A Computational model-based approach for atlas construction of aortic Doppler velocity profiles for segmentation purposes

Echocardiography is the leading imaging modality for cardiac disorders in clinical practice. During an echocardiographic exam, geometry and blood flow are quantified in order to assess cardiac function. In clinical practice, these imagebased measurements are currently performed manually. An automated approach is needed if more advanced analysis is desired. In this article, we propose a new hybrid framework for the construction of a disease-specific atlas to improve Doppler aortic outflow velocity profile segmentation. The proposed method is based on combining realistic computational simulations of the cardiovascular system for common cardiac conditions (using CircAdapt) with a validated image-based atlas construction method. The coupling is realized via model-based generation of echocardiographic images of virtual populations with a statistically approved parameter variation. We created virtual populations of 100 healthy individuals and 100 patients with aortic stenosis, synthesized their aortic Doppler velocity images and constructed the corresponding atlases. We validated atlases’ performances by comparing their segmentation of real clinical images with the manually segmented ground truth. The experimental results show that the segmentation accuracy obtained using the proposed atlases is comparable to the accuracy obtained using classical clinical image-based atlases. Moreover, this framework eliminates the time-consuming acquisition of a sufficient number of representative images in clinical practice, offering a substantial time efficiency and flexibility in creating a disease specific atlas and ensuring an observer-independent automated segmentation. The proposed approach can easily be extended towards the creation of atlases for segmenting any Doppler trace in the cardiovascular circulation in a specific disease.Research leading to these results has received funding from the Ministry of Science, Education and Sports, Republic of Croatia (036-0362214-1989), Subprograma de Proyectos de Investigacin en Salud (FIS), Instituto de Salud Carlos III, Spain (ref. PI11/01709); the Spanish Ministry of Economy and Competitiveness (grant TIN2014-52923-R) and FEDER and the Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 611823. Additionally, we would like to thank Frank Weidemann for a subset of the patient images, and Catalina Tobon-Gomez and Georgina Palau-Caballero for provided CircAdapt support

A Computational model-based approach for atlas construction of aortic Doppler velocity profiles for segmentation purposes

Echocardiography is the leading imaging modality for cardiac disorders in clinical practice. During an echocardiographic exam, geometry and blood flow are quantified in order to assess cardiac function. In clinical practice, these imagebased measurements are currently performed manually. An automated approach is needed if more advanced analysis is desired. In this article, we propose a new hybrid framework for the construction of a disease-specific atlas to improve Doppler aortic outflow velocity profile segmentation. The proposed method is based on combining realistic computational simulations of the cardiovascular system for common cardiac conditions (using CircAdapt) with a validated image-based atlas construction method. The coupling is realized via model-based generation of echocardiographic images of virtual populations with a statistically approved parameter variation. We created virtual populations of 100 healthy individuals and 100 patients with aortic stenosis, synthesized their aortic Doppler velocity images and constructed the corresponding atlases. We validated atlases’ performances by comparing their segmentation of real clinical images with the manually segmented ground truth. The experimental results show that the segmentation accuracy obtained using the proposed atlases is comparable to the accuracy obtained using classical clinical image-based atlases. Moreover, this framework eliminates the time-consuming acquisition of a sufficient number of representative images in clinical practice, offering a substantial time efficiency and flexibility in creating a disease specific atlas and ensuring an observer-independent automated segmentation. The proposed approach can easily be extended towards the creation of atlases for segmenting any Doppler trace in the cardiovascular circulation in a specific disease.Research leading to these results has received funding from the Ministry of Science, Education and Sports, Republic of Croatia (036-0362214-1989), Subprograma de Proyectos de Investigacin en Salud (FIS), Instituto de Salud Carlos III, Spain (ref. PI11/01709); the Spanish Ministry of Economy and Competitiveness (grant TIN2014-52923-R) and FEDER and the Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 611823. Additionally, we would like to thank Frank Weidemann for a subset of the patient images, and Catalina Tobon-Gomez and Georgina Palau-Caballero for provided CircAdapt support

Whole heart detailed and quantitative anatomy, myofibre structure and vasculature from X-ray phase-contrast synchrotron radiation-based micro computed tomography

While individual cardiac myocytes only have a limited ability to shorten, the heart efficiently pumps a large volume-fraction thanks to a cell organization in a complex 3D fibre structure. Subclinical subtle cardiac structural remodelling is often present before symptoms arise. Understanding and early detection of these subtle changes is crucial for diagnosis and prevention. Additionally, personalized computational modelling requires knowledge on the multi-scale structure of the whole heart and vessels.This study was partly supported by Ministerio de Economia y Competitividad (SAF2012-37196;TIN2014-52923-R); Instituto de Salud Carlos III (PI11/00051, PI11/01709, PI12/00801, PI14/00226) integrados en el Plan Nacional de I + D+I y cofinanciados por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) ‘Otra manera de hacer Europa’; the EU-FP7 for research, technological development and demonstration under grant agreement VP2HF (no611823); The Cerebra Foundation for the Brain Injured Child (Carmarthen, UK); Obra Social ‘la Caixa’ (Barcelona, Spain); Fundació Mutua Madrileña and Fundació Agrupació Mutua (Spain)

Whole heart detailed and quantitative anatomy, myofibre structure and vasculature from X-ray phase-contrast synchrotron radiation-based micro computed tomography

While individual cardiac myocytes only have a limited ability to shorten, the heart efficiently pumps a large volume-fraction thanks to a cell organization in a complex 3D fibre structure. Subclinical subtle cardiac structural remodelling is often present before symptoms arise. Understanding and early detection of these subtle changes is crucial for diagnosis and prevention. Additionally, personalized computational modelling requires knowledge on the multi-scale structure of the whole heart and vessels.This study was partly supported by Ministerio de Economia y Competitividad (SAF2012-37196;TIN2014-52923-R); Instituto de Salud Carlos III (PI11/00051, PI11/01709, PI12/00801, PI14/00226) integrados en el Plan Nacional de I + D+I y cofinanciados por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) ‘Otra manera de hacer Europa’; the EU-FP7 for research, technological development and demonstration under grant agreement VP2HF (no611823); The Cerebra Foundation for the Brain Injured Child (Carmarthen, UK); Obra Social ‘la Caixa’ (Barcelona, Spain); Fundació Mutua Madrileña and Fundació Agrupació Mutua (Spain)

Complex congenital heart disease associated with disordered myocardial architecture in a midtrimester human fetus

In the era of increasingly successful corrective interventions in patients with congenital heart disease (CHD), global and regional myocardial remodeling are emerging as important sources of long-term morbidity/mortality. Changes in organization of the myocardium in CHD, and in its mechanical properties, conduction, and blood supply, result in altered myocardial function both before and after surgery. To gain a better understanding and develop appropriate and individualized treatment strategies, the microscopic organization of cardiomyocytes, and their integration at a macroscopic level, needs to be completely understood. The aim of this study is to describe, for the first time, in 3 dimensions and nondestructively the detailed remodeling of cardiac microstructure present in a human fetal heart with complex CHD.This study was partially supported by the Spanish Ministry of Economy and Competitiveness (grant TIN2014-52923-R and the Maria de Maeztu Units of Excellence Programme - MDM- 2015-0502) and FEDER. CB is supported by Fundació La Marató de TV3 (Spain), grant Nº: 20154031. JAS is supported by the Center of Excellence CompBioMed funded under H2020-EU.1.4.1.3. under grant agreement Nº 675451. DJS is supported by the British Heart Foundation under the grant Nº FS/15/33/31608

A two dimensional electromechanical model of a cardiomyocyte to assess intra-cellular regional mechanical heterogeneities

Experimental studies on isolated cardiomyocytes from different animal species and human hearts have demonstrated that there are regional differences in the Ca2+ release, Ca2+ decay and sarcomere deformation. Local deformation heterogeneities can occur due to a combination of factors: regional/local differences in Ca2+ release and/or re-uptake, intra-cellular material properties, sarcomere proteins and distribution of the intracellular organelles. To investigate the possible causes of these heterogeneities, we developed a two-dimensional finite-element electromechanical model of a cardiomyocyte that takes into account the experimentally measured local deformation and cytosolic [Ca2+] to locally define the different variables of the constitutive equations describing the electro/mechanical behaviour of the cell. Then, the model was individualised to three different rat cardiac cells. The local [Ca2+] transients were used to define the [Ca2+]-dependent activation functions. The cell-specific local Young’s moduli were estimated by solving an inverse problem, minimizing the error between the measured and simulated local deformations along the longitudinal axis of the cell. We found that heterogeneities in the deformation during contraction were determined mainly by the local elasticity rather than the local amount of Ca2+, while in the relaxation phase deformation was mainly influenced by Ca2+ re-uptake. Our electromechanical model was able to successfully estimate the local elasticity along the longitudinal direction in three different cells. In conclusion, our proposed model seems to be a good approximation to assess the heterogeneous intracellular mechanical properties to help in the understanding of the underlying mechanisms of cardiomyocyte dysfunction.This study was partly supported by grants from Ministerio de Economia y Competitividad (ref. SAF2012-37196, TIN2014-52923-R); the Instituto de Salud Carlos III (ref. PI11/01709, PI14/00226) integrado en el Plan Nacional de I+D+I y cofinanciado por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) “Otra manera de hacer Europa”; the EU FP7 for research, technological development and demonstration under grant agreement VP2HF (n° 611823); The Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); Obra Social “la Caixa” (Barcelona, Spain); Fundació Mutua Madrileña; Fundació Agrupació Mutua (Spain) and AGAUR 2014 SGR grant n° 928 (Barcelona, Spain). P.G.C. was supported by the Programa de Ayudas Predoctorales de Formación en investigación en Salud (FI12/00362) from the Instituto Carlos III, Spain. P.G.C wants to acknowledge to Boehringer Ingelhiem Fonds for the travel grant to do her research stay at LaBS group in Politecnico di Milano

A two dimensional electromechanical model of a cardiomyocyte to assess intra-cellular regional mechanical heterogeneities.

Experimental studies on isolated cardiomyocytes from different animal species and human hearts have demonstrated that there are regional differences in the Ca2+ release, Ca2+ decay and sarcomere deformation. Local deformation heterogeneities can occur due to a combination of factors: regional/local differences in Ca2+ release and/or re-uptake, intra-cellular material properties, sarcomere proteins and distribution of the intracellular organelles. To investigate the possible causes of these heterogeneities, we developed a twodimensional finite-element electromechanical model of a cardiomyocyte that takes into account the experimentally measured local deformation and cytosolic [Ca2+] to locally define the different variables of the constitutive equations describing the electro/mechanical behaviour of the cell. Then, the model was individualised to three different rat cardiac cells. The local [Ca2+] transients were used to define the [Ca2+]-dependent activation functions. The cell-specific local Young's moduli were estimated by solving an inverse problem, minimizing the error between the measured and simulated local deformations along the longitudinal axis of the cell. We found that heterogeneities in the deformation during contraction were determined mainly by the local elasticity rather than the local amount of Ca2+, while in the relaxation phase deformation was mainly influenced by Ca2+ re-uptake. Our electromechanical model was able to successfully estimate the local elasticity along the longitudinal direction in three different cells. In conclusion, our proposed model seems to be a good approximation to assess the heterogeneous intracellular mechanical properties to help in the understanding of the underlying mechanisms of cardiomyocyte dysfunction

Different images recorded during the cardiomyocyte electrical stimulation experiments, with a pacing rate of 1Hz.

<p>A: Transmitted light image of the whole cell. The blue arrow corresponds to the line-scan where the images acquisition was performed. B: Line-scan transmitted light image. The red box indicates a region within the cell with zero displacement. C: Confocal FM4-64 image where the T-Tubule and sarcolemma are visible. D: Confocal Fluo-4 image corresponding to cytosolic [<i>Ca</i>²⁺]. The vertical axis corresponds to the line-scan (blue arrow) and the horizontal one to the time. The line-scan images resolution is 3.2 ⋅ 10⁻³ <i>s</i> × 0.28<i>μm</i>.</p

Synthetic data generated for validating the inverse problem procedure and results of the proposed framework validation in presence of gaussian noise.

<p>A: Local [<i>Ca</i>²⁺] transients. B: Active stress <i>S</i>_<i>act</i>(<i>t</i>) at different longitudinal positions (Long. pos) of the synthetic cell. C: Undeformed (grey) and deformed mesh of the synthetic cell at maximum contraction time frame. Colormap indicates the simulated longitudinal strain. D: Original (black solid line) and simulated strains along the longitudinal axis of the cell at maximum contraction time frame after the optimisation process with 0% (*), 5% (□), 10% (◇) and 15% (∘) of noise. E: Original (black solid line) and estimated local Young’s moduli along the longitudinal axis (line-scan) of the cell with 0% (*), 5% (□), 10% (◇) and 15% (∘) of noise.</p

Results of the cell-specific simulations performed for three different cardiomyocytes, for both [<i>Ca</i>²⁺]-activation (Act.) scenarios: Homogeneous (homo.) and heterogeneous (hetero.)

<p>Results of the cell-specific simulations performed for three different cardiomyocytes, for both [<i>Ca</i>²⁺]-activation (Act.) scenarios: Homogeneous (homo.) and heterogeneous (hetero.)</p