602 results on '"Kurtcuoglu, Vartan"'
Search Results
102. Computational modeling of coupled blood-wall mass transport of LDL: effects of local wall shear stress
- Author
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Olgac, Ufuk, Kurtcuoglu, Vartan, and Poulikakos, Dimos
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Low density lipoproteins -- Research ,Vascular endothelium -- Research ,Epithelial cells -- Research ,Blood lipids -- Research ,Atherosclerosis -- Research ,Cardiovascular research ,Biological sciences - Abstract
The work herein represents a novel approach for the modeling of low-density lipoprotein (LDL) transport from the artery lumen into the arterial wall, taking into account the effects of local wall shear stress (WSS) on the endothelial cell layer and its pathways of volume and solute flux. We have simulated LDL transport in an axisymmetric representation of a stenosed coronary artery, where the endothelium is represented by a three-pore model that takes into account the contributions of the vesicular pathway, normal junctions, and leaky junctions also employing the local WSS to yield the overall volume and solute flux. The fraction of leaky junctions is calculated as a function of the local WSS based on published experimental data and is used in conjunction with the pore theory to determine the transport properties of this pathway. We have found elevated levels of solute flux at low shear stress regions because of the presence of a larger number of leaky junctions compared with high shear stress regions. Accordingly, we were able to observe high LDL concentrations in the arterial wall in these low shear stress regions despite increased filtration velocity, indicating that the increase in filtration velocity is not sufficient for the convective removal of LDL. low-density lipoprotein transport; lipid accumulation; atherosclerosis; leaky junction
- Published
- 2008
103. RAQ: a novel surrogate for the craniospinal pressure-volume relationship
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Spiegelberg, Andreas, Krause, Matthias, Meixensberger, Juergen, Kurtcuoglu, Vartan, and University of Zurich
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2737 Physiology (medical) ,10076 Center for Integrative Human Physiology ,570 Life sciences ,biology ,2204 Biomedical Engineering ,610 Medicine & health ,1314 Physiology ,10064 Neuroscience Center Zurich ,10052 Institute of Physiology ,1304 Biophysics - Published
- 2020
104. Mixing and modes of mass transfer in the third cerebral ventricle: a computational analysis
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Kurtcuoglu, Vartan, Soellinger, Michaela, Summers, Paul, Poulikakos, Dimos, and Boesiger, Peter
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Mass transfer -- Evaluation ,Fluid dynamics -- Research ,Biomechanics -- Research ,Brain -- Ventricles ,Brain -- Properties ,Engineering and manufacturing industries ,Science and technology - Abstract
Anatomic, velocimetric, and brain motion MRI scans were combined with a computational fluid dynamics model to investigate cerebrospinal fluid (CSF) mixing in the third cerebral ventricle of a healthy male adult. It was found that advection dominates over diffusion in most of the third ventricle. Three zones where diffusion plays an important role in the mixing process were identified. One of these zones, consisting of recessus infundibulus, recessus opticus and the adjacent regions up to commissura anterior, is likely to exist in the general population. We hypothesize that this zone may act as a buffer to flatten concentration peaks of pituitary gland hormones released into the CSF of the third ventricle. We further hypothesize that this zone may facilitate the communication between hypothalamus and the pituitary gland through the third ventricle cerebrospinal fluid by prolonging residence times of the communicated hormones. [DOI: 10.1115/1.2768376]
- Published
- 2007
105. Radiomics approach to quantify shape irregularity from crowd-based qualitative assessment of intracranial aneurysms
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Juchler, Norman, Schilling, Sabine, Glüge, Stefan, Bijlenga, Philippe, Rüfenacht, Daniel, Kurtcuoglu, Vartan, Hirsch, Sven, Juchler, Norman, Schilling, Sabine, Glüge, Stefan, Bijlenga, Philippe, Rüfenacht, Daniel, Kurtcuoglu, Vartan, and Hirsch, Sven
- Abstract
This is an Accepted Manuscript of an article published by Taylor & Francis in Computer Methods in Biomechanics and Biomedical Engineering : Imaging & Visualization on 17.03.2020, available online: https://www.tandfonline.com/doi/full/10.1080/21681163.2020.1728579, The morphological assessment of anatomical structures is clinically relevant, but often falls short of quantitative or standardised criteria. Whilst human observers are able to assess morphological characteristics qualitatively, the development of robust shape features remains challenging. In this study, we employ psychometric and radiomic methods to develop quantitative models of the perceived irregularity of intracranial aneurysms (IAs). First, we collect morphological characteristics (e.g. irregularity, asymmetry) in imaging-derived data and aggregated the data using rank-based analysis. Second, we compute regression models relating quantitative shape features to the aggregated qualitative ratings (ordinal or binary). We apply our method for quantifying perceived shape irregularity to a dataset of 134 IAs using a pool of 179 different shape indices. Ratings given by 39 participants show good agreement with the aggregated ratings (Spearman rank correlation ρSp=0.84). The best-performing regression model based on quantitative shape features predicts the perceived irregularity with R2:0.84±0.05.
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- 2020
106. Extending statistical learning for aneurysm rupture assessment to Finnish and Japanese populations using morphology, hemodynamics, and patient characteristics
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Detmer, Felicitas J., Hadad, Sara, Chung, Bong Jae, Mut, Fernando, Slawski, Martin, Juchler, Norman, Kurtcuoglu, Vartan, Hirsch, Sven, Bijlenga, Philippe, Uchiyama, Yuya, Fujimura, Soichiro, Yamamoto, Makoto, Murayama, Yuichi, Takao, Hiroyuki, Koivisto, Timo, Frösen, Juhana, Cebral, Juan R., Detmer, Felicitas J., Hadad, Sara, Chung, Bong Jae, Mut, Fernando, Slawski, Martin, Juchler, Norman, Kurtcuoglu, Vartan, Hirsch, Sven, Bijlenga, Philippe, Uchiyama, Yuya, Fujimura, Soichiro, Yamamoto, Makoto, Murayama, Yuichi, Takao, Hiroyuki, Koivisto, Timo, Frösen, Juhana, and Cebral, Juan R.
- Abstract
OBJECTIVE: Incidental aneurysms pose a challenge for physicians, who need to weigh the rupture risk against the risks associated with treatment and its complications. A statistical model could potentially support such treatment decisions. A recently developed aneurysm rupture probability model performed well in the US data used for model training and in data from two European cohorts for external validation. Because Japanese and Finnish patients are known to have a higher aneurysm rupture risk, the authors’ goals in the present study were to evaluate this model using data from Japanese and Finnish patients and to compare it with new models trained with Finnish and Japanese data. METHODS: Patient and image data on 2129 aneurysms in 1472 patients were used. Of these aneurysm cases, 1631 had been collected mainly from US hospitals, 249 from European (other than Finnish) hospitals, 147 from Japanese hospitals, and 102 from Finnish hospitals. Computational fluid dynamics simulations and shape analyses were conducted to quantitatively characterize each aneurysm’s shape and hemodynamics. Next, the previously developed model’s discrimination was evaluated using the Finnish and Japanese data in terms of the area under the receiver operating characteristic curve (AUC). Models with and without interaction terms between patient population and aneurysm characteristics were trained and evaluated including data from all four cohorts obtained by repeatedly randomly splitting the data into training and test data. RESULTS: The US model’s AUC was reduced to 0.70 and 0.72, respectively, in the Finnish and Japanese data compared to 0.82 and 0.86 in the European and US data. When training the model with Japanese and Finnish data, the average AUC increased only slightly for the Finnish sample (to 0.76 ± 0.16) and Finnish and Japanese cases combined (from 0.74 to 0.75 ± 0.14) and decreased for the Japanese data (to 0.66 ± 0.33). In models including interaction terms, the AUC in the Finnish
- Published
- 2020
107. X-ray phase tomography with near-field speckles for three-dimensional virtual histology
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Zdora, Marie-Christine; https://orcid.org/0000-0001-6953-6709, Thibault, Pierre, Kuo, Willy, Fernandez, Vincent, Deyhle, Hans, Vila-Comamala, Joan, Olbinado, Margie P, Rack, Alexander; https://orcid.org/0000-0001-9486-3621, Lackie, Peter M, Katsamenis, Orestis L, Lawson, Matthew J, Kurtcuoglu, Vartan, Rau, Christoph, Pfeiffer, Franz, Zanette, Irene, Zdora, Marie-Christine; https://orcid.org/0000-0001-6953-6709, Thibault, Pierre, Kuo, Willy, Fernandez, Vincent, Deyhle, Hans, Vila-Comamala, Joan, Olbinado, Margie P, Rack, Alexander; https://orcid.org/0000-0001-9486-3621, Lackie, Peter M, Katsamenis, Orestis L, Lawson, Matthew J, Kurtcuoglu, Vartan, Rau, Christoph, Pfeiffer, Franz, and Zanette, Irene
- Abstract
High-contrast, high-resolution imaging of biomedical specimens is indispensable for studying organ function and pathologies. Conventional histology, the gold standard for soft-tissue visualization, is limited by its anisotropic spatial resolution, elaborate sample preparation, and lack of quantitative image information. X-ray absorption or phase tomography have been identified as promising alternatives enabling non-destructive, distortion-free three-dimensional (3D) imaging. However, reaching sufficient contrast and resolution with a simple experimental procedure remains a major challenge. Here, we present a solution based on x-ray phase tomography through speckle-based imaging (SBI). We demonstrate on a mouse kidney that SBI delivers comprehensive 3D maps of hydrated, unstained soft tissue, revealing its microstructure and delivering quantitative tissue-density values at a density resolution of better than 2mg/cm3 and spatial resolution of better than 8 µm. We expect that SBI virtual histology will find widespread application in biomedicine and will open up new possibilities for research and histopathology.
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- 2020
108. Shape irregularity of the intracranial aneurysm lumen exhibits diagnostic value
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Juchler, Norman; https://orcid.org/0000-0001-8518-7211, Schilling, Sabine, Bijlenga, Philippe, Morel, Sandrine, Rüfenacht, Daniel, Kurtcuoglu, Vartan, Hirsch, Sven, Juchler, Norman; https://orcid.org/0000-0001-8518-7211, Schilling, Sabine, Bijlenga, Philippe, Morel, Sandrine, Rüfenacht, Daniel, Kurtcuoglu, Vartan, and Hirsch, Sven
- Abstract
BACKGROUND Morphological irregularity is linked to intracranial aneurysm wall instability and manifests in the lumen shape. Yet there is currently no consent on how to assess shape irregularity. The aims of this work are to quantify irregularity as perceived by clinicians, to break down irregularity into morphological attributes, and to relate these to clinically relevant factors such as rupture status, aneurysm location, and patient age or sex. METHODS Thirteen clinicians and 26 laypersons assessed 134 aneurysm lumen segmentations in terms of overall perceived irregularity and five different morphological attributes (presence/absence of a rough surface, blebs, lobules, asymmetry, complex geometry of the parent vasculature). We examined rater agreement and compared the ratings with clinical factors by means of regression analysis or binary classification. RESULTS Using rank-based aggregation, the irregularity ratings of clinicians and laypersons did not differ statistically. Perceived irregularity showed good agreement with curvature (coefficient of determination R$^{2}$ = 0.68 ± 0.08) and was modeled very accurately using the five morphological rating attributes plus shape elongation (R$^{2}$ = 0.95 ± 0.02). In agreement with previous studies, irregularity was associated with aneurysm rupture status (AUC = 0.81 ± 0.08); adding aneurysm location as an explanatory variable increased the AUC to 0.87 ± 0.09. Besides irregularity, perceived asymmetry, presence of blebs or lobules, aneurysm size, non-sphericity, and curvature were linked to rupture. No association was found between morphology and any of patient sex, age, and history of smoking or hypertension. Aneurysm size was linked to morphology. CONCLUSIONS Irregular lumen shape carries significant information on the aneurysm's disease status. Irregularity constitutes a continuous parameter that shows a strong association with the rupture status. To improve the objectivity of morphological assessment, we suggest exam
- Published
- 2020
109. Computational investigation of subject-specific cerebrospinal fluid flow in the third ventricle and aqueduct of Sylvius
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Kurtcuoglu, Vartan, Soellinger, Michaela, Summers, Paul, Boomsma, Kevin, Poulikakos, Dimos, Boesiger, Peter, and Ventikos, Yiannis
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- 2007
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110. Computational modeling of the mechanical behavior of cerebrospinal fluid system
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Kurtcuoglu, Vartan, Poulikakos, Dimos, and Ventikos, Yiannis
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Brain tissue transplantation -- Research ,Cerebrospinal fluid -- Research ,Brain -- Ventricles ,Brain -- Research ,Engineering and manufacturing industries ,Science and technology - Abstract
A computational fluid dynamics (CFD) model of the cerebrospinal fluid system was constructed based on a simplified geometry of the brain ventricles and their connecting pathways. The flow is driven by a prescribed sinusoidal motion of the third ventricle lateral walls, with all other boundaries being rigid. The pressure propagation between the third and lateral ventricles was examined and compared to data obtained from a similar geometry with a stenosed aqueduct. It could be shown that the pressure amplitude in the lateral ventricles increases in the presence of aqueduct stenosis. No difference in phase shift between the motion of the third ventricle walls and the pressure in the lateral ventricles because of the aqueduct stenosis could be observed. It is deduced that CFD can be used to analyze the pressure propagation and its phase shift relative to the ventricle wall motion. It is further deduced that only models that take into account the coupling between ventricles, which feature a representation of the original geometry that is as accurate as possible and which represent the ventricle boundary motion realistically, should be used to make quantitative statements on flow and pressure in the ventricular space. [DOI: 10.1115/1.1865191]
- Published
- 2005
111. Computational Fluid Dynamics for the Assessment of Cerebrospinal Fluid Flow and Its Coupling with Cerebral Blood Flow
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Kurtcuoglu, Vartan, primary
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- 2011
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112. Identification of Atherosclerotic Lesion-Prone Sites through Patient-Specific Simulation of Low-Density Lipoprotein Accumulation
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Olgac, Ufuk, primary, Kurtcuoglu, Vartan, additional, Saur, Stefan C., additional, and Poulikakos, Dimos, additional
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- 2008
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113. X-ray phase tomography with near-field speckles for three-dimensional virtual histology
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Zdora, Marie-Christine, primary, Thibault, Pierre, additional, Kuo, Willy, additional, Fernandez, Vincent, additional, Deyhle, Hans, additional, Vila-Comamala, Joan, additional, Olbinado, Margie P., additional, Rack, Alexander, additional, Lackie, Peter M., additional, Katsamenis, Orestis L., additional, Lawson, Matthew J., additional, Kurtcuoglu, Vartan, additional, Rau, Christoph, additional, Pfeiffer, Franz, additional, and Zanette, Irene, additional
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- 2020
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114. RAQ: a novel surrogate for the craniospinal pressure–volume relationship
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Spiegelberg, Andreas, primary, Krause, Matthias, additional, Meixensberger, Juergen, additional, and Kurtcuoglu, Vartan, additional
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- 2020
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115. Radiomics approach to quantify shape irregularity from crowd-based qualitative assessment of intracranial aneurysms
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Juchler, Norman, primary, Schilling, Sabine, additional, Glüge, Stefan, additional, Bijlenga, Philippe, additional, Rüfenacht, Daniel, additional, Kurtcuoglu, Vartan, additional, and Hirsch, Sven, additional
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- 2020
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116. Crosslinkable polymeric contrast agent for high-resolution X-ray imaging of the vascular system
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Le, Ngoc An, primary, Kuo, Willy, additional, Müller, Bert, additional, Kurtcuoglu, Vartan, additional, and Spingler, Bernhard, additional
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- 2020
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117. Long-term follow-up, computed tomography, and computational fluid dynamics of the Cabrol procedure
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Knight, Joseph, Baumüller, Stephan, Kurtcuoglu, Vartan, Turina, Marko, Turina, Juraj, Schurr, Ulrich, Poulikakos, Dimos, Marshall, William, Jr., and Alkadhi, Hatem
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- 2010
118. Analysis of L-leucine amino acid transporter species activity and gene expression by human blood brain barrier hCMEC/D3 model reveal potential LAT1, LAT4, B 0 AT2 and y + LAT1 functional cooperation.
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Taslimifar, Mehdi, Faltys, Martin, Kurtcuoglu, Vartan, Verrey, François, and Makrides, Victoria
- Abstract
In the CNS, amino acid (AA) neurotransmitters and neurotransmitter precursors are subject to tight homeostatic control mediated by blood-brain barrier (BBB) solute carrier amino acid transporters (AATs). Since the BBB is composed of multiple closely apposed cell types and opportunities for human in vivo studies are limited, we used in vitro and computational approaches to investigate human BBB AAT activity and regulation. Quantitative real-time PCR (qPCR) of the human BBB endothelial cell model hCMEC/D3 (D3) was used to determine expression of selected AAT, tight junction (TJ), and signal transduction (ST) genes under various culture conditions. L-leucine uptake data were interrogated with a computational model developed by our group for calculating AAT activity in complex cell cultures. This approach is potentially applicable to in vitro cell culture drug studies where multiple "receptors" may mediate observed responses. Of 7 Leu AAT genes expressed by D3 only the activity of SLC7A5-SLC3A2/LAT1-4F2HC (LAT1), SLC43A2/LAT4 (LAT4) and sodium-dependent AATs, SLC6A15/B
0 AT2 (B0 AT2), and SLC7A7/y+ LAT1 (y+ LAT1) were calculated to be required for Leu uptake. Therefore, D3 Leu transport may be mediated by a potentially physiologically relevant functional cooperation between the known BBB AAT, LAT1 and obligatory exchange (y+ LAT1), facilitative diffusion (LAT4), and sodium symporter (B0 AT2) transporters. [ABSTRACT FROM AUTHOR]- Published
- 2022
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119. Identification of clinically relevant characteristics of intracranial aneurysm morphology
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Juchler, Norman, Schilling, Sabine, Bijlenga, Philippe, Rüfenacht, Daniel, Kurtcuoglu, Vartan, and Hirsch, Sven
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Morphology ,616.8: Neurologie und Krankheiten des Nervensystems ,Intracranial aneurysms - Abstract
Intracranial aneurysms are focal deformations of larger cerebral arteries that occur in 2-5% of the population. Although they remain quiescent most of the time, aneurysms may rupture at a rate of about 1% per year, leading to subarachnoid hemorrhage with potentially catastrophic effects on the patient. It is exceedingly challenging to predict the clinical fate of intracranial aneurysms. Currently, physicians associate shape irregularity with vessel wall instability. However, there is no consensus on which shape features reliably predict aneurysm rupture. Here we present two approaches that aim to eliminate the subjectivity of rater assessment. In a first approach, we have implemented a semi-automated classification pipeline to predict the rupture status using morphometric parameters. These parameters were computed from 3D geometries of intracranial aneurysms obtained from 3D rotational angiographies. The main objective of this first study was to identify morphometric parameters that efficiently encode the disease status and understand how well morphology predicts disease status in general. In the second study, we followed a psychometric approach to better understand how human raters assess aneurysm morphology. We acquired rating data from 39 clinical experts and informed laypersons on perceived irregularity and the presence of 5 different morphological attributes (presence of a rough surface, of blebs, lobules, asymmetry and a complex parent vasculature). We related this data to clinically relevant parameters using regression analysis and binary classification. Our investigations confirmed that aneurysm morphology provides significant information about the disease. For example, a logistic regression model based on perceived irregularity alone is able to discriminate relatively well ruptured from unruptured aneurysms (AUC=0.81±0.04). Extending that model by aneurysm location increased the AUC significantly to 0.87±0.08, suggesting that morphology varies with location. Morphometric parameters well correlating to perceived irregularity (e.g. non-sphericity NSI, or total Gaussian curvature GLN) likewise predict the disease status well, but to a lesser extent. More specific parameters are required that are able to encode relevant morphological structure such as blebs/lobules or asymmetry.
- Published
- 2019
120. Understanding morphological irregularity : a rater-based study
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Juchler, Norman, Schilling, Sabine, Bijlenga, Philippe, Rüfenacht, Daniel, Kurtcuoglu, Vartan, and Hirsch, Sven
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Morphology ,610: Medizin und Gesundheit ,Intracranial aneurysms - Abstract
The shape of intracranial aneurysms is used by clinicians for risk assessment. It has been suggested that irregular shape is linked to degenerate wall conditions and rupture. With the goal to better characterize shape irregularity, we acquired rating data of 27 participants (9 clinical experts, 18 laypersons) that assessed 134 aneurysms for perceived irregularity. 9 raters additionally examined the presence of 5 morphological attributes. Alongside with quantitative metrics for morphology, we used this rating data to model perceived irregularity. Preliminary results suggest that a combination of quantitative and qualitative shape assessment may characterize perceived irregularity the best.
- Published
- 2019
121. Integrated flow chamber device for live cell microscopy
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Kriesi, Carlo, Steinert, Martin, Marmaras, Anastasios, Danzer, Claudia, Meskenaite, Virginia, and Kurtcuoglu, Vartan
- Abstract
In vitro quantification of the effect of mechanical loads on cells by live microscopy requires precise control of load and culture environment. Corresponding systems are often bulky, their setup and maintenance are time consuming, or the cell yield is low. Here, we show the design and initial testing of a new cell culture system that fits on standard light microscope stages. Based on the parallel plate principle, the system allows for live microscopy of cells exposed to flow-induced shear stress, features short setup time and requires little user interaction. An integrated feedback-controlled heater and a bubble trap enable long observation times. The key design feature is the possibility for quick exchange of the cultured cells. We present first test results that focus on verifying the robustness, biocompatibility, and ease of use of the device. Copyright © 2019 Kriesi, Steinert, Marmaras, Danzer, Meskenaite and Kurtcuoglu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
- Published
- 2019
122. Modelling of Cerebrospinal Fluid Flow by Computational Fluid Dynamics
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Miller, Karol, Miller, K ( Karol ), Kurtcuoglu, Vartan; https://orcid.org/0000-0003-2665-0995, Jain, Kartik, Martin, Bryn A, Miller, Karol, Miller, K ( Karol ), Kurtcuoglu, Vartan; https://orcid.org/0000-0003-2665-0995, Jain, Kartik, and Martin, Bryn A
- Published
- 2019
123. Fluid Dynamics in the HeartMate 3: Influence of the Artificial Pulse Feature and Residual Cardiac Pulsation
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Wiegmann, Lena, Thamsen, Bente; https://orcid.org/0000-0002-1300-7637, de Zélicourt, Diane; https://orcid.org/0000-0001-5300-1355, Granegger, Marcus; https://orcid.org/0000-0002-1425-1236, Boës, Stefan; https://orcid.org/0000-0001-5809-2823, Schmid Daners, Marianne; https://orcid.org/0000-0002-6411-8871, Meboldt, Mirko; https://orcid.org/0000-0001-5828-5406, Kurtcuoglu, Vartan; https://orcid.org/0000-0003-2665-0995, Wiegmann, Lena, Thamsen, Bente; https://orcid.org/0000-0002-1300-7637, de Zélicourt, Diane; https://orcid.org/0000-0001-5300-1355, Granegger, Marcus; https://orcid.org/0000-0002-1425-1236, Boës, Stefan; https://orcid.org/0000-0001-5809-2823, Schmid Daners, Marianne; https://orcid.org/0000-0002-6411-8871, Meboldt, Mirko; https://orcid.org/0000-0001-5828-5406, and Kurtcuoglu, Vartan; https://orcid.org/0000-0003-2665-0995
- Abstract
Ventricular assist devices (VADs), among which the HeartMate 3 (HM3) is the latest clinically approved representative, are often the therapy of choice for patients with end‐stage heart failure. Despite advances in the prevention of pump thrombosis, rates of stroke and bleeding remain high. These complications are attributed to the flow field within the VAD, among other factors. One of the HM3’s characteristic features is an artificial pulse that changes the rotor speed periodically by 4000 rpm, which is meant to reduce zones of recirculation and stasis. In this study, we investigated the effect of this speed modulation on the flow fields and stresses using high‐resolution computational fluid dynamics. To this end, we compared Eulerian and Lagrangian features of the flow fields during constant pump operation, during operation with the artificial pulse feature, and with the effect of the residual native cardiac cycle. We observed good washout in all investigated situations, which may explain the low incidence rates of pump thrombosis. The artificial pulse had no additional benefit on scalar washout performance, but it induced rapid variations in the flow velocity and its gradients. This may be relevant for the removal of deposits in the pump. Overall, we found that viscous stresses in the HM3 were lower than in other current VADs. However, the artificial pulse substantially increased turbulence, and thereby also total stresses, which may contribute to clinically observed issues related to hemocompatibility.
- Published
- 2019
124. Integrated Flow Chamber System for Live Cell Microscopy
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Kriesi, Carlo, Steinert, Martin, Marmaras, Anastasios, Danzer, Claudia, Meskenaite, Virginia, Kurtcuoglu, Vartan, Kriesi, Carlo, Steinert, Martin, Marmaras, Anastasios, Danzer, Claudia, Meskenaite, Virginia, and Kurtcuoglu, Vartan
- Abstract
In vitro quantification of the effect of mechanical loads on cells by live microscopy requires precise control of load and culture environment. Corresponding systems are often bulky, their setup and maintenance are time consuming, or the cell yield is low. Here, we show the design and initial testing of a new cell culture system that fits on standard light microscope stages. Based on the parallel plate principle, the system allows for live microscopy of cells exposed to flow-induced shear stress, features short setup time and requires little user interaction. An integrated feedback-controlled heater and a bubble trap enable long observation times. The key design feature is the possibility for quick exchange of the cultured cells. We present first test results that focus on verifying the robustness, biocompatibility, and ease of use of the device.
- Published
- 2019
125. Reduced-order modeling of blood flow for noninvasive functional evaluation of coronary artery disease
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Buoso, Stefano; https://orcid.org/0000-0002-1293-3225, Manzoni, Andrea, Alkadhi, Hatem, Plass, André, Quarteroni, Alfio; https://orcid.org/0000-0002-5947-6885, Kurtcuoglu, Vartan; https://orcid.org/0000-0003-2665-0995, Buoso, Stefano; https://orcid.org/0000-0002-1293-3225, Manzoni, Andrea, Alkadhi, Hatem, Plass, André, Quarteroni, Alfio; https://orcid.org/0000-0002-5947-6885, and Kurtcuoglu, Vartan; https://orcid.org/0000-0003-2665-0995
- Abstract
We present a novel computational approach, based on a parametrized reduced-order model, for accelerating the calculation of pressure drop along blood vessels. Vessel lumina are defined by a geometric parametrization using the discrete empirical interpolation method on control points located on the surface of the vessel. Hemodynamics are then computed using a reduced-order representation of the parametrized three-dimensional unsteady Navier-Stokes and continuity equations. The reduced-order model is based on an offline-online splitting of the solution process, and on the projection of a finite volume full-order model on a low-dimensionality subspace generated by proper orthogonal decomposition of pressure and velocity fields. The algebraic operators of the hemodynamic equations are assembled efficiently during the online phase using the discrete empirical interpolation method. Our results show that with this approach calculations can be sped up by a factor of about 25 compared to the conventional full-order model, while maintaining prediction errors within the uncertainty limits of invasive clinical measurement of pressure drop. This is of importance for a clinically viable implementation of noninvasive, medical imaging-based computation of fractional flow reserve.
- Published
- 2019
126. Propagation of Plasma L-Phenylalanine Concentration Fluctuations to the Neurovascular Unit in Phenylketonuria: An in silico Study.
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Taslimifar, Mehdi, Buoso, Stefano, Verrey, Francois, Kurtcuoglu, Vartan, Taslimifar, Mehdi, Buoso, Stefano, Verrey, Francois, and Kurtcuoglu, Vartan
- Abstract
Phenylketonuria (PKU) is an inherited metabolic disease characterized by abnormally high concentrations of the essential amino acid L-phenylalanine (Phe) in blood plasma caused by reduced activity of phenylalanine hydroxylase (PAH). While numerous studies have shown association between high plasma Phe concentration and intellectual impairment, it is not clear whether increased Phe fluctuations also observed in PKU affect the brain as well. To investigate this, time-resolved data on Phe and competing large neutral amino acid (LNAA) concentrations in neurons are needed, but cannot be acquired readily with current methods. We have used modeling as an alternative approach to characterize the interactive dynamics of Phe and competing LNAAs (CL) in the neurovascular unit (NVU). Our results suggest that plasma Phe fluctuations can propagate into the NVU cells and change there the concentration of LNAAs, with the highest magnitude of this effect observed at low frequency and high amplitude-to-mean ratio of the plasma Phe concentration fluctuations. Our model further elucidates the effect of therapeutic LNAA supplementation in PKU, showing how abnormal concentrations of Phe and CL in the NVU move thereby toward normal physiologic levels.
- Published
- 2019
127. Influence of Standard Laboratory Procedures on Measures of Erythrocyte Damage
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Wiegmann, Lena, De Zélicourt, Diane A., Speer, Oliver, Muller, Alissa, Goede, Jeroen S., Seifert, Burkhardt, Kurtcuoglu, Vartan, University of Zurich, and Kurtcuoglu, Vartan
- Subjects
2737 Physiology (medical) ,red blood cells ,Erythrocytes ,Centrifugation ,vortexing ,pipetting ,free hemoglobin ,ektacytometry ,10036 Medical Clinic ,10076 Center for Integrative Human Physiology ,610 Medicine & health ,10060 Epidemiology, Biostatistics and Prevention Institute (EBPI) ,1314 Physiology ,10064 Neuroscience Center Zurich ,10052 Institute of Physiology - Abstract
The ability to characterize the mechanical properties of erythrocytes is important in clinical and research contexts: to diagnose and monitor hematologic disorders, as well as to optimize the design of cardiovascular implants and blood circulating devices with respect to blood damage. However, investigation of red blood cell (RBC) properties generally involves preparatory and processing steps. Even though these impose mechanical stresses on cells, little is known about their impact on the final measurement results. In this study, we investigated the effect of centrifuging, vortexing, pipetting, and high pressures on several markers of mechanical blood damage and RBC membrane properties. Using human venous blood, we analyzed erythrocyte damage by measuring free hemoglobin, phosphatidylserine exposure by flow cytometry, RBC deformability by ektacytometry and the parameters of a complete blood count. We observed increased levels of free hemoglobin for all tested procedures. The release of hemoglobin into plasma depended significantly on the level of stress. Elevated pressures and centrifuging also altered mean cell volume (MCV) and mean corpuscular hemoglobin (MCH), suggesting changes in erythrocyte population, and membrane properties. Our results show that the effects of blood handling can significantly influence erythrocyte damage metrics. Careful quantification of this influence as well as other unwanted secondary effects should thus be included in experimental protocols and accounted for in clinical laboratories. ISSN:1664-042X
- Published
- 2017
128. Thrombotic Risk of Rotor Speed Modulation Regimes of Contemporary Centrifugal Continuous-flow Left Ventricular Assist Devices.
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BORASCHI, ANDREA, BOZZI, SILVIA, THAMSEN, BENTE, GRANEGGER, MARCUS, WIEGMANN, LENA, PAPPALARDO, FEDERICO, SLEPIAN, MARVIN J., KURTCUOGLU, VARTAN, REDAELLI, ALBERTO, DE ZÉLICOURT, DIANE, and CONSOLO, FILIPPO
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- 2021
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129. Clinical data sharing : a data scientist's perspective
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Juchler, Norman, Schilling, Sabine, Watanabe, Kazuhiro, Anzai, Hitomi, Rüfenacht, Daniel, Bijlenga, Philippe, Kurtcuoglu, Vartan, and Hirsch, Sven
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610: Medizin und Gesundheit ,005: Computerprogrammierung, Programme und Daten ,Intracranial aneurysms ,Clinical data sharing - Abstract
An ever increasing amount of medical data is collected and used for scientific and clinical purposes. To benefit from the abundance of data, however, one has to deal with several challenges. The diversity of data sources, the variability seen in the biological systems and the biases and distortions inherent in the acquired data request for robust and flexible data processing pipelines. Here, we illustrate some of these challenges at the hand of our research on intracranial aneurysms and share insights how to deal with these challenges. We present the AneuX AneurysmDataBase. It stores data acquired at multiple clinical centers, supports heterogeneous data (clinical data, imaging data, genetic data, morphological and histological data, etc.) and is aimed for use in both scientific and industrial contexts. We further present five scientific studies that demonstrate the usage of the AneurysmDataBase. In the first application, we evaluated the PHASES score, a recent scoring scheme to guide the clinicians whether to treat an unruptured intracranial aneurysm. We further examined and improved existing morphological descriptors with the goal to associate aneurysm shape with its disease status. In a third study, we quantified the qualitative rating of aneurysm shape by humans. A fourth study aims at inferring information about the disease directly from imaging data by means of convolutional neural nets. Finally, we sketch how to query aneurysms with similar anatomical and morphological properties from a database. With our work, we demonstrate how clinical data sharing can be used for quantitative analyses of aneurysm properties and for the development of diagnostic and prognostic tools.
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- 2018
130. Reproducing qualitative irregularity ratings by means of quantitative shape descriptors in intracranial aneurysms
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Juchler, Norman, Schilling, Sabine, Philippe, Bijlenga, Rüfenacht, Daniel, Kurtcuoglu, Vartan, and Hirsch, Sven
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Irregularity ratings ,Quantitative morphology ,Intracranial aneurysms ,616: Innere Medizin und Krankheiten - Abstract
Introduction: Current methods of medical imaging provide key information for the clinical assessment of intracranial aneurysms. To date, broadly accepted quantitative criteria to compare aneurysm morphology are yet lacking. In this study, we relate established shape descriptors to expert assessments of aneurysm irregularity in view of establishing clinically meaningful descriptors. Method: To address morphology in an isolated manner, from 3D angiographies, we produced replicas of aneurysms and adjacent segments of the parent vascular tree, extracted computed geometry indices and measures based on curvature, surface writhe number and geometry moments. Independently, experts evaluated the morphology of these aneurysms in a 3D viewer by inspecting their shapes and rating the degree of irregularity on a 9-point rating scale. Besides these 3D views, no further information was given to the raters. We then examined the univariate and multivariate correlations between the aggregated ratings and the quantitative descriptions of the 3D models. Results: Preliminary results are based on 134 aneurysm models and 15 raters, who all assessed the perceived irregularity of the aneurysm shape. Univariate analysis shows that curvature metrics reproduce the rater assessment of shape irregularity the best (Spearman correlation ρ=0.86, p
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- 2018
131. Aneurysm shape as a diagnostic tool
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Juchler, Norman, Schilling, Sabine, Rüfenacht, Daniel, Bijlenga, Philippe, Kurtcuoglu, Vartan, and Hirsch, Sven
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006: Spezielle Computerverfahren ,616: Innere Medizin und Krankheiten - Published
- 2018
132. Virtual surgical planning, flow simulation, and 3-dimensional electrospinning of patient-specific grafts to optimize Fontan hemodynamics
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Siallagan, Dominik, Loke, Yue-Hin, Olivieri, Laura, Opfermann, Justin, Ong, Chin Siang, de Zélicourt, Diane, Petrou, Anastasios, Daners, Marianne Schmid, Kurtcuoglu, Vartan, Meboldt, Mirko, Nelson, Kevin, Vricella, Luca, Johnson, Jed, Hibino, Narutoshi, Krieger, Axel, University of Zurich, and Hibino, Narutoshi
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Pulmonary and Respiratory Medicine ,2740 Pulmonary and Respiratory Medicine ,570 Life sciences ,biology ,610 Medicine & health ,Surgery ,Cardiology and Cardiovascular Medicine ,2705 Cardiology and Cardiovascular Medicine ,10052 Institute of Physiology ,2746 Surgery - Published
- 2018
133. Aneurysm shape as a diagnostic tool : a machine learning approach
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Juchler, Norman, Schilling, Sabine, Bijlenga, Philippe, Rüfenacht, Daniel, Kurtcuoglu, Vartan, and Hirsch, Sven
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cardiovascular system ,cardiovascular diseases ,006: Spezielle Computerverfahren ,Intracranial aneurysms ,616: Innere Medizin und Krankheiten - Abstract
Recent studies have found supporting evidence that the shape of an intracranial aneurysm can be used as a proxy for disease status. Although the shape, as seen in 3D imaging data, already plays a role in the clinical assessment of aneurysms today, tools to quantify and compare aneurysm morphology in a generic, standardized way are still lacking. Here, we present a machine learning approach based on a broad spectrum of shape descriptors to predict the aneurysm rupture status. Results are based on a dataset consisting of over 400 segmented aneurysm models. We extended our analysis by including human ratings of aneurysm shape. A correlation analysis of these ratings with quantifiable morphological parameters allowed us to identify shape descriptors mimicking the human assessment. Preliminary results based on 134 geometric aneurysm models and 15 assessments of human raters show that human assessment of irregular shape correlates well with curvature metrics, spread of the writhe number distribution and non-sphericity index.
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- 2018
134. Evaluation of metal nanoparticle- and plastic resin-based x-ray contrast agents for kidney capillary imaging
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Kuo, Willy, primary, Schulz, Georg, additional, Müller, Bert, additional, and Kurtcuoglu, Vartan, additional
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- 2019
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135. Extending statistical learning for aneurysm rupture assessment to Finnish and Japanese populations using morphology, hemodynamics, and patient characteristics
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Detmer, Felicitas J., primary, Hadad, Sara, additional, Chung, Bong Jae, additional, Mut, Fernando, additional, Slawski, Martin, additional, Juchler, Norman, additional, Kurtcuoglu, Vartan, additional, Hirsch, Sven, additional, Bijlenga, Philippe, additional, Uchiyama, Yuya, additional, Fujimura, Soichiro, additional, Yamamoto, Makoto, additional, Murayama, Yuichi, additional, Takao, Hiroyuki, additional, Koivisto, Timo, additional, Frösen, Juhana, additional, and Cebral, Juan R., additional
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- 2019
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136. Reduced-order modeling of blood flow for noninvasive functional evaluation of coronary artery disease
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Buoso, Stefano, primary, Manzoni, Andrea, additional, Alkadhi, Hatem, additional, Plass, André, additional, Quarteroni, Alfio, additional, and Kurtcuoglu, Vartan, additional
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- 2019
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137. Integrated Flow Chamber System for Live Cell Microscopy
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Kriesi, Carlo, primary, Steinert, Martin, additional, Marmaras, Anastasios, additional, Danzer, Claudia, additional, Meskenaite, Virginia, additional, and Kurtcuoglu, Vartan, additional
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- 2019
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138. Propagation of Plasma L-Phenylalanine Concentration Fluctuations to the Neurovascular Unit in Phenylketonuria: An in silico Study
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Taslimifar, Mehdi, primary, Buoso, Stefano, additional, Verrey, Francois, additional, and Kurtcuoglu, Vartan, additional
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- 2019
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139. Generation of renal Epo-producing cell lines by conditional gene tagging reveals rapid HIF-2 driven Epo kinetics, cell autonomous feedback regulation, and a telocyte phenotype
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Imeri, Faik, primary, Nolan, Karen A., additional, Bapst, Andreas M., additional, Santambrogio, Sara, additional, Abreu-Rodríguez, Irene, additional, Spielmann, Patrick, additional, Pfundstein, Svende, additional, Libertini, Silvana, additional, Crowther, Lisa, additional, Orlando, Ilaria M.C., additional, Dahl, Sophie L., additional, Keodara, Anna, additional, Kuo, Willy, additional, Kurtcuoglu, Vartan, additional, Scholz, Carsten C., additional, Qi, Weihong, additional, Hummler, Edith, additional, Hoogewijs, David, additional, and Wenger, Roland H., additional
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- 2019
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140. Fluid Dynamics in the HeartMate 3: Influence of the Artificial Pulse Feature and Residual Cardiac Pulsation
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Wiegmann, Lena, primary, Thamsen, Bente, additional, de Zélicourt, Diane, additional, Granegger, Marcus, additional, Boës, Stefan, additional, Schmid Daners, Marianne, additional, Meboldt, Mirko, additional, and Kurtcuoglu, Vartan, additional
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- 2018
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141. In Vitro Testing and Comparison of Additively Manufactured Polymer Impellers for the CentriMag Blood Pump.
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VON PETERSDORFF-CAMPEN, KAI, ABEKEN, JONAS, DE ZÉLICOURT, DIANE, KURTCUOGLU, VARTAN, MEBOLDT, MIRKO, and DANERS, MARIANNE SCHMID
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- 2021
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142. Using shape descriptors to categorize intracranial aneurysms
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Juchler, Norman, Schilling, Sabine, Wanke, Isabel, Rüfenacht, Daniel, Bijlenga, Philippe, Kurtcuoglu, Vartan, Hirsch, Sven, Juchler, Norman, Schilling, Sabine, Wanke, Isabel, Rüfenacht, Daniel, Bijlenga, Philippe, Kurtcuoglu, Vartan, and Hirsch, Sven
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Working towards a system to match intracranial aneurysms of similar morphology, we examine how a variety of established shape descriptors relate to expert assessments of aneurysm morphology. For this purpose, we extract 3D models of aneurysms from 3D angiographies and calculate numerical values (geometry indices and moment invariants) that describe the size and shape of the aneurysm and the surrounding arteries. We then compare these shape descriptors with human assessments of qualitative morphological characteristics like irregularity or the presence/absence of blebs. Here, we present preliminary results based on 137 aneurysm models.
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- 2018
143. Shape-based modeling of aneurysmal disease status
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Juchler, Norman, Schilling, Sabine, Wanke, Isabel, Rüfenacht, Daniel, Bijlenga, Philippe, Kurtcuoglu, Vartan, Hirsch, Sven, Juchler, Norman, Schilling, Sabine, Wanke, Isabel, Rüfenacht, Daniel, Bijlenga, Philippe, Kurtcuoglu, Vartan, and Hirsch, Sven
- Abstract
Introduction: To date, it is difficult for clinicians to judge the associated risks of intracranial aneurysms reliably. Because the 3D-shape of an aneurysm is strongly linked to the underlying formation processes it is very likely that the presence or absence of certain shape features indicate the disease status of the aneurysm. Shape (extracted from medical imaging data) already plays a significant role in the qualitative assessment of the aneurysm by the clinician and has been associated with risk prediction. Still, no consensus exists about which shape features reliably predict instability or whether there exist any that qualify as biomarkers at all. In an effort to find support for the assumption that aneurysm shape carries information about the aneurysm status, we developed a flexible classification pipeline that extracts shape features and tests their applicability. Methods: 3D models of aneurysms are extracted from medical imaging data (mostly 3DRA) by a standardized vessel segmentation method. The aneurysm is cut from its parent vessels according to a simple and reproducible cut protocol. Different representations of the 3D shape that have been suggested by literature are calculated for the extracted aneurysm. So far we have looked at Zernike moments (ZM), their invariants (ZMI) and simple geometry indices such as undulation or non-sphericity. Different feature reduction techniques (for ZMI) and machine-learning methods are applied to find linking patterns between shape features and aneurysm stability. This processing pipeline is applied to a relatively large clinical dataset (ca. 400 cases), whereas the collection of new cases is an on-going effort. We will present the findings on the latest state of the database. Results: Initial results indicate that the ZMI alone are insufficient to classify aneurysms reliably in terms of rupture or stability status. Because of their global support, ZMI bare a strong dependency on the placement of the cuts. In a prelimin
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- 2018
144. On the utility of 3D Zernike Moment Invariants to assess aneurysm disease status
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Juchler, Norman, Ebnöther, Ueli, Schilling, Sabine, Hirsch, Sven, Kurtcuoglu, Vartan, Juchler, Norman, Ebnöther, Ueli, Schilling, Sabine, Hirsch, Sven, and Kurtcuoglu, Vartan
- Abstract
Intracranial aneurysms are pathological deformations of brain arteries. Although remaining asymptomatic most of the time, aneurysms expose the patient to an increased risk of subarachnoid hemorrhage, which can cause severe brain damage and death. To this date, it is difficult for clinicians to judge the aneurysm risk status reliably, even though availability and quality of imaging modalities have much improved recently. The goal of this project is to investigate whether a quantitative description of 3D-shape can be used to judge the disease status of intracranial aneurysms, and, ultimately, to equip clinicians with a tool to assess the risks of treatment. In recent scientific literature, various candidates of 3D-shape descriptors are discussed, out of which Zernike Moment Invariants (ZMIs) belong to the most popular ones. In an attempt to understand their mode of operation, we applied them to classify the rupture-risk status of intracranial aneurysms. Based on the analysis of synthetic and real data we accumulated evidence and are presenting first results on the utility of ZMI and alternative representations.
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- 2018
145. Shape-based assessment of intracranial aneurysm disease status – a machine learning approach
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Juchler, Norman, Schilling, Sabine, Bijlenga, Philippe, Kurtcuoglu, Vartan, Hirsch, Sven, Juchler, Norman, Schilling, Sabine, Bijlenga, Philippe, Kurtcuoglu, Vartan, and Hirsch, Sven
- Abstract
It is exceedingly challenging to assess the clinical significance of intracranial aneurysms. Currently, clinicians associate aneurysm shape irregularity with wall instability. However, there is no consensus on which shape features reliably predict aneurysm rupture risk. Here we present a machine learning approach to tackle this problem: We implemented a classification pipeline to identify shape features with predictive power of aneurysm instability. 3D models of aneurysms are extracted from medical imaging data (mostly 3D rotational angiography) using a standardized vessel segmentation protocol. A variety of established representations of the 3D shape are calculated for the extracted aneurysm segment. These include the calculation of Zernike moment invariants (ZMI) and simpler geometry indices such as undulation, ellipticity and non-sphericity. Feature reduction techniques (for ZMI) and classification methods are applied to find patterns linking shape features to aneurysm stability in an exploratory way. This processing pipeline was applied to a clinical dataset of approximately 250 aneurysms registered in the AneurysmDataBase (SwissNeuroFoundation and AneuriskWeb database. Classification based on ZMI alone allowed us to distinguish between sidewall and bifurcation aneurysms, but failed to forecast an aneurysm’s rupture status reliably. Remarkably, simpler geometry indices performed similarly well in rupture status prediction. It remains to be investigated whether further stratification of the aneurysms in terms of location, size and clinical factors will increase the robustness of the applied classification methods. This study was performed within the scope of the AneuX project, funded by SystemsX.ch, and received support by SNSF NCCR Kidney.CH.
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- 2018
146. Measuring the perceived morphological complexity of intracranial aneurysms
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Juchler, Norman, Schilling, Sabine, Bijlenga, Philippe, Kurtcuoglu, Vartan, Hirsch, Sven, Juchler, Norman, Schilling, Sabine, Bijlenga, Philippe, Kurtcuoglu, Vartan, and Hirsch, Sven
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The rupture of intracranial aneurysms is a potentially deadly event. Aneurysm detection is based on imaging techniques, amongst which 3D angiograms deliver the highest quality. Currently, neuroradiologists assess such images only in a qualitative manner, even though it remains unclear how morphological properties relate to the disease status quantitatively. In an effort to identify suitable descriptors that capture the irregularity of aneurysms, we relate a range of shape descriptors to expert assessments of aneurysm morphology. In a first step, we extracted 3D models of aneurysms from 3D angiographies and calculated geometry indices and moment invariants describing size and shape of aneurysms and surrounding arteries. In a second step, we compared these descriptors to human assessments of irregularity of the aneurysm dome. Preliminary results are presented based on 134 aneurysm models and 15 raters (5 clinicians, 10 informed laymen). Univariate correlation revealed that curvature-based metrics predict most accurately the human assessment of irregularity (rank correlation: ?=0.86). This study was performed within the scope of the AneuX project, funded by SystemsX.ch, and received support by SNSF NCCR Kidney.CH.
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- 2018
147. Significant association of slow vasogenic ICP waves with normal pressure hydrocephalus diagnosis
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Heldt, Thomas, Heldt, T ( Thomas ), Spiegelberg, Andreas, Krause, Matthias, Meixensberger, Juergen, Seifert, Burkhardt, Kurtcuoglu, Vartan, Heldt, Thomas, Heldt, T ( Thomas ), Spiegelberg, Andreas, Krause, Matthias, Meixensberger, Juergen, Seifert, Burkhardt, and Kurtcuoglu, Vartan
- Abstract
OBJECTIVE: We aimed to test whether there is an association of slow vasogenic wave (SVW) occurrence with positive response to external lumbar drainage (ELD) and ventriculoperitoneal shunting and to design a method for the recognition and quantification of SVWs in the intracranial pressure (ICP) signal. MATERIALS AND METHODS: We constructed SVW templates using normalized sine waves. We calculated the cross-correlation between the respective SVW template and the ICP signal. This was followed by shifting the templates forward and performing the cross-correlation analysis again until the end of the recording. Cross-correlation values above a threshold were considered to be indicative of SVWs. This threshold was previously determined and validated on a sample of ICP records of six patients. We calculated the root mean square of the recognized SVW periods as a measure of signal strength. Time-averaged signal strength was calculated over the full recording time (ICP) and over the wave periods (ICP). RESULTS: We determined ICPand ICPin recordings of 2 groups of patients presenting with Hakim's triad: 26 normal pressure hydrocephalus (NPH) patients and 20 non-NPH patients. We then tested whether there was an association between ICPor ICPand the respective diagnosis using a Mann-Whitney test. We found significant association between ICP(p = 0.014) and ICP(p = 0.022) and the diagnoses. CONCLUSIONS: The described method based on pattern recognition in the time domain is suitable for the detection and quantification of SVWs in ICP signals. We found a significant association between the occurrence of SVWs and independent NPH diagnosis.
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- 2018
148. Functional Polarity of Microvascular Brain Endothelial Cells Supported by Neurovascular Unit Computational Model of Large Neutral Amino Acid Homeostasis
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Taslimifar, Mehdi, Buoso, Stefano, Verrey, Francois, Kurtcuoglu, Vartan, Taslimifar, Mehdi, Buoso, Stefano, Verrey, Francois, and Kurtcuoglu, Vartan
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The homeostatic regulation of large neutral amino acid (LNAA) concentration in the brain interstitial fluid (ISF) is essential for proper brain function. LNAA passage into the brain is primarily mediated by the complex and dynamic interactions between various solute carrier (SLC) transporters expressed in the neurovascular unit (NVU), among which SLC7A5/LAT1 is considered to be the major contributor in microvascular brain endothelial cells (MBEC). The LAT1-mediated trans-endothelial transport of LNAAs, however, could not be characterized precisely by available and standard methods so far. To circumvent these limitations, we have incorporated published data of rat brain into a robust computational model of NVU-LNAA homeostasis, allowing us to evaluate hypotheses concerning LAT1-mediated trans-endothelial transport of LNAAs across the blood brain barrier (BBB). We show that accounting for functional polarity of MBECs with either asymmetric LAT1 distribution between membranes and/or intrinsic LAT1 asymmetry with low intraendothelial binding affinity is required to reproduce the experimentally measured brain ISF response to intraperitoneal (IP) L-tyrosine and L-phenylalanine injection. On the basis of these findings, we have also investigated the effect of IP administrated L-tyrosine and L-phenylalanine on the dynamics of LNAAs in MBECs, astrocytes and neurons. Finally, the computational model was shown to explain the trans-stimulation of LNAA uptake across the BBB observed upon ISF perfusion with a competitive LAT1 inhibitor.
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- 2018
149. Remodelling of the aortic root in severe tricuspid aortic stenosis: implications for transcatheter aortic valve implantation
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Stolzmann, Paul, Knight, Joseph, Desbiolles, Lotus, Maier, Willibald, Scheffel, Hans, Plass, André, Kurtcuoglu, Vartan, Leschka, Sebastian, Poulikakos, Dimos, Marincek, Borut, Alkadhi, Hatem, Stolzmann, Paul, Knight, Joseph, Desbiolles, Lotus, Maier, Willibald, Scheffel, Hans, Plass, André, Kurtcuoglu, Vartan, Leschka, Sebastian, Poulikakos, Dimos, Marincek, Borut, and Alkadhi, Hatem
- Abstract
Detailed knowledge of aortic root geometry is a prerequisite to anticipate complications of transcatheter aortic valve (TAV) implantation. We determined coronary ostial locations and aortic root dimensions in patients with aortic stenosis (AS) and compared these values with normal subjects using computed tomography (CT). One hundred consecutive patients with severe tricuspid AS and 100 consecutive patients without valvular pathology (referred to as the controls) undergoing cardiac dual-source CT were included. Distances from the aortic annulus (AA) to the left coronary ostium (LCO), right coronary ostium (RCO), the height of the left coronary sinus (HLS), right coronary sinus (HRS), and aortic root dimensions [diameters of AA, sinus of Valsalva (SV), and sino-tubular junction(STJ)] were measured. LCO and RCO were 14.9 ± 3.2mm (8.2-25.9) and 16.8 ± 3.6mm (12.0-25.7) in the controls, 15.5 ± 2.9mm (8.8-24.3) and 17.3 ± 3.6mm (7.3-26.0) in patients with AS. Controls and patients with AS had similar values for LCO (P = 0.18), RCO (P = 0.33) and HLS (P = 0.88), whereas HRS (P < 0.05) was significantly larger in patients with AS. AA (r = 0.55,P < 0.001), SV (r = 0.54,P < 0.001), and STJ (r = 0.52,P < 0.001) significantly correlated with the body surface area in the controls; whereas no correlation was found in patients with AS. Patients with AS had significantly larger AA (P < 0.01) and STJ (P < 0.01) diameters when compared with the controls. In patients with severe tricuspid AS, coronary ostial locations were similar to the controls, but a transverse remodelling of the aortic root was recognized. Owing to the large distribution of ostial locations and the dilatation of the aortic root, CT is recommended before TAV implantation in each patient
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- 2018
150. Ex vivo and in vivo coronary ostial locations in humans
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Knight, Joseph, Kurtcuoglu, Vartan, Muffly, Karl, Marshall Jr, William, Stolzmann, Paul, Desbiolles, Lotus, Seifert, Burkhardt, Poulikakos, Dimos, Alkadhi, Hatem, Knight, Joseph, Kurtcuoglu, Vartan, Muffly, Karl, Marshall Jr, William, Stolzmann, Paul, Desbiolles, Lotus, Seifert, Burkhardt, Poulikakos, Dimos, and Alkadhi, Hatem
- Abstract
Purpose: Knowledge of the normal in vivo distribution and variation of coronary ostial locations is essential in the planning of various interventional and surgical procedures. However, all studies to date have reported the distribution of coronary ostia locations only in cadaver hearts. In this study, we sought to assess the distribution of coronary ostial locations in patients using cardiac dual-source computed tomography (CT) and compare these values to those of human cadaveric specimens. Methods: Measurements of the coronary ostia location were performed in 150 patients undergoing dual-source CT and in 75 cadavers using open measurement techniques. All 150 patients had a normal aortic valve function and no previous cardiac intervention or surgery. The location of the right and left coronary origin in relation to the aortic annulus and the height of the sinus of Valsalva were measured. Results: Mean ostial locations at CT were 17.0 (±3.6)mm and 15.3 (±3.1)mm for the right and left coronary ostia, with large variations of both sides (right: 10.4-28.5mm; left: 9.8-29.3mm). In cadavers, mean locations were 14.9 (±4.3)mm [5-24mm] for right and 16.0 (±3.6)mm [9-24mm] for left coronary ostia. Comparison of CT and cadaver data showed statistically significant differences for right (P<0.0001) but not left (P=0.1675) coronary ostia. Conclusions: This study provides data of normal coronary ostial origins and demonstrates significant differences between in vivo and ex vivo measurements regarding the right coronary ostium. The observed large variations of coronary ostia origins emphasize the importance of considering such anatomic variations in the development of treatments
- Published
- 2018
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