Development of an Anatomically Realistic Left Ventricle Physical Model and Multi-Modality Experimental Platform for Validation of Patient-Specific Computational Simulations

2012 ◽  
Author(s):  
Brandon Chaffins ◽  
Trung Le ◽  
Arvind Santhanakrishnan ◽  
Lucia Mirabella ◽  
Fotis Sotiropoulos ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Physical Model ◽  
Heart Diseases ◽  
Normal Volunteer ◽  
Patient Specific ◽  
Immersed Boundary ◽  
Reconstruction Method ◽  
Left Heart ◽  
Recent Trends ◽  
Numerical Solver

Recent trends in bioengineering, also supported by the FDA [1], highlight the importance of experimental validation of numerical solvers used in medicine in order to use numerical solvers for surgical planning. Efforts to improve the diagnosis of left heart diseases have pointed to the importance of hemodynamic patterns in the left ventricle [2] and the use of CFD simulations could aid in repair and treatment of left heart disease. In this study, we aim to experimentally validate the Curvilinear Immersed Boundary solver (CURVIB) [3] to use patient specific data for simulations. As a first step, an idealized left heart model with a single deforming wall was used for comparison of the diastolic intra-ventricular flow field between experimental and CFD results. The inputs for the numerical solver include the dynamics of LV wall motion as well as the mitral and aortic flows. We have achieved good agreement between the experimental and CFD and our goal is to translate the solver to use clinical data. We present a reconstruction method for the LV deformation from normal volunteer MRI images and an anatomically realistic LV physical model that has been designed for validation.

3D Reconstruction of the Left Ventricle From Four Echocardiographic Projections

2014 ◽  
Author(s):  
Navaneetha Krishnan Rajan ◽  
Zeying Song ◽  
Kenneth R. Hoffmann ◽  
Marek Belohlavek ◽  
Eileen M. McMahon ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Three Dimensional ◽  
Image Data ◽  
Left Ventricular ◽  
The Body ◽  
Patient Specific ◽  
Immersed Boundary ◽  
Cross Sectional ◽  
Standard Format ◽  
Automated Method

The left ventricle (LV) of a human heart receives oxygenated blood from the lungs and pumps it throughout the body via the aortic valve. Characterizing the LV geometry, its motion, and the ventricular flow is critical in assessing the heart’s health. An automated method has been developed in this work to generate a three-dimensional (3D) model of the LV from multiple-axis echocardiography (echo). Image data from three long-axis sections and a basal section is processed to compute spatial nodes on the LV surface. The generated surfaces are output in a standard format such that it can be imported into the curvilinear-immersed boundary (CURVIB) framework for numerical simulation of the flow inside the LV. The 3D LV model can be used for better understanding of the ventricular motion and the simulation framework provides a powerful tool for studying left ventricular flows on a patient specific basis. Future work would incorporate data from additional cross-sectional images.

scholarly journals Patient-specific genomics and cross-species functional analysis implicate LRP2 in hypoplastic left heart syndrome

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jeanne L Theis ◽  
Georg Vogler ◽  
Maria A Missinato ◽  
Xing Li ◽  
Tanja Nielsen ◽  
...  
Keyword(s):  
Hypoplastic Left Heart Syndrome ◽  
Heart Development ◽  
Heart Diseases ◽  
Heart Defects ◽  
Patient Specific ◽  
Left Heart ◽  
Hypoplastic Left Heart ◽  
Healthy Human ◽  
Altered Expression ◽  
Left Heart Syndrome

Congenital heart diseases (CHDs), including hypoplastic left heart syndrome (HLHS), are genetically complex and poorly understood. Here, a multidisciplinary platform was established to functionally evaluate novel CHD gene candidates, based on whole-genome and iPSC RNA sequencing of a HLHS family-trio. Filtering for rare variants and altered expression in proband iPSCs prioritized 10 candidates. siRNA/RNAi-mediated knockdown in healthy human iPSC-derived cardiomyocytes (hiPSC-CM) and in developing Drosophila and zebrafish hearts revealed that LDL receptor-related protein LRP2 is required for cardiomyocyte proliferation and differentiation. Consistent with hypoplastic heart defects, compared to parents the proband’s iPSC-CMs exhibited reduced proliferation. Interestingly, rare, predicted-damaging LRP2 variants were enriched in a HLHS cohort; however, understanding their contribution to HLHS requires further investigation. Collectively, we have established a multi-species high-throughput platform to rapidly evaluate candidate genes and their interactions during heart development, which are crucial first steps toward deciphering oligogenic underpinnings of CHDs, including hypoplastic left hearts.

Scaffolds for Drug Delivery in Tissue Engineering

2008 ◽  
Vol 1 (2) ◽  
pp. 113-123 ◽  
Author(s):  
Vikas V. Gaikwad ◽  
Abasaheb B. Patil ◽  
Madhuri V. Gaikwad
Keyword(s):  
Drug Delivery ◽  
Tissue Engineering ◽  
Heart Diseases ◽  
Cartilage Regeneration ◽  
Tissue Growth ◽  
The Body ◽  
Patient Specific ◽  
In Situ Gel ◽  
Heart Muscle Cells

Scaffolds are used for drug delivery in tissue engineering as this system is a highly porous structure to allow tissue growth.  Although several tissues in the body can regenerate, other tissue such as heart muscles and nerves lack regeneration in adults. However, these can be regenerated by supplying the cells generated using tissue engineering from outside. For instance, in many heart diseases, there is need for heart valve transplantation and unfortunately, within 10 years of initial valve replacement, 50–60% of patients will experience prosthesis associated problems requiring reoperation. This could be avoided by transplantation of heart muscle cells that can regenerate. Delivery of these cells to the respective tissues is not an easy task and this could be done with the help of scaffolds. In situ gel forming scaffolds can also be used for the bone and cartilage regeneration. They can be injected anywhere and can take the shape of a tissue defect, avoiding the need for patient specific scaffold prefabrication and they also have other advantages. Scaffolds are prepared by biodegradable material that result in minimal immune and inflammatory response. Some of the very important issues regarding scaffolds as drug delivery systems is reviewed in this article.

Total anomalous pulmonary venous connection mimicking hypoplastic left heart syndrome

2021 ◽  
pp. 1-3
Author(s):  
Ryohei Matsuoka ◽  
Jun Muneuchi ◽  
Yoshie Ochiai
Keyword(s):  
Left Ventricle ◽  
Systemic Circulation ◽  
Z Score ◽  
Left Heart ◽  
Hypoplastic Left Heart ◽  
Transverse Arch ◽  
Anomalous Pulmonary Vein ◽  
Pulmonary Arterial ◽  
Left Heart Syndrome ◽  
Anomalous Pulmonary Venous Connection

Abstract A newborn with supracardiac total anomalous pulmonary venous connection vein presented the small left ventricle with z score of −7.5, retrograde blood supply in the transverse arch, and the dutcus-dependent systemic circulation. The patient underwent the repair of the anomalous pulmonary vein and bilateral pulmonary arterial banding soon after the birth and then transcatheter pulmonary arterial debanding at the age of 10 months because of an appropriate growth of the left ventricle.

Echocardiographic assessment of the aortic valve and left ventricular outflow tract

2005 ◽  
Vol 15 (S1) ◽  
pp. 27-36 ◽  
Author(s):  
Alfred Asante-Korang ◽  
Robert H. Anderson
Keyword(s):  
Aortic Valve ◽  
Left Ventricle ◽  
Left Ventricular Outflow Tract ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Outflow Tract ◽  
Left Heart ◽  
Transesophageal Echocardiogram ◽  
Left Ventricular Outflow ◽  
Echocardiographic Assessment

The previous reviews in this section of our Supplement1,2 have summarized the anatomic components of the ventriculo-arterial junctions, and then assessed the echocardiographic approach to the ventriculo-arterial junction or junctions as seen in the morphologically right ventricle. In this complementary review, we discuss the echocardiographic assessment of the comparable components found in the morphologically left ventricle, specifically the outflow tract and the arterial root. We will address the echocardiographic anatomy of the aortic valvar complex, and we will review the causes of congenital arterial valvar stenosis, using the aortic valve as our example. We will also review the various lesions that, in the outflow of the morphologically left ventricle, can produce subvalvar and supravalvar stenosis. We will then consider the salient features of the left ventricular outflow tract in patients with discordant ventriculo-arterial connections, and double outlet ventricles. To conclude the review, we will briefly address some rarer anomalies that involve the left ventricular outflow tract, showing how the transesophageal echocardiogram is used to assist the surgeon preparing for repair. The essence of the approach will be to consider the malformations as seen at valvar, subvalvar, or supravalvar levels,1 but we should not lose sight of the fact that aortic coarctation or interruption, hypoplasia of the left heart, and malformations of the mitral valve are all part of the spectrum of lesions associated with obstruction to the left ventricular outflow tract. These additional malformations, however, are beyond the scope of this review.

Abstract 248: Aberrant TGFβ Signaling as an Etiology of Left Ventricular Non-compaction Cardiomyopathy

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Kazuki Kodo ◽  
Sang-Ging Ong ◽  
Fereshteh Jahanbani ◽  
Vittavat Termglinchan ◽  
Kolsoum InanlooRahatloo ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Induced Pluripotent Stem Cell ◽  
Left Ventricular ◽  
Patient Specific ◽  
Developmental Defect ◽  
Tgfβ Signaling ◽  
Growth Factor Beta ◽  
Induced Pluripotent

Left ventricular non-compaction (LVNC) is the third most prevalent cardiomyopathy in children and has a unique phenotype with characteristically extensive hypertrabeculation of the left ventricle, similar to the embryonic left ventricle, suggesting a developmental defect of the embryonic myocardium. However, studying this disease has been challenging due to the lack of an animal model that can faithfully recapitulate the clinical phenotype of LVNC. To address this, we showed that patient-specific induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) generated from a family with LVNC history recapitulated a developmental defect consistent with the LVNC phenotype at the single-cell level. We then utilized hiPSC-CMs to show that increased transforming growth factor beta (TGFβ) signaling is one of the central mechanisms underlying the pathogenesis of LVNC. LVNC hiPSC-CMs demonstrated decreased proliferative capacity due to abnormal activation of TGFβ signaling (Figs A-B). Exome sequencing demonstrated a mutation in TBX20, which regulates TGFβ signaling through upregulation of ITGAV, contributing to the LVNC phenotype. Inhibition of abnormal TGFβ signaling or genetic correction of the TBX20 mutation (Figs C-D) using TALEN reversed the proliferation defects seen in LVNC hiPSC-CMs. Our results demonstrate that hiPSC-CMs are a useful tool for the exploration of novel mechanisms underlying poorly understood cardiomyopathies such as LVNC. Here we provide the first evidence of activation of TGFβ signaling as playing a role in the pathogenesis of LVNC.

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