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1.
Article in English | MEDLINE | ID: mdl-38271164

ABSTRACT

Numerous physical objects in our daily lives are grouped or ranked according to a stereotyped presentation style. For example, in a library, books are typically grouped and ranked based on classification numbers. However, for better comparison, we often need to re-group or re-rank the books using additional attributes such as ratings, publishers, comments, publication years, keywords, prices, etc., or a combination of these factors. In this paper, we propose a novel mobile DR/MR-based application framework named DRCmpVis to achieve in-context multi-attribute comparisons of physical objects with text labels or textual information. The physical objects are scanned in the real world using mobile cameras. All scanned objects are then segmented and labeled by a convolutional neural network and replaced (diminished) by their virtual avatars in a DR environment. We formulate three visual comparison strategies, including filtering, re-grouping, and re-ranking, which can be intuitively, flexibly, and seamlessly performed on their avatars. This approach avoids breaking the original layouts of the physical objects. The computation resources in virtual space can be fully utilized to support efficient object searching and multi-attribute visual comparisons. We demonstrate the usability, expressiveness, and efficiency of DRCmpVis through a user study, NASA TLX assessment, quantitative evaluation, and case studies involving different scenarios.

2.
Med Phys ; 2023 Dec 03.
Article in English | MEDLINE | ID: mdl-38043097

ABSTRACT

BACKGROUND: Deep learning in medical applications is limited due to the low availability of large labeled, annotated, or segmented training datasets. With the insufficient data available for model training comes the inability of these networks to learn the fine nuances of the space of possible images in a given medical domain, leading to the possible suppression of important diagnostic features hence making these deep learning systems suboptimal in their performance and vulnerable to adversarial attacks. PURPOSE: We formulate a framework to address this lack of labeled data problem. We test this formulation in computed tomographic images domain and present an approach that can synthesize large sets of novel CT images at high resolution across the full Hounsfield (HU) range. METHODS: Our method only requires a small annotated dataset of lung CT from 30 patients (available online at the TCIA) and a large nonannotated dataset with high resolution CT images from 14k patients (received from NIH, not publicly available). It then converts the small annotated dataset into a large annotated dataset, using a sequence of steps including texture learning via StyleGAN, label learning via U-Net and semi-supervised learning via CycleGAN/Pixel-to-Pixel (P2P) architectures. The large annotated dataset so generated can then be used for the training of deep learning networks for medical applications. It can also be put to use for the synthesis of CT images with varied anatomies that were nonexistent within either of the input datasets, enriching the dataset even further. RESULTS: We demonstrate our framework via lung CT-Scan synthesis along with their novel generated annotations and compared it with other state of the art generative models that only produce images without annotations. We evaluate our framework effectiveness via a visual turing test with help of a few doctors and radiologists. CONCLUSIONS: We gain the capability of generating an unlimited amount of annotated CT images. Our approach works for all HU windows with minimal depreciation in anatomical plausibility and hence could be used as a general purpose framework for annotated data augmentation for deep learning applications in medical imaging.

3.
Article in English | MEDLINE | ID: mdl-37030815

ABSTRACT

In volume visualization transfer functions are widely used for mapping voxel properties to color and opacity. Typically, volume density data are scalars which require simple 1D transfer functions to achieve this mapping. If the volume densities are vectors of three channels, one can straightforwardly map each channel to either red, green or blue, which requires a trivial extension of the 1D transfer function editor. We devise a new method that applies to volume data with more than three channels. These types of data often arise in scientific scanning applications, where the data are separated into spectral bands or chemical elements. Our method expands on prior work in which a multivariate information display, RadViz, was fused with a radial color map, in order to visualize multi-band 2D images. In this work, we extend this joint interface to blended volume rendering. The information display allows users to recognize the presence and value distribution of the multivariate voxels and the joint volume rendering display visualizes their spatial distribution. We design a set of operators and lenses that allow users to interactively control the mapping of the multivariate voxels to opacity and color. This enables users to isolate or emphasize volumetric structures with desired multivariate properties. Furthermore, it turns out that our method also enables more insightful displays even for RGB data. We demonstrate our method with three datasets obtained from spectral electron microscopy, high energy X-ray scanning, and atmospheric science.

4.
Article in English | MEDLINE | ID: mdl-37028285

ABSTRACT

Multivariate datasets with many variables are increasingly common in many application areas. Most methods approach multivariate data from a singular perspective. Subspace analysis techniques, on the other hand. provide the user a set of subspaces which can be used to view the data from multiple perspectives. However, many subspace analysis methods produce a huge amount of subspaces, a number of which are usually redundant. The enormity of the number of subspaces can be overwhelming to analysts, making it difficult for them to find informative patterns in the data. In this paper, we propose a new paradigm that constructs semantically consistent subspaces. These subspaces can then be expanded into more general subspaces by ways of conventional techniques. Our framework uses the labels/meta-data of a dataset to learn the semantic meanings and associations of the attributes. We employ a neural network to learn a semantic word embedding of the attributes and then divide this attribute space into semantically consistent subspaces. The user is provided with a visual analytics interface that guides the analysis process. We show via various examples that these semantic subspaces can help organize the data and guide the user in finding interesting patterns in the dataset.

5.
IEEE Trans Vis Comput Graph ; 29(9): 3775-3787, 2023 Sep.
Article in English | MEDLINE | ID: mdl-35482700

ABSTRACT

An exemplar is an entity that represents a desirable instance in a multi-attribute configuration space. It offers certain strengths in some of its attributes without unduly compromising the strengths in other attributes. Exemplars are frequently sought after in real life applications, such as systems engineering, investment banking, drug advisory, product marketing and many others. We study a specific method for the visualization of multi-attribute configuration spaces, the Data Context Map (DCM), for its capacity in enabling users to identify proper exemplars. The DCM produces a 2D embedding where users can view the data objects in the context of the data attributes. We ask whether certain graphical enhancements can aid users to gain a better understanding of the attribute-wise tradeoffs and so select better exemplar sets. We conducted several user studies for three different graphical designs, namely iso-contour, value-shaded topographic rendering and terrain topographic rendering, and compare these with a baseline DCM display. As a benchmark we use an exemplar set generated via Pareto optimization which has similar goals but unlike humans can operate in the native high-dimensional data space. Our study finds that the two topographic maps are statistically superior to both the iso-contour and the DCM baseline display.

6.
IEEE Trans Vis Comput Graph ; 29(1): 473-482, 2023 01.
Article in English | MEDLINE | ID: mdl-36155458

ABSTRACT

With the rise of AI, algorithms have become better at learning underlying patterns from the training data including ingrained social biases based on gender, race, etc. Deployment of such algorithms to domains such as hiring, healthcare, law enforcement, etc. has raised serious concerns about fairness, accountability, trust and interpretability in machine learning algorithms. To alleviate this problem, we propose D-BIAS, a visual interactive tool that embodies human-in-the-loop AI approach for auditing and mitigating social biases from tabular datasets. It uses a graphical causal model to represent causal relationships among different features in the dataset and as a medium to inject domain knowledge. A user can detect the presence of bias against a group, say females, or a subgroup, say black females, by identifying unfair causal relationships in the causal network and using an array of fairness metrics. Thereafter, the user can mitigate bias by refining the causal model and acting on the unfair causal edges. For each interaction, say weakening/deleting a biased causal edge, the system uses a novel method to simulate a new (debiased) dataset based on the current causal model while ensuring a minimal change from the original dataset. Users can visually assess the impact of their interactions on different fairness metrics, utility metrics, data distortion, and the underlying data distribution. Once satisfied, they can download the debiased dataset and use it for any downstream application for fairer predictions. We evaluate D-BIAS by conducting experiments on 3 datasets and also a formal user study. We found that D-BIAS helps reduce bias significantly compared to the baseline debiasing approach across different fairness metrics while incurring little data distortion and a small loss in utility. Moreover, our human-in-the-loop based approach significantly outperforms an automated approach on trust, interpretability and accountability.


Subject(s)
Algorithms , Computer Graphics , Female , Humans , Causality , Machine Learning , Bias
7.
IEEE Trans Vis Comput Graph ; 29(12): 5342-5356, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36121965

ABSTRACT

Current work on using visual analytics to determine causal relations among variables has mostly been based on the concept of counterfactuals. As such the derived static causal networks do not take into account the effect of time as an indicator. However, knowing the time delay of a causal relation can be crucial as it instructs how and when actions should be taken. Yet, similar to static causality, deriving causal relations from observational time-series data, as opposed to designed experiments, is not a straightforward process. It can greatly benefit from human insight to break ties and resolve errors. We hence propose a set of visual analytics methods that allow humans to participate in the discovery of causal relations associated with windows of time delay. Specifically, we leverage a well-established method, logic-based causality, to enable analysts to test the significance of potential causes and measure their influences toward a certain effect. Furthermore, since an effect can be a cause of other effects, we allow users to aggregate different temporal cause-effect relations found with our method into a visual flow diagram to enable the discovery of temporal causal networks. To demonstrate the effectiveness of our methods we constructed a prototype system named DOMINO and showcase it via a number of case studies using real-world datasets. Finally, we also used DOMINO to conduct several evaluations with human analysts from different science domains in order to gain feedback on the utility of our system in practical scenarios.

8.
IEEE Trans Vis Comput Graph ; 29(1): 299-309, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36166525

ABSTRACT

The success of DL can be attributed to hours of parameter and architecture tuning by human experts. Neural Architecture Search (NAS) techniques aim to solve this problem by automating the search procedure for DNN architectures making it possible for non-experts to work with DNNs. Specifically, One-shot NAS techniques have recently gained popularity as they are known to reduce the search time for NAS techniques. One-Shot NAS works by training a large template network through parameter sharing which includes all the candidate NNs. This is followed by applying a procedure to rank its components through evaluating the possible candidate architectures chosen randomly. However, as these search models become increasingly powerful and diverse, they become harder to understand. Consequently, even though the search results work well, it is hard to identify search biases and control the search progression, hence a need for explainability and human-in-the-loop (HIL) One-Shot NAS. To alleviate these problems, we present NAS-Navigator, a visual analytics (VA) system aiming to solve three problems with One-Shot NAS; explainability, HIL design, and performance improvements compared to existing state-of-the-art (SOTA) techniques. NAS-Navigator gives full control of NAS back in the hands of the users while still keeping the perks of automated search, thus assisting non-expert users. Analysts can use their domain knowledge aided by cues from the interface to guide the search. Evaluation results confirm the performance of our improved One-Shot NAS algorithm is comparable to other SOTA techniques. While adding Visual Analytics (VA) using NAS-Navigator shows further improvements in search time and performance. We designed our interface in collaboration with several deep learning researchers and evaluated NAS-Navigator through a control experiment and expert interviews.

9.
IEEE Trans Vis Comput Graph ; 29(1): 712-722, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36166527

ABSTRACT

Parallel coordinate plots (PCPs) have been widely used for high-dimensional (HD) data storytelling because they allow for presenting a large number of dimensions without distortions. The axes ordering in PCP presents a particular story from the data based on the user perception of PCP polylines. Existing works focus on directly optimizing for PCP axes ordering based on some common analysis tasks like clustering, neighborhood, and correlation. However, direct optimization for PCP axes based on these common properties is restrictive because it does not account for multiple properties occurring between the axes, and for local properties that occur in small regions in the data. Also, many of these techniques do not support the human-in-the-loop (HIL) paradigm, which is crucial (i) for explainability and (ii) in cases where no single reordering scheme fits the users' goals. To alleviate these problems, we present PC-Expo, a real-time visual analytics framework for all-in-one PCP line pattern detection and axes reordering. We studied the connection of line patterns in PCPs with different data analysis tasks and datasets. PC-Expo expands prior work on PCP axes reordering by developing real-time, local detection schemes for the 12 most common analysis tasks (properties). Users can choose the story they want to present with PCPs by optimizing directly over their choice of properties. These properties can be ranked, or combined using individual weights, creating a custom optimization scheme for axes reordering. Users can control the granularity at which they want to work with their detection scheme in the data, allowing exploration of local regions. PC-Expo also supports HIL axes reordering via local-property visualization, which shows the regions of granular activity for every axis pair. Local-property visualization is helpful for PCP axes reordering based on multiple properties, when no single reordering scheme fits the user goals. A comprehensive evaluation was done with real users and diverse datasets confirm the efficacy of PC-Expo in data storytelling with PCPs.

10.
Front Surg ; 9: 881433, 2022.
Article in English | MEDLINE | ID: mdl-35711712

ABSTRACT

Background: Autologous pericardium is considered gold standard for various reconstructive surgical procedures in children. However, processed bovine, equine, and porcine pericardial tissue are also widely used. We investigated structural differences and analyzed alterations caused by industrial processing. Additionally human and equine pericardium explants, used during aortic valve reconstruction were analyzed. Methods: Pericardial tissues (native, processed and explanted) were gathered and stained with HE and EvG to visualize collagen as well as elastic fibers. Fiber structures were visualized by light and polarization microscopy. Antibody staining against CD 3, CD 20, and CD 68 was performed to identify inflammation. Results: Native pericardium of different species showed small differences in thickness, with bovine pericardium being the thickest [bovine: 390 µm (± 40.6 µm); porcine: 223 µm (± 30.1 µm); equine: 260 µm (± 28.4 µm)]. Juvenile pericardium was 277 µm (± 26.7 µm). Single collagen bundle diameter displayed variations (~3-20 µm). Parallel collagen fibers were densely packed with small inter-fibrillary space. After industrial tissue processing, loosening of collagen network with inter-fibrillary gapping was observed. Pericardium appeared thicker (mean values ranging from 257-670 µm). Processed tissue showed less birefringence under polarized light. All analyzed tissues showed a small number of elastic fibers. Fibrosis, calcification and inflammatory processes of autologous and equine pericardium were observed in patient explants. Conclusion: None of the analyzed tissues resembled the exact structure of the autologous pericardial explant. Degeneration of pericardium starts during industrial processing, suggesting a potential harm on graft longevity in children. A careful surgical approach prior to the implantation of xenografts is therefore needed.

11.
Nat Mach Intell ; 4(11): 922-929, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36935774

ABSTRACT

The metaverse integrates physical and virtual realities, enabling humans and their avatars to interact in an environment supported by technologies such as high-speed internet, virtual reality, augmented reality, mixed and extended reality, blockchain, digital twins and artificial intelligence (AI), all enriched by effectively unlimited data. The metaverse recently emerged as social media and entertainment platforms, but extension to healthcare could have a profound impact on clinical practice and human health. As a group of academic, industrial, clinical and regulatory researchers, we identify unique opportunities for metaverse approaches in the healthcare domain. A metaverse of 'medical technology and AI' (MeTAI) can facilitate the development, prototyping, evaluation, regulation, translation and refinement of AI-based medical practice, especially medical imaging-guided diagnosis and therapy. Here, we present metaverse use cases, including virtual comparative scanning, raw data sharing, augmented regulatory science and metaversed medical intervention. We discuss relevant issues on the ecosystem of the MeTAI metaverse including privacy, security and disparity. We also identify specific action items for coordinated efforts to build the MeTAI metaverse for improved healthcare quality, accessibility, cost-effectiveness and patient satisfaction.

12.
IEEE Trans Vis Comput Graph ; 28(12): 4728-4740, 2022 Dec.
Article in English | MEDLINE | ID: mdl-34347601

ABSTRACT

The widespread adoption of algorithmic decision-making systems has brought about the necessity to interpret the reasoning behind these decisions. The majority of these systems are complex black box models, and auxiliary models are often used to approximate and then explain their behavior. However, recent research suggests that such explanations are not overly accessible to lay users with no specific expertise in machine learning and this can lead to an incorrect interpretation of the underlying model. In this article, we show that a predictive and interactive model based on causality is inherently interpretable, does not require any auxiliary model, and allows both expert and non-expert users to understand the model comprehensively. To demonstrate our method we developed Outcome Explorer, a causality guided interactive interface, and evaluated it by conducting think-aloud sessions with three expert users and a user study with 18 non-expert users. All three expert users found our tool to be comprehensive in supporting their explanation needs while the non-expert users were able to understand the inner workings of a model easily.

13.
Interact Cardiovasc Thorac Surg ; 33(6): 969-977, 2021 11 22.
Article in English | MEDLINE | ID: mdl-34252191

ABSTRACT

OBJECTIVES: We aim to investigate the impact of cardiac fibrosis and collagens on right ventricular failure (RVF) and acute kidney injury (AKI) in patients receiving continuous flow left ventricular assist devices. METHODS: Heart tissues from 34 patients were obtained from continuous flow left ventricular assist device insertion sites and corresponding clinical data were collected. The participants were divided into 2 groups according to the extent of the cardiac fibrosis or collagens. RESULTS: Overall, 18 patients developed RVF with 14 receiving right ventricular assist device (RVAD), and 22 patients developed AKI with 12 needing new-onset renal replacement therapy. Higher collagen I (Col1) was significantly associated with increased incidences of RVF (76.5% vs 29.4%, P = 0.015), RVAD support (64.7% vs 17.6%, P = 0.013) and stage 3 AKI (58.8% vs 17.6%, P = 0.032), and patients with higher Col1 were more prone to renal replacement therapy (52.9% vs 17.6%, P = 0.071). Receiver operating characteristic curves showed that Col1 had good predictive effects on RVF [area under the curve (AUC) = 0.806, P = 0.002], RVAD support (AUC = 0.789, P = 0.005), stage 3 AKI (AUC = 0.740, P = 0.020) and renal replacement therapy (AUC = 0.731, P = 0.028) after continuous-flow left ventricular assist device. Moreover, patients with higher Col1 had significantly longer postoperative duration of mechanical ventilation, duration of intensive care unit stay and hospital length of stay (all P < 0.05). Cardiac fibrosis, collagen III (Col3) and Col1/Col3 shared similar results or trends with Col1. CONCLUSIONS: Cardiac fibrosis and related collagens in the apical left ventricular tissue are associated with increased risks of RVF, RVAD use and worse renal function. Further study is warranted owing to the small sample size.


Subject(s)
Acute Kidney Injury , Heart Failure , Heart-Assist Devices , Ventricular Dysfunction, Right , Acute Kidney Injury/diagnosis , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Collagen , Fibrosis , Heart Failure/diagnosis , Heart Failure/etiology , Heart Failure/therapy , Heart-Assist Devices/adverse effects , Humans , Retrospective Studies
14.
J Physiol ; 599(9): 2435-2451, 2021 05.
Article in English | MEDLINE | ID: mdl-31696938

ABSTRACT

KEY POINTS: Two groups of inexperienced brain-computer interface users underwent a purely mental EEG-BCI session that rapidly impacted on their brain. Modulations in structural and functional MRI were found after only 1 h of BCI training. Two different types of BCI (based on motor imagery or visually evoked potentials) were employed and analyses showed that the brain plastic changes are spatially specific for the respective neurofeedback. This spatial specificity promises tailored therapeutic interventions (e.g. for stroke patients). ABSTRACT: A brain-computer-interface (BCI) allows humans to control computational devices using only neural signals. However, it is still an open question, whether performing BCI also impacts on the brain itself, i.e. whether brain plasticity is induced. Here, we show rapid and spatially specific signs of brain plasticity measured with functional and structural MRI after only 1 h of purely mental BCI training in BCI-naive subjects. We employed two BCI approaches with neurofeedback based on (i) modulations of EEG rhythms by motor imagery (MI-BCI) or (ii) event-related potentials elicited by visually targeting flashing letters (ERP-BCI). Before and after the BCI session we performed structural and functional MRI. For both BCI approaches we found increased T1-weighted MR signal in the grey matter of the respective target brain regions, such as occipital/parietal areas after ERP-BCI and precuneus and sensorimotor regions after MI-BCI. The latter also showed increased functional connectivity and higher task-evoked BOLD activity in the same areas. Our results demonstrate for the first time that BCI by means of targeted neurofeedback rapidly impacts on MRI measures of brain structure and function. The spatial specificity of BCI-induced brain plasticity promises therapeutic interventions tailored to individual functional deficits, for example in patients after stroke.


Subject(s)
Brain-Computer Interfaces , Neurofeedback , Brain/diagnostic imaging , Electroencephalography , Humans , Imagination , Neuronal Plasticity
15.
IEEE Trans Biomed Eng ; 67(12): 3317-3326, 2020 12.
Article in English | MEDLINE | ID: mdl-32305886

ABSTRACT

OBJECTIVE: According to the European Reference Organization for Quality Assured Breast Cancer Screening and Diagnostic Services (EUREF) image quality in mammography is assessed by recording and analyzing a set of images of the CDMAM phantom. The EUREF procedure applies an automated analysis combining image registration, signal detection and nonlinear fitting. We present a proof of concept for an end-to-end deep learning framework that assesses image quality on the basis of single images as an alternative. METHODS: Virtual mammography is used to generate a database with known ground truth for training a regression convolutional neural net (CNN). Training is carried out by continuously extending the training data and applying transfer learning. RESULTS: The trained net is shown to correctly predict the image quality of simulated and real images. Specifically, image quality predictions on the basis of single images are of similar quality as those obtained by applying the EUREF procedure with 16 images. Our results suggest that the trained CNN generalizes well. CONCLUSION: Mammography image quality assessment can benefit from the proposed deep learning approach. SIGNIFICANCE: Deep learning avoids cumbersome pre-processing and allows mammography image quality to be estimated reliably using single images.


Subject(s)
Breast Neoplasms , Deep Learning , Breast Neoplasms/diagnostic imaging , Female , Humans , Image Processing, Computer-Assisted , Mammography , Neural Networks, Computer , Phantoms, Imaging
16.
IEEE Trans Vis Comput Graph ; 26(4): 1650-1660, 2020 04.
Article in English | MEDLINE | ID: mdl-32031940

ABSTRACT

The formation of social groups is defined by the interactions among the group members. Studying this group formation process can be useful in understanding the status of members, decision-making behaviors, spread of knowledge and diseases, and much more. A defining characteristic of these groups is the pecking order or hierarchy the members form which help groups work towards their goals. One area of social science deals with understanding the formation and maintenance of these hierarchies, and in our work we provide social scientists with a visual analytics tool - PeckVis - to aid this process. While online social groups or social networks have been studied deeply and lead to a variety of analyses and visualization tools, the study of smaller groups in the field of social science lacks the support of suitable tools. Domain experts believe that visualizing their data can save them time as well as reveal findings they may have failed to observe. We worked alongside domain experts to build an interactive visual analytics system to investigate social hierarchies. Our system can discover patterns and relationships between the members of a group as well as compare different groups. The results are presented to the user in the form of an interactive visual analytics dashboard. We demonstrate that domain experts were able to effectively use our tool to analyze animal behavior data.

17.
IEEE Trans Vis Comput Graph ; 26(9): 2875-2890, 2020 09.
Article in English | MEDLINE | ID: mdl-30735999

ABSTRACT

Organizing multivariate data spaces by their dimensions or attributes can be a rather difficult task. Most of the work in this area focuses on the statistical aspects such as correlation clustering, dimension reduction, and the like. These methods typically produce hierarchies in which the leaf nodes are labeled by the attribute names while the inner nodes are often represented by just a statistical measure and criterion, such as a threshold. This makes them difficult to understand for mainstream users. Taxonomies in science, biology, engineering, etc. on the other hand, are easy to comprehend since they provide meaningful labels at the inner nodes as well. Labeling inner nodes of taxonomies automatically requires the identification of hypernyms. Our proposed framework, called Taxonomizer, takes a visual analytics approach to meet this challenge. It appeals to the wisdom of humans to liaise with state of the art data analytics, neural word embeddings, and lexical databases. It consists of a set of visual tools that starts out with an automatically computed hierarchy where the leaf nodes are the original data attributes, and it then allows users to sculpt high-quality taxonomies for any multivariate dataset.

18.
J Exp Clin Cancer Res ; 38(1): 434, 2019 Oct 29.
Article in English | MEDLINE | ID: mdl-31665089

ABSTRACT

BACKGROUND: Breast cancer (BC) is the most frequent malignant tumor in females and the 2nd most common cause of brain metastasis (BM), that are associated with a fatal prognosis. The increasing incidence from 10% up to 40% is due to more effective treatments of extracerebral sites with improved prognosis and increasing use of MRI in diagnostics. A frequently administered, potent chemotherapeutic group of drugs for BC treatment are taxanes usually used in the adjuvant and metastatic setting, which, however, have been suspected to be associated with a higher incidence of BM. The aim of our study was to experimentally analyze the impact of the taxane docetaxel (DTX) on brain metastasis formation, and to elucidate the underlying molecular mechanism. METHODS: A monocentric patient cohort was analyzed to determine the association of taxane treatment and BM formation. To identify the specific impact of DTX, a murine brain metastatic model upon intracardial injection of breast cancer cells was conducted. To approach the functional mechanism, dynamic contrast-enhanced MRI and electron microscopy of mice as well as in-vitro transendothelial electrical resistance (TEER) and tracer permeability assays using brain endothelial cells (EC) were carried out. PCR-based, immunohistochemical and immunoblotting analyses with additional RNA sequencing of murine and human ECs were performed to explore the molecular mechanisms by DTX treatment. RESULTS: Taxane treatment was associated with an increased rate of BM formation in the patient cohort and the murine metastatic model. Functional studies did not show unequivocal alterations of blood-brain barrier properties upon DTX treatment in-vivo, but in-vitro assays revealed a temporary DTX-related barrier disruption. We found disturbance of tubulin structure and upregulation of tight junction marker claudin-5 in ECs. Furthermore, upregulation of several members of the tubulin family and downregulation of tetraspanin-2 in both, murine and human ECs, was induced. CONCLUSION: In summary, a higher incidence of BM was associated with prior taxane treatment in both a patient cohort and a murine mouse model. We could identify tubulin family members and tetraspanin-2 as potential contributors for the destabilization of the blood-brain barrier. Further analyses are needed to decipher the exact role of those alterations on tumor metastatic processes in the brain.


Subject(s)
Antineoplastic Agents/administration & dosage , Blood-Brain Barrier/drug effects , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/secondary , Breast Neoplasms/drug therapy , Docetaxel/administration & dosage , Animals , Antineoplastic Agents/pharmacokinetics , Brain Neoplasms/genetics , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/genetics , Cell Line, Tumor , Claudin-5/genetics , Docetaxel/pharmacokinetics , Female , Gene Expression Profiling , Gene Expression Regulation, Neoplastic/drug effects , Humans , Magnetic Resonance Imaging , Mice , Microscopy, Electron , Sequence Analysis, RNA , Tubulin/genetics , Xenograft Model Antitumor Assays
19.
IEEE Trans Vis Comput Graph ; 25(11): 3049, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31581072

ABSTRACT

Welcome to the November 2019 issue of the IEEE Transactions on Visualization and Computer Graphics (TVCG). This issue contains selected papers accepted at the IEEE International Symposium on Mixed and Augmented Reality (ISMAR), held this year in Beijing, China from October 14 to October 18, 2019.

20.
Eur J Cardiothorac Surg ; 56(6): 1154-1161, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31280306

ABSTRACT

OBJECTIVES: Currently, Contegra® grafts (processed bovine jugular vein conduits) are widely used for reconstructive surgery of the right ventricular outflow tract in patients with congenital heart disease (CHD). We analysed explanted Contegra conduits from 2 institutions histologically to get a possible hint at the underlying pathomechanisms of degenerative alterations and to find histological correlations of graft failure. Additionally, we compared the explants with a non-implanted processed graft and a native jugular vein obtained from a young bull. METHODS: The explanted Contegra grafts were gathered during reoperations of 13 patients (male: n = 9, 69.2%; female: n = 4, 30.8%). After standardized histological preparation, samples were stained with dyes haematoxylin and eosin and Elastica van Gieson. Additionally, X-ray pictures revealed the extent of calcification and chelaplex (III)-descaling agent was used to decalcify selected explants. RESULTS: Processing of the native jugular vein leads to tissue loosening and a loss of elastic fibres. For graft failure after implantation, 2 pathomechanisms were identified: original graft alteration as well as intimal hyperplasia. Elastica degeneration and rearrangement with interfibrillary matrix structures were the main developments observed within the graft itself. Intimal hyperplasia was characterized by fibrous tissue apposition, calcification and heterotopic ossification. CONCLUSIONS: Regression of the elastic fibre network leads to rigidification of the conduit. In Contegra grafts, atherosclerosis-like changes can be considered the leading cause of graft stenosis and insufficiency. We conclude that both observed mechanisms lead to early reoperation in CHD patients.


Subject(s)
Bioprosthesis/adverse effects , Blood Vessel Prosthesis/adverse effects , Prosthesis Failure , Tunica Intima/pathology , Adolescent , Animals , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Cattle , Child , Child, Preschool , Device Removal , Female , Heart Defects, Congenital/surgery , Humans , Hyperplasia/etiology , Hyperplasia/pathology , Infant , Male , Rubber , Ventricular Outflow Obstruction/surgery
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