Coherent Point Drift Peak Alignment Algorithms Using Distance and Similarity Measures for Two-Dimensional Gas Chromatography Mass Spectrometry Data.

The peak alignment is a vital preprocessing step before downstream analysis, such as biomarker discovery and pathway analysis, for two-dimensional gas chromatography mass spectrometry (2DGCMS)-based metabolomics data. Due to uncontrollable experimental conditions, e.g., the differences in temperature or pressure, matrix effects on samples, and stationary phase degradation, a shift of retention times among samples inevitably occurs during 2DGCMS experiments, making it difficult to align peaks. Various peak alignment algorithms have been developed to correct retention time shifts for homogeneous, heterogeneous or both type of mass spectrometry data. However, almost all existing algorithms have been focused on a local alignment and are suffering from low accuracy especially when aligning dense biological data with many peaks. We have developed four global peak alignment (GPA) algorithms using coherent point drift (CPD) point matching algorithms: retention time-based CPD-GPA (RT), prior CPD-GPA (P), mixture CPD-GPA (M), and prior mixture CPD-GPA (P+M). The method RT performs the peak alignment based only on the retention time distance, while the methods P, M, and P+M carry out the peak alignment using both the retention time distance and mass spectral similarity. The method P incorporates the mass spectral similarity through prior information and the methods M and P+M use the mixture distance measure. Four developed algorithms are applied to homogeneous and heterogeneous spiked-in data as well as two real biological data and compared with three existing algorithms, mSPA, SWPA, and BiPACE-2D. The results show that our CPD-GPA algorithms perform better than all existing algorithms in terms of F1 score.

VC-Net: Deep Volume-Composition Networks for Segmentation and Visualization of Highly Sparse and Noisy Image Data.

The fundamental motivation of the proposed work is to present a new visualization-guided computing paradigm to combine direct 3D volume processing and volume rendered clues for effective 3D exploration. For example, extracting and visualizing microstructures in-vivo have been a long-standing challenging problem. However, due to the high sparseness and noisiness in cerebrovasculature data as well as highly complex geometry and topology variations of micro vessels, it is still extremely challenging to extract the complete 3D vessel structure and visualize it in 3D with high fidelity. In this paper, we present an end-to-end deep learning method, VC-Net, for robust extraction of 3D microvascular structure through embedding the image composition, generated by maximum intensity projection (MIP), into the 3D volumetric image learning process to enhance the overall performance. The core novelty is to automatically leverage the volume visualization technique (e.g., MIP - a volume rendering scheme for 3D volume images) to enhance the 3D data exploration at the deep learning level. The MIP embedding features can enhance the local vessel signal (through canceling out the noise) and adapt to the geometric variability and scalability of vessels, which is of great importance in microvascular tracking. A multi-stream convolutional neural network (CNN) framework is proposed to effectively learn the 3D volume and 2D MIP feature vectors, respectively, and then explore their inter-dependencies in a joint volume-composition embedding space by unprojecting the 2D feature vectors into the 3D volume embedding space. It is noted that the proposed framework can better capture the small/micro vessels and improve the vessel connectivity. To our knowledge, this is the first time that a deep learning framework is proposed to construct a joint convolutional embedding space, where the computed vessel probabilities from volume rendering based 2D projection and 3D volume can be explored and integrated synergistically. Experimental results are evaluated and compared with the traditional 3D vessel segmentation methods and the state-of-the-art in deep learning, by using extensive public and real patient (micro- )cerebrovascular image datasets. The application of this accurate segmentation and visualization of sparse and complicated 3D microvascular structure facilitated by our method demonstrates the potential in a powerful MR arteriogram and venogram diagnosis of vascular disease.

Surface Registration with Eigenvalues and Eigenvectors.

This paper presents a novel surface registration technique using the spectrum of the shapes, which can facilitate accurate localization and visualization of non-isometric deformations of the surfaces. In order to register two surfaces, we map both eigenvalues and eigenvectors of the Laplace-Beltrami of the shapes through optimizing an energy function. The function is defined by the integration of a smoothness term to align the eigenvalues and a distance term between the eigenvectors at feature points to align the eigenvectors. The feature points are generated using the static points of certain eigenvectors of the surfaces. By using both the eigenvalues and the eigenvectors on these feature points, the computational efficiency is improved considerably without losing the accuracy in comparison to the approaches that use the eigenvectors for all vertices. In our technique, the variation of the shape is expressed using a scale function defined at each vertex. Consequently, the total energy function to align the two given surfaces can be defined using the linear interpolation of the scale function derivatives. Through the optimization of the energy function, the scale function can be solved and the alignment is achieved. After the alignment, the eigenvectors can be employed to calculate the point-to-point correspondence of the surfaces. Therefore, the proposed method can accurately define the displacement of the vertices. We evaluate our method by conducting experiments on synthetic and real data using hippocampus, heart, and hand models. We also compare our method with non-rigid Iterative Closest Point (ICP) and a similar spectrum-based methods. These experiments demonstrate the advantages and accuracy of our method.

DeepOrganNet: On-the-Fly Reconstruction and Visualization of 3D / 4D Lung Models from Single-View Projections by Deep Deformation Network.

This paper introduces a deep neural network based method, i.e., DeepOrganNet, to generate and visualize fully high-fidelity 3D / 4D organ geometric models from single-view medical images with complicated background in real time. Traditional 3D / 4D medical image reconstruction requires near hundreds of projections, which cost insufferable computational time and deliver undesirable high imaging / radiation dose to human subjects. Moreover, it always needs further notorious processes to segment or extract the accurate 3D organ models subsequently. The computational time and imaging dose can be reduced by decreasing the number of projections, but the reconstructed image quality is degraded accordingly. To our knowledge, there is no method directly and explicitly reconstructing multiple 3D organ meshes from a single 2D medical grayscale image on the fly. Given single-view 2D medical images, e.g., 3D / 4D-CT projections or X-ray images, our end-to-end DeepOrganNet framework can efficiently and effectively reconstruct 3D / 4D lung models with a variety of geometric shapes by learning the smooth deformation fields from multiple templates based on a trivariate tensor-product deformation technique, leveraging an informative latent descriptor extracted from input 2D images. The proposed method can guarantee to generate high-quality and high-fidelity manifold meshes for 3D / 4D lung models; while, all current deep learning based approaches on the shape reconstruction from a single image cannot. The major contributions of this work are to accurately reconstruct the 3D organ shapes from 2D single-view projection, significantly improve the procedure time to allow on-the-fly visualization, and dramatically reduce the imaging dose for human subjects. Experimental results are evaluated and compared with the traditional reconstruction method and the state-of-the-art in deep learning, by using extensive 3D and 4D examples, including both synthetic phantom and real patient datasets. The efficiency of the proposed method shows that it only needs several milliseconds to generate organ meshes with 10K vertices, which has great potential to be used in real-time image guided radiation therapy (IGRT).

Global Plasma Profiling for Colorectal Cancer-Associated Volatile Organic Compounds: a Proof-of-Principle Study.

Volatile organic compounds (VOCs) could reflect changes resulting from ongoing pathophysiological processes and altered body metabolisms, and thus have been studied for various types of cancers. We aimed to test an advanced global metabolomic technique to characterize circulating VOCs in patients diagnosed with colorectal cancer (CRC). We employed solid-phase microextraction (SPME) and comprehensive two-dimensional gas chromatography mass-spectrometry (GC × GC-MS). We analyzed 30 random plasma samples from incident cases of CRC. The 30 samples were from population controls enrolled in a large population-based case-control study. The number of metabolite peaks detected in the cases was significantly lower than that detected in the controls (median 1530 vs. 1694, P = 0.02). Partial least squares-discriminant analysis showed clear VOC profile differences between the CRC and the controls. After adjustment for multiple comparisons at the 5% false discovery rate level, five VOCs were differentially expressed between the cases and the controls. Among these five VOCs, 2,3,4-trimethyl-hexane (decreased) and 2,4-dimethylhept-1-ene (increased) were both lipid peroxidation products but not previously reported for CRC. In summary, this study pointed to an intriguing observation that the richness of volatile metabolites may be reduced in CRC cases and demonstrated the utility of SPME GC × GC-MS in discovery of candidate markers for further validation.

Internal Motion Estimation by Internal-external Motion Modeling for Lung Cancer Radiotherapy.

The aim of this study is to develop an internal-external correlation model for internal motion estimation for lung cancer radiotherapy. Deformation vector fields that characterize the internal-external motion are obtained by respectively registering the internal organ meshes and external surface meshes from the 4DCT images via a recently developed local topology preserved non-rigid point matching algorithm. A composite matrix is constructed by combing the estimated internal phasic DVFs with external phasic and directional DVFs. Principle component analysis is then applied to the composite matrix to extract principal motion characteristics, and generate model parameters to correlate the internal-external motion. The proposed model is evaluated on a 4D NURBS-based cardiac-torso (NCAT) synthetic phantom and 4DCT images from five lung cancer patients. For tumor tracking, the center of mass errors of the tracked tumor are 0.8(±0.5)mm/0.8(±0.4)mm for synthetic data, and 1.3(±1.0)mm/1.2(±1.2)mm for patient data in the intra-fraction/inter-fraction tracking, respectively. For lung tracking, the percent errors of the tracked contours are 0.06(±0.02)/0.07(±0.03) for synthetic data, and 0.06(±0.02)/0.06(±0.02) for patient data in the intra-fraction/inter-fraction tracking, respectively. The extensive validations have demonstrated the effectiveness and reliability of the proposed model in motion tracking for both the tumor and the lung in lung cancer radiotherapy.

Investigating rectal toxicity associated dosimetric features with deformable accumulated rectal surface dose maps for cervical cancer radiotherapy.

BACKGROUND: Better knowledge of the dose-toxicity relationship is essential for safe dose escalation to improve local control in cervical cancer radiotherapy. The conventional dose-toxicity model is based on the dose volume histogram, which is the parameter lacking spatial dose information. To overcome this limit, we explore a comprehensive rectal dose-toxicity model based on both dose volume histogram and dose map features for accurate radiation toxicity prediction. METHODS: Forty-two cervical cancer patients treated with combined external beam radiotherapy (EBRT) and brachytherapy (BT) were retrospectively studied, including 12 with Grade ≥ 2 rectum toxicity and 30 patients with Grade 0-1 toxicity (non-toxicity patients). The cumulative equivalent 2-Gy rectal surface dose was deformably summed using the deformation vector fields obtained through a recent developed local topology preserved non-rigid point matching algorithm. The cumulative three-dimensional (3D) dose was flattened and mapped to a two-dimensional (2D) plane to obtain the rectum surface dose map (RSDM). The dose volume parameters (DVPs) were calculated from the 3D rectum surface, while the texture features and the dose geometric parameters (DGPs) were extracted from the 2D RSDM. Representative features further computed from DVPs, textures and DGPs by principle component analysis (PCA) and statistical analysis were respectively fed into a support vector machine equipped with a sequential feature selection procedure. The predictive powers of the representative features were compared with the GEC-ESTRO dosimetric parameters D0.1/1/2cm3. RESULTS: Satisfactory predictive accuracy of sensitivity 74.75 and 84.75%, specificity 72.67 and 79.87%, and area under the receiver operating characteristic curve (AUC) 0.82 and 0.91 were respectively achieved by the PCA features and statistical significant features, which were superior to the D0.1/1/2cm3 (AUC 0.71). The relative area in dose levels of 64Gy, 67Gy, 68Gy, 87Gy, 88Gy and 89Gy, perimeters in dose levels of 89Gy, as well as two texture features were ranked as the important factors that were closely correlated with rectal toxicity. CONCLUSIONS: Our extensive experimental results have demonstrated the feasibility of the proposed scheme. A future large patient cohort study is still needed for model validation.

Visualizing Shape Deformations with Variation of Geometric Spectrum.

This paper presents a novel approach based on spectral geometry to quantify and visualize non-isometric deformations of 3D surfaces by mapping two manifolds. The proposed method can determine multi-scale, non-isometric deformations through the variation of Laplace-Beltrami spectrum of two shapes. Given two triangle meshes, the spectra can be varied from one to another with a scale function defined on each vertex. The variation is expressed as a linear interpolation of eigenvalues of the two shapes. In each iteration step, a quadratic programming problem is constructed, based on our derived spectrum variation theorem and smoothness energy constraint, to compute the spectrum variation. The derivation of the scale function is the solution of such a problem. Therefore, the final scale function can be solved by integral of the derivation from each step, which, in turn, quantitatively describes non-isometric deformations between two shapes. To evaluate the method, we conduct extensive experiments on synthetic and real data. We employ real epilepsy patient imaging data to quantify the shape variation between the left and right hippocampi in epileptic brains. In addition, we use longitudinal Alzheimer data to compare the shape deformation of diseased and healthy hippocampus. In order to show the accuracy and effectiveness of the proposed method, we also compare it with spatial registration-based methods, e.g., non-rigid Iterative Closest Point (ICP) and voxel-based method. These experiments demonstrate the advantages of our method.

Surface Approximation via Asymptotic Optimal Geometric Partition.

In this paper, we present a novel method on surface partition from the perspective of approximation theory. Different from previous shape proxies, the ellipsoidal variance proxy is proposed to penalize the partition results falling into disconnected parts. On its support, the Principle Component Analysis (PCA) based energy is developed for asymptotic cluster aspect ratio and size control. We provide the theoretical explanation on how the minimization of the PCA-based energy leads to the optimal asymptotic behavior for approximation. Moreover, we show the partitions on densely sampled triangular meshes converge to the theoretic expectations. To evaluate the effectiveness of surface approximation, polygonal/triangular surface remeshing results are generated. The experimental results demonstrate the high approximation quality of our method.

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.

4D cone-beam CT reconstruction using multi-organ meshes for sliding motion modeling.

A simultaneous motion estimation and image reconstruction (SMEIR) strategy was proposed for 4D cone-beam CT (4D-CBCT) reconstruction and showed excellent results in both phantom and lung cancer patient studies. In the original SMEIR algorithm, the deformation vector field (DVF) was defined on voxel grid and estimated by enforcing a global smoothness regularization term on the motion fields. The objective of this work is to improve the computation efficiency and motion estimation accuracy of SMEIR for 4D-CBCT through developing a multi-organ meshing model. Feature-based adaptive meshes were generated to reduce the number of unknowns in the DVF estimation and accurately capture the organ shapes and motion. Additionally, the discontinuity in the motion fields between different organs during respiration was explicitly considered in the multi-organ mesh model. This will help with the accurate visualization and motion estimation of the tumor on the organ boundaries in 4D-CBCT. To further improve the computational efficiency, a GPU-based parallel implementation was designed. The performance of the proposed algorithm was evaluated on a synthetic sliding motion phantom, a 4D NCAT phantom, and four lung cancer patients. The proposed multi-organ mesh based strategy outperformed the conventional Feldkamp-Davis-Kress, iterative total variation minimization, original SMEIR and single meshing method based on both qualitative and quantitative evaluations.

3D-2D Deformable Image Registration Using Feature-Based Nonuniform Meshes.

By using prior information of planning CT images and feature-based nonuniform meshes, this paper demonstrates that volumetric images can be efficiently registered with a very small portion of 2D projection images of a Cone-Beam Computed Tomography (CBCT) scan. After a density field is computed based on the extracted feature edges from planning CT images, nonuniform tetrahedral meshes will be automatically generated to better characterize the image features according to the density field; that is, finer meshes are generated for features. The displacement vector fields (DVFs) are specified at the mesh vertices to drive the deformation of original CT images. Digitally reconstructed radiographs (DRRs) of the deformed anatomy are generated and compared with corresponding 2D projections. DVFs are optimized to minimize the objective function including differences between DRRs and projections and the regularity. To further accelerate the above 3D-2D registration, a procedure to obtain good initial deformations by deforming the volume surface to match 2D body boundary on projections has been developed. This complete method is evaluated quantitatively by using several digital phantoms and data from head and neck cancer patients. The feature-based nonuniform meshing method leads to better results than either uniform orthogonal grid or uniform tetrahedral meshes.

A non-rigid point matching method with local topology preservation for accurate bladder dose summation in high dose rate cervical brachytherapy.

GEC-ESTRO guidelines for high dose rate cervical brachytherapy advocate the reporting of the D2cc (the minimum dose received by the maximally exposed 2cc volume) to organs at risk. Due to large interfractional organ motion, reporting of accurate cumulative D2cc over a multifractional course is a non-trivial task requiring deformable image registration and deformable dose summation. To efficiently and accurately describe the point-to-point correspondence of the bladder wall over all treatment fractions while preserving local topologies, we propose a novel graphic processing unit (GPU)-based non-rigid point matching algorithm. This is achieved by introducing local anatomic information into the iterative update of correspondence matrix computation in the 'thin plate splines-robust point matching' (TPS-RPM) scheme. The performance of the GPU-based TPS-RPM with local topology preservation algorithm (TPS-RPM-LTP) was evaluated using four numerically simulated synthetic bladders having known deformations, a custom-made porcine bladder phantom embedded with twenty one fiducial markers, and 29 fractional computed tomography (CT) images from seven cervical cancer patients. Results show that TPS-RPM-LTP achieved excellent geometric accuracy with landmark residual distance error (RDE) of 0.7 ± 0.3 mm for the numerical synthetic data with different scales of bladder deformation and structure complexity, and 3.7 ± 1.8 mm and 1.6 ± 0.8 mm for the porcine bladder phantom with large and small deformation, respectively. The RDE accuracy of the urethral orifice landmarks in patient bladders was 3.7 ± 2.1 mm. When compared to the original TPS-RPM, the TPS-RPM-LTP improved landmark matching by reducing landmark RDE by 50 ± 19%, 37 ± 11% and 28 ± 11% for the synthetic, porcine phantom and the patient bladders, respectively. This was achieved with a computational time of less than 15 s in all cases with GPU acceleration. The efficiency and accuracy shown with the TPS-RPM-LTP indicate that it is a practical and promising tool for bladder dose summation in adaptive cervical cancer brachytherapy.

A novel markerless technique to evaluate daily lung tumor motion based on conventional cone-beam CT projection data.

PURPOSE: In this study, we present a novel markerless technique, based on cone beam computed tomography (CBCT) raw projection data, to evaluate lung tumor daily motion. METHOD AND MATERIALS: The markerless technique, which uses raw CBCT projection data and locates tumors directly on every projection, consists of three steps. First, the tumor contour on the planning CT is used to create digitally reconstructed radiographs (DRRs) at every projection angle. Two sets of DRRs are created: one showing only the tumor, and another with the complete anatomy without the tumor. Second, a rigid two-dimensional image registration is performed to register the DRR set without the tumor to the CBCT projections. After the registration, the projections are subtracted from the DRRs, resulting in a projection dataset containing primarily tumor. Finally, a second registration is performed between the subtracted projection and tumor-only DRR. The methodology was evaluated using a chest phantom containing a moving tumor, and retrospectively in 4 lung cancer patients treated by stereotactic body radiation therapy. Tumors detected on projection images were compared with those from three-dimensional (3D) and four-dimensional (4D) CBCT reconstruction results. RESULTS: Results in both static and moving phantoms demonstrate that the accuracy is within 1 mm. The subsequent application to 22 sets of CBCT scan raw projection data of 4 lung cancer patients includes about 11,000 projections, with the detected tumor locations consistent with 3D and 4D CBCT reconstruction results. This technique reveals detailed lung tumor motion and provides additional information than conventional 4D images. CONCLUSION: This technique is capable of accurately characterizing lung tumor motion on a daily basis based on a conventional CBCT scan. It provides daily verification of the tumor motion to ensure that these motions are within prior estimation and covered by the treatment planning volume.