CT-based synthetic iodine map generation using conditional denoising diffusion probabilistic model.

BACKGROUND: Iodine maps, derived from image-processing of contrast-enhanced dual-energy computed tomography (DECT) scans, highlight the differences in tissue iodine intake. It finds multiple applications in radiology, including vascular imaging, pulmonary evaluation, kidney assessment, and cancer diagnosis. In radiation oncology, it can contribute to designing more accurate and personalized treatment plans. However, DECT scanners are not commonly available in radiation therapy centers. Additionally, the use of iodine contrast agents is not suitable for all patients, especially those allergic to iodine agents, posing further limitations to the accessibility of this technology. PURPOSE: The purpose of this work is to generate synthetic iodine map images from non-contrast single-energy CT (SECT) images using conditional denoising diffusion probabilistic model (DDPM). METHODS: One-hundered twenty-six head-and-neck patients' images were retrospectively investigated in this work. Each patient underwent non-contrast SECT and contrast DECT scans. Ground truth iodine maps were generated from contrast DECT scans using commercial software syngo.via installed in the clinic. A conditional DDPM was implemented in this work to synthesize iodine maps. Three-fold cross-validation was conducted, with each iteration selecting the data from 42 patients as the test dataset and the remainder as the training dataset. Pixel-to-pixel generative adversarial network (GAN) and CycleGAN served as reference methods for evaluating the proposed DDPM method. RESULTS: The accuracy of the proposed DDPM was evaluated using three quantitative metrics: mean absolute error (MAE) (1.039 ± 0.345 mg/mL), structural similarity index measure (SSIM) (0.89 ± 0.10) and peak signal-to-noise ratio (PSNR) (25.4 ± 3.5 db) respectively. Compared to the reference methods, the proposed technique showcased superior performance across the evaluated metrics, further validated by the paired two-tailed t-tests. CONCLUSION: The proposed conditional DDPM framework has demonstrated the feasibility of generating synthetic iodine map images from non-contrast SECT images. This method presents a potential clinical application, which is providing accurate iodine contrast map in instances where only non-contrast SECT is accessible.

High-resolution MRI synthesis using a data-driven framework with denoising diffusion probabilistic modeling.

Objective. High-resolution magnetic resonance imaging (MRI) can enhance lesion diagnosis, prognosis, and delineation. However, gradient power and hardware limitations prohibit recording thin slices or sub-1 mm resolution. Furthermore, long scan time is not clinically acceptable. Conventional high-resolution images generated using statistical or analytical methods include the limitation of capturing complex, high-dimensional image data with intricate patterns and structures. This study aims to harness cutting-edge diffusion probabilistic deep learning techniques to create a framework for generating high-resolution MRI from low-resolution counterparts, improving the uncertainty of denoising diffusion probabilistic models (DDPM).Approach. DDPM includes two processes. The forward process employs a Markov chain to systematically introduce Gaussian noise to low-resolution MRI images. In the reverse process, a U-Net model is trained to denoise the forward process images and produce high-resolution images conditioned on the features of their low-resolution counterparts. The proposed framework was demonstrated using T2-weighted MRI images from institutional prostate patients and brain patients collected in the Brain Tumor Segmentation Challenge 2020 (BraTS2020).Main results. For the prostate dataset, the bicubic interpolation model (Bicubic), conditional generative-adversarial network (CGAN), and our proposed DDPM framework improved the noise quality measure from low-resolution images by 4.4%, 5.7%, and 12.8%, respectively. Our method enhanced the signal-to-noise ratios by 11.7%, surpassing Bicubic (9.8%) and CGAN (8.1%). In the BraTS2020 dataset, the proposed framework and Bicubic enhanced peak signal-to-noise ratio from resolution-degraded images by 9.1% and 5.8%. The multi-scale structural similarity indexes were 0.970 ± 0.019, 0.968 ± 0.022, and 0.967 ± 0.023 for the proposed method, CGAN, and Bicubic, respectively.Significance. This study explores a deep learning-based diffusion probabilistic framework for improving MR image resolution. Such a framework can be used to improve clinical workflow by obtaining high-resolution images without penalty of the long scan time. Future investigation will likely focus on prospectively testing the efficacy of this framework with different clinical indications.

CBCT-Based synthetic CT image generation using conditional denoising diffusion probabilistic model.

BACKGROUND: Daily or weekly cone-beam computed tomography (CBCT) scans are commonly used for accurate patient positioning during the image-guided radiotherapy (IGRT) process, making it an ideal option for adaptive radiotherapy (ART) replanning. However, the presence of severe artifacts and inaccurate Hounsfield unit (HU) values prevent its use for quantitative applications such as organ segmentation and dose calculation. To enable the clinical practice of online ART, it is crucial to obtain CBCT scans with a quality comparable to that of a CT scan. PURPOSE: This work aims to develop a conditional diffusion model to perform image translation from the CBCT to the CT distribution for the image quality improvement of CBCT. METHODS: The proposed method is a conditional denoising diffusion probabilistic model (DDPM) that utilizes a time-embedded U-net architecture with residual and attention blocks to gradually transform the white Gaussian noise sample to the target CT distribution conditioned on the CBCT. The model was trained on deformed planning CT (dpCT) and CBCT image pairs, and its feasibility was verified in brain patient study and head-and-neck (H&N) patient study. The performance of the proposed algorithm was evaluated using mean absolute error (MAE), peak signal-to-noise ratio (PSNR) and normalized cross-correlation (NCC) metrics on generated synthetic CT (sCT) samples. The proposed method was also compared to four other diffusion model-based sCT generation methods. RESULTS: In the brain patient study, the MAE, PSNR, and NCC of the generated sCT were 25.99 HU, 30.49 dB, and 0.99, respectively, compared to 40.63 HU, 27.87 dB, and 0.98 of the CBCT images. In the H&N patient study, the metrics were 32.56 HU, 27.65 dB, 0.98 and 38.99 HU, 27.00, 0.98 for sCT and CBCT, respectively. Compared to the other four diffusion models and one Cycle generative adversarial network (Cycle GAN), the proposed method showed superior results in both visual quality and quantitative analysis. CONCLUSIONS: The proposed conditional DDPM method can generate sCT from CBCT with accurate HU numbers and reduced artifacts, enabling accurate CBCT-based organ segmentation and dose calculation for online ART.

Deep learning-based synthetic dose-weighted LET map generation for intensity modulated proton therapy.

The advantage of proton therapy as compared to photon therapy stems from the Bragg peak effect, which allows protons to deposit most of their energy directly at the tumor while sparing healthy tissue. However, even with such benefits, proton therapy does present certain challenges. The biological effectiveness differences between protons and photons are not fully incorporated into clinical treatment planning processes. In current clinical practice, the relative biological effectiveness (RBE) between protons and photons is set as constant 1.1. Numerous studies have suggested that the RBE of protons can exhibit significant variability. Given these findings, there is a substantial interest in refining proton therapy treatment planning to better account for the variable RBE. Dose-average linear energy transfer (LETd) is a key physical parameter for evaluating the RBE of proton therapy and aids in optimizing proton treatment plans. Calculating precise LETddistributions necessitates the use of intricate physical models and the execution of specialized Monte-Carlo simulation software, which is a computationally intensive and time-consuming progress. In response to these challenges, we propose a deep learning based framework designed to predict the LETddistribution map using the dose distribution map. This approach aims to simplify the process and increase the speed of LETdmap generation in clinical settings. The proposed CycleGAN model has demonstrated superior performance over other GAN-based models. The mean absolute error (MAE), peak signal-to-noise ratio and normalized cross correlation of the LETdmaps generated by the proposed method are 0.096 ± 0.019 keVµm-1, 24.203 ± 2.683 dB, and 0.997 ± 0.002, respectively. The MAE of the proposed method in the clinical target volume, bladder, and rectum are 0.193 ± 0.103, 0.277 ± 0.112, and 0.211 ± 0.086 keVµm-1, respectively. The proposed framework has demonstrated the feasibility of generating synthetic LETdmaps from dose maps and has the potential to improve proton therapy planning by providing accurate LETdinformation.

Synthetic CT generation from MRI using 3D transformer-based denoising diffusion model.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI)-based synthetic computed tomography (sCT) simplifies radiation therapy treatment planning by eliminating the need for CT simulation and error-prone image registration, ultimately reducing patient radiation dose and setup uncertainty. In this work, we propose a MRI-to-CT transformer-based improved denoising diffusion probabilistic model (MC-IDDPM) to translate MRI into high-quality sCT to facilitate radiation treatment planning. METHODS: MC-IDDPM implements diffusion processes with a shifted-window transformer network to generate sCT from MRI. The proposed model consists of two processes: a forward process, which involves adding Gaussian noise to real CT scans to create noisy images, and a reverse process, in which a shifted-window transformer V-net (Swin-Vnet) denoises the noisy CT scans conditioned on the MRI from the same patient to produce noise-free CT scans. With an optimally trained Swin-Vnet, the reverse diffusion process was used to generate noise-free sCT scans matching MRI anatomy. We evaluated the proposed method by generating sCT from MRI on an institutional brain dataset and an institutional prostate dataset. Quantitative evaluations were conducted using several metrics, including Mean Absolute Error (MAE), Peak Signal-to-Noise Ratio (PSNR), Multi-scale Structure Similarity Index (SSIM), and Normalized Cross Correlation (NCC). Dosimetry analyses were also performed, including comparisons of mean dose and target dose coverages for 95% and 99%. RESULTS: MC-IDDPM generated brain sCTs with state-of-the-art quantitative results with MAE 48.825 ± 21.491 HU, PSNR 26.491 ± 2.814 dB, SSIM 0.947 ± 0.032, and NCC 0.976 ± 0.019. For the prostate dataset: MAE 55.124 ± 9.414 HU, PSNR 28.708 ± 2.112 dB, SSIM 0.878 ± 0.040, and NCC 0.940 ± 0.039. MC-IDDPM demonstrates a statistically significant improvement (with p < 0.05) in most metrics when compared to competing networks, for both brain and prostate synthetic CT. Dosimetry analyses indicated that the target dose coverage differences by using CT and sCT were within ± 0.34%. CONCLUSIONS: We have developed and validated a novel approach for generating CT images from routine MRIs using a transformer-based improved DDPM. This model effectively captures the complex relationship between CT and MRI images, allowing for robust and high-quality synthetic CT images to be generated in a matter of minutes. This approach has the potential to greatly simplify the treatment planning process for radiation therapy by eliminating the need for additional CT scans, reducing the amount of time patients spend in treatment planning, and enhancing the accuracy of treatment delivery.

Single energy CT-based mass density and relative stopping power estimation for proton therapy using deep learning method.

Background: The number of patients undergoing proton therapy has increased in recent years. Current treatment planning systems (TPS) calculate dose maps using three-dimensional (3D) maps of relative stopping power (RSP) and mass density. The patient-specific maps of RSP and mass density were obtained by translating the CT number (HU) acquired using single-energy computed tomography (SECT) with appropriate conversions and coefficients. The proton dose calculation uncertainty of this approach is 2.5%-3.5% plus 1 mm margin. SECT is the major clinical modality for proton therapy treatment planning. It would be intriguing to enhance proton dose calculation accuracy using a deep learning (DL) approach centered on SECT. Objectives: The purpose of this work is to develop a deep learning method to generate mass density and relative stopping power (RSP) maps based on clinical single-energy CT (SECT) data for proton dose calculation in proton therapy treatment. Methods: Artificial neural networks (ANN), fully convolutional neural networks (FCNN), and residual neural networks (ResNet) were used to learn the correlation between voxel-specific mass density, RSP, and SECT CT number (HU). A stoichiometric calibration method based on SECT data and an empirical model based on dual-energy CT (DECT) images were chosen as reference models to evaluate the performance of deep learning neural networks. SECT images of a CIRS 062M electron density phantom were used as the training dataset for deep learning models. CIRS anthropomorphic M701 and M702 phantoms were used to test the performance of deep learning models. Results: For M701, the mean absolute percentage errors (MAPE) of the mass density map by FCNN are 0.39%, 0.92%, 0.68%, 0.92%, and 1.57% on the brain, spinal cord, soft tissue, bone, and lung, respectively, whereas with the SECT stoichiometric method, they are 0.99%, 2.34%, 1.87%, 2.90%, and 12.96%. For RSP maps, the MAPE of FCNN on M701 are 0.85%, 2.32%, 0.75%, 1.22%, and 1.25%, whereas with the SECT reference model, they are 0.95%, 2.61%, 2.08%, 7.74%, and 8.62%. Conclusion: The results show that deep learning neural networks have the potential to generate accurate voxel-specific material property information, which can be used to improve the accuracy of proton dose calculation. Advances in knowledge: Deep learning-based frameworks are proposed to estimate material mass density and RSP from SECT with improved accuracy compared with conventional methods.

Rapid unpaired CBCT-based synthetic CT for CBCT-guided adaptive radiotherapy.

In this work, we demonstrate a method for rapid synthesis of high-quality CT images from unpaired, low-quality CBCT images, permitting CBCT-based adaptive radiotherapy. We adapt contrastive unpaired translation (CUT) to be used with medical images and evaluate the results on an institutional pelvic CT dataset. We compare the method against cycleGAN using mean absolute error, structural similarity index, root mean squared error, and Frèchet Inception Distance and show that CUT significantly outperforms cycleGAN while requiring less time and fewer resources. The investigated method improves the feasibility of online adaptive radiotherapy over the present state-of-the-art.

Data-Driven Volumetric Image Generation from Surface Structures using a Patient-Specific Deep Leaning Model.

The advent of computed tomography significantly improves patients' health regarding diagnosis, prognosis, and treatment planning and verification. However, tomographic imaging escalates concomitant radiation doses to patients, inducing potential secondary cancer by 4%. We demonstrate the feasibility of a data-driven approach to synthesize volumetric images using patients' surface images, which can be obtained from a zero-dose surface imaging system. This study includes 500 computed tomography (CT) image sets from 50 patients. Compared to the ground truth CT, the synthetic images result in the evaluation metric values of 26.9 ± 4.1 Hounsfield units, 39.1 ± 1.0 dB, and 0.965 ± 0.011 regarding the mean absolute error, peak signal-to-noise ratio, and structural similarity index measure. This approach provides a data integration solution that can potentially enable real-time imaging, which is free of radiation-induced risk and could be applied to image-guided medical procedures.

Abdomen CT multi-organ segmentation using token-based MLP-Mixer.

BACKGROUND: Manual contouring is very labor-intensive, time-consuming, and subject to intra- and inter-observer variability. An automated deep learning approach to fast and accurate contouring and segmentation is desirable during radiotherapy treatment planning. PURPOSE: This work investigates an efficient deep-learning-based segmentation algorithm in abdomen computed tomography (CT) to facilitate radiation treatment planning. METHODS: In this work, we propose a novel deep-learning model utilizing U-shaped multi-layer perceptron mixer (MLP-Mixer) and convolutional neural network (CNN) for multi-organ segmentation in abdomen CT images. The proposed model has a similar structure to V-net, while a proposed MLP-Convolutional block replaces each convolutional block. The MLP-Convolutional block consists of three components: an early convolutional block for local features extraction and feature resampling, a token-based MLP-Mixer layer for capturing global features with high efficiency, and a token projector for pixel-level detail recovery. We evaluate our proposed network using: (1) an institutional dataset with 60 patient cases and (2) a public dataset (BCTV) with 30 patient cases. The network performance was quantitatively evaluated in three domains: (1) volume similarity between the ground truth contours and the network predictions using the Dice score coefficient (DSC), sensitivity, and precision; (2) surface similarity using Hausdorff distance (HD), mean surface distance (MSD) and residual mean square distance (RMS); and (3) the computational complexity reported by the number of network parameters, training time, and inference time. The performance of the proposed network is compared with other state-of-the-art networks. RESULTS: In the institutional dataset, the proposed network achieved the following volume similarity measures when averaged over all organs: DSC = 0.912, sensitivity = 0.917, precision = 0.917, average surface similarities were HD = 11.95 mm, MSD = 1.90 mm, RMS = 3.86 mm. The proposed network achieved DSC = 0.786 and HD = 9.04 mm on the public dataset. The network also shows statistically significant improvement, which is evaluated by a two-tailed Wilcoxon Mann-Whitney U test, on right lung (MSD where the maximum p-value is 0.001), spinal cord (sensitivity, precision, HD, RMSD where p-value ranges from 0.001 to 0.039), and stomach (DSC where the maximum p-value is 0.01) over all other competing networks. On the public dataset, the network report statistically significant improvement, which is shown by the Wilcoxon Mann-Whitney test, on pancreas (HD where the maximum p-value is 0.006), left (HD where the maximum p-value is 0.022) and right adrenal glands (DSC where the maximum p-value is 0.026). In both datasets, the proposed method can generate contours in less than 5 s. Overall, the proposed MLP-Vnet demonstrates comparable or better performance than competing methods with much lower memory complexity and higher speed. CONCLUSIONS: The proposed MLP-Vnet demonstrates superior segmentation performance, in terms of accuracy and efficiency, relative to state-of-the-art methods. This reliable and efficient method demonstrates potential to streamline clinical workflows in abdominal radiotherapy, which may be especially important for online adaptive treatments.

Male pelvic multi-organ segmentation using token-based transformer Vnet.

Objective. This work aims to develop an automated segmentation method for the prostate and its surrounding organs-at-risk in pelvic computed tomography to facilitate prostate radiation treatment planning.Approach. In this work, we propose a novel deep learning algorithm combining a U-shaped convolutional neural network (CNN) and vision transformer (VIT) for multi-organ (i.e. bladder, prostate, rectum, left and right femoral heads) segmentation in male pelvic CT images. The U-shaped model consists of three components: a CNN-based encoder for local feature extraction, a token-based VIT for capturing global dependencies from the CNN features, and a CNN-based decoder for predicting the segmentation outcome from the VIT's output. The novelty of our network is a token-based multi-head self-attention mechanism used in the transformer, which encourages long-range dependencies and forwards informative high-resolution feature maps from the encoder to the decoder. In addition, a knowledge distillation strategy is deployed to further enhance the learning capability of the proposed network.Main results. We evaluated the network using: (1) a dataset collected from 94 patients with prostate cancer; (2) and a public dataset CT-ORG. A quantitative evaluation of the proposed network's performance was performed on each organ based on (1) volume similarity between the segmented contours and ground truth using Dice score, segmentation sensitivity, and precision, (2) surface similarity evaluated by Hausdorff distance (HD), mean surface distance (MSD) and residual mean square distance (RMS), (3) and percentage volume difference (PVD). The performance was then compared against other state-of-art methods. Average volume similarity measures obtained by the network overall organs were Dice score = 0.91, sensitivity = 0.90, precision = 0.92, average surface similarities were HD = 3.78 mm, MSD = 1.24 mm, RMS = 2.03 mm; average percentage volume difference was PVD = 9.9% on the first dataset. The network also obtained Dice score = 0.93, sensitivity = 0.93, precision = 0.93, average surface similarities were HD = 5.82 mm, MSD = 1.16 mm, RMS = 1.24 mm; average percentage volume difference was PVD = 6.6% on the CT-ORG dataset.Significance. In summary, we propose a token-based transformer network with knowledge distillation for multi-organ segmentation using CT images. This method provides accurate and reliable segmentation results for each organ using CT imaging, facilitating the prostate radiation clinical workflow.

Dual-energy CT based mass density and relative stopping power estimation for proton therapy using physics-informed deep learning.

Proton therapy requires accurate dose calculation for treatment planning to ensure the conformal doses are precisely delivered to the targets. The conversion of CT numbers to material properties is a significant source of uncertainty for dose calculation. The aim of this study is to develop a physics-informed deep learning (PIDL) framework to derive accurate mass density and relative stopping power maps from dual-energy computed tomography (DECT) images. The PIDL framework allows deep learning (DL) models to be trained with a physics loss function, which includes a physics model to constrain DL models. Five DL models were implemented including a fully connected neural network (FCNN), dual-FCNN (DFCNN), and three variants of residual networks (ResNet): ResNet-v1 (RN-v1), ResNet-v2 (RN-v2), and dual-ResNet-v2 (DRN-v2). An artificial neural network (ANN) and the five DL models trained with and without physics loss were explored to evaluate the PIDL framework. Two empirical DECT models were implemented to compare with the PIDL method. DL training data were from CIRS electron density phantom 062M (Computerized Imaging Reference Systems, Inc., Norfolk, VA). The performance of DL models was tested by CIRS adult male, adult female, and 5-year-old child anthropomorphic phantoms. For density map inference, the physics-informed RN-v2 was 3.3%, 2.9% and 1.9% more accurate than ANN for the adult male, adult female, and child phantoms. The physics-informed DRN-v2 was 0.7%, 0.6%, and 0.8% more accurate than DRN-v2 without physics training for the three phantoms, respectfully. The results indicated that physics-informed training could reduce uncertainty when ANN/DL models without physics training were insufficient to capture data structures or derived significant errors. DL models could also achieve better image noise control compared to the empirical DECT parametric mapping methods. The proposed PIDL framework can potentially improve proton range uncertainty by offering accurate material properties conversion from DECT.