Whole-tumoral metabolic heterogeneity in 18F-FDG PET/CT is a novel prognostic marker for neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the heterogeneity of whole-body tumor lesions remains clinical challenge. This study aims to quantify whole-tumoral metabolic heterogeneity (WMH) derived from whole-body tumor lesions, and investigate the prognostic value of WMH in NB. METHODS: We retrospectively enrolled 95 newly diagnosed pediatric NB patients in our department. Traditional semi-quantitative PET/CT parameters including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. These PET/CT parameters were expressed as PSUVmax, PSUVmean, PSUVpeak, PMTV, PTLG for primary tumor, WSUVmax, WSUVmean, WSUVpeak, WMTV, WTLG for whole-body tumor lesions. The metabolic heterogeneity was quantified using the areas under the curve of the cumulative SUV-volume histogram index (AUC-CSH index). Intra-tumoral metabolic heterogeneity (IMH) and WMH were extracted from primary tumor and whole-body tumor lesions, respectively. The outcome endpoints were overall survival (OS) and progression-free survival (PFS). Survival analysis was performed utilizing the univariate and multivariate Cox proportional hazards regression. The optimal cut-off values for metabolic parameters were obtained by receiver operating characteristic curve (ROC). RESULTS: During follow up, 27 (28.4%) patients died, 21 (22.1%) patients relapsed and 47 (49.5%) patients remained progression-free survival, with a median follow-up of 35.0 months. In survival analysis, WMTV and WTLG were independent indicators of PFS, and WMH was an independent risk factor of PFS and OS. However, IMH only showed association with PFS and OS. In addition to metabolic parameters, the International Neuroblastoma Staging System (INSS) was identified as an independent risk factor for PFS, and neuron-specific enolase (NSE) served as an independent predictor of OS. CONCLUSION: WMH was an independent risk factor for PFS and OS, suggesting its potential as a novel prognostic marker for newly diagnosed NB patients.

Characterization of N-glycosylation and its functional role in SIDT1-Mediated RNA uptake.

The mammalian SID-1 transmembrane family members, SIDT1 and SIDT2, are multipass transmembrane proteins that mediate the cellular uptake and intracellular trafficking of nucleic acids, playing important roles in the immune response and tumorigenesis. Previous work has suggested that human SIDT1 and SIDT2 are N-glycosylated, but the precise site-specific N-glycosylation information and its functional contribution remain unclear. In this study, we use high-resolution liquid chromatography tandem mass spectrometry to comprehensively map the N-glycosites and quantify the N-glycosylation profiles of SIDT1 and SIDT2. Further molecular mechanistic probing elucidates the essential role of N-linked glycans in regulating cell surface expression, RNA binding, protein stability, and RNA uptake of SIDT1. Our results provide crucial information about the potential functional impact of N-glycosylation in the regulation of SIDT1-mediated RNA uptake and provide insights into the molecular mechanisms of this promising nucleic acid delivery system with potential implications for therapeutic applications.

Coarse-Super-Resolution-Fine Network (CoSF-Net): A Unified End-to-End Neural Network for 4D-MRI With Simultaneous Motion Estimation and Super-Resolution.

Four-dimensional magnetic resonance imaging (4D-MRI) is an emerging technique for tumor motion management in image-guided radiation therapy (IGRT). However, current 4D-MRI suffers from low spatial resolution and strong motion artifacts owing to the long acquisition time and patients' respiratory variations. If not managed properly, these limitations can adversely affect treatment planning and delivery in IGRT. In this study, we developed a novel deep learning framework called the coarse-super-resolution-fine network (CoSF-Net) to achieve simultaneous motion estimation and super-resolution within a unified model. We designed CoSF-Net by fully excavating the inherent properties of 4D-MRI, with consideration of limited and imperfectly matched training datasets. We conducted extensive experiments on multiple real patient datasets to assess the feasibility and robustness of the developed network. Compared with existing networks and three state-of-the-art conventional algorithms, CoSF-Net not only accurately estimated the deformable vector fields between the respiratory phases of 4D-MRI but also simultaneously improved the spatial resolution of 4D-MRI, enhancing anatomical features and producing 4D-MR images with high spatiotemporal resolution.

Ultra-fast multi-parametric 4D-MRI image reconstruction for real-time applications using a downsampling-invariant deformable registration (D2R) model.

BACKGROUND AND PURPOSE: Motion estimation from severely downsampled 4D-MRI is essential for real-time imaging and tumor tracking. This simulation study developed a novel deep learning model for simultaneous MR image reconstruction and motion estimation, named the Downsampling-Invariant Deformable Registration (D2R) model. MATERIALS AND METHODS: Forty-three patients undergoing radiotherapy for liver tumors were recruited for model training and internal validation. Five prospective patients from another center were recruited for external validation. Patients received 4D-MRI scans and 3D MRI scans. The 4D-MRI was retrospectively down-sampled to simulate real-time acquisition. Motion estimation was performed using the proposed D2R model. The accuracy and robustness of the proposed D2R model and baseline methods, including Demons, Elastix, the parametric total variation (pTV) algorithm, and VoxelMorph, were compared. High-quality (HQ) 4D-MR images were also constructed using the D2R model for real-time imaging feasibility verification. The image quality and motion accuracy of the constructed HQ 4D-MRI were evaluated. RESULTS: The D2R model showed significantly superior and robust registration performance than all the baseline methods at downsampling factors up to 500. HQ T1-weighted and T2-weighted 4D-MR images were also successfully constructed with significantly improved image quality, sub-voxel level motion error, and real-time efficiency. External validation demonstrated the robustness and generalizability of the technique. CONCLUSION: In this study, we developed a novel D2R model for deformation estimation of downsampled 4D-MR images. HQ 4D-MR images were successfully constructed using the D2R model. This model may expand the clinical implementation of 4D-MRI for real-time motion management during liver cancer treatment.

Respiratory-Correlated 4-Dimensional Magnetic Resonance Fingerprinting for Liver Cancer Radiation Therapy Motion Management.

PURPOSE: The objective of this study was to develop a respiratory-correlated (RC) 4-dimensional (4D) imaging technique based on magnetic resonance fingerprinting (MRF) (RC-4DMRF) for liver tumor motion management in radiation therapy. METHODS AND MATERIALS: Thirteen patients with liver cancer were prospectively enrolled in this study. k-space MRF signals of the liver were acquired during free-breathing using the fast acquisition with steady-state precession sequence on a 3T scanner. The signals were binned into 8 respiratory phases based on respiratory surrogates, and interphase displacement vector fields were estimated using a phase-specific low-rank optimization method. Hereafter, the tissue property maps, including T1 and T2 relaxation times, and proton density, were reconstructed using a pyramid motion-compensated method that alternatively optimized interphase displacement vector fields and subspace images. To evaluate the efficacy of RC-4DMRF, amplitude motion differences and Pearson correlation coefficients were determined to assess measurement agreement in tumor motion between RC-4DMRF and cine magnetic resonance imaging (MRI); mean absolute percentage errors of the RC-4DMRF-derived tissue maps were calculated to reveal tissue quantification accuracy using digital human phantom; and tumor-to-liver contrast-to-noise ratio of RC-4DMRF images was compared with that of planning CT and contrast-enhanced MRI (CE-MRI) images. A paired Student t test was used for statistical significance analysis with a P value threshold of .05. RESULTS: RC-4DMRF achieved excellent agreement in motion measurement with cine MRI, yielding the mean (± standard deviation) Pearson correlation coefficients of 0.95 ± 0.05 and 0.93 ± 0.09 and amplitude motion differences of 1.48 ± 1.06 mm and 0.81 ± 0.64 mm in the superior-inferior and anterior-posterior directions, respectively. Moreover, RC-4DMRF achieved high accuracy in tissue property quantification, with mean absolute percentage errors of 8.8%, 9.6%, and 5.0% for T1, T2, and proton density, respectively. Notably, the tumor contrast-to-noise ratio in RC-4DMRI-derived T1 maps (6.41 ± 3.37) was found to be the highest among all tissue property maps, approximately equal to that of CE-MRI (6.96 ± 1.01, P = .862), and substantially higher than that of planning CT (2.91 ± 1.97, P = .048). CONCLUSIONS: RC-4DMRF demonstrated high accuracy in respiratory motion measurement and tissue properties quantification, potentially facilitating tumor motion management in liver radiation therapy.

Structural Insight Into hnRNP A2/B1 Homodimerization and DNA Recognition.

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) has been identified as a nuclear DNA sensor. Upon viral infection, hnRNP A2/B1 recognizes pathogen-derived DNA as a homodimer, which is a prerequisite for its translocation to the cytoplasm to activate the interferon response. However, the DNA binding mechanism inducing hnRNP A2/B1 homodimerization is unknown. Here, we show the crystal structure of the RNA recognition motif (RRM) of hnRNP A2/B1 in complex with a U-shaped ssDNA, which mediates the formation of a newly observed protein dimer. Our biochemical assays and mutagenesis studies confirm that the hnRNP A2/B1 homodimer forms in solution by binding to pre-generated ssDNA or dsDNA with a U-shaped bulge. These results depict a potential functional state of hnRNP A2/B1 in antiviral immunity and other cellular processes.

Improving radiomic model reliability using robust features from perturbations for head-and-neck carcinoma.

Background: Using high robust radiomic features in modeling is recommended, yet its impact on radiomic model is unclear. This study evaluated the radiomic model's robustness and generalizability after screening out low-robust features before radiomic modeling. The results were validated with four datasets and two clinically relevant tasks. Materials and methods: A total of 1,419 head-and-neck cancer patients' computed tomography images, gross tumor volume segmentation, and clinically relevant outcomes (distant metastasis and local-regional recurrence) were collected from four publicly available datasets. The perturbation method was implemented to simulate images, and the radiomic feature robustness was quantified using intra-class correlation of coefficient (ICC). Three radiomic models were built using all features (ICC > 0), good-robust features (ICC > 0.75), and excellent-robust features (ICC > 0.95), respectively. A filter-based feature selection and Ridge classification method were used to construct the radiomic models. Model performance was assessed with both robustness and generalizability. The robustness of the model was evaluated by the ICC, and the generalizability of the model was quantified by the train-test difference of Area Under the Receiver Operating Characteristic Curve (AUC). Results: The average model robustness ICC improved significantly from 0.65 to 0.78 (P< 0.0001) using good-robust features and to 0.91 (P< 0.0001) using excellent-robust features. Model generalizability also showed a substantial increase, as a closer gap between training and testing AUC was observed where the mean train-test AUC difference was reduced from 0.21 to 0.18 (P< 0.001) in good-robust features and to 0.12 (P< 0.0001) in excellent-robust features. Furthermore, good-robust features yielded the best average AUC in the unseen datasets of 0.58 (P< 0.001) over four datasets and clinical outcomes. Conclusions: Including robust only features in radiomic modeling significantly improves model robustness and generalizability in unseen datasets. Yet, the robustness of radiomic model has to be verified despite building with robust radiomic features, and tightly restricted feature robustness may prevent the optimal model performance in the unseen dataset as it may lower the discrimination power of the model.

Corrigendum: Investigation of a novel deep learning-based computed tomography perfusion mapping framework for functional lung avoidance radiotherapy.

[This corrects the article DOI: 10.3389/fonc.2021.644703.].

A Transfer Learning Framework for Deep Learning-Based CT-to-Perfusion Mapping on Lung Cancer Patients.

Purpose: Deep learning model has shown the feasibility of providing spatial lung perfusion information based on CT images. However, the performance of this method on lung cancer patients is yet to be investigated. This study aims to develop a transfer learning framework to evaluate the deep learning based CT-to-perfusion mapping method specifically on lung cancer patients. Methods: SPECT/CT perfusion scans of 33 lung cancer patients and 137 non-cancer patients were retrospectively collected from two hospitals. To adapt the deep learning model on lung cancer patients, a transfer learning framework was developed to utilize the features learned from the non-cancer patients. These images were processed to extract features from three-dimensional CT images and synthesize the corresponding CT-based perfusion images. A pre-trained model was first developed using a dataset of patients with lung diseases other than lung cancer, and subsequently fine-tuned specifically on lung cancer patients under three-fold cross-validation. A multi-level evaluation was performed between the CT-based perfusion images and ground-truth SPECT perfusion images in aspects of voxel-wise correlation using Spearman's correlation coefficient (R), function-wise similarity using Dice Similarity Coefficient (DSC), and lobe-wise agreement using mean perfusion value for each lobe of the lungs. Results: The fine-tuned model yielded a high voxel-wise correlation (0.8142 ± 0.0669) and outperformed the pre-trained model by approximately 8%. Evaluation of function-wise similarity indicated an average DSC value of 0.8112 ± 0.0484 (range: 0.6460-0.8984) for high-functional lungs and 0.8137 ± 0.0414 (range: 0.6743-0.8902) for low-functional lungs. Among the 33 lung cancer patients, high DSC values of greater than 0.7 were achieved for high functional volumes in 32 patients and low functional volumes in all patients. The correlations of the mean perfusion value on the left upper lobe, left lower lobe, right upper lobe, right middle lobe, and right lower lobe were 0.7314, 0.7134, 0.5108, 0.4765, and 0.7618, respectively. Conclusion: For lung cancer patients, the CT-based perfusion images synthesized by the transfer learning framework indicated a strong voxel-wise correlation and function-wise similarity with the SPECT perfusion images. This suggests the great potential of the deep learning method in providing regional-based functional information for functional lung avoidance radiation therapy.

Volumetric multiphase ventilation imaging based on four-dimensional computed tomography for functional lung avoidance radiotherapy.

PURPOSE: Current computed tomography (CT)-based lung ventilation imaging (CTVI) techniques derive a static ventilation image without temporal information. This research aims to develop a four-dimensional CT (4DCT)-based multiphase dynamic ventilation imaging framework capable of recovering the entire ventilation process throughout the breathing cycle for functional lung avoidance radiotherapy (FLART). METHODS: A total of 15 free-breathing thoracic 4DCT scans of lung or esophageal cancer patients were collected from the public datasets. The lung region of each phase image was first delineated, and then the mask-free isotropic total variation image registration algorithm was used to derive the deformation vector fields between the end-expiration (EE) phase and other phases. As a surrogate of ventilation, the voxel-wise local expansion ratio of each phase relative to the EE phase was estimated using the parameterized Integrated Jacobian Formulation method in the EE phase coordinate. Lastly, the dynamic ventilation images were generated by warping these phase-specific local expansion distributions with a same geometry into their respective breathing phases. Quantitative analysis, including interphase Spearman correlation coefficients, voxel-wise, and regional-wise expansion/contraction tracking, were performed to indirectly validate the proposed method. RESULTS: The proposed method maintains the physiological meaning of ventilation on each phase and enables to recover the dynamic lung ventilation process. The mean interphase Spearman correlations ranged between 0.23 ± 0.20 and 0.93 ± 0.04 and decreased near the EE phase. Only 26.2% (2.59E + 6 out of 9.89E + 6) of lung voxels exhibited the same expansion/contraction pattern as the global lung. Qualitative and quantitative evaluations of the interphase ventilation distribution difference show that ventilation spatiotemporal heterogeneities generally exist during respiration. CONCLUSIONS: In contrast to conventional CTVI metrics, our method enables to extract additional phase-resolved respiration-correlated information and reflects the generally existed ventilation spatiotemporal heterogeneities. Subsequent studies with quantitative phase-by-phase cross-modality evaluations will further explore its potential to deepen our understanding of lung function and respiration mechanics and also to facilitate more accurate implementation of FLART.

Building reliable radiomic models using image perturbation.

Radiomic model reliability is a central premise for its clinical translation. Presently, it is assessed using test-retest or external data, which, unfortunately, is often scarce in reality. Therefore, we aimed to develop a novel image perturbation-based method (IPBM) for the first of its kind toward building a reliable radiomic model. We first developed a radiomic prognostic model for head-and-neck cancer patients on a training (70%) and evaluated on a testing (30%) cohort using C-index. Subsequently, we applied the IPBM to CT images of both cohorts (Perturbed-Train and Perturbed-Test cohort) to generate 60 additional samples for both cohorts. Model reliability was assessed using intra-class correlation coefficient (ICC) to quantify consistency of the C-index among the 60 samples in the Perturbed-Train and Perturbed-Test cohorts. Besides, we re-trained the radiomic model using reliable RFs exclusively (ICC > 0.75) to validate the IPBM. Results showed moderate model reliability in Perturbed-Train (ICC: 0.565, 95%CI 0.518-0.615) and Perturbed-Test (ICC: 0.596, 95%CI 0.527-0.670) cohorts. An enhanced reliability of the re-trained model was observed in Perturbed-Train (ICC: 0.782, 95%CI 0.759-0.815) and Perturbed-Test (ICC: 0.825, 95%CI 0.782-0.867) cohorts, indicating validity of the IPBM. To conclude, we demonstrated capability of the IPBM toward building reliable radiomic models, providing community with a novel model reliability assessment strategy prior to prospective evaluation.

A dual-supervised deformation estimation model (DDEM) for constructing ultra-quality 4D-MRI based on a commercial low-quality 4D-MRI for liver cancer radiation therapy.

BACKGROUND: Most available four-dimensional (4D)-magnetic resonance imaging (MRI) techniques are limited by insufficient image quality and long acquisition times or require specially designed sequences or hardware that are not available in the clinic. These limitations have greatly hindered the clinical implementation of 4D-MRI. PURPOSE: This study aims to develop a fast ultra-quality (UQ) 4D-MRI reconstruction method using a commercially available 4D-MRI sequence and dual-supervised deformation estimation model (DDEM). METHODS: Thirty-nine patients receiving radiotherapy for liver tumors were included. Each patient was scanned using a time-resolved imaging with interleaved stochastic trajectories (TWIST)-lumetric interpolated breath-hold examination (VIBE) MRI sequence to acquire 4D-magnetic resonance (MR) images. They also received 3D T1-/T2-weighted MRI scans as prior images, and UQ 4D-MRI at any instant was considered a deformation of them. A DDEM was developed to obtain a 4D deformable vector field (DVF) from 4D-MRI data, and the prior images were deformed using this 4D-DVF to generate UQ 4D-MR images. The registration accuracies of the DDEM, VoxelMorph (normalized cross-correlation [NCC] supervised), VoxelMorph (end-to-end point error [EPE] supervised), and the parametric total variation (pTV) algorithm were compared. Tumor motion on UQ 4D-MRI was evaluated quantitatively using region of interest (ROI) tracking errors, while image quality was evaluated using the contrast-to-noise ratio (CNR), lung-liver edge sharpness, and perceptual blur metric (PBM). RESULTS: The registration accuracy of the DDEM was significantly better than those of VoxelMorph (NCC supervised), VoxelMorph (EPE supervised), and the pTV algorithm (all, p < 0.001), with an inference time of 69.3 ± 5.9 ms. UQ 4D-MRI yielded ROI tracking errors of 0.79 ± 0.65, 0.50 ± 0.55, and 0.51 ± 0.58 mm in the superior-inferior, anterior-posterior, and mid-lateral directions, respectively. From the original 4D-MRI to UQ 4D-MRI, the CNR increased from 7.25 ± 4.89 to 18.86 ± 15.81; the lung-liver edge full-width-at-half-maximum decreased from 8.22 ± 3.17 to 3.65 ± 1.66 mm in the in-plane direction and from 8.79 ± 2.78 to 5.04 ± 1.67 mm in the cross-plane direction, and the PBM decreased from 0.68 ± 0.07 to 0.38 ± 0.01. CONCLUSION: This novel DDEM method successfully generated UQ 4D-MR images based on a commercial 4D-MRI sequence. It shows great promise for improving liver tumor motion management during radiation therapy.

Virtual Contrast-Enhanced Magnetic Resonance Images Synthesis for Patients With Nasopharyngeal Carcinoma Using Multimodality-Guided Synergistic Neural Network.

PURPOSE: To investigate a novel deep-learning network that synthesizes virtual contrast-enhanced T1-weighted (vceT1w) magnetic resonance images (MRI) from multimodality contrast-free MRI for patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: This article presents a retrospective analysis of multiparametric MRI, with and without contrast enhancement by gadolinium-based contrast agents (GBCAs), obtained from 64 biopsy-proven cases of NPC treated at Hong Kong Queen Elizabeth Hospital. A multimodality-guided synergistic neural network (MMgSN-Net) was developed to leverage complementary information between contrast-free T1-weighted and T2-weighted MRI for vceT1w MRI synthesis. Thirty-five patients were randomly selected for model training, whereas 29 patients were selected for model testing. The synthetic images generated from MMgSN-Net were quantitatively evaluated against real GBCA-enhanced T1-weighted MRI using a series of statistical evaluating metrics, which include mean absolute error (MAE), mean squared error (MSE), structural similarity index (SSIM), and peak signal-to-noise ratio (PSNR). Qualitative visual assessment between the real and synthetic MRI was also performed. Effectiveness of our MMgSN-Net was compared with 3 state-of-the-art deep-learning networks, including U-Net, CycleGAN, and Hi-Net, both quantitatively and qualitatively. Furthermore, a Turing test was performed by 7 board-certified radiation oncologists from 4 hospitals for assessing authenticity of the synthesized vceT1w MRI against the real GBCA-enhanced T1-weighted MRI. RESULTS: Results from the quantitative evaluations demonstrated that our MMgSN-Net outperformed U-Net, CycleGAN and Hi-Net, yielding the top-ranked scores in averaged MAE (44.50 ± 13.01), MSE (9193.22 ± 5405.00), SSIM (0.887 ± 0.042), and PSNR (33.17 ± 2.14). Furthermore, the mean accuracy of the 7 readers in the Turing tests was determined to be 49.43%, equivalent to random guessing (ie, 50%) in distinguishing between real GBCA-enhanced T1-weighted and synthetic vceT1w MRI. Qualitative evaluation indicated that MMgSN-Net gave the best approximation to the ground-truth images, particularly in visualization of tumor-to-muscle interface and the intratumor texture information. CONCLUSIONS: Our MMgSN-Net was capable of synthesizing highly realistic vceT1w MRI that outperformed the 3 comparable state-of-the-art networks.

Deep learning-based bone suppression in chest radiographs using CT-derived features: a feasibility study.

BACKGROUND: Bone suppression of chest X-ray holds the potential to improve the accuracy of target localization in image-guided radiation therapy (IGRT). However, the training dataset for bone suppression is limited because of the scarcity of bone-free radiographs. This study aims to develop a deep learning-based bone suppression method using CT-derived features to reduce the reliance on the bone-free dataset. METHODS: In this study, 59 high-resolution lung CT scans were processed to generate the lung digital radiographs (DRs), bone DRs, and bone-free DRs, for the training and internal validation of the proposed cascade convolutional neural network (CCNN). A three-stage image processing framework (CT segmentation, DR simulation, and feature expansion) was developed to expand simulated lung DRs with different weightings of bone intensity. The CCNN consists of a bone detection network and a bone suppression network. In external validation, the trained CCNN was evaluated using 30 chest radiographs. The synthesized bone-suppressed radiographs were compared with the bone-suppressed reference in terms of peak signal-to-noise ratio (PSNR), mean absolute error (MAE), structural similarity index measure (SSIM), and Spearman's correlation coefficient. Furthermore, the effectiveness of the proposed feature expansion method and CCNN model were assessed via the ablation experiment and replacement experiment, respectively. RESULTS: Evaluation on real chest radiographs showed that the bone-suppressed chest radiographs closely matched with the bone-suppressed reference, achieving an accuracy of MAE =0.0087±0.0030, SSIM =0.8458±0.0317, correlation of 0.9554±0.0170, and PNSR of 20.86±1.60. After removing the feature expansion from the CCNN model, the performance decreased in terms of MAE (0.0294±0.0093, -237.9%), SSIM (0.7747±0.0.0416, -8.4%), correlation (0.8772±0.0271, -8.2%), and PSNR (15.53±1.42, -25.5%) metrics. CONCLUSIONS: We successfully demonstrated a novel deep learning-based bone suppression method using CT-derived features to reduce the reliance on the bone-free dataset. Implementation of the feature expansion procedures resulted in a remarkable reinforcement of the model performance. For the application of target localization in IGRT, the clinical testing of the proposed method in the context of radiation therapy is a necessary procedure to move from theory into practice.

Deep learning for automatic target volume segmentation in radiation therapy: a review.

Deep learning, a new branch of machine learning algorithm, has emerged as a fast growing trend in medical imaging and become the state-of-the-art method in various clinical applications such as Radiology, Histo-pathology and Radiation Oncology. Specifically in radiation oncology, deep learning has shown its power in performing automatic segmentation tasks in radiation therapy for Organs-At-Risks (OAR), given its potential in improving the efficiency of OAR contouring and reducing the inter- and intra-observer variabilities. The similar interests were shared for target volume segmentation, an essential step of radiation therapy treatment planning, where the gross tumor volume is defined and microscopic spread is encompassed. The deep learning-based automatic segmentation method has recently been expanded into target volume automatic segmentation. In this paper, the authors summarized the major deep learning architectures of supervised learning fashion related to target volume segmentation, reviewed the mechanism of each infrastructure, surveyed the use of these models in various imaging domains (including Computational Tomography with and without contrast, Magnetic Resonant Imaging and Positron Emission Tomography) and multiple clinical sites, and compared the performance of different models using standard geometric evaluation metrics. The paper concluded with a discussion of open challenges and potential paths of future research in target volume automatic segmentation and how it may benefit the clinical practice.

A review of deep learning-based three-dimensional medical image registration methods.

Medical image registration is a vital component of many medical procedures, such as image-guided radiotherapy (IGRT), as it allows for more accurate dose-delivery and better management of side effects. Recently, the successful implementation of deep learning (DL) in various fields has prompted many research groups to apply DL to three-dimensional (3D) medical image registration. Several of these efforts have led to promising results. This review summarized the progress made in DL-based 3D image registration over the past 5 years and identify existing challenges and potential avenues for further research. The collected studies were statistically analyzed based on the region of interest (ROI), image modality, supervision method, and registration evaluation metrics. The studies were classified into three categories: deep iterative registration, supervised registration, and unsupervised registration. The studies are thoroughly reviewed and their unique contributions are highlighted. A summary is presented following a review of each category of study, discussing its advantages, challenges, and trends. Finally, the common challenges for all categories are discussed, and potential future research topics are identified.

Multi-contrast four-dimensional magnetic resonance imaging (MC-4D-MRI): Development and initial evaluation in liver tumor patients.

PURPOSE: To develop a novel multi-contrast four-dimensional magnetic resonance imaging (MC-4D-MRI) technique that expands single image contrast 4D-MRI to a spectrum of native and synthetic image contrasts and to evaluate its feasibility in liver tumor patients. METHODS AND MATERIALS: The MC-4D-MRI technique integrates multi-parametric MRI fusion, 4D-MRI, and deformable image registration (DIR) techniques. The fusion technique consists of native MRI as input, image pre-processing, fusion algorithm, adaptation, and fused multi-contrast MRI as output. Four-dimensional deformation vector fields (4D-DVF) were generated from an original T2/T1-w 4D-MRI by deforming end-of-inhalation (EOI) to nine other phase volumes via DIR. The 4D-DVF were applied to multi-contrast MRI to generate a spectrum of 4D-MRI in different image contrasts. The MC-4D-MRI technique was evaluated in five liver tumor patients on tumor contrast-to-noise ratio (CNR), internal target volume (ITV) contouring consistency, diaphragm motion range, and tumor motion trajectory; and in digital anthropomorphic phantoms on 4D-DIR introduced errors in tumor motion range, centroid location, extent, and volume. RESULTS: MC-4D-MRI consisting of 4D-MRIs in native image contrasts (T1-w, T2-w, and T2/T1-w) and synthetic image contrasts, such as tumor-enhanced contrast (TEC) were generated in five liver tumor patients. Patient tumor CNR increased from 2.6 ± 1.8 in the T2/T1-w MRI, to -4.4 ± 2.4, 6.6 ± 3.0, and 9.6 ± 3.9 in the T1-w, T2-w, and TEC MRI, respectively. Patient ITV inter-observer mean Dice similarity coefficient (mDSC) increased from 0.65 ± 0.10 in the original T2/T1-w 4D-MRI, to 0.76 ± 0.14, 0.77 ± 0.12, and 0.86 ± 0.05 in the T1-w, T2-w, and TEC 4D-MRI, respectively. Patient diaphragm motion range absolute differences between the three new 4D-MRIs and original T2/T1-w 4D-MRI were 1.2 ± 1.3, 0.3 ± 0.7, and 0.5 ± 0.5 mm, respectively. Patient tumor displacement phase-averaged absolute differences between the three 4D-MRIs and the original 4D-MRI were 0.72 ± 0.33, 0.62 ± 0.54, and 0.74 ± 0.43 mm in the superior-inferior (SI) direction, and 0.59 ± 0.36, 0.51 ± 0.30, and 0.50 ± 0.24 mm in the anterior-posterior (AP) direction, respectively. In the digital phantoms, phase-averaged absolute tumor centroid shift caused by the 4D-DIR were at or below 0.5 mm in SI, AP, and left-right (LR) directions. CONCLUSION: We developed an MC-4D-MRI technique capable of expanding single image contrast 4D-MRI along a new dimension of image contrast. Initial evaluations in liver tumor patients showed enhancements in image contrast variety, tumor contrast, and ITV contouring consistencies using MC-4D-MRI. The technique might offer new perspectives on the image contrast of MRI and 4D-MRI in MR-guided radiotherapy.

MRI super-resolution via realistic downsampling with adversarial learning.

Many deep learning (DL) frameworks have demonstrated state-of-the-art performance in the super-resolution (SR) task of magnetic resonance imaging, but most performances have been achieved with simulated low-resolution (LR) images rather than LR images from real acquisition. Due to the limited generalizability of the SR network, enhancement is not guaranteed for real LR images because of the unreality of the training LR images. In this study, we proposed a DL-based SR framework with an emphasis on data construction to achieve better performance on real LR MR images. The framework comprised two steps: (a) downsampling training using a generative adversarial network (GAN) to construct more realistic and perfectly matched LR/high-resolution (HR) pairs. The downsampling GAN input was real LR and HR images. The generator translated the HR images to LR images and the discriminator distinguished the patch-level difference between the synthetic and real LR images. (b) SR training was performed using an enhance4d deep super-resolution network (EDSR). In the controlled experiments, three EDSRs were trained using our proposed method, Gaussian blur, and k-space zero-filling. As for the data, liver MR images were obtained from 24 patients using breath-hold serial LR and HR scans (only HR images were used in the conventional methods). The k-space zero-filling group delivered almost zero enhancement on the real LR images and the Gaussian group produced a considerable number of artifacts. The proposed method exhibited significantly better resolution enhancement and fewer artifacts compared with the other two networks. Our method outperformed the Gaussian method by an improvement of 0.111 ± 0.016 in the structural similarity index and 2.76 ± 0.98 dB in the peak signal-to-noise ratio. The blind/reference-less image spatial quality evaluator metric of the conventional Gaussian method and proposed method were 46.6 ± 4.2 and 34.1 ± 2.4, respectively.

Investigation of a Novel Deep Learning-Based Computed Tomography Perfusion Mapping Framework for Functional Lung Avoidance Radiotherapy.

Functional lung avoidance radiation therapy aims to minimize dose delivery to the normal lung tissue while favoring dose deposition in the defective lung tissue based on the regional function information. However, the clinical acquisition of pulmonary functional images is resource-demanding, inconvenient, and technically challenging. This study aims to investigate the deep learning-based lung functional image synthesis from the CT domain. Forty-two pulmonary macro-aggregated albumin SPECT/CT perfusion scans were retrospectively collected from the hospital. A deep learning-based framework (including image preparation, image processing, and proposed convolutional neural network) was adopted to extract features from 3D CT images and synthesize perfusion as estimations of regional lung function. Ablation experiments were performed to assess the effects of each framework component by removing each element of the framework and analyzing the testing performances. Major results showed that the removal of the CT contrast enhancement component in the image processing resulted in the largest drop in framework performance, compared to the optimal performance (~12%). In the CNN part, all the three components (residual module, ROI attention, and skip attention) were approximately equally important to the framework performance; removing one of them resulted in a 3-5% decline in performance. The proposed CNN improved ~4% overall performance and ~350% computational efficiency, compared to the U-Net model. The deep convolutional neural network, in conjunction with image processing for feature enhancement, is capable of feature extraction from CT images for pulmonary perfusion synthesis. In the proposed framework, image processing, especially CT contrast enhancement, plays a crucial role in the perfusion synthesis. This CTPM framework provides insights for relevant research studies in the future and enables other researchers to leverage for the development of optimized CNN models for functional lung avoidance radiation therapy.