Coordinates in low-dimensional cell shape-space discriminate migration dynamics from single static cell images.

Cell shape has long been used to discern cell phenotypes and states, but the underlying premise has not been quantitatively tested. Here, we show that a single cell image can be used to discriminate its migration behavior by analyzing a large number of cell migration data in vitro. We analyzed a large number of two-dimensional cell migration images over time and found that the cell shape variation space has only six dimensions, and migration behavior can be determined by the coordinates of a single cell image in this 6-dimensional shape-space. We further show that this is possible because persistent cell migration is characterized by spatial-temporally coordinated protrusion and contraction, and a distribution signature in the shape-space. Our findings provide a quantitative underpinning for using cell morphology to differentiate cell dynamical behavior.

Patient specific prior cross attention for kV decomposition in paraspinal motion tracking.

BACKGROUND: X-ray image quality is critical for accurate intrafraction motion tracking in radiation therapy. PURPOSE: This study aims to develop a deep-learning algorithm to improve kV image contrast by decomposing the image into bony and soft tissue components. In particular, we designed a priori attention mechanism in the neural network framework for optimal decomposition. We show that a patient-specific prior cross-attention (PCAT) mechanism can boost the performance of kV image decomposition. We demonstrate its use in paraspinal SBRT motion tracking with online kV imaging. METHODS: Online 2D kV projections were acquired during paraspinal SBRT for patient motion monitoring. The patient-specific prior images were generated by randomly shifting and rotating spine-only DRR created from the setup CBCT, simulating potential motions. The latent features of the prior images were incorporated into the PCAT using multi-head cross attention. The neural network aimed to learn to selectively amplify the transmission of the projection image features that correlate with features of the priori. The PCAT network structure consisted of (1) a dual-branch generator that separates the spine and soft tissue component of the kV projection image and (2) a dual-function discriminator (DFD) that provides the realness score of the predicted images. For supervision, we used a loss combining mean absolute error loss, discriminator loss, perceptual loss, total variation, and mean squared error loss for soft tissues. The proposed PCAT approach was benchmarked against previous work using the ResNet generative adversarial network (ResNetGAN) without prior information. RESULTS: The trained PCAT had improved performance in effectively retaining and preserving the spine structure and texture information while suppressing the soft tissues from the kV projection images. The decomposed spine-only x-ray images had the submillimeter matching accuracy at all beam angles. The decomposed spine-only x-ray significantly reduced the maximum errors to 0.44 mm (<2 pixels) in comparison to 0.92 mm (∼4 pixels) of ResNetGAN. The PCAT decomposed spine images also had higher PSNR and SSIM (p-value < 0.001). CONCLUSION: The PCAT selectively learned the important latent features by incorporating the patient-specific prior knowledge into the deep learning algorithm, significantly improving the robustness of the kV projection image decomposition, and leading to improved motion tracking accuracy in paraspinal SBRT.

Enhancing the target visibility with synthetic target specific digitally reconstructed radiograph for intrafraction motion monitoring: A proof-of-concept study.

BACKGROUND: Intrafraction motion monitoring in External Beam Radiation Therapy (EBRT) is usually accomplished by establishing a correlation between the tumor and the surrogates such as an external infrared reflector, implanted fiducial markers, or patient skin surface. These techniques either have unstable surrogate-tumor correlation or are invasive. Markerless real-time onboard imaging is a noninvasive alternative that directly images the target motion. However, the low target visibility due to overlapping tissues along the X-ray projection path makes tumor tracking challenging. PURPOSE: To enhance the target visibility in projection images, a patient-specific model was trained to synthesize the Target Specific Digitally Reconstructed Radiograph (TS-DRR). METHODS: Patient-specific models were built using a conditional Generative Adversarial Network (cGAN) to map the onboard projection images to TS-DRR. The standard Pix2Pix network was adopted as our cGAN model. We synthesized the TS-DRR based on the onboard projection images using phantom and patient studies for spine tumors and lung tumors. Using previously acquired CT images, we generated DRR and its corresponding TS-DRR to train the network. For data augmentation, random translations were applied to the CT volume when generating the training images. For the spine, separate models were trained for an anthropomorphic phantom and a patient treated with paraspinal stereotactic body radiation therapy (SBRT). For lung, separate models were trained for a phantom with a spherical tumor insert and a patient treated with free-breathing SBRT. The models were tested using Intrafraction Review Images (IMR) for the spine and CBCT projection images for the lung. The performance of the models was validated using phantom studies with known couch shifts for the spine and known tumor deformation for the lung. RESULTS: Both the patient and phantom studies showed that the proposed method can effectively enhance the target visibility of the projection images by mapping them into synthetic TS-DRR (sTS-DRR). For the spine phantom with known shifts of 1 mm, 2 mm, 3 mm, and 4 mm, the absolute mean errors for tumor tracking were 0.11 ± 0.05 mm in the x direction and 0.25 ± 0.08 mm in the y direction. For the lung phantom with known tumor motion of 1.8 mm, 5.8 mm, and 9 mm superiorly, the absolute mean errors for the registration between the sTS-DRR and ground truth are 0.1 ± 0.3 mm in both the x and y directions. Compared to the projection images, the sTS-DRR has increased the image correlation with the ground truth by around 83% and increased the structural similarity index measure with the ground truth by around 75% for the lung phantom. CONCLUSIONS: The sTS-DRR can greatly enhance the target visibility in the onboard projection images for both the spine and lung tumors. The proposed method could be used to improve the markerless tumor tracking accuracy for EBRT.

Markerless motion tracking with simultaneous MV and kV imaging in spine SBRT treatment-a feasibility study.

Objective. Motion tracking with simultaneous MV-kV imaging has distinct advantages over single kV systems. This research is a feasibility study of utilizing this technique for spine stereotactic body radiotherapy (SBRT) through phantom and patient studies.Approach. A clinical spine SBRT plan was developed using 6xFFF beams and nine sliding-window IMRT fields. The plan was delivered to a chest phantom on a linear accelerator. Simultaneous MV-kV image pairs were acquired during beam delivery. KV images were triggered at predefined intervals, and synthetic MV images showing enlarged MLC apertures were created by combining multiple raw MV frames with corrections for scattering and intensity variation. Digitally reconstructed radiograph (DRR) templates were generated using high-resolution CBCT reconstructions (isotropic voxel size (0.243 mm)3) as the reference for 2D-2D matching. 3D shifts were calculated from triangulation of kV-to-DRR and MV-to-DRR registrations. To evaluate tracking accuracy, detected shifts were compared to known phantom shifts as introduced before treatment. The patient study included a T-spine patient and an L-spine patient. Patient datasets were retrospectively analyzed to demonstrate the performance in clinical settings.Main results. The treatment plan was delivered to the phantom in five scenarios: no shift, 2 mm shift in one of the longitudinal, lateral and vertical directions, and 2 mm shift in all the three directions. The calculated 3D shifts agreed well with the actual couch shifts, and overall, the uncertainty of 3D detection is estimated to be 0.3 mm. The patient study revealed that with clinical patient image quality, the calculated 3D motion agreed with the post-treatment cone beam CT. It is feasible to automate both kV-to-DRR and MV-to-DRR registrations using a mutual information-based method, and the difference from manual registration is generally less than 0.3 mm.Significance. The MV-kV imaging-based markerless motion tracking technique was validated through a feasibility study. It is a step forward toward effective motion tracking and accurate delivery for spinal SBRT.

Automatic stent recognition using perceptual attention U-net for quantitative intrafraction motion monitoring in pancreatic cancer radiotherapy.

PURPOSE: Stent has often been used as an internal surrogate to monitor intrafraction tumor motion during pancreatic cancer radiotherapy. Based on the stent contours generated from planning CT images, the current intrafraction motion review (IMR) system on Varian TrueBeam only provides a tool to verify the stent motion visually but lacks quantitative information. The purpose of this study is to develop an automatic stent recognition method for quantitative intrafraction tumor motion monitoring in pancreatic cancer treatment. METHODS: A total of 535 IMR images from 14 pancreatic cancer patients were retrospectively selected in this study, with the manual contour of the stent on each image serving as the ground truth. We developed a deep learning-based approach that integrates two mechanisms that focus on the features of the segmentation target. The objective attention modeling was integrated into the U-net framework to deal with the optimization difficulties when training a deep network with 2D IMR images and limited training data. A perceptual loss was combined with the binary cross-entropy loss and a Dice loss for supervision. The deep neural network was trained to capture more contextual information to predict binary stent masks. A random-split test was performed, with images of ten patients (71%, 380 images) randomly selected for training, whereas the rest of four patients (29%, 155 images) were used for testing. Sevenfold cross-validation of the proposed PAUnet on the 14 patients was performed for further evaluation. RESULTS: Our stent segmentation results were compared with the manually segmented contours. For the random-split test, the trained model achieved a mean (±standard deviation) stent Dice similarity coefficient (DSC), 95% Hausdorff distance (HD95), the center-of-mass distance (CMD), and volume difference V o l d i f f $Vo{l_{diff}}$ were 0.96 (±0.01), 1.01 (±0.55) mm, 0.66 (±0.46) mm, and 3.07% (±2.37%), respectively. The sevenfold cross-validation of the proposed PAUnet had the mean (±standard deviation) of 0.96 (±0.02), 0.72 (±0.49) mm, 0.85 (±0.96) mm, and 3.47% (±3.27%) for the DSC, HD95, CMD, and V o l d i f f $Vo{l_{diff}}$ . CONCLUSION: We developed a novel deep learning-based approach to automatically segment the stent from IMR images, demonstrated its clinical feasibility, and validated its accuracy compared to manual segmentation. The proposed technique could be a useful tool for quantitative intrafraction motion monitoring in pancreatic cancer radiotherapy.

Extracellular matrix in cancer progression and therapy.

The tumor ecosystem with heterogeneous cellular compositions and the tumor microenvironment has increasingly become the focus of cancer research in recent years. The extracellular matrix (ECM), the major component of the tumor microenvironment, and its interactions with the tumor cells and stromal cells have also enjoyed tremendously increased attention. Like the other components of the tumor microenvironment, the ECM in solid tumors differs significantly from that in normal organs and tissues. We review recent studies of the complex roles the tumor ECM plays in cancer progression, from tumor initiation, growth to angiogenesis and invasion. We highlight that the biomolecular, biophysical, and mechanochemical interactions between the ECM and cells not only regulate the steps of cancer progression, but also affect the efficacy of systemic cancer treatment. We further discuss the strategies to target and modify the tumor ECM to improve cancer therapy.

Decompose kV projection using neural network for improved motion tracking in paraspinal SBRT.

PURPOSE:  On-treatment kV images have been used in tracking patient motion. One challenge of markerless motion tracking in paraspinal SBRT is the reduced contrast when the X-ray beam needs to pass through a large portion of the patient's body, for example, from the lateral direction. Besides, due to the spine's overlapping with the surrounding moving organs in the X-ray images, auto-registration could lead to potential errors. This work aims to automatically extract the spine component from the conventional 2D X-ray images, to achieve more robust and more accurate motion management. METHODS:  A ResNet generative adversarial network (ResNetGAN) consisting of one generator and one discriminator was developed to learn the mapping between 2D kV image and the reference spine digitally reconstructed radiograph (DRR). A tailored multi-channel multi-domain loss function was used to improve the quality of the decomposed spine image. The trained model took a 2D kV image as input and learned to generate the spine component of the X-ray image. The training dataset included 1347 2D kV thoracic and lumbar region X-ray images from 20 randomly selected patients, and the corresponding matched reference spine DRR. Another 226 2D kV images from the remaining four patients were used for evaluation. The resulted decomposed spine images and the original X-ray images were registered to the reference spine DRRs, to compare the spine tracking accuracy. RESULTS:  The decomposed spine image had the mean peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) of 60.08 and 0.99, respectively, indicating the model retained and enhanced the spine structure information in the original 2D X-ray image. The decomposed spine image matching with the reference spine DRR had submillimeter accuracy (in mm) with a mean error of 0.13, 0.12, and a maximum of 0.58, 0.49 in the x - and y -directions (in the imager coordinates), respectively. The accuracy improvement is robust in all lateral and anteroposterior X-ray beam angles. CONCLUSION:  We developed a deep learning-based approach to remove soft tissues in the kV image, leading to more accurate spine tracking in paraspinal SBRT.

Thyroid gland delineation in noncontrast-enhanced CTs using deep convolutional neural networks.

The purpose of this study is to develop a deep learning method for thyroid delineation with high accuracy, efficiency, and robustness in noncontrast-enhanced head and neck CTs. The cross-sectional analysis consisted of six tests, including randomized cross-validation and hold-out experiments, tests of prediction accuracy between cancer and benign and cross-gender analysis were performed to evaluate the proposed deep-learning-based performance method. CT images of 1977 patients with suspected thyroid carcinoma were retrospectively investigated. The automatically segmented thyroid gland volume was compared against physician-approved clinical contours using metrics, the Pearson correlation and Bland-Altman analysis. Quantitative metrics included: the Dice similarity coefficient (DSC), sensitivity, specificity, Jaccard index (JAC), Hausdorff distance (HD), mean surface distance (MSD), residual mean square distance (RMSD) and the center of mass distance (CMD). The robustness of the proposed method was further tested using the nonparametric Kruskal-Wallis test to assess the equality of distribution of DSC values. The proposed method's accuracy remained high through all the tests, with the median DSC, JAC, sensitivity and specificity higher than 0.913, 0.839, 0.856 and 0.979, respectively. The proposed method also resulted in median MSD, RMSD, HD and CMD, of less than 0.31 mm, 0.48 mm, 2.06 mm and 0.50 mm, respectively. The MSD and RMSD were 0.40 ± 0.29 mm and 0.70 ± 0.46 mm, respectively. Concurrent testing of the proposed method with 3D U-Net and V-Net showed that the proposed method had significantly improved performance. The proposed deep-learning method achieved accurate and robust performance through six cross-sectional analysis tests.

Breast tumor segmentation in 3D automatic breast ultrasound using Mask scoring R-CNN.

PURPOSE: Automatic breast ultrasound (ABUS) imaging has become an essential tool in breast cancer diagnosis since it provides complementary information to other imaging modalities. Lesion segmentation on ABUS is a prerequisite step of breast cancer computer-aided diagnosis (CAD). This work aims to develop a deep learning-based method for breast tumor segmentation using three-dimensional (3D) ABUS automatically. METHODS: For breast tumor segmentation in ABUS, we developed a Mask scoring region-based convolutional neural network (R-CNN) that consists of five subnetworks, that is, a backbone, a regional proposal network, a region convolutional neural network head, a mask head, and a mask score head. A network block building direct correlation between mask quality and region class was integrated into a Mask scoring R-CNN based framework for the segmentation of new ABUS images with ambiguous regions of interest (ROIs). For segmentation accuracy evaluation, we retrospectively investigated 70 patients with breast tumor confirmed with needle biopsy and manually delineated on ABUS, of which 40 were used for fivefold cross-validation and 30 were used for hold-out test. The comparison between the automatic breast tumor segmentations and the manual contours was quantified by I) six metrics including Dice similarity coefficient (DSC), Jaccard index, 95% Hausdorff distance (HD95), mean surface distance (MSD), residual mean square distance (RMSD), and center of mass distance (CMD); II) Pearson correlation analysis and Bland-Altman analysis. RESULTS: The mean (median) DSC was 85% ± 10.4% (89.4%) and 82.1% ± 14.5% (85.6%) for cross-validation and hold-out test, respectively. The corresponding HD95, MSD, RMSD, and CMD of the two tests was 1.646 ± 1.191 and 1.665 ± 1.129 mm, 0.489 ± 0.406 and 0.475 ± 0.371 mm, 0.755 ± 0.755 and 0.751 ± 0.508 mm, and 0.672 ± 0.612 and 0.665 ± 0.729 mm. The mean volumetric difference (mean and ± 1.96 standard deviation) was 0.47 cc ([-0.77, 1.71)) for the cross-validation and 0.23 cc ([-0.23 0.69]) for hold-out test, respectively. CONCLUSION: We developed a novel Mask scoring R-CNN approach for the automated segmentation of the breast tumor in ABUS images and demonstrated its accuracy for breast tumor segmentation. Our learning-based method can potentially assist the clinical CAD of breast cancer using 3D ABUS imaging.

Automatic quantification of myocardium and pericardial fat from coronary computed tomography angiography: a multicenter study.

OBJECTIVES: To develop a deep learning-based method for simultaneous myocardium and pericardial fat quantification from coronary computed tomography angiography (CCTA) for the diagnosis and treatment of cardiovascular disease (CVD). METHODS: We retrospectively identified CCTA data obtained between May 2008 and July 2018 in a multicenter (six centers) CVD study. The proposed method was evaluated on 422 patients' data by two studies. The first overall study involves training model on CVD patients and testing on non-CVD patients, as well as training on non-CVD patients and testing on CVD patients. The second study was performed using the leave-center-out approach. The method performance was evaluated using Dice similarity coefficient (DSC), Jaccard index (JAC), 95% Hausdorff distance (HD95), mean surface distance (MSD), residual mean square distance (RMSD), and the center of mass distance (CMD). The robustness of the proposed method was tested using the nonparametric Kruskal-Wallis test and post hoc test to assess the equality of distribution of DSC values among different tests. RESULTS: The automatic segmentation achieved a strong correlation with contour (ICC and R > 0.97, p value < 0.001 throughout all tests). The accuracy of the proposed method remained high through all the tests, with the median DSC higher than 0.88 for pericardial fat and 0.96 for myocardium. The proposed method also resulted in mean MSD, RMSD, HD95, and CMD of less than 1.36 mm for pericardial fat and 1.00 mm for myocardium. CONCLUSIONS: The proposed deep learning-based segmentation method enables accurate simultaneous quantification of myocardium and pericardial fat in a multicenter study. KEY POINTS: • Deep learning-based myocardium and pericardial fat segmentation method tested on 422 patients' coronary computed tomography angiography in a multicenter study. • The proposed method provides segmentations with high volumetric accuracy (ICC and R > 0.97, p value < 0.001) and similar shape as manual annotation by experienced radiologists (median Dice similarity coefficient ≥ 0.88 for pericardial fat and 0.96 for myocardium).

Tensile force-induced cytoskeletal remodeling: Mechanics before chemistry.

Understanding cellular remodeling in response to mechanical stimuli is a critical step in elucidating mechanical activation of biochemical signaling pathways. Experimental evidence indicates that external stress-induced subcellular adaptation is accomplished through dynamic cytoskeletal reorganization. To study the interactions between subcellular structures involved in transducing mechanical signals, we combined experimental data and computational simulations to evaluate real-time mechanical adaptation of the actin cytoskeletal network. Actin cytoskeleton was imaged at the same time as an external tensile force was applied to live vascular smooth muscle cells using a fibronectin-functionalized atomic force microscope probe. Moreover, we performed computational simulations of active cytoskeletal networks under an external tensile force. The experimental data and simulation results suggest that mechanical structural adaptation occurs before chemical adaptation during filament bundle formation: actin filaments first align in the direction of the external force by initializing anisotropic filament orientations, then the chemical evolution of the network follows the anisotropic structures to further develop the bundle-like geometry. Our findings present an alternative two-step explanation for the formation of actin bundles due to mechanical stimulation and provide new insights into the mechanism of mechanotransduction.

Automatic segmentation and quantification of epicardial adipose tissue from coronary computed tomography angiography.

Epicardial adipose tissue (EAT) is a visceral fat deposit, that's known for its association with factors, such as obesity, diabetes mellitus, age, and hypertension. Segmentation of the EAT in a fast and reproducible way is important for the interpretation of its role as an independent risk marker intricate. However, EAT has a variable distribution, and various diseases may affect the volume of the EAT, which can increase the complexity of the already time-consuming manual segmentation work. We propose a 3D deep attention U-Net method to automatically segment the EAT from coronary computed tomography angiography (CCTA). Five-fold cross-validation and hold-out experiments were used to evaluate the proposed method through a retrospective investigation of 200 patients. The automatically segmented EAT volume was compared with physician-approved clinical contours. Quantitative metrics used were the Dice similarity coefficient (DSC), sensitivity, specificity, Jaccard index (JAC), Hausdorff distance (HD), mean surface distance (MSD), residual mean square distance (RMSD), and the center of mass distance (CMD). For cross-validation, the median DSC, sensitivity, and specificity were 92.7%, 91.1%, and 95.1%, respectively, with JAC, HD, CMD, MSD, and RMSD are 82.9% ± 8.8%, 3.77 ± 1.86 mm, 1.98 ± 1.50 mm, 0.37 ± 0.24 mm, and 0.65 ± 0.37 mm, respectively. For the hold-out test, the accuracy of the proposed method remained high. We developed a novel deep learning-based approach for the automated segmentation of the EAT on CCTA images. We demonstrated the high accuracy of the proposed learning-based segmentation method through comparison with ground truth contour of 200 clinical patient cases using 8 quantitative metrics, Pearson correlation, and Bland-Altman analysis. Our automatic EAT segmentation results show the potential of the proposed method to be used in computer-aided diagnosis of coronary artery diseases (CADs) in clinical settings.

Automated left ventricular myocardium segmentation using 3D deeply supervised attention U-net for coronary computed tomography angiography; CT myocardium segmentation.

PURPOSE: Segmentation of left ventricular myocardium (LVM) in coronary computed tomography angiography (CCTA) is important for diagnosis of cardiovascular diseases. Due to poor image contrast and large variation in intensity and shapes, LVM segmentation for CCTA is a challenging task. The purpose of this work is to develop a region-based deep learning method to automatically detect and segment the LVM solely based on CCTA images. METHODS: We developed a 3D deeply supervised U-Net, which incorporates attention gates (AGs) to focus on the myocardial boundary structures, to segment LVM contours from CCTA. The deep attention U-Net (DAU-Net) was trained on the patients' CCTA images, with a manual contour-derived binary mask used as the learning-based target. The network was supervised by a hybrid loss function, which combined logistic loss and Dice loss to simultaneously measure the similarities and discrepancies between the prediction and training datasets. To evaluate the accuracy of the segmentation, we retrospectively investigated 100 patients with suspected or confirmed coronary artery disease (CAD). The LVM volume was segmented by the proposed method and compared with physician-approved clinical contours. Quantitative metrics used were Dice similarity coefficient (DSC), Hausdorff distance (HD), mean surface distance (MSD), residual mean square distance (RMSD), the center of mass distance (CMD), and volume difference (VOD). RESULTS: The proposed method created contours with very good agreement to the ground truth contours. Our proposed segmentation approach is benchmarked primarily using fivefold cross validation. Model prediction correlated and agreed well with manual contour. The mean DSC of the contours delineated by our method was 91.6% among all patients. The resultant HD was 6.840 ± 4.410 mm. The proposed method also resulted in a small CMD (1.058 ± 1.245 mm) and VOD (1.640 ± 1.777 cc). Among all patients, the MSD and RMSD were 0.433 ± 0.209 mm and 0.724 ± 0.375 mm, respectively, between ground truth and LVM volume resulting from the proposed method. CONCLUSIONS: We developed a novel deep learning-based approach for the automated segmentation of the LVM on CCTA images. We demonstrated the high accuracy of the proposed learning-based segmentation method through comparison with ground truth contour of 100 clinical patient cases using six quantitative metrics. These results show the potential of using automated LVM segmentation for computer-aided delineation of CADs in the clinical setting.

Multi-Needle Detection in 3D Ultrasound Images Using Unsupervised Order-Graph Regularized Sparse Dictionary Learning.

Accurate and automatic multi-needle detection in three-dimensional (3D) ultrasound (US) is a key step of treatment planning for US-guided brachytherapy. However, most current studies are concentrated on single-needle detection by only using a small number of images with a needle, regardless of the massive database of US images without needles. In this paper, we propose a workflow for multi-needle detection by considering the images without needles as auxiliary. Concretely, we train position-specific dictionaries on 3D overlapping patches of auxiliary images, where we develop an enhanced sparse dictionary learning method by integrating spatial continuity of 3D US, dubbed order-graph regularized dictionary learning. Using the learned dictionaries, target images are reconstructed to obtain residual pixels which are then clustered in every slice to yield centers. With the obtained centers, regions of interest (ROIs) are constructed via seeking cylinders. Finally, we detect needles by using the random sample consensus algorithm per ROI and then locate the tips by finding the sharp intensity drops along the detected axis for every needle. Extensive experiments were conducted on a phantom dataset and a prostate dataset of 70/21 patients without/with needles. Visualization and quantitative results show the effectiveness of our proposed workflow. Specifically, our method can correctly detect 95% of needles with a tip location error of 1.01 mm on the prostate dataset. This technique provides accurate multi-needle detection for US-guided HDR prostate brachytherapy, facilitating the clinical workflow.

Enhancement and Mechanism of a Lignin Amphoteric Surfactant on the Production of Cellulosic Ethanol from a High-Solid Corncob Residue.

A lignin amphoteric surfactant and betaine could enhance the enzymatic hydrolysis of lignocellulose and recover cellulase. The effects of lignosulfonate quaternary ammonium salt (SLQA) and dodecyl dimethyl betaine (BS12) on enzymatic hydrolysis digestibility, ethanol yield, yeast cell viability, and other properties of high-solid enzymatic hydrolysis and fermentation of a corncob residue were studied in this research. The results suggested that SLQA and 1 g/L BS12 effectively improved the ethanol yield through enhancing enzymatic hydrolysis. SLQA had no significant effect on the yeast cell membrane and glucose fermentation. However, 5 g/L BS12 reduced the ethanol yield as a result of the fact that 5 g/L BS12 damaged the yeast cell membrane and inhibited the conversion of glucose to ethanol. Our research also suggested that 1 g/L BS12 enhanced the ethanol yield of corncob residue fermentation, which was attributed to the fact that lignin in the corncob adsorbed BS12 and decreased its concentration in solution to a safe level for the yeast.

Ultrasound prostate segmentation based on multidirectional deeply supervised V-Net.

PURPOSE: Transrectal ultrasound (TRUS) is a versatile and real-time imaging modality that is commonly used in image-guided prostate cancer interventions (e.g., biopsy and brachytherapy). Accurate segmentation of the prostate is key to biopsy needle placement, brachytherapy treatment planning, and motion management. Manual segmentation during these interventions is time-consuming and subject to inter- and intraobserver variation. To address these drawbacks, we aimed to develop a deep learning-based method which integrates deep supervision into a three-dimensional (3D) patch-based V-Net for prostate segmentation. METHODS AND MATERIALS: We developed a multidirectional deep-learning-based method to automatically segment the prostate for ultrasound-guided radiation therapy. A 3D supervision mechanism is integrated into the V-Net stages to deal with the optimization difficulties when training a deep network with limited training data. We combine a binary cross-entropy (BCE) loss and a batch-based Dice loss into the stage-wise hybrid loss function for a deep supervision training. During the segmentation stage, the patches are extracted from the newly acquired ultrasound image as the input of the well-trained network and the well-trained network adaptively labels the prostate tissue. The final segmented prostate volume is reconstructed using patch fusion and further refined through a contour refinement processing. RESULTS: Forty-four patients' TRUS images were used to test our segmentation method. Our segmentation results were compared with the manually segmented contours (ground truth). The mean prostate volume Dice similarity coefficient (DSC), Hausdorff distance (HD), mean surface distance (MSD), and residual mean surface distance (RMSD) were 0.92 ± 0.03, 3.94 ± 1.55, 0.60 ± 0.23, and 0.90 ± 0.38 mm, respectively. CONCLUSION: We developed a novel deeply supervised deep learning-based approach with reliable contour refinement to automatically segment the TRUS prostate, demonstrated its clinical feasibility, and validated its accuracy compared to manual segmentation. The proposed technique could be a useful tool for diagnostic and therapeutic applications in prostate cancer.

Substrate curvature regulates cell migration.

Cell migration is essential in many aspects of biology. Many basic migration processes, including adhesion, membrane protrusion and tension, cytoskeletal polymerization, and contraction, have to act in concert to regulate cell migration. At the same time, substrate topography modulates these processes. In this work, we study how substrate curvature at micrometer scale regulates cell motility. We have developed a 3D mechanical model of single cell migration and simulated migration on curved substrates with different curvatures. The simulation results show that cell migration is more persistent on concave surfaces than on convex surfaces. We have further calculated analytically the cell shape and protrusion force for cells on curved substrates. We have shown that while cells spread out more on convex surfaces than on concave ones, the protrusion force magnitude in the direction of migration is larger on concave surfaces than on convex ones. These results offer a novel biomechanical explanation to substrate curvature regulation of cell migration: geometric constrains bias the direction of the protrusion force and facilitates persistent migration on concave surfaces.

Cell-ECM Interactions in Tumor Invasion.

The cancer cells obtain their invasion potential not only by genetic mutations, but also by changing their cellular biophysical and biomechanical features and adapting to the surrounding microenvironments. The extracellular matrix, as a crucial component of the tumor microenvironment, provides the mechanical support for the tissue, mediates the cell-microenvironment interactions, and plays a key role in cancer cell invasion. The biomechanics of the extracellular matrix, particularly collagen, have been extensively studied in the biomechanics community. Cell migration has also enjoyed much attention from both the experimental and modeling efforts. However, the detailed mechanistic understanding of tumor cell-ECM interactions, especially during cancer invasion, has been unclear. This chapter reviews the recent advances in the studies of ECM biomechanics, cell migration, and cell-ECM interactions in the context of cancer invasion.

[Nitrogen removal characteristics of mixed aerobic denitrification bacteria under in-situ biological inoculation].

Objective: We studied the influences of water pressure and temperature on denitrification, and detected its nitrogen removal characteristics for providing evidence to remediate the micro-polluted reservoir source water. Methods: Mixed oligotrophic aerobic denitrification bacteria was obtained through enrichment, domestication, and screening processes, which was isolated from sediment in the source water reservoir; and the nitrogen removal characteristics was detected by an in-situ biological inoculation experiment (DO at 3­8 mg/L). Results: Nitrate of the hard flask system (with water pressure influence) was removed completely, however, at 0.5, 5 m water layer, the nitrate removal rate of the soft flask reached 90.66%, 100%, other layers reached 99.61%, 80.55%, 67.01%, 64.73%. No nitrite accumulated. Because of bacteria death, ammonia had a slight increase. At the end of the experiment, in the 0.5, 5.0, 7.5, 10.0, 12.5 and 15.0 m water layer, the total nitrogen removal rates of hard flask reached 50.11%, 61.49%, 56.24%, 44.50%, 36.80% and 38.73%, however, that of soft system reached 33.47%, 60.61%, 43.98%, 36.28%, 27.52% and 28.57%. OD600 and pH first rose and then dropped. The mixed bacteria had prominent nitrogen removal ability between 11 °C and 30 °C. Conclusion: The mixed bacteria have a strong adaptability to temperature and the water pressure has a disadvantage to the nitrogen removal.

Nitrogen Removal Characteristics of a Newly Isolated Indigenous Aerobic Denitrifier from Oligotrophic Drinking Water Reservoir, Zoogloea sp. N299.

Nitrogen is considered to be one of the most widespread pollutants leading to eutrophication of freshwater ecosystems, especially in drinking water reservoirs. In this study, an oligotrophic aerobic denitrifier was isolated from drinking water reservoir sediment. Nitrogen removal performance was explored. The strain was identified by 16S rRNA gene sequence analysis as Zoogloea sp. N299. This species exhibits a periplasmic nitrate reductase gene (napA). Its specific growth rate was 0.22 h-1. Obvious denitrification and perfect nitrogen removal performances occurred when cultured in nitrate and nitrite mediums, at rates of 75.53%±1.69% and 58.65%±0.61%, respectively. The ammonia removal rate reached 44.12%±1.61% in ammonia medium. Zoogloea sp. N299 was inoculated into sterilized and unsterilized reservoir source waters with a dissolved oxygen level of 5-9 mg/L, pH 8-9, and C/N 1.14:1. The total nitrogen removal rate reached 46.41%±3.17% (sterilized) and 44.88%±4.31% (unsterilized). The cell optical density suggested the strain could survive in oligotrophic drinking water reservoir water conditions and perform nitrogen removal. Sodium acetate was the most favorable carbon source for nitrogen removal by strain N299 (p<0.05). High C/N was beneficial for nitrate reduction (p<0.05). The nitrate removal efficiencies showed no significant differences among the tested inoculums dosage (p>0.05). Furthermore, strain N299 could efficiently remove nitrate at neutral and slightly alkaline and low temperature conditions. These results, therefore, demonstrate that Zoogloea sp. N299 has high removal characteristics, and can be used as a nitrogen removal microbial inoculum with simultaneous aerobic nitrification and denitrification in a micro-polluted reservoir water ecosystem.