Xin Zhen

CT to Cone-beam CT Deformable Registration With Simultaneous Intensity Correction

Computed tomography (CT) to cone-beam CT (CBCT) deformable image registration (DIR) is a crucial step in adaptive radiation therapy. Current intensity-based registration algorithms, such as demons, may fail in the context of CT-CBCT DIR because of inconsistent intensities between the two modalities. In this paper, we propose a variant of demons, called deformation with intensity simultaneously corrected (DISC), to deal with CT-CBCT DIR. DISC distinguishes itself from the original demons algorithm by performing an adaptive intensity correction step on the CBCT image at every iteration step of the demons registration. Specifically, the intensity correction of a voxel in CBCT is achieved by matching the first and the second moments of the voxel intensities inside a patch around the voxel with those on the CT image. It is expected that such a strategy can remove artifacts in the CBCT image, as well as ensuring the intensity consistency between the two modalities. DISC is implemented on computer graphics processing units in compute unified device architecture (CUDA) programming environment. The performance of DISC is evaluated on a simulated patient case and six clinical head-and-neck cancer patient data. It is found that DISC is robust against the CBCT artifacts and intensity inconsistency and significantly improves the registration accuracy when compared with the original demons.

A hybrid reconstruction algorithm for fast and accurate 4D cone‐beam CT imaging

PURPOSE 4D cone beam CT (4D-CBCT) has been utilized in radiation therapy to provide 4D image guidance in lung and upper abdomen area. However, clinical application of 4D-CBCT is currently limited due to the long scan time and low image quality. The purpose of this paper is to develop a new 4D-CBCT reconstruction method that restores volumetric images based on the 1-min scan data acquired with a standard 3D-CBCT protocol. METHODS The model optimizes a deformation vector field that deforms a patient-specific planning CT (p-CT), so that the calculated 4D-CBCT projections match measurements. A forward-backward splitting (FBS) method is invented to solve the optimization problem. It splits the original problem into two well-studied subproblems, i.e., image reconstruction and deformable image registration. By iteratively solving the two subproblems, FBS gradually yields correct deformation information, while maintaining high image quality. The whole workflow is implemented on a graphic-processing-unit to improve efficiency. Comprehensive evaluations have been conducted on a moving phantom and three real patient cases regarding the accuracy and quality of the reconstructed images, as well as the algorithm robustness and efficiency. RESULTS The proposed algorithm reconstructs 4D-CBCT images from highly under-sampled projection data acquired with 1-min scans. Regarding the anatomical structure location accuracy, 0.204 mm average differences and 0.484 mm maximum difference are found for the phantom case, and the maximum differences of 0.3-0.5 mm for patients 1-3 are observed. As for the image quality, intensity errors below 5 and 20 HU compared to the planning CT are achieved for the phantom and the patient cases, respectively. Signal-noise-ratio values are improved by 12.74 and 5.12 times compared to results from FDK algorithm using the 1-min data and 4-min data, respectively. The computation time of the algorithm on a NVIDIA GTX590 card is 1-1.5 min per phase. CONCLUSIONS High-quality 4D-CBCT imaging based on the clinically standard 1-min 3D CBCT scanning protocol is feasible via the proposed hybrid reconstruction algorithm.

Impaired renal function and dysbiosis of gut microbiota contribute to increased trimethylamine-N-oxide in chronic kidney disease patients

Chronic kidney disease (CKD) patients have an increased risk of cardiovascular diseases (CVDs). The present study aimed to investigate the gut microbiota and blood trimethylamine-N-oxide concentration (TMAO) in Chinese CKD patients and explore the underlying explanations through the animal experiment. The median plasma TMAO level was 30.33 μmol/L in the CKD patients, which was significantly higher than the 2.08 μmol/L concentration measured in the healthy controls. Next-generation sequence revealed obvious dysbiosis of the gut microbiome in CKD patients, with reduced bacterial diversity and biased community constitutions. CKD patients had higher percentages of opportunistic pathogens from gamma-Proteobacteria and reduced percentages of beneficial microbes, such as Roseburia, Coprococcus, and Ruminococcaceae. The PICRUSt analysis demonstrated that eight genes involved in choline, betaine, L-carnitine and trimethylamine (TMA) metabolism were changed in the CKD patients. Moreover, we transferred faecal samples from CKD patients and healthy controls into antibiotic-treated C57BL/6 mice and found that the mice that received gut microbes from the CKD patients had significantly higher plasma TMAO levels and different composition of gut microbiota than did the comparative mouse group. Our present study demonstrated that CKD patients had increased plasma TMAO levels due to contributions from both impaired renal functions and dysbiosis of the gut microbiota.

Deformable Image Registration of CT and Truncated Cone-beam CT for Adaptive Radiation Therapy

Truncation of a cone-beam computed tomography (CBCT) image, mainly caused by the limited field of view (FOV) of CBCT imaging, poses challenges to the problem of deformable image registration (DIR) between computed tomography (CT) and CBCT images in adaptive radiation therapy (ART). The missing information outside the CBCT FOV usually causes incorrect deformations when a conventional DIR algorithm is utilized, which may introduce significant errors in subsequent operations such as dose calculation. In this paper, based on the observation that the missing information in the CBCT image domain does exist in the projection image domain, we propose to solve this problem by developing a hybrid deformation/reconstruction algorithm. As opposed to deforming the CT image to match the truncated CBCT image, the CT image is deformed such that its projections match all the corresponding projection images for the CBCT image. An iterative forward-backward projection algorithm is developed. Six head-and-neck cancer patient cases are used to evaluate our algorithm, five with simulated truncation and one with real truncation. It is found that our method can accurately register the CT image to the truncated CBCT image and is robust against image truncation when the portion of the truncated image is less than 40% of the total image.

Progressive cone beam CT dose control in image-guided radiation therapy

PURPOSE Cone beam CT (CBCT) in image-guided radiotherapy (IGRT) offers a tremendous advantage for treatment guidance. The associated imaging dose is a clinical concern. One unique feature of CBCT-based IGRT is that the same patient is repeatedly scanned during a treatment course, and the contents of CBCT images at different fractions are similar. The authors propose a progressive dose control (PDC) scheme to utilize this temporal correlation for imaging dose reduction. METHODS A dynamic CBCT scan protocol, as opposed to the static one in the current clinical practice, is proposed to gradually reduce the imaging dose in each treatment fraction. The CBCT image from each fraction is processed by a prior-image based nonlocal means (PINLM) module to enhance its quality. The increasing amount of prior information from previous CBCT images prevents degradation of image quality due to the reduced imaging dose. Two proof-of-principle experiments have been conducted using measured phantom data and Monte Carlo simulated patient data with deformation. RESULTS In the measured phantom case, utilizing a prior image acquired at 0.4 mAs, PINLM is able to improve the image quality of a CBCT acquired at 0.2 mAs by reducing the noise level from 34.95 to 12.45 HU. In the synthetic patient case, acceptable image quality is maintained at four consecutive fractions with gradually decreasing exposure levels of 0.4, 0.1, 0.07, and 0.05 mAs. When compared with the standard low-dose protocol of 0.4 mAs for each fraction, an overall imaging dose reduction of more than 60% is achieved. CONCLUSIONS PINLM-PDC is able to reduce CBCT imaging dose in IGRT utilizing the temporal correlations among the sequence of CBCT images while maintaining the quality.PURPOSE Cone beam CT (CBCT) in image-guided radiotherapy (IGRT) offers a tremendous advantage for treatment guidance. The associated imaging dose is a clinical concern. One unique feature of CBCT-based IGRT is that the same patient is repeatedly scanned during a treatment course, and the contents of CBCT images at different fractions are similar. The authors propose a progressive dose control (PDC) scheme to utilize this temporal correlation for imaging dose reduction. METHODS A dynamic CBCT scan protocol, as opposed to the static one in the current clinical practice, is proposed to gradually reduce the imaging dose in each treatment fraction. The CBCT image from each fraction is processed by a prior-image based nonlocal means (PINLM) module to enhance its quality. The increasing amount of prior information from previous CBCT images prevents degradation of image quality due to the reduced imaging dose. Two proof-of-principle experiments have been conducted using measured phantom data and Monte Carlo simulated patient data with deformation. RESULTS In the measured phantom case, utilizing a prior image acquired at 0.4 mAs, PINLM is able to improve the image quality of a CBCT acquired at 0.2 mAs by reducing the noise level from 34.95 to 12.45 HU. In the synthetic patient case, acceptable image quality is maintained at four consecutive fractions with gradually decreasing exposure levels of 0.4, 0.1, 0.07, and 0.05 mAs. When compared with the standard low-dose protocol of 0.4 mAs for each fraction, an overall imaging dose reduction of more than 60% is achieved. CONCLUSIONS PINLM-PDC is able to reduce CBCT imaging dose in IGRT utilizing the temporal correlations among the sequence of CBCT images while maintaining the quality.

Deep convolutional neural network with transfer learning for rectum toxicity prediction in cervical cancer radiotherapy: a feasibility study

Better understanding of the dose-toxicity relationship is critical for safe dose escalation to improve local control in late-stage cervical cancer radiotherapy. In this study, we introduced a convolutional neural network (CNN) model to analyze rectum dose distribution and predict rectum toxicity. Forty-two cervical cancer patients treated with combined external beam radiotherapy (EBRT) and brachytherapy (BT) were retrospectively collected, including twelve toxicity patients and thirty non-toxicity patients. We adopted a transfer learning strategy to overcome the limited patient data issue. A 16-layers CNN developed by the visual geometry group (VGG-16) of the University of Oxford was pre-trained on a large-scale natural image database, ImageNet, and fine-tuned with patient rectum surface dose maps (RSDMs), which were accumulated EBRT  +  BT doses on the unfolded rectum surface. We used the adaptive synthetic sampling approach and the data augmentation method to address the two challenges, data imbalance and data scarcity. The gradient-weighted class activation maps (Grad-CAM) were also generated to highlight the discriminative regions on the RSDM along with the prediction model. We compare different CNN coefficients fine-tuning strategies, and compare the predictive performance using the traditional dose volume parameters, e.g. D 0.1/1/2cc, and the texture features extracted from the RSDM. Satisfactory prediction performance was achieved with the proposed scheme, and we found that the mean Grad-CAM over the toxicity patient group has geometric consistence of distribution with the statistical analysis result, which indicates possible rectum toxicity location. The evaluation results have demonstrated the feasibility of building a CNN-based rectum dose-toxicity prediction model with transfer learning for cervical cancer radiotherapy.

SPARSE: Seed point auto-generation for random walks segmentation enhancement in medical inhomogeneous targets delineation of morphological MR and CT images

In medical image processing, robust segmentation of inhomogeneous targets is a challenging problem. Because of the complexity and diversity in medical images, the commonly used semiautomatic segmentation algorithms usually fail in the segmentation of inhomogeneous objects. In this study, we propose a novel algorithm imbedded with a seed point autogeneration for random walks segmentation enhancement, namely SPARSE, for better segmentation of inhomogeneous objects. With a few user‐labeled points, SPARSE is able to generate extended seed points by estimating the probability of each voxel with respect to the labels. The random walks algorithm is then applied upon the extended seed points to achieve improved segmentation result. SPARSE is implemented under the compute unified device architecture (CUDA) programming environment on graphic processing unit (GPU) hardware platform. Quantitative evaluations are performed using clinical homogeneous and inhomogeneous cases. It is found that the SPARSE can greatly decrease the sensitiveness to initial seed points in terms of location and quantity, as well as the freedom of selecting parameters in edge weighting function. The evaluation results of SPARSE also demonstrate substantial improvements in accuracy and robustness to inhomogeneous target segmentation over the original random walks algorithm. PACS number: 87.57.nm

Geometric Correction for Cone-Beam CT Reconstruction and Artifacts Reduction

The FDK algorithm is one of the most widely referenced and used algorithm for cone-beam CT reconstruction in circular trajectory because of its simplicity of implementation and computational efficiency. However, images reconstructed by the FDK algorithm of real projection data may be blurred without electronic correction and geometric calibration, and are often plagued by deleterious ring artifacts and shading artifacts. In this paper, images reconstructed with and without detector correction are compared base on computer experiment of real biological object. Furthermore, Algorithms for shading artifacts reduction and fast ring artifacts reduction are also introduced. The experimental simulation shows that these algorithms are effective in reducing ring and shading artifacts without compromising the image resolution, and produce satisfactory results.

Comprehensive evaluation of ten deformable image registration algorithms for contour propagation between CT and cone-beam CT images in adaptive head & neck radiotherapy

Deformable image registration (DIR) is a critical technic in adaptive radiotherapy (ART) for propagating contours between planning computerized tomography (CT) images and treatment CT/cone-beam CT (CBCT) images to account for organ deformation for treatment re-planning. To validate the ability and accuracy of DIR algorithms in organ at risk (OAR) contour mapping, ten intensity-based DIR strategies, which were classified into four categories—optical flow-based, demons-based, level-set-based and spline-based—were tested on planning CT and fractional CBCT images acquired from twenty-one head & neck (H&N) cancer patients who underwent 6~7-week intensity-modulated radiation therapy (IMRT). Three similarity metrics, i.e., the Dice similarity coefficient (DSC), the percentage error (PE) and the Hausdorff distance (HD), were employed to measure the agreement between the propagated contours and the physician-delineated ground truths of four OARs, including the vertebra (VTB), the vertebral foramen (VF), the parotid gland (PG) and the submandibular gland (SMG). It was found that the evaluated DIRs in this work did not necessarily outperform rigid registration. DIR performed better for bony structures than soft-tissue organs, and the DIR performance tended to vary for different ROIs with different degrees of deformation as the treatment proceeded. Generally, the optical flow-based DIR performed best, while the demons-based DIR usually ranked last except for a modified demons-based DISC used for CT-CBCT DIR. These experimental results suggest that the choice of a specific DIR algorithm depends on the image modality, anatomic site, magnitude of deformation and application. Therefore, careful examinations and modifications are required before accepting the auto-propagated contours, especially for automatic re-planning ART systems.

An anthropomorphic abdominal phantom for deformable image registration accuracy validation in adaptive radiation therapy

Purpose To design and construct a three‐dimensional (3D) anthropomorphic abdominal phantom for geometric accuracy and dose summation accuracy evaluations of deformable image registration (DIR) algorithms for adaptive radiation therapy (ART). Method Organ molds, including liver, kidney, spleen, stomach, vertebra, and two metastasis tumors, were 3D printed using contours from an ovarian cancer patient. The organ molds were molded with deformable gels made of different mixtures of polyvinyl chloride (PVC) and the softener dioctyl terephthalate. Gels with different densities were obtained by a polynomial fitting curve that described the relation between the Hounsfield unit (HU) and PVC‐softener blending ratio. The rigid vertebras were constructed by molding of white cement and cellulose pulp. The final abdominal phantom was assembled by arranging all the fabricated organs inside a hollow dummy according to their anatomies, and sealed by deformable gel with averaged HU of muscle and fat. Fiducial landmarks were embedded inside the phantom for spatial accuracy and dose accumulation accuracy studies. Two channels were excavated to facilitate ionization chamber insertion for dosimetric measurements. Phantom properties such as deformable gel elasticity and HU stability were studied. The dosimetric measurement accuracy in the phantom was performed, and the DIR accuracies of three DIR algorithms available in the open source DIR toolkit‐DIRART were also validated. Results The constructed deformable gel showed elastic behavior and was stable in HU values over times, proving to be a practical material for the deformable phantom. The constructed abdominal phantom consisted of realistic anatomies in terms of both anatomical shapes and densities when compared with its reference patient. The dosimetric measurements showed a good agreement with the calculated doses from the treatment planning system. Fiducial‐based accuracy analysis conducted on the constructed phantom demonstrated the feasibility of applying the phantom for organ‐wise DIR accuracy assessment. Conclusions We have designed and constructed an anthropomorphic abdominal deformable phantom with satisfactory elastic property, realistic organ density, and anatomy. This physical phantom can be used for routine validations of DIR geometric accuracy and dose accumulation accuracy in ART.