In Vivo MRI-Based Three-Dimensional Fluid-Structure Interaction Models and Mechanical Image Analysis for Human Carotid Atherosclerotic Plaques

Introduction. Atherosclerotic plaque rupture may occur without warning leading to severe clinical events such as heart attack and stroke. The mechanisms causing plaque rupture are not well understood. It is hypothesized that mechanical forces may play an important role in the plaque rupture process and that image-based computational mechanical analysis may provide useful information for more accurate plaque vulnerability assessment. The objectives of this dissertation are: a) develop in vivo magnetic resonance imaging (MRI)-based 3D computational models with fluid-structure Interactions (FSI) for human atherosclerotic carotid plaques; b) perform mechanical analysis using 3D FSI models to identify critical stress/strain conditions which may be used for possible plaque rupture predictions. Data, Model, and Methods. Histological, ex vivo/ in vivo MRI data of human carotid plaques were provided by the University of Washington Medical School and Washington University Medical School. Blood flow was assumed to be laminar, Newtonian, viscous and incompressible. The Navier-Stokes equations with arbitrary Lagrangian-Eulerian (ALE) formulation were used as the governing equations for the flow model. The vessel and plaque components were assumed to be hyperelastic, isotropic, nearly-incompressible and homogeneous. The nonlinear Mooney-Rivlin model was used to describe the nonlinear properties of the materials with parameter values chosen to match available experimental data. The fully-coupled FSI models were solved by a commercial finite element software ADINA to obtain full 3D flow and stress/strain distributions for analysis. Validation of the computational models and Adina software were provided by comparing computational solutions with analytic solutions and experimental data. Several novel methods were introduced to address some fundamental issues for construction of in vivo MRI-based 3D FSI models: a) an automated MRI segmentation technique using a Bayes theorem with normal probability distribution was implemented to obtain plaque geometry with enclosed components; b) a pre-shrink process was introduced to shrink the in vivo MRI geometry to obtain the no-load shape of the plaque; c) a Volume Component-Fitting Method was introduced to generate a 3D computational mesh for the plaque model with deformable complex geometry, FSI and inclusions; d) a method using MRI data obtained under in vitro pressurized conditions was introduced to determine vessel material properties. Results. The effects of material properties on flow and wall stress/strain behaviors were evaluated. The results indicate that a 100% stiffness increase may decrease maximal values of maximum principal stress (Stress-P1) and maximum principal strain (Strain-P1) by about 20% and 40%, respectively; flow Maximum-Shear-Stress (FMSS) and flow velocity did not show noticeable changes. By comparing ex vivo and in vivo data of 10 plaque samples, the average axial (25%) and inner circumferential (7.9%) shrinkages of the plaques between loaded and unloaded state were obtained. Effects of the shrink-stretch process on plaque stress/strain distributions were demonstrated based on six adjusted 3D FSI models with different shrinkages. Stress-P1 and Strain-P1 increased 349.8% and 249% respectively with 33% axial stretch. The effects of a lipid-rich necrotic core and fibrous cap thickness on structure/flow behaviors were investigated. The mean values of wall Stress-P1 and Strain-P1 from lipid nodes from a ruptured plaque were significantly higher than those from a non-ruptured plaque (112.3 kPa, 0.235 & 80.1 kPa, 0.185), which was 40.2% and 26.8% higher, respectively (p\u3c0.001). High stress/strain concentrations were found at the thin fibrous cap regions. These results indicate that high stress concentrations and thin fibrous cap thickness might be critical indicators for plaque vulnerability. Conclusion. In vivo image-based 3D FSI models and mechanical image analysis may have the potential to provide quantitative risk indicators for plaque vulnerability assessment

Segmentation of Patient-Specific 3D Cardiac Magnetic Resonance Images of Human Right Ventricle

Right Ventricular (RV) dysfunction is a common cause of heart failure in patients with congenital heart defects and often leads to impaired functional capacity and premature death. 3D cardiac magnetic resonance imaging (CMR)-based RV/LV combination models with fluid-structure interactions have been introduced to perform mechanical analysis and optimize RV remodeling surgery. Obtaining accurate RV/LV morphology is a very important step in the model-constructing process. A semi-automatic segmentation process was introduced in this project to obtain RV/LV/Valve geometry from patient-specific 3D CMR images. A total of 420 contour results were obtained from one patient CMRI data using QMASS software package at Department of Cardiology of Children¡¯s hospital. The digital contour data were automatically acquired using a self-developed program written in MATLAB. 3D visualizations of the RV/LV combination model at different phases throughout the cardiac cycle were presented and RV/LV volume curves were given showing the volume variation based on digital contour data under MATLAB environment. For the patient considered, the RV stoke volume (SV) is 190.8 ml (normal value is 60-136 ml) and ejection fraction is 43.5% (normal value is 47%-63%). In future work, the surgical, CMR imaging and computational modeling will be integrated together to optimize patch design and RV volume reduction surgery procedures to maximize recovery of RV cardiac function

Domain Generalization via Balancing Training Difficulty and Model Capability

Domain generalization (DG) aims to learn domain-generalizable models from one or multiple source domains that can perform well in unseen target domains. Despite its recent progress, most existing work suffers from the misalignment between the difficulty level of training samples and the capability of contemporarily trained models, leading to over-fitting or under-fitting in the trained generalization model. We design MoDify, a Momentum Difficulty framework that tackles the misalignment by balancing the seesaw between the model's capability and the samples' difficulties along the training process. MoDify consists of two novel designs that collaborate to fight against the misalignment while learning domain-generalizable models. The first is MoDify-based Data Augmentation which exploits an RGB Shuffle technique to generate difficulty-aware training samples on the fly. The second is MoDify-based Network Optimization which dynamically schedules the training samples for balanced and smooth learning with appropriate difficulty. Without bells and whistles, a simple implementation of MoDify achieves superior performance across multiple benchmarks. In addition, MoDify can complement existing methods as a plug-in, and it is generic and can work for different visual recognition tasks.Comment: 11 pages, 6 figures, Accepted by ICCV 202

Liver Damage in Patients with HCV/HIV Coinfection Is Linked to HIV-Related Oxidative Stress

HIV infection aggravates the progression of liver damage in HCV-coinfected patients, with the underlying pathogenesis being multifactorial. Although high level of oxidative stress has been observed frequently in patients infected with HIV or HCV, the status of oxidative stress in HIV/HCV coinfection and its contribution to HCV liver damage have not been determined. This study involved 363 HBsAg-negative, anti-HCV-positive former blood donors recruited from a village in central China in July 2005; of these, 140 were positive for HIV. Of these 363 subjects, 282 were successfully followed up through July 2009. HIV/HCV-coinfected subjects had higher rates of end-stage liver disease-related death than those monoinfected with HCV. Liver ultrasound manifestations were poor in HIV-positive than in HIV-negative individuals, in both chronic HCV carriers and those with resolved HCV. Serum concentrations of total glutathione (tGSH), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), GSSG, and reduced GSH were higher in HIV-positive than HIV-negative subjects. GSSG concentrations were higher in HIV-infected subjects with abnormal ALT/AST levels than in those with normal ALT/AST levels and were associated with poorer liver ultrasound manifestations. These finding indicated that HIV infection accelerated HCV-associated liver damage in HIV/HCV-coinfected individuals. Increased oxidative stress, induced primarily by HIV coinfection, may contribute to aggravated liver damage

An experimental study of satisfaction response: Evaluation of online collaborative learning

On the one hand, a growing amount of research discusses support for improving online collaborative learning quality, and many indicators are focused to assess its success. On the other hand, thinkLets for designing reputable and valuable collaborative processes have been developed for more than ten years. However, few studies try to apply thinkLets to online collaborative learning. This paper introduces thinkLets to online collaborative learning and experimentally tests its effectiveness with participants' responses on their satisfaction. Yield Shift Theory (YST), a causal theory explaining inner satisfaction, is adopted. In the experiment, 113 students from Universities in Beijing, China are chosen as a sample. They were divided into two groups, collaborating online in a simulated class. Then, YST in student groups under online collaborative learning is validated, a comparison study of online collaborative learning with and without thinkLets is implemented, and the satisfaction response of participants are analyzed. As a result of this comparison, YST is proved applicable in this context, and satisfaction is higher in online collaborative learning with thinkLets

Practical Parallel Algorithms for Non-Monotone Submodular Maximization

Submodular maximization has found extensive applications in various domains within the field of artificial intelligence, including but not limited to machine learning, computer vision, and natural language processing. With the increasing size of datasets in these domains, there is a pressing need to develop efficient and parallelizable algorithms for submodular maximization. One measure of the parallelizability of a submodular maximization algorithm is its adaptive complexity, which indicates the number of sequential rounds where a polynomial number of queries to the objective function can be executed in parallel. In this paper, we study the problem of non-monotone submodular maximization subject to a knapsack constraint, and propose the first combinatorial algorithm achieving an $(8+\epsilon)$-approximation under $\mathcal{O}(\log n)$ adaptive complexity, which is \textit{optimal} up to a factor of $\mathcal{O}(\log\log n)$. Moreover, we also propose the first algorithm with both provable approximation ratio and sublinear adaptive complexity for the problem of non-monotone submodular maximization subject to a $k$-system constraint. As a by-product, we show that our two algorithms can also be applied to the special case of submodular maximization subject to a cardinality constraint, and achieve performance bounds comparable with those of state-of-the-art algorithms. Finally, the effectiveness of our approach is demonstrated by extensive experiments on real-world applications.Comment: Part of the contribution appears in AAAI-202

Intraplaque hemorrhage is associated with higher structural stresses in human atherosclerotic plaques: an in vivo MRI-based 3D fluid-structure interaction study.

BACKGROUND: Studies using medical images have shown that intraplaque hemorrhage may accelerate plaque progression and may produce a stimulus for atherosclerosis development by increasing lipid core and plaque volume and creating new destabilizing factors. Image-based 3D computational models with fluid-structure interactions (FSI) will be used to perform plaque mechanical analysis and investigate possible associations between intraplaque hemorrhage and both plaque wall stress (PWS) and flow shear stress (FSS). METHODS: In vivo MRI data of carotid plaques from 5 patients with intraplaque hemorrhage confirmed by histology were acquired. 3D multi-component FSI models were constructed for each plaque to obtain mechanical stresses. Plaque Wall Stress (PWS) and Flow Shear Stress (FSS) were extracted from all nodal points on the lumen surface of each plaque for analysis. RESULTS: The mean PWS value from all hemorrhage nodes of the 5 plaques combined was higher than that from non-hemorrhage nodes (75.6 versus 68.1 kPa, P = 0.0003). The mean PWS values from hemorrhage nodes for each of the 5 plaques were all significantly higher (5 out of 5) than those from non-hemorrhage nodes (P < 0.05). The mean FSS value from all hemorrhage nodes of the 5 plaques combined was 30.4% higher than that from all non-hemorrhage nodes (15.0 versus 11.5 dyn/cm2, P = 0.0002). However, the mean flow shear stress values from individual cases showed mixed results: only one out of five plaques showed mean FSS value from hemorrhage nodes was higher than that from non-hemorrhage nodes; three out of five plaques showed that their mean FSS values from hemorrhage nodes were lower than those from non-hemorrhage nodes; and one plaque showed that the difference had no statistical significance. CONCLUSION: The results of this study suggested that intraplaque hemorrhage nodes were associated with higher plaque wall stresses. Compared to flow shear stress, plaque wall stress has a better correlation with plaque component feature (hemorrhage) linked to plaque progression and vulnerability. With further validation, plaque stress analysis may provide additional stress indicators for image-based vulnerability assessment.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

"Genotype-first" approaches on a curious case of idiopathic progressive cognitive decline

Background In developing countries, many cases with rare neurological diseases remain undiagnosed due to limited diagnostic experience. We encountered a case in China where two siblings both began to develop idiopathic progressive cognitive decline starting from age six, and were suspected to have an undiagnosed neurological disease. Methods Initial clinical assessments included review of medical history, comprehensive physical examination, genetic testing for metabolic diseases, blood tests and brain imaging. We performed exome sequencing with Agilent SureSelect exon capture and Illumina HiSeq2000 platform, followed by variant annotation and selection of rare, shared mutations that fit a recessive model of inheritance. To assess functional impacts of candidate variants, we performed extensive biochemical tests in blood and urine, and examined their possible roles by protein structure modeling. Results Exome sequencing identified NAGLU as the most likely candidate gene with compound heterozygous mutations (chr17:40695717C > T and chr17:40693129A > G in hg19 coordinate), which were documented to be pathogenic. Sanger sequencing confirmed the recessive patterns of inheritance, leading to a genetic diagnosis of Sanfilippo syndrome (mucopolysaccharidosis IIIB). Biochemical tests confirmed the complete loss of activity of alpha-N-acetylglucosaminidase (encoded by NAGLU) in blood, as well as significantly elevated dermatan sulfate and heparan sulfate in urine. Structure modeling revealed the mechanism on how the two variants affect protein structural stability. Conclusions Successful diagnosis of a rare genetic disorder with an atypical phenotypic presentation confirmed that such “genotype-first” approaches can particularly succeed in areas of the world with insufficient medical genetics expertise and with cost-prohibitive in-depth phenotyping

Semiquantum key distribution using initial states in only one basis without the classical user measuring

From the perspective of resource theory, it is interesting to achieve the same quantum task using as few quantum resources as possible. Semiquantum key distribution (SQKD), which allows a quantum user to share a confidential key with a classical user who prepares and operates qubits in only one basis, is an important example for studying this issue. To further limit the quantum resources used by users, in this paper, we constructed the first SQKD protocol which restricts the quantum user to prepare quantum states in only one basis and removes the classical user's measurement capability. Furthermore, we prove that the constructed protocol is unconditionally secure by deriving a key rate expression of the error rate in the asymptotic scenario. The work of this paper provides inspiration for achieving quantum superiority with minimal quantum resources.Comment: 13 pages, 3 figure