System and methods for computational simulation of the anatomical structures and intracardiac hemodynamics of heart with aortic valve disease in a patient

Abstract

The present invention relates to computational modeling of the heart and intracardiac hemodynamics in patients with Aortic Valve Disease (AVD), aiming to create personalized anatomical models. The system of the present invention generates patient-specific 3D models of the heart and valve, integrating anatomical structures with hemodynamic simulations. The system is based on inputting spatial and hemodynamic data, visualizing anatomical and hemodynamic changes, and generating a detailed 3D model. The system also calculates an "AVD Factor" to quantify valve abnormalities and can simulate the progression of heart pathology for further analysis.

Description

[0001] System and Methods for computational simulation of the Anatomical structures and intracardiac hemodynamics of heart with Aortic Valve Disease in a patient

[0002] FIELD OF THE INVENTION

[0003] The present invention relates generally to the field of heart modeling and more specifically to computational simulation of the anatomical structures and intracardiac hemodynamics of heart with Aortic Valve Disease in a patient.

[0004] BACKGROUND OF THE INVENTION

[0005] Aortic valve disease is a relatively common heart pathology which refers to a group of conditions that affect the aortic valve, one of the four valves in the human heart. The aortic valve is located between the left ventricle (the heart's main pumping chamber) and the aorta (the largest artery in the body), and its primary function is to ensure that oxygen-rich blood flows from the heart into the aorta and subsequently to the rest of the body.

[0006] There are two main types of aortic valve disease:

[0007] 1. Aortic Stenosis: Aortic stenosis occurs when the aortic valve becomes narrow and stiff, making it difficult for the valve to open fully. This narrowing restricts the flow of blood from the left ventricle into the aorta, forcing the heart to work harder to pump blood. Aortic stenosis is often caused by age-related degeneration of the valve (calcific aortic stenosis) or congenital abnormalities. 2. Aortic Regurgitation (Aortic Insufficiency): Aortic regurgitation happens when the aortic valve doesn't close tightly, allowing blood to leak back into the left ventricle during the heart's relaxation phase. This condition can lead to an increased workload on the heart and may eventually result in heart failure.

[0008] The diagnosis of aortic valve disease typically involves a combination of physical examinations, imaging tests (such as echocardiography), and sometimes cardiac catheterization.

[0009] Therefore, there is a long felt unmet need for methodologies that facilitate the generation of patient-specific, personalized anatomical models of the cardiac system with integrated blood flow dynamics.

[0010] SUMMARY OF THE INVENTION

[0011] The present invention relates generally to the field of heart modeling and more specifically to computational simulation of the anatomical structures and intracardiac hemodynamics of heart with Aortic Valve Disease in a patient.

[0012] The object of the present invention is to disclose a system for computational simulation of heart with Aortic Valve Disease (AVD) in a patient, comprising at least one computer system configured to: a. generate patient-specific editable animated three-dimensional anatomic model of heart and Aortic Valve, wherein said computer system comprises (i) Data input module of spatial dimensions and other measurements of the heart and (ii) computer readable instructions for:

[0013] Detalization of the pathology-specific (AVD) spatial dimensions and other measurements of the heart;

[0014] Visualization of the spatial-anatomic alterations in the heart;

[0015] Implementation of statistical rendition of the physiological / pathophysiological divergence in the heart; b. generate patient-specific editable animated mechanistic intracardiac hemodynamic model, wherein said computer system comprises (i) Data input module of hemodynamic parameters (ii) Data output module of AVD- related Hemodynamic parameters and (iii) Computer readable instructions for:

[0016] Detalization of the hemodynamic input and output parameters and introduction of the hemodynamics-specific parameter (denoted “AVD Factor”) for AVD pathology;

[0017] Visualization of the hemodynamic alterations in the heart;

[0018] Elaboration of the intracardiac hemodynamic processes; c. generate patient-specific editable animated three-dimensional anatomic model of heart and aortic valve with integrated intracardiac hemodynamics, said model comprising combining of said patient-specific editable animated three-dimensional anatomic model of heart and aortic valve with said patient-specific editable mechanistic intracardiac hemodynamic model.

[0019] It is another object of the present invention to disclose a method for determining a form and properties of the Aortic Valve Disease in a patient, wherein said method comprises steps of: a. receiving patient-specific data regarding (a) spatial dimensions and other measurements of the heart and (b) hemodynamic parameters; b. Detailing the pathology-specific (AVD) spatial dimensions and other measurements of the heart; c. Visualizing the spatial-anatomic alterations in the heart; d. Applying statistical rendition of the physiological / pathophysiological divergence in the heart; e. generating patient-specific editable animated three-dimensional anatomic model of heart and aortic valve; f. Detailing the hemodynamic input parameters and hemodynamics-specific parameter (denoted “AVD Factor”) for AVD pathology; g. Visualizing the hemodynamic alterations in the heart; h. Elaborating the intracardiac hemodynamic processes; i. generating patient-specific editable animated mechanistic intracardiac hemodynamic model; j . generating patient-specific editable animated three-dimensional geometric model of heart and aortic valve with Integrated Intracardiac Hemodynamics wherein said patient-specific editable animated three-dimensional geometric model of heart and aortic valve with integrated intracardiac hemodynamics of step j is obtained by combining said patient-specific editable animated three-dimensional anatomic model of heart and aortic valve of step e with said patient-specific editable animated mechanistic intracardiac hemodynamic model of step i.

[0020] It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said spatial dimensions and other measurements of the heart are selected from Table A-2; further wherein said data of spatial dimensions of the heart includes at least 4 one-dimensional spatial parameters, selected from TABLE A-2.

[0021] It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said data of spatial dimensions of the heart is obtained from Echocardiography or any other suitable method.

[0022] It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said data of hemodynamic parameters includes at least 9 onedimensional spatial parameters, 5 two-dimensional spatial parameters, and 5 three-dimensional spatial parameters, selected from TABLE A-2.1, TABLE A-2.2 and TABLE A-2.3.

[0023] It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said AVD Factor is determined for aortic valve stenosis (AoS) by calculating relative value of aortic valve (AV) opening area by the whole AV area.

[0024] It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said AVD Factor is determined for aortic valve insufficiency (Aol) by calculating relative value of AV non-closed at the diastole phase area by the whole AV area. It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said data of hemodynamic parameters is obtained from Echocardiography or any other suitable method.

[0025] It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said mechanistic intracardiac hemodynamic model is based on the fundamental laws of natural sciences, including physical and biochemical principles.

[0026] It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said system is further configured to simulate a patient-specific development of pathological processes attributed to the Aortic Valve Disease by a. extracting pathology-specific (AVD) spatial dimensions and hemodynamics parameters from data input of spatial dimensions and hemodynamic parameters selected from TABLE A-2.2 and TABLE A-2.3. b. visualizing the pathological process in an integrated model of heart anatomy and hemodynamics by applying 3D computer graphics configured for rendering to web browsers.

[0027] It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said simulation is obtained by using computer-aided rendition (mechanistic modeling) of the natural hemodynamic processes.

[0028] It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said pathological processes include abnormal blood flow from left ventricle to aortic valve, thickening and / or enlargement of left ventricle.

[0029] It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said system provides data for further What-If Analysis.

[0030] BRIEF DESCRIPTION OF THE FIGURES

[0031] FIGURES 1A and IB disclose flow charts illustrating the process for obtaining computational simulation of heart (Figure 1A) and 3D heart model of a patient with Aortic Valve Disease in a patient, according to the present invention (Figure IB).

[0032] FIGURE 2 is a schematic representation of hierarchical-component of physiological- hemodynamic relationships underlying the functioning of the system according to the present invention.

[0033] FIGURES 3A-I to 3C-III represent development of linear measurement adjustment tools for basic views.

[0034] FIGURES 4A-4D represent stages of formation of animated 3D model of the heart.

[0035] FIGURES 5A to 8B represent heart models with different raphes configurations (RC1-RC4) of aortic valve in A VS. FIGURES 9A-I to 9B-II represent steps for building a patient-specific 3D heart model from a normal 3D heart template, by using linear measurement adjustment tools to change the sizes of chambers (the atria).

[0036] FIGURES 10A-10D represent a chamber-based blood flow model as a concept of a holistic indivisible model of intracardiac hemodynamics in healthy heart (Figure 10A-B), heart with aortic valve stenosis (Figure IOC) and heart with aortic valve insufficiency (Figure 10D).

[0037] FIGURES 11A-11B represent the means for hemodynamic model (monitors, indicators, setting and control tools).

[0038] FIGURES 12A-12B represent patient-specific integrated hemodynamic model of an adult (Figure 12A) and a child (Figure 12B).

[0039] FIGURES 13A-13D represent BSA-based patient-specific 3D heart model and integrated hemodynamic model of an adult (Figure 13A and 13B) and a child (Figure 13C and 13D).

[0040] FIGURES 14A-I to 14B-II represent virtual patient’s condition before surgery (Figures 14AI- 14A-II) and after surgery (Figures 14B-I- 14B-II).

[0041] DETAILED DESCRIPTION OF THE INVENTION

[0042] The following description is provided, alongside all chapters of the present invention, so as to enable any person skilled in the art to make use of the invention and sets forth the best modes contemplated by the inventor of carrying out this invention. Various modifications, however, are adapted to remain apparent to those skilled in the art, since the generic principles of the present invention have been defined specifically to provide system and methods for computational simulation of the Anatomical structures and intracardiac hemodynamics of heart with Aortic Valve Disease in a patient.

[0043] Despite significant medical advances in recent years that have provided improvements in the diagnosis and treatment of aortic valve disease, the incidence of premature morbidity and mortality remains substantial. These challenges are, in part, attributed to the lack of accurate estimates of patient-specific parameters that adequately characterize the heart and aortic anatomy, physiology, and hemodynamics. Consequently, early disease prediction and progression models often rely on generic data, limiting their efficacy for tailoring therapeutic interventions to individual patients.

[0044] In recent years there is a significant progress in determining patient-specific geometry for the heart and adjacent structures using various medical imaging modalities, including computed tomography (CT), magnetic resonance (MR), rotational X-ray, and Ultrasound. However, there has been relatively little emphasis on extending hemodynamic analyses by incorporating patient-specific geometry, boundary conditions, and material properties for vascular structures. Mathematical models of the heart, such as statistical shape models, hold the potential to revolutionize the clinical assessment and treatment of heart disease. Nonetheless, conventional heart models have significant limitations, often being generic.

[0045] The AVD diagnosis setting and condition severity assessment require high degree of precision. The present invention provides system and methods for building of a patient-specific combined anatomy / hemodynamics enabling to verify correctness of the collected data and monitor a patient’s condition. The model’s flexibility and editability allow simulating of human heart’s compensatory efforts (chambers’ contractile force regulation), thus opening promising perspectives of condition development / improvement predictions.

[0046] The present disclosure provides system and methods thereof for computational simulation of the anatomical structures and intracardiac hemodynamics of heart with Aortic Valve Disease in a patient. The system and methods according to the present invention provide patient-specific editable animated three-dimensional anatomic model of heart and aortic valve with integrated intracardiac hemodynamics. The system and methods according to the present invention further provide a computational simulation for development of pathological processes attributed to the Aortic Valve Disease in a patient and provide data for What-If analysis.

[0047] TERMS AND DEFINITIONS

[0048] In the present invention the term, "spatial dimensions" refers to the physical extent or size of heart compartments, including one-dimensional spatial parameters, two-dimensional spatial parameters, and three-dimensional spatial parameters.

[0049] The term "hemodynamic parameters" refers to the physiological measurements that describe the flow of blood and the forces involved in the circulatory system, and more specifically the heart.

[0050] The term " Detalization" refers to data refinement, based on data granularity, teaching how finely the data is collected, categorized, or recorded in terms of features and attributes. This aspect has a significant impact on the effectiveness of machine learning algorithms and the insights that can be extracted from the data.

[0051] The term " statistical rendition", according to the present invention, refers to data visualization to highlight patterns, trends, relationships, or other insights from data of physiological / pathophysiological divergence in the heart.

[0052] The term " mechanistic intracardiac hemodynamic model" refers to a model that is designed to capture the underlying physiological mechanisms and interactions that govern blood flow, pressure changes, and other hemodynamic factors within the heart. Said model is used to simulate and understand the complex interactions among the heart's chambers, valves, and blood vessels, providing insights into how changes in different parameters can affect cardiac function.

[0053] The term "raphe" refers to a partial or complete fusion of two valve leaflets.

[0054] The terms "RN", "LN" and "RL" refer to the classification of the pathological bicuspid aortic valve forms, based on the presence or location of the raphe. The location of the raphe is defined by which valve leaflets are fused together, right-left coronary (RL), right-noncoronary (RN) or left-noncoronary (LN). Reference is now made to Figures 1-14 describing a system and methods for computational simulation of the anatomical structures and intracardiac hemodynamics of heart with Aortic Valve Disease in a patient.

[0055] FIGURES 1A and IB represent a flow chart illustrating the process for obtaining computational simulation of heart with Aortic Valve Disease in a patient, according to the present invention. As a first step, input values of spatial dimensions are converted into a geometric constituent for 3D Heart Model construction. Said input data array is then expanded with pathology-specific (AVD) parameters and converted into the geometric constituent for construction / display of the pathological changes in the 3D Heart Model (Figure 1A). Figure IB represents the implementation of the system and methods of the present invention for obtaining a patient-specific 3D heart model with integrated intracardiac hemodynamics.

[0056] FIGURE 2 is a schematic representation of hierarchical-component of physiological- hemodynamic relationships underlying the functioning of the system according to the present invention.

[0057] Panel A: 3D layer of the anatomical (geometrical) representation of the human heart.

[0058] Panel B: Hemodynamic layer of the functional representation of the human heart.

[0059] Stages I and II represent the data input levels, wherein:

[0060] A, B stage I: Obtaining the initial / input spatial dimensions and other measurements of the heart ;

[0061] A stage II: Detalization of the pathology-specific (AVD) spatial dimensions and other measurements of the heart;

[0062] B stage II: Detalization of the hemodynamic input parameters based on A-I, and expansion of the hemodynamics-specific parameters for the norm and pathology (AVD);

[0063] Stages III and IV represent the data output levels, wherein:

[0064] A, B stage III: Visualization of the spatial (anatomic) and hemodynamic alterations in the anatomic (A-III) and hemodynamic (B-III) models of the heart.

[0065] A stage IV : Statistical rendition of the physiological / pathological divergence in the heart (Z- Score, etc.)

[0066] B stage IV: Deeper detalization of the intracardiac hemodynamic processes. FIGURES 3AI-3C-III represent development of linear measurement adjustment tools for basic views. Spatial parameters, selected from Table A-2 are measured from echocardiography data, using different standard Echo views.

[0067] FIGURES 4A-4D represent stages of formation of animated 3D model of the heart. Figure 4A, Formation of the animated anatomical components: valves and myocardium; figure 4B, Formation of larger animated structure; figure 4C, Formation of animated structures of all the chambers, pulmonary arteries, pulmonary veins, aortic arch, and figure 4D, completion of the full animated 3D model of the heart.

[0068] FIGURES 5A-8B represent heart models with different raphes configurations of aortic valve in AVS:

[0069] FIGURE5A represents raphes configuration 1 (RC-1), with symmetrical Horizontal position.

[0070] FIGURE5B represents raphes configuration 1 (RC-1), symmetrical Vertical position.

[0071] FIGURE 6A represents raphes configuration 2 (RC-2), with RN.

[0072] FIGURE 6B represents raphes configuration 2 (RC-2), with RL.

[0073] FIGURE 7A represents raphes configuration 3 (RC-3), with RN+LN.

[0074] FIGURE 7B represents raphes configuration 3 (RC-3), with RN+RL.

[0075] FIGURE 8A represents raphes configuration 4 (RC-4) with LN+RL.

[0076] FIGURE 8B represents raphes configuration 4 (RC-4) with LN.

[0077] FIGURES 9A-I-9B-II represent the use of the linear measurement adjustment tools to change the sizes of chambers (the atria, 9A-I and 9AII for basic views, compared to 9B-I and 9BII).

[0078] FIGURES 10A-10D represent a chamber-based blood flow model as a concept of a holistic indivisible model of intracardiac hemodynamics. Figures 10A and 10B illustrate normal blood flow by demonstrating the normal direction of fluid movement from chamber Al to vessel A2 through a valve duct with a diameter of dl. The volume of flowing fluid is influenced by its viscosity, the pressure difference, and the diameter of the opening. The direction of fluid flow is determined by the pressure gradient between a chamber and a vessel. In chamber Al, the pressure Pl created by piston W1 is greater than the pressure P2 in vessel A2. As a result, a portion of the fluid (blood) moves back into chamber Al from vessel A2. This movement is possible when the valve duct with a diameter of d2 is open. If the valve duct with a diameter of d2 is closed (valve closed, as shown in Figure 10A), then this portion of the fluid is stored in container F since it is expandable (compliant). In such conditions, a flow QI is generated through the valve duct with a diameter of d 1. When the piston W 1 does not create pressure P 1 , the pressure P2 in vessel A2 becomes greater than in chamber Al, causing the fluid to move along the pressure gradient from vessel A2 to chamber Al . This movement is prevented by the valve duct with a diameter of d 1 , which is closed (valve closes, as shown in Figure 10B). During this time, the valve duct with a diameter of d2 opens, and the stored fluid in container F, under the action of stretching forces, moves into chamber A 1. Under these conditions, a flow Q3 is generated, and it is equal to the flow Q2 created through the valve duct with a diameter of d2.

[0079] Figure IOC illustrates aortic valve stenosis by demonstrating stenosis of the valve duct with a diameter of dl (Figure IOC), when the pressure Pl in chamber Al created by piston W1 is greater than the pressure P2 in vessel A2, the fluid leaves chamber A 1. Due to the obstruction created by stenosis, the flow QI becomes less than normal (as in Figure 10A). As a result, less fluid is deposited in container F. When the valve duct with a diameter of d2 opens, and the stored fluid in container F, under the action of stretching forces, moves into chamber Al, it creates a reduced flow Q2 through the valve duct with a diameter of d2 (as in Figure 10B). In these conditions, to achieve normal flow rates Q 1 and Q2, piston W 1 needs to generate pressure Pl greater than normal to overcome the resistance created by the stenosis of the valve duct with a diameter of dl. Overcoming this resistance requires piston W1 to perform additional work.

[0080] Figure 10D illustrates aortic valve insufficiency by demonstrating insufficiency of the valve duct with a diameter of dl. When piston W1 does not create pressure Pl, the pressure P2 in vessel A2 becomes greater than in chamber Al, and the fluid tends to move along the pressure gradient from vessel A2 to chamber A 1. This movement is not hindered by the valve duct with a diameter of dl, as it is not equal to zero, as the valve does not completely close. The stored fluid in container F, under the action of stretching forces, moves into chamber Al from both ends of vessel A2. Under these conditions, not only is flow Q3 generated, but also flow Q4. One portion of the fluid flows through the valve duct with a diameter of d2, and the other portion flows through the valve duct with a diameter of dl .

[0081] FIGURES 11A-11B represent patient's specific Integrated Hemodynamics and anatomic model of the Norma. Figure HA demonstrates the cardiac output graphs. Figure 11B demonstrates Blood Prcssurc / Vohimc graphs. FIGURES 12A-12B represent patient's specific BSA-based Integrated Hemodynamics model of the Norma. Figure 12A demonstrates BSA-based parameters for an adult. Figure 12B demonstrates BSA-based parameters for a child.

[0082] FIGURES 13A-13D represent patient's specific Integrated Hemodynamics and BSA-based 3D anatomic model of the Norma in an adult and a child. Figure 13A demonstrates BSA-based reconstruction of the 3D heart model parameters for an adult and the BSA-based parameters are presented in Figure 13B. Figure 13C demonstrates BSA-based reconstruction of the 3D heart model parameters for a child and the BSA-based parameters are presented in Figure 13D.

[0083] FIGURE 14 represents virtual patient’s condition before surgery (Figures 14A-I and 14A-II) and after surgery (Figures 14B-I and 14B-II). Figure 14A-I demonstrates 3D Model showing the RN+LN Raphes Configuration with related parameters and Figure 14A-II represents intracardiac hemodynamics parameters and model in a virtual patient before surgery. Figure 14B-I demonstrates 3D Model showing the RN+LN normal Raphes Configuration with related parameters and Figure 14B-II demonstrates normalized intracardiac hemodynamics parameters and model in a virtual patient after surgery.

[0084] EXAMPLE 1

[0085] A concept of a holistic indivisible model of intracardiac hemodynamics.: A chamber to- vessel flow model

[0086] FIGURES 10A-10D represent a chamber-based blood flow model as a concept of a holistic indivisible model of intracardiac hemodynamics. The blood flow through the aortic valve is calculated based on the pressure gradient created by the myocardium, the diameter of the opening, and consequently, the continuity of the flow of incompressible fluid (Bernoulli's equations) from one chamber into the aorta. a. Norma

[0087] In Figure 10A, the normal direction of fluid movement from chamber Al to vessel A2 through a valve duct with a diameter of dl is shown. The volume of flowing fluid is influenced by its viscosity, the pressure difference, and the diameter of the opening. This corresponds to the Poiseuille's formula: 8piL

[0088] Wherein:

[0089] Q= the flow rate (cm3 / s or m3 / s) r= the radius of the tube (cm or m)

[0090] Po= the outlet fluid pressure (dynes / cm2 or Pa)

[0091] P'= the inlet fluid pressure (dynes / cm2 or Pa) p= the dynamic viscosity of the fluid (poise or Pa.s)

[0092] L= the length of the tube (cm or m)

[0093] According to this formula, the volumetric flow rate of the fluid is proportional to the pressure drop per unit length of the tube, the fourth power of the tube's radius, and inversely proportional to the viscosity coefficient. However, since the length of the tube (duct) is negligible, it can be disregarded.

[0094] In this context, the direction of fluid flow is determined by the pressure gradient between a chamber and a vessel. In chamber Al, the pressure Pl created by piston W1 is greater than the pressure P2 in vessel A2. As a result, a portion of the fluid (blood) moves back into chamber Al from vessel A2. This movement is possible when the valve duct with a diameter of d2 is open. If the valve duct with a diameter of d2 is closed (valve closed, as shown in Figure 10A), then this portion of the fluid is stored in container F since it is expandable (compliant). In such conditions, a flow Q 1 is generated through the valve duct with a diameter of dl .

[0095] When the piston W1 does not create pressure Pl, the pressure P2 in vessel A2 becomes greater than in chamber Al, causing the fluid to move along the pressure gradient from vessel A2 to chamber Al. This movement is prevented by the valve duct with a diameter of dl, which is closed (valve closes, as shown in Figure 10B).

[0096] During this time, the valve duct with a diameter of d2 opens, and the stored fluid in container F, under the action of stretching forces, moves into chamber Al. Under these conditions, a llow Q3 is generated, and it is equal to the flow Q2 created through the valve duct with a diameter of d2. The described process repeats cyclically, and, in the normal state, these two flows - QI and Q2 - in two cycles (systole -diastole) are cumulatively equal. b. Stenosis

[0097] In the case of stenosis of the valve duct with a diameter of dl (Figure IOC), when the pressure Pl in chamber Al created by piston W1 is greater than the pressure P2 in vessel A2, the fluid leaves chamber A 1. However, due to the obstruction created by stenosis, the flow Q 1 becomes less than normal (as in Figure 10A). As a result, less fluid is deposited in container F.

[0098] When the valve duct with a diameter of d2 opens, and the stored fluid in container F, under the action of stretching forces, moves into chamber Al, it creates a reduced flow Q2 through the valve duct with a diameter of d2.

[0099] In these conditions, to achieve normal flow rates QI and Q2, piston W1 needs to generate pressure P 1 greater than normal to overcome the resistance created by the stenosis of the valve duct with a diameter of d 1. Overcoming this resistance requires piston W1 to perform additional work. c. Insufficiency

[0100] In the case of insufficiency of the valve duct with a diameter of dl, when piston W1 does not create pressure Pl, the pressure P2 in vessel A2 becomes greater than in chamber Al, and the fluid tends to move along the pressure gradient from vessel A2 to chamber Al .

[0101] Now, unlike the normal state, this movement is not hindered by the valve duct with a diameter of dl, as it is not equal to zero; in other words, the valve does not completely close (as in Figure 10D).

[0102] In such a case, the stored fluid in container F, under the action of stretching forces, moves into chamber Al from both ends of vessel A2. Under these conditions, not only is flow Q3 generated, but also flow Q4. One portion of the fluid flows through the valve duct with a diameter of d2, and the other portion flows through the valve duct with a diameter of dl.

[0103] EXAMPLE 2

[0104] The hemodynamic model The functional Hemodynamic model incorporating the above principles of hydrodynamics combines a number of sequential and concurrent processes in such a way that patient-specific simulations of the Aortic Valve Disease are provided not only with a high degree of precision, but also with a possibility to vary the form and course of this pathological condition, including complete elimination of the defect with subsequent improvement of the heart’s hemodynamic performance, thus providing a powerful prognostic tool

[0105] The Hemodynamic model allows setting, changing, and managing the blood flow in all the compartments of the heart with automatic recalculation of the values of interdependent parameters. The current stand-alone embodiment even makes it possible to follow the processes in the loops of both pulmonary and systemic circulation.

[0106] EXAMPLE 3

[0107] The Aortic Valve Disease (AVD) is subdivided into three categories: Aortic Stenosis (AoS), Aortic Insufficiency (Aol), and a combination of those two - Aortic Valve Stenosis with Insufficiency (AoS / Aol). The model of the present invention (3D editable patient-specific heart model plus patient-specific hemodynamics model) allows simulating any condition representing any category thanks to the complex of the spatial and hemodynamic parameters covering it all. The differences between the categories are limited to the parameters shown in TABLES A-3, A-2.2 and A-2.3. The severity-setting parameters shown in TABLE A-3 are the Percentage of aortic valve stenosis (AV_Stenosis) and the Percentage of aortic valve insufficiency (AV Insufficiency); in case a combination of two conditions is simulated, both parameters will still be calculated and provided separately, but within a combined conditionspecific set of parameters. The parameters shown in TABLE A-2.2 are required to simulate AoS, and those shown in TABLE A-2.3 are meant to be used in Aol simulations. As with parameters from TABLE A-3, in case a combination of two conditions is simulated, both sets of parameters will be calculated and provided separately, but within a combined conditionspecific set of parameters. The extended set of hemodynamic parameters is shown in TABLE A-2.1. TABLE B-l contains AVD-related hemodynamic outputs.

[0108] TABLE A-2. Input Hemodynamic AoS and Aol Spatial Parameters TABLE A-2.1 Extended Input Hemodynamic AVD Related Parameters (continued) TABLE A-2.2. AoS-specific parameters TABLE A-2.3. Aol-specific parameters (continued)

[0109] TABLE A-3. Input Hemodynamic AoS and Aol Severity-Setting Parameter TABLE B-l. AVD-related Hemodynamic Outputs

Claims

CLAIMS1. A system for computational simulation of heart with Aortic Valve Disease (AVD) in a patient, comprising at least one computer system configured to: a. generate patient-specific editable animated three-dimensional anatomic model of heart and Aortic Valve, wherein said computer system comprises (i) Data input module of spatial dimensions and other measurements of the heart and (ii) computer readable instructions for:Detalization of the pathology-specific (AVD) spatial dimensions and other measurements of the heart;Visualization of the spatial-anatomic alterations in the heart;Implementation of statistical rendition of the physiological / pathophysiological divergence in the heart; b. generate patient-specific editable animated mechanistic intracardiac hemodynamic model, wherein said computer system comprises (i) Data input module of hemodynamic parameters (ii) Data output module of AVD- related Hemodynamic parameters and (iii) Computer readable instructions for:Detalization of the hemodynamic input and output parameters and introduction of the hemodynamics-specific parameter (denoted “AVD Factor”) for AVD pathology;Visualization of the hemodynamic alterations in the heart;Elaboration of the intracardiac hemodynamic processes; c. generate patient-specific editable animated three-dimensional anatomic model of heart and aortic valve with integrated intracardiac hemodynamics, said model comprising combining of said patient-specific editable animated three-dimensional anatomic model of heart and aortic valve with said patient-specific editable mechanistic intracardiac hemodynamic model.

2. The system according to claim 1, wherein said spatial dimensions and other measurements of the heart are selected from Table A-2; further wherein said data of spatial dimensions of the heart includes at least 4 one-dimensional spatial parameters, selected from TABLE A-2.

3. The system according to claim 2, wherein said data of spatial dimensions of the heart is obtained from Echocardiography or any other suitable method.

4. The system according to claim 1, wherein said data of hemodynamic parameters includes at least 9 one-dimensional spatial parameters, 5 two-dimensional spatial parameters, and 5 three-dimensional spatial parameters, selected from TABLE A-2.1, TABLE A-2.2 and TABLE A-2.3.

5. The system according to claim 1, wherein said AVD Factor is determined for aortic valve stenosis (AoS) by calculating relative value of aortic valve (AV) opening area as a total of AV area.

6. The system according to claim 1, wherein said AVD Factor is determined for aortic valve insufficiency (Aol) by calculating the relative value of the open AV in diastole as a total of AV area.

7. The system according to claim 1, wherein said data of hemodynamic parameters is obtained from Echocardiography or any other suitable method.

8. The system according to claim 1, wherein said mechanistic intracardiac hemodynamic model is based on the fundamental laws of natural sciences, including physical and biochemical principles.

9. The system according to claim 1, wherein said system is further configured to simulate a patient-specific development of pathological processes attributed to the Aortic Valve Disease by a. extracting pathology-specific (AVD) spatial dimensions and hemodynamics parameters from data input of spatial dimensions and hemodynamic parameters selected from TABLE A-2.2 and TABLE A-2.

3. b. visualizing the pathological process in an integrated model of heart anatomy and hemodynamics by applying 3D computer graphics (Unity 3D), configured for rendering to web browsers.

10. The system according to claim 9, wherein said simulation is obtained by using computer-aided rendition (mechanistic modeling) of the natural hemodynamic processes.

11. The system according to claim 9, wherein said pathological processes include abnormal blood flow from left ventricle to aortic valve, thickening and / or enlargement of left ventricle.

12. The system according to claim 9, wherein said system provides data for further What- If Analysis.

13. A method for determining a form and properties of the Aortic Valve Disease in a patient, wherein said method comprises steps of: a. receiving patient-specific data regarding (a) spatial dimensions and other measurements of the heart and (b) hemodynamic parameters; b. Detailing the pathology-specific (AVD) spatial dimensions and other measurements of the heart; c. Visualizing the spatial-anatomic alterations in the heart; d. Applying statistical rendition of the physiological / pathophysiological divergence in the heart; e. generating patient-specific editable animated three-dimensional anatomic model of heart and aortic valve; f. Detailing the hemodynamic input parameters and hemodynamics -specific parameter (denoted “AVD Factor”) for AVD pathology; g. Visualizing the hemodynamic alterations in the heart; h. Elaborating the intracardiac hemodynamic processes; i. generating patient-specific editable animated mechanistic intracardiac hemodynamic model; j. generating patient-specific editable animated three-dimensional geometric model of heart and aortic valve with Integrated Intracardiac Hemodynamics wherein said patient-specific editable animated three-dimensional geometric model of heart and aortic valve with integrated intracardiac hemodynamics of step j is obtained by combining said patient-specific editable animated three-dimensional anatomic model of heart and aortic valve of step e with said patient- specific editable animated mechanistic intracardiac hemodynamic model of step i.

14. The method according to claim 13, wherein said spatial dimensions and other measurements of the heart are selected from TABLE A-2; further whereinsaid data of spatial dimensions of the heart includes at least 4 one-dimensional spatial parameters, selected from TABLE A-2.

15. The method according to claim 14, wherein said data of spatial dimensions of the heart is obtained from Echocardiography or any other suitable method.

16. The method according to claim 13, wherein said data of hemodynamic parameters includes at least 9 one-dimensional spatial parameters, 5 two-dimensional spatial parameters, and 5 three-dimensional spatial parameters, selected from TABLE A-2.1, TABLE A-2.2 and TABLE A-2.3.

17. The method according to claim 13, wherein said AVD Factor is determined for aortic valve stenosis (AoS) by calculating relative value of aortic valve (AV) opening area by the whole AV area.

18. The method according to claim 13, wherein said AVD Factor is determined aortic valve insufficiency (Aol) by calculating relative value of AV non-closed at the diastole phase area by the whole AV area.

19. The method according to claim 13, wherein said data of hemodynamic parameters is obtained from Echocardiography or any other suitable method.

20. The method according to claim 13, wherein said mechanistic intracardiac hemodynamic model is based on the fundamental laws of natural sciences, including physical and biochemical principles.

21. The method according to claim 13, wherein said method comprises steps of simulating a patient-specific development of pathological processes attributed to the Aortic Valve Disease (AVD) by a. extracting pathology-specific (AVD) spatial dimensions and hemodynamics parameters from data input of spatial dimensions and hemodynamic parameters selected from TABLE A-2.2 and TABLE A-2.

3. b. visualizing the pathological process in an integrated model of heart anatomy and hemodynamics by applying 3D computer graphics (Unity 3D), configured for rendering to web browsers.

22. The method according to claim 21, wherein said simulation is obtained by using computer-aided rendition (mechanistic modeling) of the natural hemodynamic processes.

23. The method according to claim 21, wherein said pathological processes include abnormal blood flow from left ventricle to aortic valve, thickening and / or enlargement of left ventricle.

24. The method according to claim 21, wherein said method provides data for further What- If Analysis.

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