Adaptive Whole-Body PET Image Denoising Using 3D Diffusion Models with ControlNet

Positron Emission Tomography (PET) is a vital imaging modality widely used in clinical diagnosis and preclinical research but faces limitations in image resolution and signal-to-noise ratio due to inherent physical degradation factors. Current deep learning-based denoising methods face challenges in adapting to the variability of clinical settings, influenced by factors such as scanner types, tracer choices, dose levels, and acquisition times. In this work, we proposed a novel 3D ControlNet-based denoising method for whole-body PET imaging. We first pre-trained a 3D Denoising Diffusion Probabilistic Model (DDPM) using a large dataset of high-quality normal-dose PET images. Following this, we fine-tuned the model on a smaller set of paired low- and normal-dose PET images, integrating low-dose inputs through a 3D ControlNet architecture, thereby making the model adaptable to denoising tasks in diverse clinical settings. Experimental results based on clinical PET datasets show that the proposed framework outperformed other state-of-the-art PET image denoising methods both in visual quality and quantitative metrics. This plug-and-play approach allows large diffusion models to be fine-tuned and adapted to PET images from diverse acquisition protocols.

Fast-DDPM: Fast Denoising Diffusion Probabilistic Models for Medical Image-to-Image Generation

Denoising diffusion probabilistic models (DDPMs) have achieved unprecedented success in computer vision. However, they remain underutilized in medical imaging, a field crucial for disease diagnosis and treatment planning. This is primarily due to the high computational cost associated with (1) the use of large number of time steps (e.g., 1,000) in diffusion processes and (2) the increased dimensionality of medical images, which are often 3D or 4D. Training a diffusion model on medical images typically takes days to weeks, while sampling each image volume takes minutes to hours. To address this challenge, we introduce Fast-DDPM, a simple yet effective approach capable of improving training speed, sampling speed, and generation quality simultaneously. Unlike DDPM, which trains the image denoiser across 1,000 time steps, Fast-DDPM trains and samples using only 10 time steps. The key to our method lies in aligning the training and sampling procedures to optimize time-step utilization. Specifically, we introduced two efficient noise schedulers with 10 time steps: one with uniform time step sampling and another with non-uniform sampling. We evaluated Fast-DDPM across three medical image-to-image generation tasks: multi-image super-resolution, image denoising, and image-to-image translation. Fast-DDPM outperformed DDPM and current state-of-the-art methods based on convolutional networks and generative adversarial networks in all tasks. Additionally, Fast-DDPM reduced the training time to 0.2x and the sampling time to 0.01x compared to DDPM. Our code is publicly available at: https://github.com/mirthAI/Fast-DDPM.

Fast Denoising Diffusion Probabilistic Models for Medical Image-to-Image Generation

Denoising diffusion probabilistic models (DDPMs) have achieved unprecedented success in computer vision. However, they remain underutilized in medical imaging, a field crucial for disease diagnosis and treatment planning. This is primarily due to the high computational cost associated with (1) the use of large number of time steps (e.g., 1,000) in diffusion processes and (2) the increased dimensionality of medical images, which are often 3D or 4D. Training a diffusion model on medical images typically takes days to weeks, while sampling each image volume takes minutes to hours. To address this challenge, we introduce Fast-DDPM, a simple yet effective approach capable of improving training speed, sampling speed, and generation quality simultaneously. Unlike DDPM, which trains the image denoiser across 1,000 time steps, Fast-DDPM trains and samples using only 10 time steps. The key to our method lies in aligning the training and sampling procedures. We introduced two efficient noise schedulers with 10 time steps: one with uniform time step sampling and another with non-uniform sampling. We evaluated Fast-DDPM across three medical image-to-image generation tasks: multi-image super-resolution, image denoising, and image-to-image translation. Fast-DDPM outperformed DDPM and current state-of-the-art methods based on convolutional networks and generative adversarial networks in all tasks. Additionally, Fast-DDPM reduced training time by a factor of 5 and sampling time by a factor of 100 compared to DDPM. Our code is publicly available at: https://github.com/mirthAI/Fast-DDPM.

Head and Neck Tumor Segmentation from F-FDG PET/CT Images Based on 3D Diffusion Model

Head and neck (H&N) cancers are among the most prevalent types of cancer worldwide, and [18F]F-FDG PET/CT is widely used for H&N cancer management. Recently, the diffusion model has demonstrated remarkable performance in various image-generation tasks. In this work, we proposed a 3D diffusion model to accurately perform H&N tumor segmentation from 3D PET and CT volumes. The 3D diffusion model was developed considering the 3D nature of PET and CT images acquired. During the reverse process, the model utilized a 3D UNet structure and took the concatenation of PET, CT, and Gaussian noise volumes as the network input to generate the tumor mask. Experiments based on the HECKTOR challenge dataset were conducted to evaluate the effectiveness of the proposed diffusion model. Several state-of-the-art techniques based on U-Net and Transformer structures were adopted as the reference methods. Benefits of employing both PET and CT as the network input as well as further extending the diffusion model from 2D to 3D were investigated based on various quantitative metrics and the uncertainty maps generated. Results showed that the proposed 3D diffusion model could generate more accurate segmentation results compared with other methods. Compared to the diffusion model in 2D format, the proposed 3D model yielded superior results. Our experiments also highlighted the advantage of utilizing dual-modality PET and CT data over only single-modality data for H&N tumor segmentation.

TauPETGen: Text-Conditional Tau PET Image Synthesis Based on Latent Diffusion Models

In this work, we developed a novel text-guided image synthesis technique which could generate realistic tau PET images from textual descriptions and the subject's MR image. The generated tau PET images have the potential to be used in examining relations between different measures and also increasing the public availability of tau PET datasets. The method was based on latent diffusion models. Both textual descriptions and the subject's MR prior image were utilized as conditions during image generation. The subject's MR image can provide anatomical details, while the text descriptions, such as gender, scan time, cognitive test scores, and amyloid status, can provide further guidance regarding where the tau neurofibrillary tangles might be deposited. Preliminary experimental results based on clinical [18F]MK-6240 datasets demonstrate the feasibility of the proposed method in generating realistic tau PET images at different clinical stages.

SwinCross: Cross-modal Swin Transformer for Head-and-Neck Tumor Segmentation in PET/CT Images

Radiotherapy (RT) combined with cetuximab is the standard treatment for patients with inoperable head and neck cancers. Segmentation of head and neck (H&N) tumors is a prerequisite for radiotherapy planning but a time-consuming process. In recent years, deep convolutional neural networks have become the de facto standard for automated image segmentation. However, due to the expensive computational cost associated with enlarging the field of view in DCNNs, their ability to model long-range dependency is still limited, and this can result in sub-optimal segmentation performance for objects with background context spanning over long distances. On the other hand, Transformer models have demonstrated excellent capabilities in capturing such long-range information in several semantic segmentation tasks performed on medical images. Inspired by the recent success of Vision Transformers and advances in multi-modal image analysis, we propose a novel segmentation model, debuted, Cross-Modal Swin Transformer (SwinCross), with cross-modal attention (CMA) module to incorporate cross-modal feature extraction at multiple resolutions.To validate the effectiveness of the proposed method, we performed experiments on the HECKTOR 2021 challenge dataset and compared it with the nnU-Net (the backbone of the top-5 methods in HECKTOR 2021) and other state-of-the-art transformer-based methods such as UNETR, and Swin UNETR. The proposed method is experimentally shown to outperform these comparing methods thanks to the ability of the CMA module to capture better inter-modality complimentary feature representations between PET and CT, for the task of head-and-neck tumor segmentation.

Investigation of Network Architecture for Multimodal Head-and-Neck Tumor Segmentation

Inspired by the recent success of Transformers for Natural Language Processing and vision Transformer for Computer Vision, many researchers in the medical imaging community have flocked to Transformer-based networks for various main stream medical tasks such as classification, segmentation, and estimation. In this study, we analyze, two recently published Transformer-based network architectures for the task of multimodal head-and-tumor segmentation and compare their performance to the de facto standard 3D segmentation network - the nnU-Net. Our results showed that modeling long-range dependencies may be helpful in cases where large structures are present and/or large field of view is needed. However, for small structures such as head-and-neck tumor, the convolution-based U-Net architecture seemed to perform well, especially when training dataset is small and computational resource is limited.

PET image denoising based on denoising diffusion probabilistic models

Due to various physical degradation factors and limited counts received, PET image quality needs further improvements. The denoising diffusion probabilistic models (DDPM) are distribution learning-based models, which try to transform a normal distribution into a specific data distribution based on iterative refinements. In this work, we proposed and evaluated different DDPM-based methods for PET image denoising. Under the DDPM framework, one way to perform PET image denoising is to provide the PET image and/or the prior image as the network input. Another way is to supply the prior image as the input with the PET image included in the refinement steps, which can fit for scenarios of different noise levels. 120 18F-FDG datasets and 140 18F-MK-6240 datasets were utilized to evaluate the proposed DDPM-based methods. Quantification show that the DDPM-based frameworks with PET information included can generate better results than the nonlocal mean and Unet-based denoising methods. Adding additional MR prior in the model can help achieve better performance and further reduce the uncertainty during image denoising. Solely relying on MR prior while ignoring the PET information can result in large bias. Regional and surface quantification shows that employing MR prior as the network input while embedding PET image as a data-consistency constraint during inference can achieve the best performance. In summary, DDPM-based PET image denoising is a flexible framework, which can efficiently utilize prior information and achieve better performance than the nonlocal mean and Unet-based denoising methods.

Spach Transformer: Spatial and Channel-wise Transformer Based on Local and Global Self-attentions for PET Image Denoising

Position emission tomography (PET) is widely used in clinics and research due to its quantitative merits and high sensitivity, but suffers from low signal-to-noise ratio (SNR). Recently convolutional neural networks (CNNs) have been widely used to improve PET image quality. Though successful and efficient in local feature extraction, CNN cannot capture long-range dependencies well due to its limited receptive field. Global multi-head self-attention (MSA) is a popular approach to capture long-range information. However, the calculation of global MSA for 3D images has high computational costs. In this work, we proposed an efficient spatial and channel-wise encoder-decoder transformer, Spach Transformer, that can leverage spatial and channel information based on local and global MSAs. Experiments based on datasets of different PET tracers, i.e., $^{18}$F-FDG, $^{18}$F-ACBC, $^{18}$F-DCFPyL, and $^{68}$Ga-DOTATATE, were conducted to evaluate the proposed framework. Quantitative results show that the proposed Spach Transformer can achieve better performance than other reference methods.

A Noise-level-aware Framework for PET Image Denoising

In PET, the amount of relative (signal-dependent) noise present in different body regions can be significantly different and is inherently related to the number of counts present in that region. The number of counts in a region depends, in principle and among other factors, on the total administered activity, scanner sensitivity, image acquisition duration, radiopharmaceutical tracer uptake in the region, and patient local body morphometry surrounding the region. In theory, less amount of denoising operations is needed to denoise a high-count (low relative noise) image than images a low-count (high relative noise) image, and vice versa. The current deep-learning-based methods for PET image denoising are predominantly trained on image appearance only and have no special treatment for images of different noise levels. Our hypothesis is that by explicitly providing the local relative noise level of the input image to a deep convolutional neural network (DCNN), the DCNN can outperform itself trained on image appearance only. To this end, we propose a noise-level-aware framework denoising framework that allows embedding of local noise level into a DCNN. The proposed is trained and tested on 30 and 15 patient PET images acquired on a GE Discovery MI PET/CT system. Our experiments showed that the increases in both PSNR and SSIM from our backbone network with relative noise level embedding (NLE) versus the same network without NLE were statistically significant with p<0.001, and the proposed method significantly outperformed a strong baseline method by a large margin.