This document presents a computational pipeline for quantifying the passive mechanical properties of mouse myocardium. The pipeline involves an experiment where a mouse heart is excised and the left ventricle is inflated from 0 to 1.44 kPa while deformation is measured via echocardiography. This deformation is used to build finite element meshes. Simulations are run across a range of parameter values for a transversely isotropic material law, and results are compared to experimental data to identify well-fitting parameter scenarios. The pipeline provides a viable method for estimating mouse myocardial stiffness parameters by comparing experimental inflation data to computer simulations.
1) The student developed a pipeline to test the ability to measure strain in carotid artery plaques using MRI.
2) Finite element models of plaques under different pressures were used to simulate MRI images.
3) Image registration software was used to measure strain by registering images at different pressures, and results were compared to the finite element models.
4) Promising results were found when the image registration grid spacing parameter was optimized, but more research is still needed to determine the effects of other MRI and registration parameters on the ability to accurately measure strain from MRI data.
The Development of Computational Fluid Dynamic Models for Studying the Detect...Cristina Staicu
This thesis presents research on developing computational fluid dynamic (CFD) models to non-invasively predict pressure drops in the aorta for patients with aortic coarctation. The research involved segmenting aortic geometries from medical images, generating 3D meshes, setting boundary conditions from flow and pressure data, and running CFD simulations. The models were validated against clinical data. A processing workflow was designed and implemented in five stages: image loading, segmentation, meshing, boundary conditions, and simulation. Efforts were made to model coarctation geometries and account for branches and collaterals. The results provide physically accurate details to supplement clinical images for diagnosing this disease.
This document discusses a study that used cardiac MRI and spectroscopy to assess myocardial triglyceride and creatine content in patients with cardiac amyloidosis compared to controls. The main findings were:
1. Patients with cardiac amyloidosis had increased left ventricular mass index and reduced global longitudinal and circumferential strain compared to controls, indicating systolic dysfunction.
2. Cardiac amyloidosis patients showed decreased myocardial triglyceride to water ratios compared to controls, but similar creatine to water ratios.
3. Lower triglyceride to water ratios correlated with worse global longitudinal and circumferential strain as well as increased left ventricular mass index.
1) Passive mechanical properties were determined for different anatomical regions of normal ovine hearts through planar biaxial stretching.
2) The left ventricle had the highest strain energy storage at 1.74 kPa, while the right atrium had the lowest at 0.36 kPa.
3) In general, tissues from the left side of the heart were stiffer than the same regions on the right side, and strain energy increased from atria to ventricles to atrial appendages.
1) The document describes a cuff-less method for measuring blood pressure non-invasively using pulse transit time (PTT), which is the time taken for blood to travel from the heart to the peripheries.
2) PTT was measured between the ECG R-wave and photoplethysmography signal from the finger. A regression equation was derived to estimate systolic and diastolic blood pressure based on PTT along with factors like age, height, weight, and heart rate.
3) The method was tested on 29 male subjects, and results showed estimated blood pressures within accepted accuracy levels compared to standard sphygmomanometry measurements. However, collecting more data could improve the
NUMERICAL SIMULATION OF BLOOD FLOW WITH SODIUM ALGINATE (SA) NANO PARTICLES I...IAEME Publication
Numerical simulation of blood flow with sodium alginate nano particles in
stenosed human arteries in the presence of body acceleration is obtained. Effect of
sodium alginate (SA) nano particles in the presence of body acceleration is observed
on velocity, flow rate and resistive impedance to blood flow in stenosed human artery.
The governing equations are discretized by explicit finite difference scheme. The
discretized equations are the simulated using MATLAB. Velocity, flow rate and
impedance to flow are observed to be influenced in the presence of both nano particles
as well as body acceleration. The joint effect of nano particles and body acceleration
is also observed. Resistance to flow is observed to be less in the presence of nano
particles. This nano particle drug delivery may be useful for patients having
cardiovascular diseases
1) The student developed a pipeline to test the ability to measure strain in carotid artery plaques using MRI.
2) Finite element models of plaques under different pressures were used to simulate MRI images.
3) Image registration software was used to measure strain by registering images at different pressures, and results were compared to the finite element models.
4) Promising results were found when the image registration grid spacing parameter was optimized, but more research is still needed to determine the effects of other MRI and registration parameters on the ability to accurately measure strain from MRI data.
The Development of Computational Fluid Dynamic Models for Studying the Detect...Cristina Staicu
This thesis presents research on developing computational fluid dynamic (CFD) models to non-invasively predict pressure drops in the aorta for patients with aortic coarctation. The research involved segmenting aortic geometries from medical images, generating 3D meshes, setting boundary conditions from flow and pressure data, and running CFD simulations. The models were validated against clinical data. A processing workflow was designed and implemented in five stages: image loading, segmentation, meshing, boundary conditions, and simulation. Efforts were made to model coarctation geometries and account for branches and collaterals. The results provide physically accurate details to supplement clinical images for diagnosing this disease.
This document discusses a study that used cardiac MRI and spectroscopy to assess myocardial triglyceride and creatine content in patients with cardiac amyloidosis compared to controls. The main findings were:
1. Patients with cardiac amyloidosis had increased left ventricular mass index and reduced global longitudinal and circumferential strain compared to controls, indicating systolic dysfunction.
2. Cardiac amyloidosis patients showed decreased myocardial triglyceride to water ratios compared to controls, but similar creatine to water ratios.
3. Lower triglyceride to water ratios correlated with worse global longitudinal and circumferential strain as well as increased left ventricular mass index.
1) Passive mechanical properties were determined for different anatomical regions of normal ovine hearts through planar biaxial stretching.
2) The left ventricle had the highest strain energy storage at 1.74 kPa, while the right atrium had the lowest at 0.36 kPa.
3) In general, tissues from the left side of the heart were stiffer than the same regions on the right side, and strain energy increased from atria to ventricles to atrial appendages.
1) The document describes a cuff-less method for measuring blood pressure non-invasively using pulse transit time (PTT), which is the time taken for blood to travel from the heart to the peripheries.
2) PTT was measured between the ECG R-wave and photoplethysmography signal from the finger. A regression equation was derived to estimate systolic and diastolic blood pressure based on PTT along with factors like age, height, weight, and heart rate.
3) The method was tested on 29 male subjects, and results showed estimated blood pressures within accepted accuracy levels compared to standard sphygmomanometry measurements. However, collecting more data could improve the
NUMERICAL SIMULATION OF BLOOD FLOW WITH SODIUM ALGINATE (SA) NANO PARTICLES I...IAEME Publication
Numerical simulation of blood flow with sodium alginate nano particles in
stenosed human arteries in the presence of body acceleration is obtained. Effect of
sodium alginate (SA) nano particles in the presence of body acceleration is observed
on velocity, flow rate and resistive impedance to blood flow in stenosed human artery.
The governing equations are discretized by explicit finite difference scheme. The
discretized equations are the simulated using MATLAB. Velocity, flow rate and
impedance to flow are observed to be influenced in the presence of both nano particles
as well as body acceleration. The joint effect of nano particles and body acceleration
is also observed. Resistance to flow is observed to be less in the presence of nano
particles. This nano particle drug delivery may be useful for patients having
cardiovascular diseases
CRMUG UK November 2015 - Testing testing! Panel Discussion with Scott Durow, ...Wesleyan
This document provides information about a panel session on testing Dynamics CRM. The panel will include Scott Durow, Sarah Critchley, and Priscilla Tse and will discuss challenges and best practices for unit testing, integration and system testing, and user acceptance testing. Brief biographies are provided for each panelist along with an agenda laying out the session structure and topics.
This document discusses different types of heart murmurs, including their locations, characteristics, and potential diagnoses. Systolic murmurs can be caused by issues with the mitral, tricuspid, aortic, or pulmonary valves closing or opening abnormally. Diastolic murmurs result from problems with the mitral, tricuspid, aortic or pulmonary valves opening or closing incorrectly. Certain murmurs like blowing, crescendo-decrescendo, or machine-like murmurs can indicate specific conditions like mitral regurgitation, aortic stenosis, or patent ductus arteriosus. The location, radiation, and changes with respiration of a murmur provide clues to determine the underlying heart problem.
The Cash Balance plan is a unique retirement tool that enables high income professionals maximize their own retirement savings while maintaining a benefit for their staffs. Actuary Chuck Munsell and pension designer Leah DeMartino will present a guide for Financial Advisors, brokers and RIAs on how cash balance plans work and provide examples of strategies to position the cash balance plan offer to win new clients and provide greater value to these high income individuals who need more aggressive options than a 401(k) or other standard retirement benefit plans.
Updated January 2015
Consulting ten commandments of small business [lesson]Fred Mmbololo
This document outlines 11 commandments or principles for small businesses to follow, including establishing a clear mission statement and strategic direction, building loyal and accountable employees while continuously upgrading management, maintaining strong relationships with vendors, customers and advisors, keeping costs and prices low while focusing on quality, growing prudently and profitably, creating operational excellence, installing management processes, and ensuring the business makes a profit.
El documento establece la constitución de la Comisión Mixta de Seguridad e Higiene de la empresa Tanques de México, S.A. de C.V. Se designa a Luis Felipe Correa Ríos como coordinador y a Valdemar Rodríguez Mendoza como secretario. También se nombra a Eusebio López Méndez, Rodrigo Solís Pérez, Germán Romo Rodríguez y Pedro Castro Gómez como vocales representantes de los patrones y los trabajadores. La comisión se reunirá según el plan de verificaciones
A research proposal on non financial reporting by Fred M'mbololoFred Mmbololo
This research proposal compares non-financial reporting practices in Australia and the European Union. Non-financial reporting enables businesses to communicate their environmental, social, and ethical performance to stakeholders. In Australia, non-financial reporting is voluntary, while the EU's Non-Financial Reporting Directive mandates certain large companies disclose information on environmental, social, and governance matters. The proposal will explore differences and similarities in non-financial reporting frameworks and common CSR activities between Australia, the EU, and the US to identify variations in reporting forms and features.
The document discusses the thyroid gland and treatment of hyperthyroidism. It covers:
1) The thyroid gland secretes hormones T3 and T4 which regulate growth, development, and metabolism. Iodine is essential for thyroid hormone synthesis.
2) Anti-thyroid drugs like methimazole, propylthiouracil and carbimazole work by inhibiting iodine uptake or coupling of iodotyrosines to prevent thyroid hormone synthesis. Radioactive iodine and beta blockers are also used to treat hyperthyroidism.
3) Corticosteroids, inorganic iodines, and iodinated contrast media have roles as adjunctive therapies for severe hyper
Bluemix Girl's Night by Keshia - Building a custom HR applicationcraftworkz
Bluemix Girls' Night - Why should boys have all the fun?
During this event, Keshia explained how she used Bluemix as a development innovation platform to create a brand new HR application in a cloud native way, fast to market,...
This study developed a programmable isolated perfused heart apparatus to characterize the effects of dynamic interaction between the heart and vasculature on cardiac function in vitro. The apparatus integrates an isolated rat heart with a lumped parameter model of the cardiovascular system. Left ventricular pressure from the isolated heart is used as input to the model to estimate ventricular volume, which is then set using a pump. This allows simulation of changes in preload and afterload to mimic heart-vasculature interaction without confounding feedback effects seen in vivo. The model includes pulmonary and systemic vascular compliances and resistances along with right and left ventricular components.
State feedback control for human inspiratory systemIJECEIAES
The mathematical modeling of human respiratory system is an essentially part in saving precision information of diagnostic about the disease of cardiovascular respiratory system. The physics of respiratory system and cardiovascular are completely interconnected with each other. In this paper, we will study the state feedback control for the inspiratory system during study the characteristics of the response output with the stability. The model of system is nonlinear and linearized it by Tayler method to be simple to matching with the control theory. We convert the system from differential equation to state equation to find the optimal control that helps to drive the respiratory system. Simulations are managed to indicate the proposed method effectiveness. The results of simulations are validated by using a real information form the health center.
PhD positions in Computational Cardiac Image Processing and ModellingAurelio Ruiz Garcia
Open positions in Computational Cardiac Image Processing and Modelling. Deadline Sept 1st 2014.
These positions are for doing research towards obtaining a PhD degree at the Department of Information & Communication Technologies (DTIC) of the Universitat Pompeu Fabra (UPF), Barcelona, Spain.
The projects will be conducted in the PhySense research group (http://physense.upf.edu), supervised by ICREA Research Prof. B. Bijnens and Dr. Oscar Camara. PhySense was recently established (2011) and focuses on integrating engineering/physics knowledge with physiology in order to provide an interdisciplinary research environment, working closely together with internationally known academic and clinical centres. This is approached by integrating and improving information acquisition, handling and processing techniques, combined with basic knowledge on pathophysiology, in order to advance clinical sciences.
This study used medical imaging and computational modeling to analyze blood flow patterns in a patient with an aortic dissection. Computational fluid dynamics (CFD) models of the patient's aorta were created using CT and MRI imaging data. Simulations were performed to: 1) Compare flow patterns in the dissected aorta to a healthy aorta model; 2) Estimate the increased workload on the heart from the dissection; and 3) Analyze the impact of secondary tears in the dissection flap on flow. The results provide insights into complex hemodynamics in dissections that may help predict patient outcomes.
Hemodynamic Assessment Series by Transonic -- Part 1: PV Loop Case StudyInsideScientific
1. PV loops provide a comprehensive examination of cardiac function by integrating measurements of pressures, volumes, flows, and metabolism.
2. The presenter uses PV loops in mini-pigs to evaluate the impacts of exercise and pharmacological therapies on heart failure with preserved ejection fraction.
3. PV loops allow the integration of data from multiple methodologies to assess global cardiovascular function and the effects of treatments. The presenter is planning to next examine different exercise intensities and combinations with therapies.
The main objective of this project is to measure the heart pumping function continuously and with maximally non-invasive methodology in a medical setting arrangement. Thus this paper is aimed to determine the study of impedance plethysmographic method to evaluate the stroke volume changes. In this paper the blood flow analysis has been carried out with fuzzy logic tool box with various activities such as Dehydration, Physical exercise, Cool skin, Warm Skin and breathes hold activity. Immediately after measuring the blood flow with the help of Impedance plethysmography, the end systolic and end diastolic values are obtained with the help of echocardiogram for the 18 subjects both in the normal condition and immediately after holding the breathe for 25 seconds. For the 18 subjects the correlation coefficient is obtained in a linear fashion between the changes in peak amplitude of forearm impedance plethysmographic waveform and changes in stroke volume before and after the 25 second breathe holding activity. Finally the forearm impedance plethysmographic waveform can be used to analyze the heart beat changes in Correlation with the changes in heart stroke volume. The process could be monitored for the series of cycles in determining the heart pumping performance.
This computational study used a fluid-solid mechanics model of the left ventricle supported by a left ventricular assist device to simulate different LVAD flow protocols. Six simulations were conducted with constant LVAD flow rates of 60 and 80 mL/s, and with sinusoidal LVAD flows synchronized and counter-synchronized with the cardiac cycle at mean rates of 60 and 80 mL/s. The results indicate that a sinusoidal LVAD flow increasing during systole and decreasing during diastole improved myocardial unloading, blood mixing in the left ventricle, and redistributed work across the myocardium compared to constant flow. Varying the LVAD flow in synchronization with the cardiac cycle had benefits over a constant flow.
This research article evaluated the diagnostic power of cardiac MRI to detect pulmonary hypertension in patients pre-selected by echocardiography. Fifty-six patients suspected of pulmonary hypertension based on echocardiography underwent right heart catheterization and cardiac MRI. The study extracted various MRI parameters proposed in previous studies as surrogates for pulmonary arterial pressure. Multivariate regression analysis identified right ventricle ejection fraction and pulmonary trunk minimum area as predictors of mean pulmonary arterial pressure, with an r-squared value of 0.5. However, the limits of agreement between MRI-predicted and catheterization-measured pressures were too wide. MRI was able to distinguish patients with normal and elevated pressures, achieving a specificity of 80% for detecting pulmonary hypertension at
A Toolkit For Forward Inverse Problems In Electrocardiography Within The SCIR...Sandra Long
This document describes a toolkit within the SCIRun problem solving environment that provides tools for constructing and manipulating electrocardiography forward and inverse models. The toolkit contains sample networks, tutorials, and documentation to guide users through assembly and execution of forward and inverse problems. It includes tools for potential-based and activation-based forward models using finite element and boundary element methods. The toolkit is demonstrated through a case study of a potential-based finite element forward model for defibrillation and an activation-based boundary element inverse model to estimate cardiac activation times from body surface potentials. The goal of the toolkit is to make relevant modeling tools accessible to researchers while facilitating integration with other software packages.
This document describes the development of an in vivo rabbit ulnar loading model to study mechanical loading effects on bone. Strain levels during ulnar loading were characterized using strain gauges and finite element models. Rabbits underwent ulnar loading at varying strain levels, and periosteal bone formation was measured using histomorphometry. Loading at 3000-4500 microstrain produced a dose-dependent increase in periosteal bone formation compared to controls, with 4500 microstrain inducing the most robust response. Loading at 5250 microstrain induced woven bone formation. The rabbit ulnar loading model provides a translatable model for studying cortical bone adaptation and responses to pharmaceuticals.
BASIC SCIENCE FOR ANAESTHETISTS BY SYLVA DOLENSKA.pdfKillerBee38
This document provides a summary of the book "Basic Science for Anaesthetists" by Sylva Dolenska. The book has been revised with a new title to better reflect its contents, which now includes additional chapters on topics relevant to the Primary FRCA examination, such as the ventilatory response to oxygen and carbon dioxide. Some chapters have been updated to reflect advances in technology for clinical measurements. The aim of the book remains to provide a concise and understandable review of the physics, mathematics, statistics, physiology and pharmacology concepts important for anaesthetists. It is intended to be an invaluable resource for trainee anaesthetists and those teaching the subject.
This document describes a study using spectral-domain optical coherence tomography (SD-OCT) to examine long-term cerebrovascular changes in response to voluntary exercise in rats. 14 rats were assigned to either an exercise or control group. SD-OCT scanning was performed under anesthesia to image the motor cortex at high resolution before and after inducing hypoxia, allowing non-invasive longitudinal assessment. Histology will also be performed and compared to SD-OCT. The results will help explore exercise-induced cerebrovascular plasticity and validate SD-OCT for mapping vascular changes over time.
CRMUG UK November 2015 - Testing testing! Panel Discussion with Scott Durow, ...Wesleyan
This document provides information about a panel session on testing Dynamics CRM. The panel will include Scott Durow, Sarah Critchley, and Priscilla Tse and will discuss challenges and best practices for unit testing, integration and system testing, and user acceptance testing. Brief biographies are provided for each panelist along with an agenda laying out the session structure and topics.
This document discusses different types of heart murmurs, including their locations, characteristics, and potential diagnoses. Systolic murmurs can be caused by issues with the mitral, tricuspid, aortic, or pulmonary valves closing or opening abnormally. Diastolic murmurs result from problems with the mitral, tricuspid, aortic or pulmonary valves opening or closing incorrectly. Certain murmurs like blowing, crescendo-decrescendo, or machine-like murmurs can indicate specific conditions like mitral regurgitation, aortic stenosis, or patent ductus arteriosus. The location, radiation, and changes with respiration of a murmur provide clues to determine the underlying heart problem.
The Cash Balance plan is a unique retirement tool that enables high income professionals maximize their own retirement savings while maintaining a benefit for their staffs. Actuary Chuck Munsell and pension designer Leah DeMartino will present a guide for Financial Advisors, brokers and RIAs on how cash balance plans work and provide examples of strategies to position the cash balance plan offer to win new clients and provide greater value to these high income individuals who need more aggressive options than a 401(k) or other standard retirement benefit plans.
Updated January 2015
Consulting ten commandments of small business [lesson]Fred Mmbololo
This document outlines 11 commandments or principles for small businesses to follow, including establishing a clear mission statement and strategic direction, building loyal and accountable employees while continuously upgrading management, maintaining strong relationships with vendors, customers and advisors, keeping costs and prices low while focusing on quality, growing prudently and profitably, creating operational excellence, installing management processes, and ensuring the business makes a profit.
El documento establece la constitución de la Comisión Mixta de Seguridad e Higiene de la empresa Tanques de México, S.A. de C.V. Se designa a Luis Felipe Correa Ríos como coordinador y a Valdemar Rodríguez Mendoza como secretario. También se nombra a Eusebio López Méndez, Rodrigo Solís Pérez, Germán Romo Rodríguez y Pedro Castro Gómez como vocales representantes de los patrones y los trabajadores. La comisión se reunirá según el plan de verificaciones
A research proposal on non financial reporting by Fred M'mbololoFred Mmbololo
This research proposal compares non-financial reporting practices in Australia and the European Union. Non-financial reporting enables businesses to communicate their environmental, social, and ethical performance to stakeholders. In Australia, non-financial reporting is voluntary, while the EU's Non-Financial Reporting Directive mandates certain large companies disclose information on environmental, social, and governance matters. The proposal will explore differences and similarities in non-financial reporting frameworks and common CSR activities between Australia, the EU, and the US to identify variations in reporting forms and features.
The document discusses the thyroid gland and treatment of hyperthyroidism. It covers:
1) The thyroid gland secretes hormones T3 and T4 which regulate growth, development, and metabolism. Iodine is essential for thyroid hormone synthesis.
2) Anti-thyroid drugs like methimazole, propylthiouracil and carbimazole work by inhibiting iodine uptake or coupling of iodotyrosines to prevent thyroid hormone synthesis. Radioactive iodine and beta blockers are also used to treat hyperthyroidism.
3) Corticosteroids, inorganic iodines, and iodinated contrast media have roles as adjunctive therapies for severe hyper
Bluemix Girl's Night by Keshia - Building a custom HR applicationcraftworkz
Bluemix Girls' Night - Why should boys have all the fun?
During this event, Keshia explained how she used Bluemix as a development innovation platform to create a brand new HR application in a cloud native way, fast to market,...
This study developed a programmable isolated perfused heart apparatus to characterize the effects of dynamic interaction between the heart and vasculature on cardiac function in vitro. The apparatus integrates an isolated rat heart with a lumped parameter model of the cardiovascular system. Left ventricular pressure from the isolated heart is used as input to the model to estimate ventricular volume, which is then set using a pump. This allows simulation of changes in preload and afterload to mimic heart-vasculature interaction without confounding feedback effects seen in vivo. The model includes pulmonary and systemic vascular compliances and resistances along with right and left ventricular components.
State feedback control for human inspiratory systemIJECEIAES
The mathematical modeling of human respiratory system is an essentially part in saving precision information of diagnostic about the disease of cardiovascular respiratory system. The physics of respiratory system and cardiovascular are completely interconnected with each other. In this paper, we will study the state feedback control for the inspiratory system during study the characteristics of the response output with the stability. The model of system is nonlinear and linearized it by Tayler method to be simple to matching with the control theory. We convert the system from differential equation to state equation to find the optimal control that helps to drive the respiratory system. Simulations are managed to indicate the proposed method effectiveness. The results of simulations are validated by using a real information form the health center.
PhD positions in Computational Cardiac Image Processing and ModellingAurelio Ruiz Garcia
Open positions in Computational Cardiac Image Processing and Modelling. Deadline Sept 1st 2014.
These positions are for doing research towards obtaining a PhD degree at the Department of Information & Communication Technologies (DTIC) of the Universitat Pompeu Fabra (UPF), Barcelona, Spain.
The projects will be conducted in the PhySense research group (http://physense.upf.edu), supervised by ICREA Research Prof. B. Bijnens and Dr. Oscar Camara. PhySense was recently established (2011) and focuses on integrating engineering/physics knowledge with physiology in order to provide an interdisciplinary research environment, working closely together with internationally known academic and clinical centres. This is approached by integrating and improving information acquisition, handling and processing techniques, combined with basic knowledge on pathophysiology, in order to advance clinical sciences.
This study used medical imaging and computational modeling to analyze blood flow patterns in a patient with an aortic dissection. Computational fluid dynamics (CFD) models of the patient's aorta were created using CT and MRI imaging data. Simulations were performed to: 1) Compare flow patterns in the dissected aorta to a healthy aorta model; 2) Estimate the increased workload on the heart from the dissection; and 3) Analyze the impact of secondary tears in the dissection flap on flow. The results provide insights into complex hemodynamics in dissections that may help predict patient outcomes.
Hemodynamic Assessment Series by Transonic -- Part 1: PV Loop Case StudyInsideScientific
1. PV loops provide a comprehensive examination of cardiac function by integrating measurements of pressures, volumes, flows, and metabolism.
2. The presenter uses PV loops in mini-pigs to evaluate the impacts of exercise and pharmacological therapies on heart failure with preserved ejection fraction.
3. PV loops allow the integration of data from multiple methodologies to assess global cardiovascular function and the effects of treatments. The presenter is planning to next examine different exercise intensities and combinations with therapies.
The main objective of this project is to measure the heart pumping function continuously and with maximally non-invasive methodology in a medical setting arrangement. Thus this paper is aimed to determine the study of impedance plethysmographic method to evaluate the stroke volume changes. In this paper the blood flow analysis has been carried out with fuzzy logic tool box with various activities such as Dehydration, Physical exercise, Cool skin, Warm Skin and breathes hold activity. Immediately after measuring the blood flow with the help of Impedance plethysmography, the end systolic and end diastolic values are obtained with the help of echocardiogram for the 18 subjects both in the normal condition and immediately after holding the breathe for 25 seconds. For the 18 subjects the correlation coefficient is obtained in a linear fashion between the changes in peak amplitude of forearm impedance plethysmographic waveform and changes in stroke volume before and after the 25 second breathe holding activity. Finally the forearm impedance plethysmographic waveform can be used to analyze the heart beat changes in Correlation with the changes in heart stroke volume. The process could be monitored for the series of cycles in determining the heart pumping performance.
This computational study used a fluid-solid mechanics model of the left ventricle supported by a left ventricular assist device to simulate different LVAD flow protocols. Six simulations were conducted with constant LVAD flow rates of 60 and 80 mL/s, and with sinusoidal LVAD flows synchronized and counter-synchronized with the cardiac cycle at mean rates of 60 and 80 mL/s. The results indicate that a sinusoidal LVAD flow increasing during systole and decreasing during diastole improved myocardial unloading, blood mixing in the left ventricle, and redistributed work across the myocardium compared to constant flow. Varying the LVAD flow in synchronization with the cardiac cycle had benefits over a constant flow.
This research article evaluated the diagnostic power of cardiac MRI to detect pulmonary hypertension in patients pre-selected by echocardiography. Fifty-six patients suspected of pulmonary hypertension based on echocardiography underwent right heart catheterization and cardiac MRI. The study extracted various MRI parameters proposed in previous studies as surrogates for pulmonary arterial pressure. Multivariate regression analysis identified right ventricle ejection fraction and pulmonary trunk minimum area as predictors of mean pulmonary arterial pressure, with an r-squared value of 0.5. However, the limits of agreement between MRI-predicted and catheterization-measured pressures were too wide. MRI was able to distinguish patients with normal and elevated pressures, achieving a specificity of 80% for detecting pulmonary hypertension at
A Toolkit For Forward Inverse Problems In Electrocardiography Within The SCIR...Sandra Long
This document describes a toolkit within the SCIRun problem solving environment that provides tools for constructing and manipulating electrocardiography forward and inverse models. The toolkit contains sample networks, tutorials, and documentation to guide users through assembly and execution of forward and inverse problems. It includes tools for potential-based and activation-based forward models using finite element and boundary element methods. The toolkit is demonstrated through a case study of a potential-based finite element forward model for defibrillation and an activation-based boundary element inverse model to estimate cardiac activation times from body surface potentials. The goal of the toolkit is to make relevant modeling tools accessible to researchers while facilitating integration with other software packages.
This document describes the development of an in vivo rabbit ulnar loading model to study mechanical loading effects on bone. Strain levels during ulnar loading were characterized using strain gauges and finite element models. Rabbits underwent ulnar loading at varying strain levels, and periosteal bone formation was measured using histomorphometry. Loading at 3000-4500 microstrain produced a dose-dependent increase in periosteal bone formation compared to controls, with 4500 microstrain inducing the most robust response. Loading at 5250 microstrain induced woven bone formation. The rabbit ulnar loading model provides a translatable model for studying cortical bone adaptation and responses to pharmaceuticals.
BASIC SCIENCE FOR ANAESTHETISTS BY SYLVA DOLENSKA.pdfKillerBee38
This document provides a summary of the book "Basic Science for Anaesthetists" by Sylva Dolenska. The book has been revised with a new title to better reflect its contents, which now includes additional chapters on topics relevant to the Primary FRCA examination, such as the ventilatory response to oxygen and carbon dioxide. Some chapters have been updated to reflect advances in technology for clinical measurements. The aim of the book remains to provide a concise and understandable review of the physics, mathematics, statistics, physiology and pharmacology concepts important for anaesthetists. It is intended to be an invaluable resource for trainee anaesthetists and those teaching the subject.
This document describes a study using spectral-domain optical coherence tomography (SD-OCT) to examine long-term cerebrovascular changes in response to voluntary exercise in rats. 14 rats were assigned to either an exercise or control group. SD-OCT scanning was performed under anesthesia to image the motor cortex at high resolution before and after inducing hypoxia, allowing non-invasive longitudinal assessment. Histology will also be performed and compared to SD-OCT. The results will help explore exercise-induced cerebrovascular plasticity and validate SD-OCT for mapping vascular changes over time.
The document summarizes a study comparing outcomes of patients who underwent aortic arch surgery using antegrade cerebral perfusion (ACP) versus without ACP. The study found significantly lower rates of postoperative stroke (2% vs 13%) and better 3-year survival (93% vs 78%) in the ACP group. Multivariate analysis confirmed ACP was associated with reduced stroke risk and improved long-term survival. The results suggest ACP provides neuroprotective and survival advantages over surgery without ACP for aortic arch pathology requiring prolonged repair periods.
Braun F. et al.: Comparing belt positions for monitoring the descending aorta...Hauke Sann
Swisstom Scientific Library; 15th International Conference on Biomedical Applications of Electrical Impedance Tomography, Gananoque, Ontario, Canada, April 24-26, 2014
INVESTIGATING THE USE OF IMPEDANCE PLETHYSMOGRAPHY FOR DETECTING DECREASED BL...Mirza Baig
Literature Review
According to Isabel Morales’ research, the foot impedance plethysmography was carried out with two distinct kinds of electrodes, using 1mA/10kHz and finding the impedance of the foot.
In this study Piuzzi research is an ultimate technique selected that makes use of a current with a frequency of 50 kHz that is injected into the thorax of the subject using a couple of textile electrodes.
In this study of Ramkumar & Babu, blood flow was performed using a fuzzy logic toolbox with many different activities, measured before and after the 25 seconds of breath-holding activity. The plethysmographic waveform of forearm impedance can be used to analyze the changes in a heartbeat that are correlated with the changes in heart stroke volume.
Contribution
In this work we are investigating using multiple electrodes to see the additional data going to make testing easier.
Our research is primarily focusing on the amount of blood flow through the finger of the upper limb for diabetic patients.
Conclusion
The finger-simplified model was created in model geometry. A framework made up of five parts was used to build the finger. (i.e., skin, fat, artery, muscle, and bone)
The study includes COMSOL simulation results compared with experimental results to obtain the optimum parameters for this technique. The COMSOL simulation uses 4 electrodes in different positions with a current of 10mA giving the optimal frequency of 100Hz.
It was shown that multiple electrodes can be useful in obtaining impedance change.
This is useful because signals can not be obtained from one pair, or to further support the results.
The study was performed under normal resting conditions where an experimental procedure was set up to measure the impedance response from the finger.
Experiment results were not conclusive as more sensitive impedance analyzers are required.
This research will be helpful to find out the heartbeat using impedance plethysmography.
This study examined the relationship between volume overhydration and endothelial dysfunction in 81 stable patients on continuous ambulatory peritoneal dialysis. Volume status was assessed by normalized extracellular water and endothelial function was estimated by flow-mediated dilation of the brachial artery. There was an independent correlation between the index of volume status (normalized extracellular water) and endothelial function (flow-mediated dilation), with higher normalized extracellular water related to worse endothelial function. Multiple regression analysis identified calcium-phosphate product, normalized extracellular water, and dialysis vintage as independent determinants of endothelial function. The results suggest that volume overhydration may lead to increased cardiovascular risk in dialysis patients through its effects on endothelial dysfunction.
This document summarizes a study that investigated the determinants of oxygen and carbon dioxide transfer during extracorporeal membrane oxygenation (ECMO) in an experimental pig model of multiple organ dysfunction syndrome (MODS). The study found that oxygen transfer was positively associated with blood flow and negatively associated with pre-membrane oxygen saturation and carbon dioxide levels, while carbon dioxide transfer was positively associated with blood and gas flows and pre-membrane carbon dioxide levels. Passing blood through the ECMO circuit increased pH and decreased carbon dioxide levels. Both oxygen and carbon dioxide transfers were significantly determined by blood flow.
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### How TDM Works
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TIME DIVISION MULTIPLEXING TECHNIQUE FOR COMMUNICATION SYSTEM
1 s2.0-s0010482514001784-main
1. A computational pipeline for quantification of mouse myocardial
stiffness parameters
Øyvind Nordbø a
, Pablo Lamata b
, Sander Land b
, Steven Niederer b
, Jan M. Aronsen c,d
,
William E. Louch c,e
, Ivar Sjaastad c
, Harald Martens f
, Arne B. Gjuvsland g
, Kristin Tøndel b
,
Hans Torp h
, Maelene Lohezic i
, Jurgen E. Schneider h
, Espen W. Remme e,j
, Nicolas Smith b
,
Stig W. Omholt k
, Jon Olav Vik g,n
a
Department of Mathematical Sciences and Technology, Centre for Integrative Genetics, Norwegian University of Life Sciences, P.O. Box 5003,
N-1432 Ås, Norway
b
Department of Biomedical Engineering, King’s College London, St. Thomas' Hospital, Westminster Bridge Road, London SE17EH, UK
c
Institute for Experimental Medical Research, Oslo University Hospital Ullevål and University of Oslo, Kirkeveien 166, 4th Floor Building 7, 0407 Oslo, Norway
d
Bjørknes College, Oslo, Norway
e
KG Jebsen Cardiac Research Center and Center for Heart Failure Research, University of Oslo, 0407 Oslo, Norway
f
Department of Engineering Cybernetics, Faculty of Information Technology, Mathematics and Electrical Engineering, Norwegian University of Science and
Technology, Trondheim, Norway
g
Department of Animal and Aquacultural Sciences, Centre for Integrative Genetics, Norwegian University of Life Sciences, P.O. Box 5003, N-1432 Ås, Norway
h
Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Postboks 8905, Medisinsk teknisk
forskningssenter, NO-7491 Trondheim, Norway
i
Radcliffe Department of Medicine, Division of Cardiovascular Medicine, University of Oxford, Welcome Trust Centre for Human Genetics, Roosevelt Drive,
Oxford OX3 7BN, UK
j
Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway
k
Faculty of Medicine, Norwegian University of Science and Technology, P.O. Box 8905, N-7491 Trondheim, Norway
a r t i c l e i n f o
Article history:
Received 12 March 2014
Accepted 20 July 2014
Keywords:
Myocardial stiffness
Parameter estimation
Passive inflation
Transversal isotropy
Speckle tracking
a b s t r a c t
The mouse is an important model for theoretical–experimental cardiac research, and biophysically based
whole organ models of the mouse heart are now within reach. However, the passive material properties
of mouse myocardium have not been much studied.
We present an experimental setup and associated computational pipeline to quantify these stiffness
properties. A mouse heart was excised and the left ventricle experimentally inflated from 0 to 1.44 kPa in
eleven steps, and the resulting deformation was estimated by echocardiography and speckle tracking. An
in silico counterpart to this experiment was built using finite element methods and data on ventricular
tissue microstructure from diffusion tensor MRI. This model assumed a hyperelastic, transversely
isotropic material law to describe the force–deformation relationship, and was simulated for many
parameter scenarios, covering the relevant range of parameter space. To identify well-fitting parameter
scenarios, we compared experimental and simulated outcomes across the whole range of pressures,
based partly on gross phenotypes (volume, elastic energy, and short- and long-axis diameter), and partly
on node positions in the geometrical mesh. This identified a narrow region of experimentally compatible
values of the material parameters. Estimation turned out to be more precise when based on changes in
gross phenotypes, compared to the prevailing practice of using displacements of the material points. We
conclude that the presented experimental setup and computational pipeline is a viable method that
deserves wider application.
& 2014 Elsevier Ltd. All rights reserved.
1. Introduction
The passive mechanical properties of the heart wall play an
important role during the filling of the ventricle; for instance,
stiffening of the myocardium can lead to diastolic dysfunction and
heart failure [1]. Incorporating patient-specific geometries and
Contents lists available at ScienceDirect
journal homepage: www.elsevier.com/locate/cbm
Computers in Biology and Medicine
http://dx.doi.org/10.1016/j.compbiomed.2014.07.013
0010-4825/& 2014 Elsevier Ltd. All rights reserved.
Abbreviations: LVP, Left Ventricular Pressure; MVO, Mitral Valve Opening; ED,
End Diastole; ES, End Systole; PV, Pressure Volume
n
Corresponding author. Tel.: þ47 45882998; fax: þ47 64965101.
E-mail address: jonovik@gmail.com (J.O. Vik).
Computers in Biology and Medicine 53 (2014) 65–75
2. material properties into biomechanical models holds promise for
the improved diagnosis and treatment of heart failure [2,3]. In
biomechanical models, the stress–strain relationship for myocar-
dial tissue is described by constitutive laws whose parameters
describe the material stiffness along the microstructural axes, e.g.
fibre and sheet directions. Several studies have quantified passive
myocardial stiffness in humans [3–5] and model organisms, such
as the pig [6,7], dog [8,9], and rat [10] (see Table 1, with
references). Less well studied, however, is the mouse, which is
an important model organism in cardiac research. Transgenic
mouse models have been extensively used in cardiac research
over the last decade, where manipulation of the mouse genome
has provided several novel insights in the development of cardiac
disease [11]. Alterations of the myocardial properties of the heart,
both in the extracellular matrix and in the cardiomyocytes, are
suggested to play a major role in development of diastolic
dysfunction and heart failure. Several mutations leading to heri-
table heart disease occur in both mouse and human [11], and the
hearts have similar composition and function with regards to
mechanical properties [12].
Here we propose a workflow for estimation of passive material
properties of mouse myocardium by comparing computer simula-
tions of soft tissue mechanics to observed deformation under
passive inflation of an excised mouse heart. Firstly, we estimate
trajectories of material points by speckle tracking of echo data
through the deformation from zero to end diastolic pressure levels.
This deformation is used, together with fibre structure obtained
from diffusion tensor MRI, to build meshes for computer simula-
tions. Secondly, we run model simulations and use full factorial
experimental designs to cover the biological relevant region of the
parameter space for the transversely isotropic Guccione law [13].
The results show that the parameters of the constitutive law are
not separately identifiable from these passive inflation measure-
ments alone, in accordance with previous studies [14–16]. For the
four-dimensional parameter space of the material law, we identify
an elongated region of parameter combinations with nearly
equivalent good fit to deformation data from passive inflation.
We describe the structure of this parameter redundancy, and
compare our findings with published estimates. Following a
discussion of its advantages and limitations, we conclude that
the presented pipeline merits wider application.
2. Methods
The quantification of the passive mechanical properties of the
myocardium relies on mechanistic models whose parameters are
tuned to reproduce the observation of a corresponding experiment
[9,14,15]. Below we describe the passive inflation experiment with
deformation measurement, MR imaging for geometric meshing,
image processing and speckle tracking to estimate deformation,
mechanics simulations, and comparison of experiment and
simulation.
2.1. Passive inflation experiment
A single mouse was anesthetized with 5% isoflurane and
sacrificed by cervical dislocation. The heart was then rapidly
excised and cannulated via the aorta and mounted on a Langen-
dorff setup (Fig. 1). The cannula was firstly placed over the level of
the aortic valves, to perfuse the myocardium with cardioplegic
solution of pH 7.4, 118.3 mM NaCl, 3.0 mM KCl, 4 mM MgSO4,
0.2 mM CaCl2, 2.4 mM KH2PO4, 24.9 mM NaHCO3, 10 mM glucose,
2.2 mM mannitol. Some calcium was included in the superfusate
since calcium-free conditions promote breakdown of gap junc-
tions and dissociation of cardiomyocytes [17], which could cause
underestimates of myocardial stiffness. The cannula was then
introduced into the left ventricle, and thereafter retracted into
the aorta. This technique allowed the cannula both to manipulate
left ventricular pressure and to perfuse the coronary arteries; the
latter was found necessary to prevent ischemia and stiffening in
preliminary experiments. Pressure was increased from 0 kPa to
approximately 1.44 kPa over 10 s by adjusting the height of a fluid
column connected to the cannula. Deformation of the left ventricle
Table 1
Studies estimating the parameters in the Guccione and Costa material laws. For the current study, parentheses show the range of each parameter among scenarios that fit
within a 25% increase from the minimum value of the objective function (i.e. least lack-of-fit). The Costa law is a generalization of the Guccione law, with separate coefficients
for each term in the parentheses in Eq. (5). See Supplementary Fig. S1 for a visualization of the stress–strain relationships corresponding to these parameter scenarios.
ED¼End Diastole, ES¼End Systole, PV¼Pressure Volume, MVO¼Mitral Valve Opening
Study Experiment Reference
configuration
Recording Time-points
used
Species a (kPa) b1 b2 b3
Guccione law
[10]a
Passive inflation Cylinder PV-curves, implanted
markers
5 Rat 2.2 9.2 2.0 3.7
Dog 2.4 26.7 2.0 14.7
[8] Epicardial
suction
Zero pressure Tagged MRI 3 Dog 0.10–1.0 39.5–93.0 6.1–61.6 3.1–73.1
[14] Passive inflation Zero pressure Tagged MRI 5 Pig 3.0 11.1 1.8 10.0
[41] In vivo MVO Tagged MRI 2 (ED, ES) Sheep 0.12–0.35 9.2–67.1 5.0–26.6 9.3–21.6
[6] Passive inflation Low pressure Tagged MRI 5 Pig 0.07–0.79 8.0–83.4 6.1–36.4 8.2–62.4
[44] In Vivo MVO Tagged MRI 2 (ED, ES) Sheep 0.95 49.3 19.2 17.4
[9]a
In Vivo MVO Tagged MRI, pressure wire 2 (MVO, ED) Dog 1.7 14.3 4.5 0.76
[24] In Vivo Zero pressure Tagged MRI, pressure wire 2 Human 0.3 41.7 9.1 51.5
[45] Passive inflation Mid Diastole PV-curves 3 Mouse 1.1 8.0 2.0 3.7
[15]a
In vivo Calculated Tagged MRI, pressure wire 4–6 Human 2 19.3 10.7 12.8
Costa lawb
[46]a
In vivo Ellipsoid Implanted markers 2 (ED, ES) Dog 1.8 6.0 3.0–12.0 3.0–7.0
[47] Shear tests Unstressed Tissue block Several Pig 0.22 42.5 7.8–18.6 10.9–11.0
[7] Shear tests Unstressed Tissue block Several Pig 0.26 37.2 9.1–18.9 12.0
[48] Passive inflation Calculated PV-curves Several Human 0.3 39.0 4.2–7.6 12.8–17.2
Current
study
Passive inflation Zero pressure Echocardiography 8 Mouse 3.1 (2.0–
5.6)
5.0 (2.7–
7.0)
3.7 (2.1–
5.2)
2.6 (1.5–
6.0)
a
These studies used a definition of a that was twice the one used in the other studies. Estimates in this table have been halved to make them directly comparable with
the others.
b
The orthotropic Costa law has three parameters in place of b2 and two in place of b3. The values in the b2 and b3 columns for Costa-law studies show the variability
between these non-isotropic coefficients.
Ø. Nordbø et al. / Computers in Biology and Medicine 53 (2014) 65–7566
3. was recorded by B-mode echocardiography (Vevo2100, VisualSo-
nics) using a 35 MHz scan head. Three short-axis (probe mounted
at the side of the ventricle) and four long-axis views (probe
mounted at apex) were recorded for each pressure level (see
Fig. 1 for details). Due to capillary forces in the cannula, the left
ventricle pressure was not equivalent to the height of the fluid
column. In a subsequent experiment, we therefore calibrated left
ventricular pressure vs. fluid column height by a Samba pressure
catheter (Samba 3000; Samba Sensors AB), inserted via the apex.
The Samba pressure catheter was autocalibrated using the Samba
memory control unit at room temperature. Proper calibration was
evaluated by pressure at 0 mmHg at no height of the water column
and 10 mmHg at the corresponding height of the water column.
2.2. Mesh of mouse ventricle with embedded microstructure
MR imaging: Diffusion tensor MRI (DTI) measurements of an
isolated mouse heart (a different individual than the one used in the
inflation experiment) embedded in 1% agarose were performed on
a 9.4 T horizontal bore MR system (Agilent Technologies, Santa Clara,
CA) equipped with a shielded gradient system (Gmax¼1 T/m, rise
time¼130 ms, inner diameter¼60 mm), using a 13 mm-diameter
volume transmit/receive coil. A 3D fast spin-echo sequence was used
as reported previously [18] with the following imaging parameters:
TR¼1 s, number of echoes¼8, TEeff¼44.25 ms, matrix size¼256Â
256 Â 192, number of averages¼4, field of view 13 Â 13 Â
13 mm3
(yielding a resolution of 51 Â 51 Â 68 mm3
), maximum
b-value¼688 s/mm2
(including imaging gradients and cross-terms
between imaging and diffusion gradients). Eight non-collinear
gradients directions were used, arranged according to an optimized
scheme based on the electrostatic repulsion principle [19].
Post-processing: The fibre field was extracted from these 3D
DTI data as described previously [20]. A smooth cubic Hermite
mesh [21] of the left ventricle was built, and the fibre field was
embedded into this mesh (see Fig. 3). The estimated transmural
gradient in fibre angle was similar to previous findings [22].
Fig. 1. (a) Sketch of experimental setup for echo measurements; (b) Mouse heart with cannula and echo recorder; (c) placement of long-axis views of the heart (451 rotation
between views, probe placed apically to the heart); (d) placement of short-axis views (2 mm vertical spacing, probe placed at the side of the heart)
Ø. Nordbø et al. / Computers in Biology and Medicine 53 (2014) 65–75 67
4. 2.3. Speckle tracking and estimation of 3D deformation
In ultrasound imaging, speckle pattern arises because sub-
resolution scatterers interfere with the incoming ultrasound pulses.
Although the reflected signal contains no information about the
underlying microstructure of the tissue [23], individual pieces of
tissue respond consistently to the ultrasound, and can thus be traced
through a sequence of images. However, there is some uncertainty
due to decorrelation of the speckle pattern between successive
frames, as may be caused by out-of-plane motion, rotation, deforma-
tion, and additive thermal noise. Apart from the ultrasound gel and
probe, no other external forces where applied to the ventricle.
Because the excised heart was still beating slightly, we removed
images that were from the systolic phase, as identified by a high
mean absolute signal difference between subsequent images. We
used block-matching [23] and followed endo- and epicardial points
between subsequent images through the inflation, as detailed in
Appendix A. The particle paths estimated from the different slices
were aligned into 3D deformed configurations for the various
pressures (methods are explained in Appendix B), and a set of
smooth cubic Hermite interpolated meshes (CH meshes) were then
constructed combining the methods described in [21,24] (see Fig. 3).
2.4. Mechanical simulations
The myocardium was modelled as a hyper-elastic incompres-
sible material [25] with homogenous, transversal isotropic
properties. The framework for mechanics is described in [26].
Adopting the approach of Ref. [14], we used the cubic Hermite
mesh corresponding to the zero pressure configuration (CH1, see
Fig. 3) of the left ventricle (Fig. 4) as the reference configuration
[27]. According to [13], the estimated stiffness parameters were
not particularly sensitive to the magnitude of the residual stress
[28], which supports our approach.
We formulate the stress equilibrium equations by using the
principle of virtual work on a general deformable body with initial
volume V and surface area A
Z
V
S : δEdV À
Z
A
pappF ÀT
NUδudA ¼ 0: ð1Þ
Here S is the second Piola–Kirchhoff stress tensor and δE is the
virtual Lagrangian strain tensor. papp is the applied ventricular
pressure acting on the endocardial surface, F ÀT
is the inverse of
the transposed deformation gradient tensor, N is the normal vector
for the undeformed material surface while δu is an arbitrary virtual
displacement. For hyper-elastic materials, the components of the
second Piola–Kirchhoff stress tensor are calculated by differentiating
the strain energy function by the corresponding components of the
Lagrangian strain tensor. For incompressible materials, the strains are
separated into distortional and dilatational components, and we
calculate the second Piola–Kirchhoff stress tensor from
S ¼
∂ ^W
∂E
ÀJpðFT
FÞÀ1
; ð2Þ
Fig. 2. Echo recordings of a left ventricle excised from a mouse, at zero pressure (left) and passively inflated to 1.44 kPa (right). Particle paths during inflation, estimated by
speckle tracking, are shown as red lines (the same paths are shown in both left and right images for reference). Red circles mark segmentation points of the inner and outer
walls at the respective pressures, so that the left and right images have the starting and ending positions circled, respectively. Image dimensions are 12 mm  11 mm (long
axis) and 12 mm  11 mm (short axis). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.).
Ø. Nordbø et al. / Computers in Biology and Medicine 53 (2014) 65–7568
5. where ^W is the strain energy function and F is the deformation
gradient tensor. The scalar P serves as a Lagrangian multiplier
interpreted as the hydrostatic pressure in the material/tissue. The
work done by the hydrostatic forces is zero due to the
incompressibility constraint, expressed on variational form as
Z
V
ðJ À1ÞpdV ¼ 0; ð3Þ
Fig. 3. Workflow for generating cubic Hermite (CH) meshes. Material points were followed by speckle tracking from different views and aligned into quadratic interpolated
meshes (Q-mesh). The zero pressure CH mesh (CH1) was built by fitting the fibre field (yellow lines) to the binary mask of the Q-mesh corresponding to zero pressure (Q1)
[21]. Then we mapped all Gauss point positions back to Q1 and calculated their displacements corresponding to the various pressures. These displacements were used
together with the CH1 mesh to build cubic Hermite meshes for the various pressures [24]. The CH1 mesh was used as reference configuration for the simulation, while the
other CH meshes constituted the experimental measured configurations for the various pressures. (For interpretation of the references to colour in this figure legend, the
reader is referred to the web version of this article.).
Fig. 4. Cubic Hermite interpolated meshes of the zero pressure (left) and maximal pressure (1.44 kPa) configuration (right) based on the deformation field captured by
experiments and speckle tracking. The nodes in the basal plane were constrained such that no material points contained on the basal surface were allowed to move in the z
direction. The endocardial basal node at the centre of the free wall (red dot) was not allowed to move at all, while one at the middle of the septum (green dot) was only
allowed to move in the radial direction. Yellow lines indicate fibre angles fitted from DTI data. (For interpretation of the references to colour in this figure legend, the reader is
referred to the web version of this article.).
Ø. Nordbø et al. / Computers in Biology and Medicine 53 (2014) 65–75 69
6. where J is the determinant of the deformation gradient tensor F. The
stress–strain relation in hyper-elastic models follows from our
assumption of a strain energy function, ^W. The strain energy density
function, ^W, was described by the Guccione law [13]
^W ¼
1
2
aðeQ
À1Þ ð4Þ
where
Q ¼ b1E2
11 þb2ðE2
22 þ2E23E32 þE2
33Þþb3ð2E12E21 þ2E13E31Þ: ð5Þ
Here, a, b1, b2 and b3 are material specific parameters, while Exy
are the various components of the Lagrangian strain tensor aligned
to the underlying tissue microstructure. The subscripts indicate
the microstructural directions (1 is along the fibres while 2 and
3 are orthogonal directions, normal to the fibres).
Table 1 summarizes published parameter estimates for the
Guccione [13] and Costa [29] laws, showing that stiffness para-
meters vary across two orders of magnitude. To comprehensively
cover the parameter space, simulations were performed with
parameters incremented based on a log scale from the minimum
to the maximum value reported in Table 1.
For the 4 Guccione law parameters, we used a full factorial
design with eight levels, resulting initially in 84
¼ 4096 parameter
sets. For each parameter set, the simulation model was run for the
same pressure steps as in the experiment (eleven levels ranging
from 0 to 1.44 kPa).
We applied boundary conditions constraining the basal plane
to not move in the z-direction, which should correspond well to
the experimental setup where the heart was attached to the
cannula through the aortic valve. Additional Dirichlet boundary
conditions to avoid whole-body rotation/translation are shown in
Fig. 4.
Inside the cavity, we assumed a homogeneous internal pres-
sure, which should be a reasonable assumption due to the low
velocity of the flow. In the model we neglected the forces between
the ultrasound gel and the heart, which is the simplest possible
assumption until such forces are measured. As in previous pub-
lished studies of similar setups [14], we also assumed that the
influence from the right ventricle was negligible.
2.5. Comparison of measured and simulated deformations
In both the simulations and the measurements, the shape of
the heart ventricle at a given pressure is represented by node
positions and an associated cubic Hermite interpolation of the
surfaces between nodes. We tried two different objective functions
for comparison of experimental and simulated deformation,
restricting the computation to the most biologically relevant
pressure range [30], 40.2 kPa.
1. Comparison of positions for all endocardial and epicardial
nodes in the CH mesh. The criterion for good fit was the L2
norm between experimental and simulated node position,
averaged over the relevant pressures M and nodes N in the
mesh
Ω1 ¼
1
MN
∑
M
m ¼ 1
∑
N
n ¼ 1
ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
ðxsim ÀxexpÞ2
þðysim ÀyexpÞ2
þðzsim ÀzexpÞ2
q
mn
ð6Þ
2. Comparison of K¼4 aggregated phenotypes (change in
Volume (ΔV), short and long axis diameter (ΔSa and ΔLa),
and elastic energy (
R
PdV, computed as the integral of the
pressure–volume curve). For each phenotypic variable, the
difference between simulation and experiment is nondimen-
sionalized as a proportion of the respective experimental
value. Then, each variable is weighted equally in averaging
over the K phenotypes and M relevant pressures
Ω2 ¼
1
MK
∑
M
m ¼ 1
∑
K
k ¼ 1
abs
Φsim ÀΦexp
Φexp
mk
ð7Þ
These objective functions were computed for all simulated para-
meter scenarios, and we identified the parameter regions that
corresponded to low values of each objective function. The
identified region of the parameter space was further analyzed by
manually selecting new parameter limits and running new simu-
lations for a full factorial design over the new parameter regions.
We did this in an iterative way (3 times), and got an overview of
the landscape of the parameter space and were able to see the
correlation between estimated parameters.
We evaluated the ability of each objective function to precisely
estimate parameters (i.e. identify a small set of well-fitting para-
meter scenarios) by asking “how many parameter scenarios lie
within a given % increase from the optimal value (least lack-of-fit)
of the objective function?” This is valid because both objective
functions have a meaningful absolute zero point.
3. Results
3.1. Experimental deformation
The deformation of the experimentally manipulated heart was
estimated by speckle tracking of four long-axis and three short-axis
image sequences. The free wall generated larger longitudinal strains
than the septum, causing the apex to tilt towards the septum during
the inflation (Fig. 2). The pressure–volume relationship was quite
linear within the interval of applied pressures (Fig. 7a), in agree-
ment with previous in vivo work [31,32]. The mesh corresponding
to zero and maximum pressures are shown in Fig. 4.
3.2. Comparison of simulated vs. experimental deformation
The objective function based on aggregated phenotypes
(Eq. (7)) was more selective than the one based on node positions
(Eq. (6)), in terms of identifying some parameter scenarios as
better fitting than others (Fig. 5). For example, the number of
parameter scenarios within a 50% increase from the minimum of
the objective functions (6) and (7) was 5729 and 65, respectively.
Likewise, the contrast between Figs. 6 and 7a shows how the
scenarios selected by the latter criterion give a much tighter match
to the observed inflation trajectory. Furthermore, the objective
function (6) tended to select scenarios with much lower compli-
ance than observed in the experiment (Fig. 6) and worse fits for
whole organ phenotypes (Fig. 7). Subsequent analyses were there-
fore based on the objective function in Eq. (7). Especially for the
volume, short axis and elastic energy, the model was able to
capture the essential dynamics.
3.3. Correlation structure of well-fitting parameter combinations
Well-fitting parameter combinations (i.e. those with a low
value of the objective function) showed considerable variation
along all individual parameter axes, though there were clear
patterns of covariation among parameters (Fig. 8). Similar to the
finding in [24], the well-fitting parameter scenarios tended to lie
nearly along a straight line in the space of (log a, log(b1 þb2 þb3)).
The estimated overall stiffness parameter a was clearly
bounded from below, while the values of the b were bounded
from above. Conditional on a value for a, the b1 and b2 parameters
were also bounded from below, but the optimal estimate of b3
approached parameter regions with bad convergence of the
Ø. Nordbø et al. / Computers in Biology and Medicine 53 (2014) 65–7570
7. mechanics solver. The tissue was stiffer along the fibres than in the
directions orthogonal to the fibres (b1 ¼5.0, b2 ¼3.7, b3 ¼2.6), with
b2 more tightly constrained than b1 and b3 (Table 1, Fig. 8).
Although the point estimate appears comfortably inside the
explored parameter region as viewed in the projections in Fig. 8,
there were convergence problems for some of the parameter
scenarios adjoining the best-fitting one as viewed in more than
two parameter dimensions. Therefore, we cannot conclude
whether the material parameters would be uniquely identifiable
with a more robust numerical integration solver.
4. Discussion
There are several advantages to the experimental and compu-
tational pipeline presented here. Echocardiography is simple to
use during pressure manipulation of excised hearts and is faster
than tagged MRI (as used in e.g. [14]), thus reducing problems
with rigor mortis. Furthermore, it can follow internal material
points over the entire geometry [9], unlike the method of video
recordings of epicardial markers (used by [33]). Passive inflation
experiments avoid the sectioning of tissue required for uni-axial
and biaxial material testing [34], which would disrupt the micro-
structure and influence the material properties. However, this
limits the possibility of experimentally inducing shear forces as
described by [35]. [8] argue that passive inflation produces
insufficient transverse shear strain to quantify the material proper-
ties in those directions, and therefore developed an epicardial
suction setup for isolated arrested hearts. However, our results
indicate that the relevant parameter (b3) is constrained from
above (Fig. 8), but shows larger relative uncertainty than the other
b parameters in the Guccione law Eqs. (4), (5).
Our numerical experiments enable parameter estimation and
an overview of the structure of parameter uncertainty across a
bounding box of all previously published parameter estimates
(Table 1; see Supplementary Fig. S1 for a visual comparison of the
corresponding stress–strain relationships). The simultaneous esti-
mation of parameters is an improvement over one-at-a-time
optimization, and highlights the possibility that many empirical
data sets may not be able to support the complexity of commonly
used models and material laws [24,36]. The robustness of an
exhaustive search comes with the associated computational
cost of a wide sweep of parameters, as compared with other
approaches [4,24,37,38].
The definition of an adequate objective function to compare
data and model is critical for a data assimilation method. Both data
and model are limited by acquisition issues and assumptions,
respectively, and a suitable choice of the space to compare them is
required. Parameters were easier to identify using aggregate
measures of cardiac deformation, rather than the more detailed
node positions, for the goodness-of-fit criterion (objective func-
tion). This may reflect an inability of our model to mimic certain
deformations that occurred in the experimental data, particularly
a bending due to larger longitudinal strains in the free ventricular
wall than the septum during inflation (Fig. 3, bottom), or circum-
ferential variation in material stiffness, violating our assumption of
homogeneity. Other possible causes originate in the experimental
data, a 3D reconstruction of 2D observations that is subject to
misregistration and out-of-plane errors. Regardless of the cause,
our results suggest that a gross description of mechanical defor-
mation introduces the benefit of a more relevant and robust
comparison between data and model.
As opposed to the traditional and more intuitive direct use of
displacement fields for the objective function [9,24], recent works
have explored the use of integral deformation metrics [37], or
advanced mathematical frameworks (using the concept of cur-
rents) [39]. Our proposed aggregated phenotypic metric is a
simple and effective solution, and offers an intuitive interpretation
of where the agreement and disagreement occurs. Preliminary
results with our echo data, not reported here, showed that the
inclusion of twist (defined as the difference in rotation between
base and apex as done clinically [40]) in the objective function was
detrimental, probably due to a combination of imaging acquisition
and analysis limitations. Further research is needed to optimize
the definition of the objective functional, and to analyse the
comparative performance of the different alternatives.
Because the excised heart kept beating a little throughout the
experiment (see “Speckle tracking” in Methods), despite perfusion
0% 25% 50% 75%
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
Eq. (6) (displacements)
Eq. (7) (aggregated)
Objective function value (percent increase from minimum)
ECDF(proportionof
simulatedparameterscenarios)
Fig. 5. The objective function based on aggregated geometry measures (Eq. (7))
was more precise in identifying a narrow set of well-fitting parameter scenarios,
compared to the objective function based on node displacements (Eq. (6)). Lines
show empirical cumulative distribution functions, i.e. the proportion of simulated
parameter scenarios for which the objective function was less than the value given
by the horizontal axis. Colour shading for the objective function value is used for
comparison with Figs. 6, 7 and 8. (For interpretation of the references to colour in
this figure legend, the reader is referred to the web version of this article.).
0 0.5 1
0
10
20
30
40
50
60
ΔV(μl)
LVP (kPa)
Fig. 6. Node positions made a poor goodness-of-fit criterion (Eq. (6)) for matching
simulations (thin lines coloured with the same colour scale used in Fig. 5) to
observation (thick red line). Compliance is unreasonably low for many of the
parameter scenarios that give low values of this objective function. Contrast with
the corresponding plot (Fig. 7a) for the other objective function (Eq. (7)), where the
best-fitting scenarios cluster more tightly around the experimental results. White
dots indicate unphysiological pressure levels that were omitted in computing the
objective function. Note that this plot shows the increase in volume as a result of
imposed pressure, and so is transposed relative to the traditional P–V loop plot.
(For interpretation of the references to colour in this figure legend, the reader is
referred to the web version of this article.).
Ø. Nordbø et al. / Computers in Biology and Medicine 53 (2014) 65–75 71
8. with cardioplegic solution, and we were unable to measure the
calcium level inside the heart, we cannot be sure about our
assumption that there were no active forces. This assumption
greatly simplifies the decoupling of active and passive relaxation
processes [15], but may overestimate the stiffness of the tissue. On
the positive side, the residual heartbeat confirmed that the excised
heart was still capable of contraction, and so its material proper-
ties remained similar to in vivo.
Our experiment showed that the fibre stress-strain relationship
for the mouse left ventricle was quite linear over a biologically
relevant range of pressures (Fig. S1). This brings challenges in
identifying, separately from the overall stiffness a, the b parameters
0 0.5 1
0
20
40
60
ΔV(μl)
0 0.5 1
0
0.5
1
ΔΔSa
(mm)
0 0.5 1
0
0.5
1
ΔLa
(mm)
0 0.5 1
0
10
20
30
PdV(μJ)
LVP (kPa)
Fig. 7. Comparison of whole-organ geometrical characteristics (see text) as a function of left ventricular pressure (LVP), between experimental data (red) and simulated data,
using a goodness-of-fit measure based on whole-organ phenotypes (Eq. (7)). Colour indicates the value of the objective function (Eq. (7)) relative to the minimum value
(colour scale as in Figs. 5 and 6). Geometric measurements are shown as differences from the zero-pressure values of volume¼V0¼58.1 μL, long-axis diame-
ter¼LA0¼6.88 mm, short-axis diameter¼SA0 ¼3.39 mm. Panel (a) contrasts with Fig. 6. White dots indicate unphysiological pressure levels that were omitted in computing
the objective function. The observed experimental relationship between pressure and volume was near-linear, in agreement with in vivo PV loop data (see references in
text). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.).
0 2 4 6
0
5
10
15
a (kPa)
b1
0 2 4 6
0
5
10
15
a (kPa)
b2
0 2 4 6
0
5
10
15
a (kPa)
b3
0 5 10 15
0
5
10
15
b1
b2
0 5 10 15
0
5
10
15
b1
b3
0 5 10 15
0
5
10
15
b2
b3
Fig. 8. Projections of the objective function onto two-dimensional slices of the stiffness-parameter space. Each panel shows, conditional on the two parameters named on
the axes, the best fit (as defined in Eq. (7); red dot) among all combinations of the remaining parameters. Black dots indicate simulated parameter sets; red dot shows the
best-fitting parameter combination among the simulations. Diagonal line shows 1:1 ratio of parameters for reference. Parameter scenarios outside the displayed axis limits
were also run, spanning the full parameter ranges reported in Table 1, but these did not fit well and are omitted here for clarity. (For interpretation of the references to colour
in this figure legend, the reader is referred to the web version of this article.).
Ø. Nordbø et al. / Computers in Biology and Medicine 53 (2014) 65–7572
9. that pertain to curvature in the material law (Fig. 8, [24]). However,
in contrast to [24], we find that a is well bounded from below while
the b's are bounded from above: No parameter scenarios with low a
or very high b's could be made to match the data well (Fig. 8).
The mouse myocardium was found to be stiffer along the fibres
than normal to the fibres, which is in agreement with the findings
in other model organisms [6]–[10]. The value of b1 was consider-
ably higher than b2 and b3, in agreement with findings in in vivo
sheep and human hearts [15,41] and in tissue blocks of pig heart
[7]. The stiffness parameters estimated in this work describe a
relatively soft material (low stress–strain relationships) compared
with most of the literature, and is most similar to the material
properties found in a similar experiment on rat hearts [10].
Complementary experiments are needed to better constrain
the material parameters of this law. We inflated the ventricle from
0 to 1.44 kPa, i.e. within the normal diastolic pressure range. In this
range the stress (or pressure) vs. deformation relationship was
relatively linear, while the nonlinear behavior occurs at higher
pressures. The estimated parameters capture the passive material
properties for normal diastolic pressures in a healthy specimen,
but extrapolation outside this range, for example for the study of
increased filling pressures, will require further characterization.
Several future refinements are possible in this parameter
estimation workflow. Better speckle tracking would improve the
ability to find regional differences in material passive properties by
following material points in a Lagrangian, moving frame of
reference, as suggested for tagged MRI by [16]. Other challenges
include the aligning of 2D data into 3D geometries. Misalignment
may cause spurious bulging in the estimated deformation of the
apex region (Fig. 4), and is probably one of the main reasons for
the lack of fit between the simulated and experimental deforma-
tion data on a nodal basis (Eq. (6) and Fig. 5). Manual interactions
could be reduced, facilitating e.g. the study of individual variation,
by automating the selection of valid end diastolic frames from the
echocardiographic recordings. Also, mesh construction might
benefit from being constrained by incompressibility [42]; our
current meshes differed in volume by 15% from the start to the
end of filling. Complementary experiments are needed to uniquely
constrain the material parameters of this law. In particular, the
application of higher pressures, e.g. of relevance to hypertension,
might bring out nonlinearities in the force-deformation relation-
ship that would constrain the possible parameter combinations.
We have demonstrated the feasibility of quantifying mouse
myocardial stiffness using the experimental setup and associated
computational pipeline described above, and found that it is a
viable method that deserves wider application. A better knowl-
edge of passive properties would shed light on diastolic dysfunc-
tion and is an important step towards understanding diastolic
heart failure in mouse and human.
Conflict of interest statement
The authors declare no competing interests.
Acknowledgments
This work was funded by the Research Council of Norway
under the eVITA programme, project number 178901/V30 and by
the Virtual Physiological Rat project funded through NIH grant
P50-GM094503. NOTUR, the Norwegian Metacenter for Computa-
tional Science, provided computing resources under project
nn4653k. JES is a BHF Senior Basic Science Research Fellow, and
acknowledges funding from the Biotechnology Biological
Sciences Research Council (BB/I012117/1).
Appendix A. Speckle tracking
Two-dimensional particle paths can be estimated from a series
of images by block-matching [23]. The algorithm compares a
region of the current image with nearby regions in the next
image, finding the best-matching displacement by optimizing
some matching criterion. This is repeated for each region of
interest in the current image, for example centred on manually
chosen landmarks to be tracked.
Each series consisted of approximately 300 images (long-axis:
512 Â 384 pixels; short-axis: 512 Â 472 pixels; pixel size
0.0234 mm). However, the heart was still beating a little during
the experiment, whereas our focus was on passive mechanics only.
We therefore removed systolic images before speckle tracking,
identifying these images by their large mean absolute signal
intensity difference between subsequent images. Because the
sampling rate was high relative to the rate of displacement, we
subsampled the data to every third image to avoid round off
problems with zero displacements. The speckle tracking algorithm
was implemented in Matlab ([43]) as follows:
We chose limits for the search algorithm, consisting of the size
of the matching kernel window and the maximum allowed
displacements. Kernel windows were 17 Â 31 and 9 Â 17 pixels
for long- and short-axis images, respectively. The maximum
allowed displacements between two subsequent images were
2 pixels (in x and y directions) for long-axis and 3 pixels for
short-axis images.
The ventricular wall was more visible and easier to segment
from the high pressure images. We therefore selected material
points along the inner and outer surface of the ventricle for the
image corresponding to maximal pressure, and worked back-
wards from high to low pressure images. The selected material
points were used as central points for block matching between
subsequent images in the following automatic procedure.
The ventricle in the current image was masked based on the
position of the material points in the preceding image (echo
intensity was set to NaN outside the ventricle).
The displacement for each material point in the current
image was estimated by matching the neighbourhood of the
material point against candidate regions in the next image,
minimizing the mean absolute difference between the sub-
images.
Due to considerable noise, especially in the basal region in
the long axis images, we imposed additional constraints on
the deformation:
The material points closest to the base were allowed to
move only in horizontal direction and the outward radial
search region was reduced.
The local wall thickness was measured. If the wall
thickness was shrinking compared with the max pres-
sure image, the material points on the inner wall were
moved inwards, normal to the surface of the outer wall.
The displacements were smoothed using a cubic spline.
(Displacements from short axis images were converted to
polar coordinates before smoothing).
The coordinate position of each material point was updated,
based on its estimated displacement, before the next image
was analysed by block-matching.
Appendix B. From 2D particle paths to 3D deformation
The individual 2D particle paths were smoothed over time and
interpolated so we could estimate the position of each 2D material
Ø. Nordbø et al. / Computers in Biology and Medicine 53 (2014) 65–75 73
10. point for any specified LVP. We used the long-axis images to find
displacement in longitudinal and radial direction, while circum-
ferential displacements were obtained from the short-axis images.
The short-axis images also contain information about the radial
movement, but this was not utilized because the out-of-plane
movement is larger for these images than for long-axis images.
The long-axis images were centred, based on the centre of mass of
the basal points in the zero pressure images, and rotated about the
z-axis (01, 451, 901 and 1351) to correspond to the experimental
views (see Fig. 1a). The apical points were defined as a weighted
average of the most apical points from the different long-axis
slices. The short-axis images were aligned to match the long-axis
images with respect to the free wall and the septum. The most
apical short-axis image was aligned with the long-axis images in
the z-direction, so that the inner diameters of the long- and short-
axis images were identical in the maximum pressure configura-
tion. The circumferential displacements of all nodes were then
interpolated in the z-direction between the short-axis slices by
using a cubic spline (we required zero circumferential displace-
ment in the base, in accordance to the experimental setup). The
nodes were then used as nodes in a triquadratic interpolated
mesh, and estimated 3D-displacements were used to calculate the
configuration for each pressure level (see Fig. 3).
Appendix C. Supplementary material
Supplementary data associated with this article can be found in
the online version at http://dx.doi.org/10.1016/j.compbiomed.
2014.07.013.
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