scholarly journals A Precision Medicine Framework for Personalized Simulation of Hemodynamics in Cerebrovascular Disease

2020 ◽  
Author(s):  
Dietmar Frey ◽  
Michelle Livne ◽  
Heiko Leppin ◽  
Ela M Akay ◽  
Orhun U Aydin ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Cerebrovascular Disease ◽  
Precision Medicine ◽  
Cerebral Hemodynamics ◽  
Successful Implementation ◽  
Dynamic Susceptibility ◽  
Brain Vessels ◽  
Vessel Lumen ◽  
Vessel Imaging ◽  
Simulation Results

AbstractIntroductionCerebrovascular disease is a major public health challenge. An important biomarker is cerebral hemodynamics. To measure cerebral hemodynamics, however, only invasive, potentially harmful or time-to-treatment prolonging methods are available. We present a simulation-based alternative which allows calculation of cerebral hemodynamics based on the individual vessel con figuration of a patient derived from structural vessel imaging.MethodsWe implemented a framework allowing annotation of extracted brain vessels from structural imaging followed by 0-dimensional lumped modelling of cerebral hemodynamics. For annotation, a 3D-graphical user interface (GUI) was implemented. For 0D-simulation, we used a modified nodal analysis (MNA), which was adapted for easy implementation by code. The code was written in-house in java. The simulation GUI allows inspection of simulation results, identification of vulnerable areas, simulation of changes due to different systemic blood pressures. Moreover, sensitivity analysis was implemented allowing the live simulation of changes of variables such as vessel lumen to simulate procedures and disease courses. In two exemplary patients, simulation results were compared to dynamic-susceptibility-weighted-contrast-enhanced magnetic- resonance(DSC-MR) perfusion imaging.ResultsThe successful implementation of the framework allowing individualized annotation and simulation of patients is presented. In two exemplary patients, both the simulation as well as DSC- MRI showed the same results pertaining to the identification of areas vulnerable to ischemia. Sensitivity analysis allows the individualized simulation of changes in vessel lumen and the effect on hemodynamics.DiscussionWe present the first precision medicine pipeline for cerebrovascular disease which allows annotation of the arterial vasculature derived from structural vessel imaging followed by personalized simulation of brain hemodynamics. This paves the way for further development of precision medicine in stroke using novel biomarkers and might make the application of harmful and complex perfusion methods obsolete for certain use cases in the future.

scholarly journals A precision medicine framework for personalized simulation of hemodynamics in cerebrovascular disease

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Dietmar Frey ◽  
Michelle Livne ◽  
Heiko Leppin ◽  
Ela M. Akay ◽  
Orhun U. Aydin ◽  
...  
Keyword(s):  
Cerebrovascular Disease ◽  
Precision Medicine ◽  
High Specificity ◽  
Cerebral Hemodynamics ◽  
Brain Vessels ◽  
Vessel Imaging ◽  
Blood Pressures ◽  
Novel Biomarkers ◽  
Public Health Challenge ◽  
Moderate Sensitivity

Abstract Background Cerebrovascular disease, in particular stroke, is a major public health challenge. An important biomarker is cerebral hemodynamics. To measure and quantify cerebral hemodynamics, however, only invasive, potentially harmful or time-to-treatment prolonging methods are available. Results We present a simulation-based approach which allows calculation of cerebral hemodynamics based on the patient-individual vessel configuration derived from structural vessel imaging. For this, we implemented a framework allowing segmentation and annotation of brain vessels from structural imaging followed by 0-dimensional lumped simulation modeling of cerebral hemodynamics. For annotation, a 3D-graphical user interface was implemented. For 0D-simulation, we used a modified nodal analysis, which was adapted for easy implementation by code. The simulation enables identification of areas vulnerable to stroke and simulation of changes due to different systemic blood pressures. Moreover, sensitivity analysis was implemented allowing the live simulation of changes to simulate procedures and disease progression. Beyond presentation of the framework, we demonstrated in an exploratory analysis in 67 patients that the simulation has a high specificity and low-to-moderate sensitivity to detect perfusion changes in classic perfusion imaging. Conclusions The presented precision medicine approach using novel biomarkers has the potential to make the application of harmful and complex perfusion methods obsolete.

scholarly journals A Precision Medicine Framework for Personalized Simulation of Hemodynamics in Cerebrovascular Disease

2021 ◽  
Author(s):  
Dietmar Frey ◽  
Michelle Livne ◽  
Heiko Leppin ◽  
Ela Marie Akay ◽  
Orhun Aydin ◽  
...  
Keyword(s):  
Cerebrovascular Disease ◽  
Precision Medicine ◽  
High Specificity ◽  
Simulation Modelling ◽  
Cerebral Hemodynamics ◽  
Brain Vessels ◽  
Vessel Imaging ◽  
Blood Pressures ◽  
Novel Biomarkers ◽  
Public Health Challenge

Abstract Cerebrovascular disease, in particular stroke, is a major public health challenge. An important biomarker is cerebral hemodynamics. To measure and quantify cerebral hemodynamics, however, only invasive, potentially harmful or time-to-treatment prolonging methods are available. We present a simulation-based approach which allows calculation of cerebral hemodynamics based on the patient-individual vessel configuration derived from structural vessel imaging. For this, we implemented a framework allowing segmentation and annotation of brain vessels from structural imaging followed by 0-dimensional lumped simulation modelling of cerebral hemodynamics. For annotation, a 3D-graphical user interface was implemented. For 0D-simulation, we used a modified nodal analysis, which was adapted for easy implementation by code. The simulation enables identification of areas vulnerable to stroke and simulation of changes due to different systemic blood pressures. Moreover, sensitivity analysis was implemented allowing the live simulation of changes to simulate procedures and disease progression. Beyond presentation of the framework, we demonstrated in an exploratory analysis in 67 patients that the simulation has a high specificity and low to moderate sensitivity to detect perfusion changes in classic perfusion imaging. The presented precision medicine approach using novel biomarkers has the potential to make the application of harmful and complex perfusion methods obsolete.

scholarly journals Sensitivity Analysis of Johnson-Cook Material Constants and Friction Coefficient Influence on Finite Element Simulation of Turning Inconel 718

Materials ◽  
2019 ◽  
Vol 12 (19) ◽  
pp. 3121 ◽  
Author(s):  
Xiaoli Qiu ◽  
Xianqiang Cheng ◽  
Penghao Dong ◽  
Huachen Peng ◽  
Yan Xing ◽  
...  
Keyword(s):  
Residual Stress ◽  
Sensitivity Analysis ◽  
Finite Element ◽  
Friction Coefficient ◽  
Constitutive Model ◽  
Cutting Force ◽  
Inconel 718 ◽  
Coulomb Friction ◽  
Cutting Conditions ◽  
Simulation Results

The Johnson-Cook (J-C) constitutive model, including five material constants (A, B, n, C, m), and the Coulomb friction coefficient (μ) are critical preprocessed data in machining simulations. Before they become reliable preprocessed data, investigating these parameters’ effect on simulation results benefits parameter-selecting. This paper aims to investigate the different influence of five settings of the J-C constitutive equation and Coulomb friction coefficient on the turning simulation results of Inconel 718 under low-high cutting conditions, including residual stress, chip morphology, cutting force and temperature. A three-dimensional (3-D) finite element model was built, meanwhile, the reliability of the model was verified by comparing the experiment with the simulation. Sensitivity analysis of J-C parameters and friction coefficient on simulation results at low-high cutting conditions was carried out by the hybrid orthogonal test. The results demonstrate that the simulation accuracy of Inconel 718 is more susceptible to strain hardening and thermal softening in the J-C constitutive model. The friction coefficient only has significant effects on axial and radial forces in the high cutting condition. The influences of the coefficient A, n, and m on the residual stress, chip thickness, cutting force and temperature are especially significant. As the cutting parameters increase, the effect of the three coefficients will change visibly. This paper provides direction for controlling simulation results through the adjustment of the J-C constitutive model of Inconel 718 and the friction coefficient.

Implementing Precision Medicine Programs and Clinical Trials in the Community-Based Oncology Practice: Barriers and Best Practices

2018 ◽  
pp. 188-196 ◽  
Author(s):  
Jennifer L. Ersek ◽  
Lora J. Black ◽  
Michael A. Thompson ◽  
Edward S. Kim
Keyword(s):  
Clinical Trials ◽  
Best Practices ◽  
Precision Medicine ◽  
Community Setting ◽  
Successful Implementation ◽  
Precision Oncology ◽  
Community Based ◽  
Molecular Tests ◽  
Core Components ◽  
Oncology Practice

There has been a rapid uptick in the pace of oncology precision medicine advancements over the past several decades as a result of increasingly sophisticated technology and the ability to study more patients through innovative trial designs. As more precision oncology approaches are developed, the need for precision medicine trials is increasing in the community setting, where most patients with cancer are treated. However, community-based practices, as well as some academic centers, may face unique barriers to implementing precision medicine programs and trials within their communities. Such challenges include understanding the tissue needs of molecular tests (e.g., tumor, blood), identifying which molecular tests are best used and when tissue should be tested, interpreting the test results and determining actionability, understanding the role of genetic counseling and/or follow-up testing, determining clinical trial eligibility, and assessing patient attitudes and financial concerns. The purpose of this article is to provide guidance to community-based oncology practices currently conducting clinical trials who want to expand their research program to include precision medicine trials. Here, we describe the core components of precision medicine programs and offer best practices for successful implementation of precision medicine trials in community-based practices.

Predicting formulae for effective length of counterpoise wires buried in ionized, dispersive and inhomogeneous soils

2020 ◽  
Vol 39 (6) ◽  
pp. 1375-1391
Author(s):  
Seyyed Sajjad Sajjadi ◽  
Saeed Reza Ostadzadeh
Keyword(s):  
Sensitivity Analysis ◽  
Transmission Line ◽  
Design Methodology ◽  
Effective Length ◽  
Transmission Line Model ◽  
Line Model ◽  
Content Type ◽  
Dispersion Effects ◽  
Simulation Results

Purpose The purpose of this paper is to investigate the ionization and dispersion effects in combination with the inhomogeneity of soil simultaneously on the effective lengths of counterpoise wires. Design/methodology/approach Improved multi-conductor transmission line model is used for computing effective length of counterpoise wires considering all aspects of soils. Findings The simulation results show that the ionization and dispersion effects simultaneously results in placing the effective length between situations where only one effect is considered. Also, predicting formulae for effective length of counterpoise wires considering all effects are proposed. Originality/value A sensitivity analysis on the effective lengths of counterpoise wires considering all aspects of soils is carried out.

Risk Management of Construction Schedule by PERT with Monte Carlo Simulation

2014 ◽  
Vol 548-549 ◽  
pp. 1646-1650 ◽  
Author(s):  
Yang Liu ◽  
Yan Li
Keyword(s):  
Sensitivity Analysis ◽  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Critical Path ◽  
Total Duration ◽  
Control Points ◽  
Schedule Management ◽  
Simulation Results ◽  
Critical Paths ◽  
Construction Schedule

It has been proved that the construction schedule management was an uncertain problem. Traditional CPM method was a good way to define the total duration and critical paths but can not solve uncertainty. The paper use CPM to define the duration and critical path firstly, then defined the parameters with Delphi and make Monte Carlo simulation. Through simulation results, it is found that the probability to finish the work on time was only 35.3%. The following step is to make sensitivity analysis, through the calculation, the work which has large influence was found and treat as key control points. It is proved that Monte Carlo simulation is useful to solve the problem of construction schedule management.

scholarly journals Implementing Precision Medicine in Community-Based Oncology Programs: Three Models

2019 ◽  
Vol 15 (6) ◽  
pp. 325-329 ◽  
Author(s):  
Laura A. Levit ◽  
Edward S. Kim ◽  
Barbara L. McAneny ◽  
Lincoln D. Nadauld ◽  
Kathryn Levit ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Cancer Care ◽  
Large Scale ◽  
Administrative Support ◽  
Clinical Pathways ◽  
Clinical Decision ◽  
Successful Implementation ◽  
Precision Oncology ◽  
Community Based ◽  
Tumor Boards

The use of precision medicine and the number of genomic-based treatments and immunotherapies is increasing. Nevertheless, oncology providers face challenges to implementing precision medicine, including in community practices, where most patients receive treatment. On January 31, 2018, ASCO hosted Precision Medicine: Expanding Opportunities, the inaugural event in ASCO’s new State of Cancer Care in America (SOCCA) event series. This article draws from the inaugural SOCCA event and the experiences of the SOCCA event participants to summarize the opportunities and challenges of precision medicine, and to highlight three successful models of implementing precision oncology in large, multisite community practices or networks: (1) Intermountain Healthcare, (2) Levine Cancer Institute, Atrium Health, and (3) National Cancer Care Alliance. The experience of these practices suggests that practice innovations that offer clinical decision support through molecular tumor boards and clinical pathways, and administrative support for prior authorization and clinical trial matching are key to successful implementation of large-scale, community-based precision medicine programs.

scholarly journals Zebrafish Models of Cerebrovascular Disease

2014 ◽  
Vol 34 (4) ◽  
pp. 571-577 ◽  
Author(s):  
Brian P Walcott ◽  
Randall T Peterson
Keyword(s):  
Blood Vessel ◽  
Cerebrovascular Disease ◽  
Large Scale ◽  
Hemorrhagic Stroke ◽  
Brain Parenchyma ◽  
Cerebral Vasculature ◽  
Vessel Lumen ◽  
Vessel Structure ◽  
Genetic And Environmental Factors ◽  
Genetically Manipulated

Perturbations in cerebral blood flow and abnormalities in blood vessel structure are the hallmarks of cerebrovascular disease. While there are many genetic and environmental factors that affect these entities through a heterogeneous group of disease processes, the ultimate final pathologic insult in humans is defined as a stroke, or damage to brain parenchyma. In the case of ischemic stroke, blood fails to reach its target destination whereas in hemorrhagic stroke, extravasation of blood occurs outside of the blood vessel lumen, resulting in direct damage to brain parenchyma. As these acute events can be neurologically devastating, if not fatal, development of novel therapeutics are urgently needed. The zebrafish ( Danio rerio) is an attractive model for the study of cerebrovascular disease because of its morphological and physiological similarity to human cerebral vasculature, its ability to be genetically manipulated, and its fecundity allowing for large-scale, phenotype-based screens.

SPICESoft: AUTOMATED TOOL FOR SENSITIVITY ANALYSIS, PERFORMANCE ANALYSIS, AND INVERSE PERFORMANCE ANALYSIS OF DIGITAL CIRCUITS

2008 ◽  
Vol 17 (02) ◽  
pp. 221-238
Author(s):  
K. S. YEO ◽  
Z. H. KONG
Keyword(s):  
Sensitivity Analysis ◽  
Performance Analysis ◽  
Digital Circuits ◽  
Circuit Analysis ◽  
Analysis Tool ◽  
Circuit Performance ◽  
Simulation Results ◽  
Differential Expansion ◽  
The Relationship ◽  
Automated Tool

An automated circuit analysis tool called SPICESoft, the main objective of which is to help designers in sensitivity computation and circuit analysis is presented. Three main features of SPICESoft are described, namely Sensitivity Analysis, Circuit Performance Analysis, and Inverse Circuit Performance Analysis. A new methodology called Binary Differential Expansion used for data interpolation is also described in this paper. The relationship between device and process parameters is covered. The simulation results obtained using the proposed automated tool are compared with those of conventional computation.

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