System and methods for computational simulation of the anatomical structures and intracardiac hemodynamics of heart with atrial septal defect in a patient

Abstract

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 Atrial Septal Defect in a patient. The present disclosure provides a new and useful system and methods thereof for computational simulation of the anatomical structures and intracardiac hemodynamics of heart with Atrial Septal Defect in a patient. The system and methods according to the present invention provide patient-specific editable animated three-dimensional anatomic model of heart and atrial septum 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 Atrial Septal Defect in a patient and provide data for What-If analysis.

Description

[0001] System and Methods for computational simulation of the Anatomical structures and intracardiac hemodynamics of heart with Atrial Septal Defect 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 Atrial Septal Defect in a patient.

[0004] BACKGROUND OF THE INVENTION

[0005] Atrial septal defects (ASDs) belong to a group of congenital cardiac anomalies that allow communication between the left and right sides of the heart. ASDs are congenital heart defects characterized by an abnormal opening in the atrial septum, the wall that separates the heart's two upper chambers (atria). Defects of the atrial septum are the third most common type of congenital heart disease, with an estimated incidence of 56 per 100,000 live births.

[0006] Despite significant medical advances in recent years that have provided improvements in the diagnosis and treatment of atrial septal defects, 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. 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.

[0007] SUMMARY OF THE INVENTION

[0008] 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 Atrial Septal Defect in a patient.

[0009] The object of the present invention is to disclose a system for computational simulation of anatomical structures and intracardiac hemodynamics of heart with Atrial Septal in a patient, comprising at least one computer system configured to: a. generate patient-specific editable animated three-dimensional anatomic model of heart and atrial septum, wherein said computer system comprises (i) Data input module of spatial dimensions and other measurements of the heart and (ii) computer readable instructions for:

[0010] Detalization of the pathology-specific (ASD) spatial dimensions and other measurements of the heart;

[0011] Visualization of the spatial-anatomic alterations in the heart;

[0012] 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 ASD-related Hemodynamic parameters and (iii) Computer readable instructions for:

[0013] Detalization of the hemodynamic input and output parameters and introduction of the hemodynamics-specific parameter (denoted “ASD Factor”) for ASD pathology;

[0014] Visualization of the hemodynamic alterations in the heart;

[0015] Elaboration of the intracardiac hemodynamic processes; c. generate patient-specific editable animated three-dimensional anatomic model of heart and atrial septum with integrated intracardiac hemodynamics, said model comprising combining of said patient-specific editable animated three-dimensional anatomic model of heart and atrial septum with said patient-specific editable mechanistic intracardiac hemodynamic model.

[0016] It is another object of the present invention to disclose a method for determining a form and properties of the Atrial Septal Defect 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 (ASD) 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 atrial septum; f. Detailing the hemodynamic input parameters and hemodynamics -specific parameter (denoted “ASD Factor”) for ASD 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 atrial septum with Integrated Intracardiac Hemodynamics wherein said patient-specific editable animated three-dimensional geometric model of heart and atrial septum with integrated intracardiac hemodynamics of step (j) is obtained by combining said patient-specific editable animated three-dimensional anatomic model of heart and atrial septum of step (e) with said patient-specific editable animated mechanistic intracardiac hemodynamic model of step (i).

[0017] 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 and TABLE C-l; further wherein said data of spatial dimensions of the heart includes at least: 59 one-dimensional spatial parameters, 6 two-dimensional spatial parameters, and 11 three-dimensional spatial parameters, selected from TABLE C-L

[0018] 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.

[0019] 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 3 one-dimensional spatial parameters, 4 two-dimensional spatial parameters, and 4 three-dimensional spatial parameters, selected from TABLE A-l and said ASD-related Hemodynamic parameters are selected from Table BL

[0020] It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said ASD Factor is determined by calculating relative value of ASD ostium area by the whole atrial septum area.

[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 hemodynamic parameters 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 mechanistic intracardiac hemodynamic model is based on the fundamental laws of natural sciences, including physical and biochemical principles.

[0023] 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 Atrial Septal Defect by: a. extracting pathology-specific (ASD) spatial dimensions and hemodynamics parameters from data input of spatial dimensions and hemodynamic parameters selected from Table Al, Table A2 and table C-l 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. 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.

[0024] 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 blood shunt from Left Atrium to the Right Atrium and changes in Pulmonary-to-Systemic Flow (Qp / Qs) Ratio.

[0025] 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.

[0026] 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 based on parameter of left ventricle volume (LVEDV).

[0027] It is another object of the present invention to disclose the system and methods as defined in any of the above, wherein said parameter of left ventricle volume (LVEDV) is associated with size of the ASD defect and QP / QS.

[0028] 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 applied by setting the value of end-diastolic volume of the left ventricle (LVEDV) to manipulate pressure gradient and QP / QS ratio.

[0029] BRIEF DESCRIPTION OF THE FIGURES

[0030] FIGURE 1 is a flow chart illustrating the process for obtaining computational simulation of heart with Atrial Septal Defect in a patient, according to the present invention.

[0031] FIGURE 2 is a schematic representation of hierarchical-component of physiological- hemodynamic relationships underlying the functioning of the system according to the present invention.

[0032] FIGURE 3 represents development of linear measurement adjustment tools for basic views.

[0033] FIGURE 4 A-C represent stages of formation of animated 3D model of the heart.

[0034] FIGURE 5 represents completion of the full animated 3D model of the heart.

[0035] FIGURE 6 represents heart model cross sections showing the ADS in the modeled heart.

[0036] FIGURE 7 represents use of the linear measurement adjustment tools to change the sizes of chambers (the atria). FIGURE 8 represents a chamber-based blood flow model as a concept of a holistic indivisible model of intracardiac hemodynamics

[0037] FIGURE 9 represents the means for hemodynamic model (monitors, indicators, setting and control tools.

[0038] FIGURE 10 represents the hemodynamic models of normal heart and ADS -heart

[0039] FIGURE 11 represents patient's specific Integrated Hemodynamics model (NORMAL)

[0040] FIGURE 12 represents BSA-based patient's specific Integrated Hemodynamics model

[0041] (NORMAL)

[0042] FIGURE 13 represents integrated hemodynamics model in heart with enlarged left atrium.

[0043] FIGURE 14 A-D represent ASD hemodynamics simulation of pre and post ASD occlusion.

[0044] FIGURE 15 represents the means for hemodynamic model, comprising sliders for setting LVESD, LVEDV, and Valve Diameter.

[0045] FIGURE 16 represents the initial stage of setting an ASD-heart in the LVEDV-based simulation.

[0046] FIGURE 17 represents the development of ASD-related conditions in the LVEDV-based simulation.

[0047] FIGURE 18 A-B represent ASD hemodynamics simulation of pre and post ASD occlusion in the LVEDV-based simulation.

[0048] FIGURE 19 presents a series of screenshots demonstrates the relationship between the size of the ASD defect and QP / QS.

[0049] FIGURE 20 provides a schematic representation of the correlation between ASD defect size, the shunting rate, and pressure in the right atrium and left atrium.

[0050] FIGURE 21 presents the correlation between the end-diastolic volume of the left ventricle (LVEDV) and the pressure gradient.

[0051] DETAILED DESCRIPTION OF THE INVENTION

[0052] 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 Atrial Septal Defect in a patient.

[0053] Despite significant medical advances in recent years that have provided improvements in the diagnosis and treatment of atrial septal defects, 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.

[0054] 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 patientspecific 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.

[0055] The present disclosure provides a new and useful system and methods thereof for computational simulation of the anatomical structures and intracardiac hemodynamics of heart with Atrial Septal Defect in a patient. The system and methods according to the present invention provide patientspecific editable animated three-dimensional anatomic model of heart and atrial septum 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 Atrial Septal Defect in a patient and provide data for What-If analysis.

[0056] TERMS AND DEFINITIONS

[0057] 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.

[0058] 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. 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.

[0059] 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.

[0060] 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.

[0061] 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 Atrial Septal Defect in a patient.

[0062] FIGURE 1 is a flow chart illustrating the process for obtaining computational simulation of heart with Atrial Septal Defect 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 (ASD) parameters and converted into the geometric constituent for construction / display of the pathological changes in the 3D Heart Model.

[0063] FIGURE 2 is a schematic representation of hierarchical-component of physiological- hemodynamic relationships underlying the functioning of the system according to the present invention.

[0064] Panel A: 3D layer of the anatomical (geometrical) representation of the human heart.

[0065] Panel B: Hemodynamic layer of the functional representation of the human heart.

[0066] Stages I and II represent the data input levels, wherein:

[0067] A, B stage I: Obtaining the initial / input spatial dimensions and other measurements of the heart ;

[0068] A stage II: Detalization of the pathology-specific (ASD) spatial dimensions and other measurements of the heart; 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 (ASD);

[0069] Stages III and IV represent the data output levels, wherein:

[0070] 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.

[0071] A stage IV: Statistical rendition of the physiological / pathological divergence in the heart (Z-Score, etc.)

[0072] B stage IV: Deeper detalization of the intracardiac hemodynamic processes.

[0073] FIGURE 3 represents development of linear measurement adjustment tools for basic views. Spatial parameters, selected from Table A-2 and TABLE C-l, are measured from echocardiography data, using different standard Echo views (Figure 3 A, B and C).

[0074] FIGURE 4 represent stages of formation of animated 3D model of the heart. A, Formation of the animated anatomical components: valves and myocardium; B, Formation of larger animated structure; C, Formation of animated structures of all the chambers, pulmonary arteries, pulmonary veins, aortic arch.

[0075] FIGURE 5 represents completion of the full animated 3D model of the heart.

[0076] FIGURE 6 represents heart model longitudinal plane (A) showing ASD-related View (Bicaval or RA / RV) formation and horizontal plane (B) showing ASD-related View (PSAX-b) formation in the modeled heart.

[0077] FIGURE 7 represents the use of the linear measurement adjustment tools to change the sizes of chambers (the atria, bottom panel compared to top panel).

[0078] FIGURE 8 represents a chamber-based blood flow model as a concept of a holistic indivisible model of intracardiac hemodynamics. Figure 81 demonstrates the direction of fluid movement from chamber Al to chamber VI through the duct with diameter dl, which is determined by the pressure gradient between two chambers. Figure 811 demonstrates the direction of fluid movement from chamber Al to chamber VI, according to the present invention, wherein chamber VI is expandable (flexible). Figure 8III demonstrates an ASD-related four-chamber blood flow model, according to the present invention, with four chambers, two of which are connected by a duct diameter d3 (ASD) with chambers VI and V2 expandable (flexible).

[0079] FIGURE 9 represents the means for hemodynamic model (monitors, indicators, setting and control tools. In Figure 9A, the graphs on the upper right screen show blood pressure and blood volume in the left heart. The bold lines stand for the dynamic representation of volume, thin lines - for pressure. The aorta is shown in red, the ventricle - in violet, and the atrium - in green. The lowest section on the left screen shows the radio-button enabling to switch over to the right heart graphs (with the pulmonary trunk instead of the aorta). The left screen features the schematic representation of major vessels, with columns of digits showing the volume (white digits against the black backdrop), quantity of in-coming blood in ml with each repeated calculation (dark red ones), out-going blood (gray ones), and pressure (blue ones). The bottom right screen is used to dynamically demonstrate the pathological blood volumes. Figure 9B demonstrates the blood volume / pressure graph.

[0080] FIGURE 10 represents the hemodynamic models of normal heart (Figure 10A) and ADS -heart (Figure 10B). In normal hemodynamics (10A) the cardiac output of the right heart equals to that of the left heart (red circles in the Heart screen of 10A left panel). The bottom right screen of 10A shows the Pulmonary / Systemic output balance. Figure 10B left panel demonstrates the Atrial Septal Defect with red arrow shows the blood shunt from the left atrium to the right one during the atrial systole. The red circles highlight the cardiac output of 4274 ml / min in the right heart and the cardiac output of 3403 ml / min in the left heart. Figure 10B right panel demonstrates Pulmonary / Systemic output misbalance (blue arrow).

[0081] FIGURE 11 represents patient's specific Integrated Hemodynamics and anatomic model of the Norma. Figure 11A demonstrates the cardiac output graphs. Figure 11B demonstrates Blood Pressure / Volume graphs.

[0082] FIGURE 12 represents patient's specific Integrated Hemodynamics and BSA-based 3D anatomic model of the Norma. Figure 12A demonstrates BSA-based reconstruction of the 3D heart model parameters for an adult. Figure 12B demonstrates Hemodynamics in the patient-specific adult heart.

[0083] Figure 13 represents integrated hemodynamics model in normal heart (13A) and in heart with enlarged left atrium (13B) .

[0084] Figure 14 A-D represent ASD hemodynamics simulation of pre and post ASD occlusion.

[0085] Figure 14A demonstrates normal heart with integrated hemodynamics model. Figure 14B demonstrates the adjustment of settings for ASD spatial parameters (left panel) and the resulting ASD-anatomic heart model (right panel). Figure 14C demonstrates the adjustment of settings for ASD hemodynamic parameters (left panel) and the resulting ASD-anatomic and hemodynamic integrated model (right panel). Figure 14C demonstrate an anatomic with integrated hemodynamic model of heart after ASD occlusion, presenting hemodynamic parameters return to norm after ASD occlusion.

[0086] EXAMPLE 1

[0087] A concept of a holistic indivisible model of intracardiac hemodynamics,: A two-chamber blood flow model

[0088] FIGURE 8 represents a two-chamber blood flow model as a concept of a holistic indivisible model of intracardiac hemodynamics. Figure 81 demonstrates the direction of fluid movement from chamber Al to chamber V 1 through the duct with diameter dl, which is determined by the pressure gradient between two chambers. In chamber Al, the pressure created by plunger W1 is greater than the pressure in chamber VI, provided that chamber VI is either empty or expandable.

[0089] Here the blood flow traveling through the atrial opening (dl) is calculated based on the pressure gradient, diameter of the opening, and, accordingly, the continuity of the flow of incompressible fluid from one chamber to another described by Bernoulli's equations: where:

[0090] In the hemodynamic model according to the present invention, chamber VI is expandable (flexible). As presented in Figure 811, the volumetric flow rate (QI) is Q = vS, v is the velocity, S is the cross-sectional area (S=Pi*dA2 / 4).

[0091] Figure 8III demonstrates an ASD-hemodynamic model, according to the present invention, with four chambers, two of which are connected by a duct diameter d3 (ASD), wherein under the same pressures in chambers Al and A2, the liquid will not flow through the connecting duct. If the expandability (flexibility) of chamber V2 is greater, the liquid will flow through the duct from chamber Al to chamber A2, and the more flexible the chamber V2 and the larger the diameter of the connecting duct are, the higher the flow rate will be. The acceleration of the liquid flow from chamber A2 to chamber V2 will lead to a drop in pressure in chamber A2, and the compensation of this pressure drop will be replenished by the inflow of liquid from chamber Al, according to the principle of the suction mechanism. The volume of liquid flowing from chamber Al to chamber A2 through the duct (Figure 4) will depend on the pressure difference, the diameter of the opening, and its viscosity.

[0092] This corresponds to the Poiseuille's formula:

[0093] Wherein:

[0094] According to this formula, the volumetric flow rate of the liquid is proportional to the pressure drop per unit length of the pipe, the fourth power of the pipe radius, and inversely proportional to the viscosity coefficient.

[0095] However, since the length of the pipe (duct) is negligible, it can be ignored.

[0096] In this case, with a certain viscosity of the blood, it is possible to calculate the volume of blood ejected through the atrial opening, provided its diameter and the pressure difference in the atria are known. The pressure difference in the atria in the simulator is determined by the model of the elasticity of the vessels and myocardium, as well as the work performed by the myocardium as to the kinetics of blood flow.

[0097] EXAMPLE 2

[0098] 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 Atrial Septal Defect 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 (occlusion simulation) with subsequent improvement of the heart’s hemodynamic performance, thus providing a powerful prognostic tool

[0099] 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.

[0100] FIGURE 9 represents the means for hemodynamic model (monitors, indicators, setting and control tools. In Figure 9A, the graphs on the upper right screen show blood pressure and blood volume in the left heart. The bold lines stand for the dynamic representation of volume, thin lines - for pressure. The aorta is shown in red, the ventricle - in violet, and the atrium - in green. The radio-button (the lowest section on the left panel screen) makes it possible to switch over to the right heart graphs (with the pulmonary trunk instead of the aorta). The left panel screen features the schematic representation of major vessels, with columns of digits showing the volume (white digits against the black backdrop), quantity of in-coming blood in ml with each repeated calculation (dark red ones), out-going blood (gray ones), and pressure (blue ones). The vessels are schematically connected to form pulmonary and systemic circulation. The digits shown at the branch where the systemic circulation starts indicate systolic and diastolic pressure. Below the heart, within the systemic circulation tract, there is a square schematically representing the total of intracellular (royal blue) and extracellular (turquoise) liquid, with digits in the line below showing the volume, pressure and osmolarity (gray ones stand for the intracellular environment). A like square above the heart in the pulmonary circulation performs the same function. The sliders at the right of the bottom square are provided to regulate the diameter and elasticity of the vessels. Below there is a slider for setting the veins’ diameter. Around the heart there are sliders that allow regulating the functioning of the muscle fibers of the chambers. E.g., the slider “force of contraction” serves to increase or decrease the contractile force. The slider “systolic ejection time” allows regulating the ejection rate. The gray arrows in the heart and next to major vessels show the shunt blood flow; the bright red digits show the pathological blood volumes. The bottom right screen will dynamically demonstrate those volumes. The “Collection” button allows storing of the pathology parameters set by users.

[0101] EXAMPLE 3 The ASD factor

[0102] For the modeling purposes, the relation of the ASD ostium area to the whole atrium septum area as a key input parameter for the hemodynamics model of the ASD defect, is calculated and denoted as “ASD Factor”. Based on the set of TABLE A-2, Input Hemodynamics ASD Spatial Parameters, triplets of such parameters [(IAS_4CH, ASD_R0_4CH, ASD_CC), (IAS_BiC, ASDJVC, ASD_SVC), (IAS_PS, ASD_RO_PS, ASD_AO)] determine the size of ASD ostium. Two maximums of the three distances between ostium margins are selected and the area of ellipse built of those is calculated as an ASD ostium area.

[0103] EXAMPLE 4

[0104] Alternative ASD Hemodynamics Model: LVEDV-based simulation

[0105] The alternative embodiment of the ASD Hemodynamics model is based on the fact that the relationship between the size of the ASD defect and QP / QS is closely associated with the left ventricular end-diastolic volume (LVEDV) .

[0106] Since blood shunting from the left atrium to the right through the shunt occurs due to pressure gradients, to increase the shunt volume, either the volume of the right ventricle must be increased, causing its pressure to drop (compliance-based solution - the embodiment already described in the Specification), or the volume of the left ventricle must be decreased, causing its pressure to increase.

[0107] Only these two methods can establish a new pressure gradient.

[0108] The alternative embodiment allows to avoid assuming the volume or compliance of the right ventricle and provides a possibility to set the end-diastolic volume of the left ventricle (LVEDV), thus regulating (increasing) the gradient (reduction of the end-diastolic volume of the left ventricle (LVEDV) increases the shunt volume, after which pressures are balanced at a higher level).

[0109] The series of screenshots in FIGURE 19 demonstrates the relationship between the size of the ASD defect and QP / QS. This relationship is closely associated with the left ventricular end- diastolic volume (LVEDV).

[0110] In the screenshots, the leftmost position represents normality (without a defect). From left to right, there is a gradual increase in ASD size from 10 mm to 24 mm. Green vertical lines separate each step of ASD enlargement .

[0111] The burgundy color on the graphs represents changing volumes in the left ventricle, from diastole to systole. The gray line at the bottom represents the end-systolic volume, while the gray line at the top represents the end-diastolic volume. Below each graph are the defect size, shunt volume, ejection volume, and in red, the QP / QS ratio.

[0112] As the defect size increases, there is a decrease in end-diastolic volume (burgundy graph) alongside an increase in the QP / QS ratio. When the defect size reaches 18 mm, the increase in shunt volume and QP / QS ratio nearly ceases. In the red squares, the diminishing response (QP / QS) to increasing defect size is evident. This effect is due to the inability to increase blood flow through the shunt with the user-set LVEDV of 148 ml. Since the deficit in the left ventricle reaches 34 ml, a real LVEDV of 116 ml is created.

[0113] Once the user sets realistic values, for example, LVEDV = 121 ml, the simulator immediately begins to respond to further increases in ASD defect size. In this case, with the same defect size of 24 mm, the QP / QS increases from 1.7 to 2.4 (highlighted by the red circle). Additionally, the left ventricle volume graph also decreases (blue line), corresponding to the newly set user value of LVEDV. Now, the LVEDV value is comparable to the deficit in the left ventricle volume.

[0114] The Mechanism of this Phenomenon

[0115] Blood shunting from the left atrium to the right through the shunt occurs due to pressure gradients.

[0116] As the ASD defect increases, the shunting increases, leading to an increase in pressure in the right atrium and a corresponding decrease in pressure in the left atrium. This continues until the pressures equalize. Once they are equalized, no additional shunting can occur. The diagram in FIGURE 20 illustrates this mechanism.

[0117] The leftmost diagram represents normality, while all subsequent ones represent increasing defect and blood shunting. Pressure values in the right and left heart chambers during diastole are shown in blue. When the defect reaches 20 mm, corresponding to a blood shunt of 35 ml (in the red square), pressures equalize, and no matter how much the defect size increases, the shunt volume will not change. This is the limit for the parameters set by the user.

[0118] In order to increase the shunt volume, either the volume of the right ventricle must be increased, causing its pressure to drop (compliance), or the volume of the left ventricle must be decreased, causing its pressure to increase.

[0119] Only these two methods can establish a new pressure gradient. (Another option is to reduce the resistance of the pulmonary trunk, allowing more blood to leave the right ventricle in systole, leading to a decrease in its pressure). However, if the user does not have data on the volume or compliance of the right ventricle, there is only one option: to set the end-diastolic volume of the left ventricle (LVEDV), which will increase the gradient.

[0120] In FIGURE 21, A series of screenshots of real pressures in the right and left heart chambers (the red graph represents the left chamber, the green graph the right chamber). In the screenshot, pressures in diastole have equalized. Only by reducing the end-diastolic volume of the left ventricle (LVEDV) does the shunt volume increase, after which pressures equalize at a higher level. In other words, a new limit is reached for this defect size. This leads to an increase in QP / QS from 1.7 to 2.4.

[0121] TABLE A-l. Input Hemodynamic Parameters ml Left Ventricle End- systolic Volume

[0122] (Simpson ’s formula) mm Maximum Atrial Septal Defect Diameter

[0123] TABLE A-2. Input Hemodynamic ASD Spatial Parameters AV_A mm Aortic Valve Annulus

[0124] TABLE B-l. ASD-related Hemodynamic Outputs

[0125] TABLE C-l. Entire List of Input Parameters

Claims

CLAIMS1. A system for computational simulation of heart with Atrial Septal Defect in a patient, comprising at least one computer system configured to: a. generate patient-specific editable animated three-dimensional anatomic model of heart and atrial septum, 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 (ASD) 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 ASD-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 “ASD Factor”) for ASD 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 atrial septum with integrated intracardiac hemodynamics, said model comprising combining of said patient-specific editable animated three-dimensional anatomic model of heart and atrial septum 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 and TABLE C-l; further wherein said data of spatial dimensions of the heart includes at least: 59 one-dimensional spatial parameters, 6 two-dimensional spatial parameters, and 11 three-dimensional spatial parameters, selected from TABLE C-L3. 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 3 one-dimensional spatial parameters, 4 two-dimensional spatial parameters, and 4 three- dimensional spatial parameters, selected from TABLE A-l and said ASD-related Hemodynamic parameters are selected from Table Bl.

5. The system according to claim 1, wherein said ASD Factor is determined by calculating relative value of ASD ostium area by the whole atrial septum area.

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

7. 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.

8. The system according to claim 1, wherein said system is further configured to simulate a patientspecific development of pathological processes attributed to the Atrial Septal Defect by a. extracting pathology-specific (ASD) spatial dimensions and hemodynamics parameters from data input of spatial dimensions and hemodynamic parameters selected from Table Al, Table A2 and table C-l 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 browsers9. The system according to claim 8, wherein said simulation is obtained by using computer-aided rendition (mechanistic modeling) of the natural hemodynamic processes.

10. The system according to claim 8, wherein said pathological processes include blood shunt from Left Atrium to the Right Atrium and changes in Pulmonary-to-Systemic Flow (Qp / Qs) Ratio.

11. The system according to claim 8, wherein said system provides data for further What-If Analysis.

12. The system according to claim 1, wherein said simulation is based on parameter of left ventricle volume (LVEDV).

13. The system according to claim 12, wherein said parameter of left ventricle volume (LVEDV) is associated with size of the ASD defect and QP / QS.

14. The system according to claim 1, wherein said system is applied by setting the value of end- diastolic volume of the left ventricle (LVEDV) to manipulate pressure gradient and QP / QS ratio.

15. A method for determining a form and properties of the Atrial Septal Defect 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 (ASD) 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 atrial septum; f. Detailing the hemodynamic input parameters and hemodynamics-specific parameter (denoted “ASD Factor”) for ASD 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 atrial septum with Integrated Intracardiac Hemodynamics wherein said patient-specific editable animated three-dimensional geometric model of heart and atrial septum with integrated intracardiac hemodynamics of step j is obtained by combining said patient-specific editable animated three-dimensional anatomic model of heart and atrial septum of step e with said patient-specific editable animated mechanistic intracardiac hemodynamic model of step i.

16. The method according to claim 12, wherein said spatial dimensions and other measurements of the heart are selected from Table A-2 and TABLE C-l; further wherein said data of spatial dimensions of the heart includes at least: 59 one-dimensional spatial parameters, 6 two-dimensional spatial parameters, and 11 three-dimensional spatial parameters, selected from TABLE C-L17. The method according to claim 13, wherein said data of spatial dimensions of the heart is obtained from Echocardiography or any other suitable method.

18. The method according to claim 12, wherein said data of hemodynamic parameters includes at least 3 one-dimensional spatial parameters, 4 two-dimensional spatial parameters, and 4 three- dimensional spatial parameters, selected from TABLE A-l and said ASD-related Hemodynamic parameters are selected from Table BL19. The method according to claim 12, wherein said ASD Factor is determined by calculating relative value of ASD ostium area by the whole atrial septum area.

20. The method according to claim 12, wherein said data of hemodynamic parameters is obtained from Echocardiography or any other suitable method.

21. The method according to claim 12, wherein said mechanistic intracardiac hemodynamic model is based on the fundamental laws of natural sciences, including physical and biochemical principles.

22. The method according to claim 12, wherein said method comprises steps of simulating a patientspecific development of pathological processes attributed to the Atrial Septal Defect by a. extracting pathology-specific (ASD) spatial dimensions and hemodynamics parameters from data input of spatial dimensions and hemodynamic parameters selected from Table Al, Table A2, Table Bl and table C-lb. 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 browsers23. the method according to claim 19, wherein said simulation is obtained by using computer-aided rendition (mechanistic modeling) of the natural hemodynamic processes.

24. The method according to claim 19, wherein said pathological processes include blood shunt from Left Atrium to the Right Atrium and changes in Pulmonary-to-Systemic Flow (Qp / Qs) Ratio.

25. The method according to claim 13, wherein said method provides data for further What-If Analysis.

26. The method according to claim 15, wherein said simulation is based on parameter of left ventricle volume (LVEDV).

27. The method according to claim 26, wherein said parameter of left ventricle volume (LVEDV) is associated with size of the ASD defect and QP / QS.

28. The method according to claim 15, wherein said system is applied by setting the value of end- diastolic volume of the left ventricle (LVEDV) to manipulate pressure gradient and QP / QS ratio.

Images