Image-based Multi-scale Modeling Framework of the Cardiopulmonary System: Longitudinal Calibration and Assessment of Therapies in Pediatric Pulmonary Hypertension

基于图像的心肺系统多尺度建模框架：小儿肺动脉高压治疗的纵向校准和评估

• 批准号: 9905410
• 负责人: Seungik Baek
• 金额: $ 53.23万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-15 至 2023-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9905410
• 关键词: Anatomy; Animal Model; Assimilations; Bayesian Analysis; Biological Markers; Biomechanics; Blood Circulation; Blood Vessels; Calibration; Cardiac; Cardiac Catheterization Procedures; Cardiopulmonary; Cardiovascular system; Cessation of life; Child; Childhood; Chronic; Clinical; Clinical Data; Clinical Research; Clinical assessments; Complex; Computer Models; Coronary artery; Coupled; Coupling; Data; Diagnosis; Disease; Disease Progression; Early Diagnosis; Engineering; Etiology; Evolution; Failure; Goals; Gold; Growth; Heart; Heart Transplantation; Heart failure; Human; Hypoxia; Image; Individual; Intervention; Intravenous; Lead; Lung; Magnetic Resonance Imaging; Measurement; Mechanics; Medication Management; Methods; Microcirculation; Modeling; Modernization; Monitor; Operative Surgical Procedures; Oral; Organ; Outcome; Patients; Pediatric cohort; Peripheral; Pharmacology; Physical Examination; Physics; Prevalence; Pulmonary Circulation; Pulmonary Hypertension; Pulmonary Vascular Resistance; Pulmonary artery structure; Right ventricular structure; Statistical Methods; Statistical Models; Structure; Study models; System; Systemic hypertension; Techniques; Time; Uncertainty; Vasodilator Agents; Ventricular; Ventricular Septal Defects; Work; base; blood pressure regulation; cardiopulmonary system; computer framework; diagnosis standard; dosage; follow-up; heart function; hemodynamics; hypertension control; insight; kinetic model; mortality; multi-scale modeling; outcome forecast; palliative; patient population; pressure; primary pulmonary hypertension; prospective; simulation; treatment strategy

ABSTRACT Pulmonary hypertension (PH) is a complex disorder associated with elevated pulmonary arterial pressure. Unlike systemic hypertension, PH is difficult to detect in routine physical examinations and the current gold standard for diagnosing PH is through invasive right heart catheterization. Unlike in systemic hypertension, for which patients have effective pharmacological management of blood pressure for decades, PH prognosis remains poor with 15% mortality within 1 year on modern therapy. Challenges in early detection of PH, as well as structural differences in the cardio-pulmonary system (e.g., thinner ventricular wall, more distributed compliance and larger number of peripheral vessels) may explain the stark differences in clinical outcomes between systemic hypertension and PH. Our current understanding of PH has largely been obtained through animal models, clinical studies and computational modeling. However, surgical banding or chronic hypoxia animal models do not fully reproduce the etiology of human PH. Invasive clinical measurements of pulmonary vascular resistance (PVR), stiffness and ventricular elastance provide limited insight into disease progression. Computational models have been developed to study growth and remodeling (G&R) in the ventricles and hemodynamics in PH. However, these models are incomplete: ventricular G&R models lack coupling with evolving pulmonary hemodynamics, whereas pulmonary hemodynamic models have not included ventricular-arterial coupling. Given that the interactions between RV and the pulmonary vasculature are a key determinant of the clinical course of PH, specifically, the transition from compensated to decompensated remodeling, we submit that there is a pressing need to develop a multi-scale (MS) computational model that can couple the short term (e.g. hemodynamics) and long-term G&R interactions between the RV and the pulmonary circulation. In this project, we propose to develop a multi-scale, multi-physics computational model of the cardio-pulmonary circulation and calibrate it using longitudinal data acquired on cohorts of pediatric pulmonary hypertension and control (e.g., cardiac transplant) subjects. The model will be the first of its kind because it will be able to describe the bi-directional interactions between evolving ventricular and vascular biomechanics and hemodynamics using human pulmonary hypertension data.

摘要 肺动脉高压（PH）是一种与肺动脉压升高相关的复杂疾病。不像 全身性高血压，PH在常规体检中很难检测，目前的金标准是 诊断PH是通过侵入性右心导管插入术。与全身性高血压不同， 几十年来，我们一直对血压进行有效的药物管理，PH预后仍然很差， 现代治疗1年内死亡率为15%。PH的早期检测以及结构检测的挑战 心肺系统的差异（例如，心室壁较薄，顺应性分布更均匀， 外周血管数量）可以解释全身性和非全身性之间临床结局的明显差异。 高血压和PH。 我们目前对PH的理解主要是通过动物模型、临床研究和 计算建模然而，外科手术结扎或慢性缺氧动物模型不能完全再现 肺血管阻力（PVR）、硬度和肺动脉压的侵入性临床测量 心室弹性对疾病进展的了解有限。计算模型已经 开发用于研究心室中的生长和重构（G&R）以及PH中的血液动力学。然而，这些 模型是不完整的：心室G&R模型缺乏与不断发展的肺血流动力学的耦合， 肺血液动力学模型不包括心室-动脉耦合。考虑到 RV和肺血管之间的相互作用是PH临床病程的关键决定因素，具体而言， 从代偿性重塑到失代偿性重塑的过渡，我们认为迫切需要开发 多尺度（MS）计算模型，可将短期（例如血液动力学）和长期G&R结合起来 RV和肺循环之间的相互作用。 在这个项目中，我们提出了一个多尺度，多物理计算模型的心肺 循环，并使用在儿科肺动脉高压队列中获得的纵向数据进行校准， 控制（例如，心脏移植）受试者。该模型将是同类中的第一个，因为它将能够描述 心室和血管生物力学与血流动力学之间的双向相互作用， 人肺动脉高压数据。

项目成果

In-silico assessment of the effects of right ventricular assist device on pulmonary arterial hypertension using an image based biventricular modeling framework.

使用基于图像的双心室建模框架对右心室辅助装置对肺动脉高压的影响进行计算机评估。

• DOI: 10.1016/j.mechrescom.2019.04.008
• 发表时间: 2019
• 期刊: Mechanics research communications
• 影响因子: 2.4
• 作者: Shavik,SheikhMohammad;Zhong,Liang;Zhao,Xiaodan;Lee,LikChuan
• 通讯作者: Lee,LikChuan

Data-driven computational models of ventricular-arterial hemodynamics in pediatric pulmonary arterial hypertension.

• DOI: 10.3389/fphys.2022.958734
• 发表时间: 2022
• 期刊: FRONTIERS IN PHYSIOLOGY
• 影响因子: 4
• 作者: Tossas-Betancourt, Christopher;Li, Nathan Y.;Shavik, Sheikh M.;Afton, Katherine;Beckman, Brian;Whiteside, Wendy;Olive, Mary K.;Lim, Heang M.;Lu, Jimmy C.;Phelps, Christina M.;Gajarski, Robert J.;Lee, Simon;Nordsletten, David A.;Grifka, Ronald G.;Dorfman, Adam L.;Baek, Seungik;Lee, Lik Chuan;Figueroa, C. Alberto
• 通讯作者: Figueroa, C. Alberto

Inverse modeling framework for characterizing patient-specific microstructural changes in the pulmonary arteries.

• DOI: 10.1016/j.jmbbm.2021.104448
• 发表时间: 2021-07
• 期刊: JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
• 影响因子: 3.9
• 作者: Pourmodheji, Reza;Jiang, Zhenxiang;Tossas-Betancourt, Christopher;Figueroa, C. Alberto;Baek, Seungik;Lee, Lik-Chuan
• 通讯作者: Lee, Lik-Chuan

Patient-Specific Computational Analysis of Hemodynamics and Wall Mechanics and Their Interactions in Pulmonary Arterial Hypertension.

• DOI: 10.3389/fbioe.2020.611149
• 发表时间: 2020
• 期刊: Frontiers in bioengineering and biotechnology
• 影响因子: 5.7
• 作者: Zambrano BA;McLean N;Zhao X;Tan JL;Zhong L;Figueroa CA;Lee LC;Baek S
• 通讯作者: Baek S

Multiscale Modeling Framework of Ventricular-Arterial Bi-directional Interactions in the Cardiopulmonary Circulation.

心肺循环中心室-动脉双向相互作用的多尺度建模框架。

• DOI: 10.3389/fphys.2020.00002
• 发表时间: 2020
• 期刊: Frontiers in physiology
• 影响因子: 4
• 作者: Shavik,SheikhMohammad;Tossas-Betancourt,Christopher;Figueroa,CAlberto;Baek,Seungik;Lee,LikChuan
• 通讯作者: Lee,LikChuan