless, the hour-long distribution period of radiopharmaceuticals post-injection complicates the determination of optimal timing for the second scan, presenting challenges in both practical applications and research. Notably, we have identified that delay time PET imaging can be framed as an image-to-image conversion problem. Motivated by this insight, we propose a novel spatial-temporal guided diffusion transformer probabilistic model (st-DTPM) to solve dual-time PET imaging prediction problem. Specifically, this architecture leverages the U-net framework that integrates patch-wise features of CNN and pixel-wise relevance of Transformer to obtain local and global information. And then employs a conditional DDPM model for image synthesis. Furthermore, on spatial condition, we concatenate early scan PET images and noisy PET images on every denoising step to guide the spatial distribution of denoising sampling. On temporal condition, we convert diffusion time steps and delay time to a universal time vector, then embed it to each layer of model architecture to further improve the accuracy of predictions. Experimental results demonstrated the superiority of our method over alternative approaches in preserving image quality and structural information, thereby affirming its efficacy in predictive task.

PET imaging is a powerful modality offering quantitative assessments of molecular and physiological processes. The necessity for PET denoising arises from the intrinsic high noise levels in PET imaging, which can significantly hinder the accurate interpretation and quantitative analysis of the scans. With advances in deep learning techniques, diffusion model-based PET denoising techniques have shown remarkable performance improvement. However, these models often face limitations when applied to volumetric data. Additionally, many existing diffusion models do not adequately consider the unique characteristics of PET imaging, such as its 3D volumetric nature, leading to the potential loss of anatomic consistency. Our Conditional Score-based Residual Diffusion (CSRD) model addresses these issues by incorporating a refined score function and 3D patch-wise training strategy, optimizing the model for efficient volumetric PET denoising. The CSRD model significantly lowers computational demands and expedites the denoising process. By effectively integrating volumetric data from PET and MRI scans, the CSRD model maintains spatial coherence and anatomical detail. Lastly, we demonstrate that the CSRD model achieves superior denoising performance in both qualitative and quantitative evaluations while maintaining image details and outperforms existing state-of-the-art methods.