Personalized safe zone for a TAVI procedure

Abstract

A computer implemented method of computing a personalized safe zone for transcatheter deployment of an aortic valve prosthesis device in a subject, comprising: identifying a location of an annulus plane of an aortic valve in at least one reference image, identifying a location of a cardiac conduction region between a perforating bundle and a branching point of the left branch bundle of a conduction system of the heart in the at least one reference image, and computing the personalized safe zone for transcatheter deployment of the aortic valve prosthesis device as a function of the location of the annulus plane and the location of the conduction region.

Description

[0001] PERSONALIZED SAFE ZONE FOR A TA VI PROCEDURE

[0002] RELATED APPLICATION

[0003] This application claims the benefit of priority of U.S. Provisional Patent Application U.S. Provisional Patent Application No. 63 / 621,140, filed on January 16, 2024; U.S. Provisional Patent Application No. 63 / 656,164, filed on June 5, 2024 and PCT Patent Application No. PCT / IB2024 / 057539 filed on August 4, 2024, and PCT Patent Application No. PCT / IB2024 / 057540 filed on August 4, 2024, the contents of which are incorporated herein by reference in their entirety.

[0004] BACKGROUND

[0005] The present invention, in some embodiments thereof, relates to image processing and, more specifically, but not exclusively, to systems and methods for processing image for computation of features for supporting a transcatheter aortic valve implantation (TAVI) procedure.

[0006] TA VI, also known as Transcatheter Aortic Valve Replacement (TAVR), is a minimally invasive procedure used to treat medical conditions impacting the aortic valve, for example, aortic valve stenosis, a condition in which the aortic valve becomes narrowed and restricts blood flow from the heart to the rest of the body. TAVI provides an alternative to traditional open-heart surgery for patients who are considered high risk or inoperable for conventional valve replacement. TAVI may be considered in some patients that a medium and / or low risk.

[0007] During a TAVI procedure, a specially designed artificial valve is implanted within the existing diseased aortic valve, without the need for open-heart surgery. The procedure is typically performed in a cardiac catheterization laboratory rather than an operating room.

[0008] SUMMARY

[0009] According to some embodiments of the present invention, there is provided a computer implemented method of computing a personalized safe zone for transcatheter deployment of an aortic valve prosthesis device in a heart of a subject, comprising: identifying a location of an annulus plane of an aortic valve in at least one reference image, identifying a location of a cardiac conduction region of the heart in the at least one reference image, and computing the personalized safe zone for transcatheter deployment of the aortic valve prosthesis device, the personalized safe zone is between the location of the annulus plane and the location of the conduction region, wherein the personalized safe zone defines where a distal end of the aortic valve prosthesis device is at least one of: to be maintained during transcatheter deployment, and to be positioned at an end of the transcatheter deployment.

[0010] Optionally, the location of the cardiac conduction region is identified as a floor of a membranous septum of the heart denoted about 1-2 millimeters (mm) above as a most inferior border of the membranous septum.

[0011] Optionally, the location of the cardiac conduction region is identified as between a perforating bundle and a branching point of the left branch bundle of the conduction system of the heart.

[0012] Optionally, the personalized safe zone is defined according to a conduction annulus depth (CAD) defined as distance between the annulus plane and the cardiac conduction region.

[0013] Optionally, when the CAD is greater than a threshold, the personalized safe zone is defined between the annulus plane and the cardiac conduction region.

[0014] Optionally, the threshold comprises about 2 millimeters.

[0015] Optionally, when the CAD is less than a threshold, the personalized safe zone is defined as greater than a defined distance from the annulus plane that is greater than the threshold.

[0016] Optionally, the personalized safe zone is defined as greater than about 3 millimeters from the annulus plane.

[0017] Optionally, the personalized safe zone denotes a region for placement of a defined portion of the aortic valve prosthesis device in a contracted state prior to expansion and deployment thereof.

[0018] Optionally, the personalized safe zone is further computed according to at least one parameter of the aortic valve prosthesis device for deployment in the subject.

[0019] Optionally, the at least one parameter of the aortic valve prosthesis device includes a deployment range within the heart for positioning of the defined portion of the aortic valve prosthesis device when deployed.

[0020] Optionally, the at least one parameter of the aortic valve prosthesis device includes an amount of foreshortening of a length of the aortic valve prosthesis device in the expanded state compared to the contracted state. Optionally, a plurality of safe zones are computed according to a plurality of momentary stages of delivery based on the foreshortening of the aortic valve prosthesis device as a function of a diameter of the aortic valve prosthesis device.

[0021] Optionally, the at least one parameter of the aortic valve prosthesis device includes at least one of: at least one dimension of the aortic valve prosthesis device in the expanded state, at least one dimension of the aortic valve prosthesis device in the compressed state, type and / or model of the aortic valve prosthesis device.

[0022] Optionally, further comprising selecting an aortic valve prosthesis device having at least one parameter enabling placement of the defined portion of the selected aortic valve prosthesis device at the personalized safe zone computed for the subject.

[0023] Optionally, further comprising: identifying a location of a defined portion of the aortic valve prosthesis device in at least one 2D fluoroscopy image captured during a TAVI procedure, and presenting an indication of whether the location of the defined portion of the aortic valve prosthesis device is within the personalized safe zone.

[0024] Optionally, the safe zone is selected according to a set of rules.

[0025] Optionally, the set of rules define implanting the aortic valve prosthesis device as close as possible to the annulus plane.

[0026] Optionally, the set of rules define reducing or preventing scratching and / or shear forces applied by the aortic valve prosthesis device to the cardiac conduction region by predicting extent of downward or upward movement of the aortic valve prosthesis device in a partially expanded or fully expanded state.

[0027] Optionally, the set of rules define implanting the aortic valve prosthesis device sufficiently below the annulus plane for preventing or reducing likelihood of migration and / or pop-out.

[0028] Optionally, the set of rules define a final target placement of leaflets of the aortic valve prosthesis device to corresponding to a location of native leaflets when the aortic valve prosthesis device is expanded from the personalized safe zone.

[0029] Optionally, the defined portion of the aortic valve prosthesis device for placement within the personalized safe zone comprises at least one of: a distal end of the aortic valve prosthesis device, and at least one marker disposed at or in proximity to the distal end of the aortic valve prosthesis device.

[0030] Optionally, the personalized safe zone is selected for reducing or preventing damage to the conduction region from expansion of the aortic valve prosthesis device and / or from deployment of the aortic valve prosthesis device, by providing a safety margin of the aortic valve prosthesis device away from the conduction region and within a deployment region of the aortic valve.

[0031] Optionally, the at least one reference image comprises a pre -procedure 3D image.

[0032] Optionally, further comprising: accessing at least one 2D fluoroscopy image during a TAVI procedure, registering the at least one 2D fluoroscopy image to the pre-procedure 3D image, and dynamically presenting the personalized safe zone as an overlay over the at least one 2D fluoroscopy image.

[0033] Optionally, further comprising dynamically adapting the personalized safe zone according to a momentary stage of delivery depicted in the at least one 2D fluoroscopy image, according to a foreshortening relationship between a current diameter of the aortic valve prosthesis device and length reduction.

[0034] Optionally, further comprising: computing a conduction angle of the cardiac conduction region, relative to an aortic valve trigone location, wherein the personalized safe zone is further computed according to the conduction angle for reducing likelihood of damage, wherein when the conduction angle is below a threshold or lower, risk to the cardiac conduction region is increased, and when the conduction angle is above the threshold or higher, risk to the cardiac conduction region is decreased.

[0035] Optionally, the conduction angle is computed between a first line and a second line, the first line is defined from a center of a virtual aortic annulus and a middle of a third line connecting a perforating bundle and branching point of a left branch bundle, the second line is measured from the center of the virtual aortic annulus to a nadir of the non-coronary cusp (NCC), and the virtual aortic annulus is defined as a circle or oval shaped plane having an outer circumference that intersects the nadirs of the NCC, the right coronary cusp (RCC), and the left coronary cusp (LCC).

[0036] Optionally, the conduction angle is computed between a first line and a second line, the first line is defined from a center of a virtual aortic annulus and a middle of a third line connecting a perforating bundle and branching point of a left branch bundle, the second line is measured from the center of the virtual aortic annulus to a right trigone, and the virtual aortic annulus is defined as a circle or oval shaped plane having an outer circumference that intersects the nadirs of the NCC, the right coronary cusp (RCC), and the left coronary cusp (LCC).

[0037] Optionally, the personalized safe zone is further computed according to anatomical data including shape and / or dimensions of a proximal aorta and / or a left ventricular outflow tract obtained from the at least one reference image. According to some embodiments of the present invention, there is provided a system for computing a personalized safe zone for transcatheter deployment of an aortic valve prosthesis device in a subject, comprising: at least one processor executing a code for: identifying a location of an annulus plane of an aortic valve in at least one reference image, identifying a location of a cardiac conduction region of the heart in the at least one reference image, and computing the personalized safe zone for transcatheter deployment of the aortic valve prosthesis device, the personalized safe zone is between the location of the annulus plane and the location of the conduction region, wherein the personalized safe zone defines where a distal end of the aortic valve prosthesis device is at least one of: to be maintained during transcatheter deployment, and to be positioned at an end of the transcatheter deployment.

[0038] Optionally, the location of the cardiac conduction region is identified as a floor of a membranous septum of the heart denoted as about 1-2 millimeters (mm) above a most inferior border of the membranous septum.

[0039] Optionally, the location of the cardiac conduction region is identified as between a perforating bundle and a branching point of the left branch bundle of the conduction system of the heart.

[0040] Optionally, the personalized safe zone is defined according to a conduction annulus depth (CAD) defined as distance between the annulus plane and the cardiac conduction region.

[0041] Optionally, when the CAD is greater than a threshold, the personalized safe zone is defined between the annulus plane and the cardiac conduction region.

[0042] Optionally, the threshold comprises about 2 millimeters.

[0043] Optionally, when the CAD is less than a threshold, the personalized safe zone is defined as greater than a defined distance from the annulus plane that is greater than the threshold.

[0044] Optionally, the personalized safe zone is defined as greater than about 3 millimeters from the annulus plane.

[0045] Optionally, the personalized safe zone denotes a region for placement of a defined portion of the aortic valve prosthesis device in a contracted state prior to expansion and deployment thereof.

[0046] Optionally, the personalized safe zone is computed according to at least one parameter of the aortic valve prosthesis device for deployment in the subject. Optionally, the at least one parameter of the aortic valve prosthesis device includes a deployment range within the heart for positioning of the defined portion of the aortic valve prosthesis device when deployed.

[0047] Optionally, the at least one parameter of the aortic valve prosthesis device includes an amount of foreshortening of a length of the aortic valve prosthesis device in the expanded state compared to the contracted state.

[0048] Optionally, a plurality of safe zones are computed according to a plurality of momentary stages of delivery based on the foreshortening of the aortic valve prosthesis device as a function of a diameter of the aortic valve prosthesis device.

[0049] Optionally, the at least one parameter of the aortic valve prosthesis device includes at least one of: at least one dimension of the aortic valve prosthesis device in the expanded state, at least one dimension of the aortic valve prosthesis device in the compressed state, type and / or model of the aortic valve prosthesis device.

[0050] Optionally, further comprising code for selecting an aortic valve prosthesis device having at least one parameter enabling placement of the defined portion of the selected aortic valve prosthesis device at the personalized safe zone computed for the subject.

[0051] Optionally, further comprising code for: identifying a location of a defined portion of the aortic valve prosthesis device in at least one 2D fluoroscopy image captured during a TAVI procedure, and presenting an indication of whether the location of the defined portion of the aortic valve prosthesis device is within the personalized safe zone.

[0052] Optionally, the safe zone is selected according to a set of rules.

[0053] Optionally, the set of rules define implanting the aortic valve prosthesis device as close as possible to the annulus plane.

[0054] Optionally, the set of rules define reducing or preventing scratching and / or shear forces applied by the aortic valve prosthesis device to the cardiac conduction region by predicting extent of downward or upward movement of the aortic valve prosthesis device in a partially expanded or fully expanded state.

[0055] Optionally, the set of rules define implanting the aortic valve prosthesis device sufficiently below the annulus plane for preventing or reducing likelihood of migration and / or pop-out.

[0056] Optionally, the set of rules define a final target placement of leaflets of the aortic valve prosthesis device to corresponding to a location of native leaflets when the aortic valve prosthesis device is expanded from the personalized safe zone. Optionally, the defined portion of the aortic valve prosthesis device for placement within the personalized safe zone comprises at least one of: a distal end of the aortic valve prosthesis device, and at least one marker disposed at or in proximity to the distal end of the aortic valve prosthesis device.

[0057] Optionally, the personalized safe zone is selected for reducing or preventing damage to the conduction region from expansion of the aortic valve prosthesis device and / or from deployment of the aortic valve prosthesis device, by providing a safety margin of the aortic valve prosthesis device away from the conduction region and within a deployment region of the aortic valve.

[0058] Optionally, the at least one reference image comprises a pre -procedure 3D image.

[0059] Optionally, further comprising code for: accessing at least one 2D fluoroscopy image during a TAVI procedure, registering the at least one 2D fluoroscopy image to the pre-procedure 3D image, and dynamically presenting the personalized safe zone as an overlay over the at least one 2D fluoroscopy image.

[0060] Optionally, further comprising code for dynamically adapting the personalized safe zone according to a momentary stage of delivery depicted in the at least one 2D fluoroscopy image, according to a foreshortening relationship between a current diameter of the aortic valve prosthesis device and length reduction.

[0061] Optionally, further comprising code for: computing a conduction angle of the cardiac conduction region, relative to an aortic valve trigone location, wherein the personalized safe zone is further computed according to the conduction angle for reducing likelihood of damage, wherein when the conduction angle is below a threshold or lower, risk to the cardiac conduction region is increased, and when the conduction angle is above the threshold or higher, risk to the cardiac conduction region is decreased.

[0062] Optionally, the conduction angle is computed between a first line and a second line, the first line is defined from a center of a virtual aortic annulus and a middle of a third line connecting a perforating bundle and branching point of a left branch bundle, the second line is measured from the center of the virtual aortic annulus to a nadir of the non-coronary cusp (NCC), and the virtual aortic annulus is defined as a circle or oval shaped plane having an outer circumference that intersects the nadirs of the NCC, the right coronary cusp (RCC), and the left coronary cusp (LCC).

[0063] Optionally, the conduction angle is computed between a first line and a second line, the first line is defined from a center of a virtual aortic annulus and a middle of a third line connecting a perforating bundle and branching point of a left branch bundle, the second line is measured from the center of the virtual aortic annulus to a right trigone, and the virtual aortic annulus is defined as a circle or oval shaped plane having an outer circumference that intersects the nadirs of the NCC, the right coronary cusp (RCC), and the left coronary cusp (LCC).

[0064] Optionally, the personalized safe zone is further computed according to anatomical data including shape and / or dimensions of a proximal aorta and / or a left ventricular outflow tract obtained from the at least one reference image.

[0065] According to some embodiments of the present invention, there is provided a computer implemented method of registering a 2D fluoroscopy image to a 3D image, comprising: accessing a 2D fluoroscopy image and a 3D image of a subject, identifying an anatomical structure in the 3D image, including a contour of the anatomical structure, identifying at least one anatomical landmark on the 3D image, identifying a contour of the anatomical structure in the 2D fluoroscopy image depicting injected contrast within the anatomical structure, extracting a pose of a sensor that captured the 2D fluoroscopy image, projecting the contour of the anatomical structure of the 3D image to a 2D plane according to the pose of the sensor, computing a registration for registering between the contour of the anatomical structure of the 2D fluoroscopy image and the projection of the contour on the 2D plane, applying the registration for registering the at least one anatomical landmark on the 3D image to the 2D fluoroscopy image, and presenting the at least one anatomical landmark registered to the 2D fluoroscopy image.

[0066] Optionally, the anatomical structure includes an ascending aorta.

[0067] Optionally, the at least one anatomical landmark is used for computing a personalized safe zone for transcatheter deployment of an aortic valve prosthesis device in a heart of a subject.

[0068] Optionally, the at least one anatomical landmark is used for displaying the personalized safe zone.

[0069] Optionally, the 3D image comprises a first 3D image captured at diastole and a second 3D image captured at systole, wherein the at least one anatomical landmark comprises an aortic annulus plane and at least one of: membranous septum and a cardiac conduction region between a perforating bundle and a branching point of the left branch bundle, and further comprising defining a safe zone between a location of the aortic annulus plane selected as a most inferior location of the first 3D image and the second 3D image, and a location of the membranous septum and / or cardiac conduction region selected as a most superior location of the first 3D image and the second 3D image.

[0070] Optionally, the 3D image comprises a multi-series 3D imaging session, wherein a plurality of 3D images depicting at least the native aortic valve are captured at different phases of a cardiac cycle, further comprising: detecting a location of at least one of the following in the plurality of 3D images depicting the different phases of the cardiac cycle: the membranous septum, commissures of the native aortic valve, nadirs of the native aortic valve, and a cardiac conduction region defined between a perforating bundle of a conduction system of the heart and a branching point of a left bundle branch of the conduction system, computing a safe zone for each of the plurality of 3D images depicting the different phases of the cardiac cycle, computing a smallest safe zone using the plurality of 3D images, wherein the at least one anatomical landmark comprises the smallest safe zone.

[0071] Optionally, further comprising: detecting a medical tool located within the heart of the subject depicted in the 2D fluoroscopy image, simulating presence of the medical tool within the heart of the subject depicted in the 3D image, extracting a pose of a sensor that captured the 2D fluoroscopy image, projecting the medical tool of the 3D image to a 2D plane according to the pose of the sensor, computing a registration for registering between the medical tool of the 2D fluoroscopy image and the medical tool of the 2D plane, applying the registration for registering the at least one anatomical landmark on the 3D image to the 2D fluoroscopy image, and presenting the at least one anatomical landmark registered to the 2D fluoroscopy image.

[0072] Optionally, the medical tool is located within the inferior vena cava, right atrium and right ventricle.

[0073] Optionally, further comprising: detecting a visual feature in the 2D fluoroscopy image, wherein the visual feature excludes anatomical features of the native heart of the subject, tracking a location of the visual feature in subsequent 2D fluoroscopy images, computing a movement of the visual feature in the subsequent 2D fluoroscopy images, and applying the movement to the at least one anatomical landmark in the subsequent 2D fluoroscopy images.

[0074] Optionally, further comprising detecting lack of sufficient contrast in the ascending aorta in the 2D fluoroscopy image.

[0075] Optionally, the visual feature is selected from: an accessory catheter positioned in the heart, a pacing wire, a pigtail catheter positioned in the heart, at least one calcification external to the heart, and at least one bone feature of a spine of the subject.

[0076] Optionally, the movement of the location of the visual feature is tracked over a time interval sufficiently long to include a plurality of cardiac cycles and / or a plurality of respiratory cycles, and further comprising at least one of: extracting a first parameter indicating motion due to the plurality of cardiac cycles, extracting a second parameter indicating motion due to the plurality of respiratory cycles, and extracting a third parameter indicating motion due to the operator, and removing the component of motion due to the plurality of cardiac cycles and / or due to the plurality of respiratory cycles from the at least one anatomical landmark presented in the fluoroscopy image, and maintaining the motion due to the operator.

[0077] According to some embodiments of the present invention, there is provided a system for registering a 2D fluoroscopy image to a 3D image, comprising: at least one processor executing a code for: accessing a 2D fluoroscopy image and a 3D image of a subject, identifying an anatomical structure in the 3D image, including a contour of the anatomical structure, identifying at least one anatomical landmark on the 3D image, identifying a contour of the anatomical structure in the 2D fluoroscopy image depicting injected contrast within the anatomical structure, extracting a pose of a sensor that captured the 2D fluoroscopy image, projecting the contour of the anatomical structure of the 3D image to a 2D plane according to the pose of the sensor, computing a registration for registering between the contour of the anatomical structure of the 2D fluoroscopy image and the projection of the contour on the 2D plane, applying the registration for registering the at least one anatomical landmark on the

[0078] 3D image to the 2D fluoroscopy image, and presenting the at least one anatomical landmark registered to the 2D fluoroscopy image.

[0079] Optionally, the anatomical structure includes an ascending aorta.

[0080] Optionally, the at least one anatomical landmark is used for computing the safe zone.

[0081] Optionally, the at least one anatomical landmark is used for displaying the safe zone.

[0082] Optionally, the 3D image comprises a first 3D image captured at diastole and a second 3D image captured at systole, wherein the at least one anatomical landmark comprises an aortic annulus plane and at least one of: membranous septum and a cardiac conduction region between a perforating bundle and a branching point of the left branch bundle, and further comprising defining a safe zone between a location of the aortic annulus plane selected as a most inferior location of the first 3D image and the second 3D image, and a location of the membranous septum and / or cardiac conduction region selected as a most superior location of the first 3D image and the second 3D image.

[0083] Optionally, the 3D image comprises a multi-series 3D imaging session, wherein a plurality of 3D images depicting at least the native aortic valve are captured at different phases of a cardiac cycle, further comprising: detecting a location of at least one of the following in the plurality of 3D images depicting the different phases of the cardiac cycle: the membranous septum, commissures of the native aortic valve, nadirs of the native aortic valve, and a cardiac conduction region defined between a perforating bundle of a conduction system of the heart and a branching point of a left bundle branch of the conduction system, computing a safe zone for each of the plurality of 3D images depicting the different phases of the cardiac cycle, computing a smallest safe zone using the plurality of 3D images, wherein the at least one anatomical landmark comprises the smallest safe zone.

[0084] Optionally, further comprising: detecting a medical tool located within the heart of the subject depicted in the 2D fluoroscopy image, simulate presence of the medical tool within the heart of the subject depicted in the 3D image, extracting a pose of a sensor that captured the 2D fluoroscopy image, projecting the medical tool of the 3D image to a 2D plane according to the pose of the sensor, compute a registration for registering between the medical tool of the 2D fluoroscopy image and the medical tool of the 2D plane, applying the registration for registering the at least one anatomical landmark on the 3D image to the 2D fluoroscopy image, and presenting the at least one anatomical landmark registered to the 2D fluoroscopy image.

[0085] Optionally, the medical tool is located within the inferior vena cava, right atrium and right ventricle.

[0086] Optionally, further comprising: detecting a visual feature in the 2D fluoroscopy image, wherein the visual feature excludes anatomical features of the native heart of the subject, tracking a location of the visual feature in subsequent 2D fluoroscopy images, computing a movement of the visual feature in the subsequent 2D fluoroscopy images, and applying the movement to the at least one anatomical landmark in the subsequent 2D fluoroscopy images.

[0087] Optionally, further comprising detecting lack of sufficient contrast in the ascending aorta in the 2D fluoroscopy image.

[0088] Optionally, the visual feature is selected from: an accessory catheter positioned in the heart, a pacing wire, a pigtail catheter positioned in the heart, at least one calcification external to the heart, and at least one bone feature of a spine of the subject.

[0089] Optionally, the movement of the location of the visual feature is tracked over a time interval sufficiently long to include a plurality of cardiac cycles and / or a plurality of respiratory cycles, and further comprising at least one of: extracting a first parameter indicating motion due to the plurality of cardiac cycles, extracting a second parameter indicating motion due to the plurality of respiratory cycles, and extracting a third parameter indicating motion due to the operator, and removing the component of motion due to the plurality of cardiac cycles and / or due to the plurality of respiratory cycles from the at least one anatomical landmark presented in the fluoroscopy image, and maintaining the motion due to the operator.

[0090] According to some embodiments of the present invention, there is provided a computer implemented method of registering a 2D fluoroscopy image to a 3D image, comprising: identifying a plurality of visible features within a 3D image of a subject, wherein the plurality of visible features are selected to be visible on a 2D fluoroscopy image of the subject, for the 3D image, computing a first signature comprising relative locations between the plurality of visible features and relative pixel intensities, detecting the plurality of visible features on a 2D fluoroscopy image of the subject, for the 2D image, computing a second signature comprising relative locations between the plurality of visible features and relative pixel intensities, computing a transformation for transforming the first signature to the second signature, applying the transformation for registering at least one anatomical landmark on the 3D image to the 2D fluoroscopy image, and presenting the at least one anatomical landmark registered to the 2D fluoroscopy image.

[0091] Optionally, the transformation further comprises converting between the pixel intensities of the 3D image and the pixel intensities of the 2D image.

[0092] Optionally, the 3D image comprises a CT scan and the relative pixel intensities of the 3D image comprise Hounsfield units (HU).

[0093] According to some embodiments of the present invention, there is provided a system for registering a 2D fluoroscopy image to a 3D image, comprising: at least one processor executing a code for: identifying a plurality of visible features within a 3D image of a subject, wherein the plurality of visible features are selected to be visible on a 2D fluoroscopy image of the subject, for the 3D image, computing a first signature comprising relative locations between the plurality of visible features and relative pixel intensities, detecting the plurality of visible features on a 2D fluoroscopy image of the subject, for the 2D image, computing a second signature comprising relative locations between the plurality of visible features and relative pixel intensities, computing a transformation for transforming the first signature to the second signature, applying the transformation for registering at least one anatomical landmark on the 3D image to the 2D fluoroscopy image, and presenting the at least one anatomical landmark registered to the 2D fluoroscopy image.

[0094] Optionally, the transformation further comprises converting between the pixel intensities of the 3D image and the pixel intensities of the 2D image. Optionally, the 3D image comprises a CT scan and the relative pixel intensities of the 3D image comprise Hounsfield units (HU).

[0095] According to some embodiments of the present invention, there is provided a computer implemented method of creating an image of at least one parallax free of at least one feature depicted in a 2D fluoroscopy image, comprising: computing a registration for registering the 2D fluoroscopy image with a 3D image of a subject, wherein the 3D image comprises a CT scan, wherein the at least one feature is located within the 3D image, and associated with CT derived information (CDI) indicating coordinates of the location within the 3D image, detecting the at least one feature on the 2D fluoroscopy image, and extracting fluoroscopy derived information (FDI) indicating the location of the at least one feature on the 2D fluoroscopy image and a pose of a sensor that captured the 2D fluoroscopy image, computing a parallax free pose of the at least one feature depicted in the 3D image that is closest to the pose of the sensor, applying the registration for projecting the at least one feature of the 3D image defined by the CDI to a 2D plane corresponding to the FDI, according to the parallax free pose for generating a synthetic parallax free view (SPFV) of the at least one feature, and providing the SPFV of the at least one feature for presentation.

[0096] Optionally, further comprising: mapping the at least one feature from the 2D fluoroscopy image to the 3D image using a reversal of the registration, and wherein applying the registration comprises projecting the 3D image including the mapped at least one feature to the 2D plane, for generating a synthetic version of the 2D fluoroscopy image.

[0097] Optionally, the at least one feature comprises a distal and of an aortic valve prosthesis device, and further comprising simulating a location of the aortic valve prosthesis device within the 3D image according to an anatomy of the ascending aorta and / or aortic valve, wherein the registration is applied to a location of the aortic valve prosthesis device within the 3D image corresponding to the location on the 2D fluoroscopy.

[0098] Optionally, the simulation is done according to a model of the aortic valve prosthesis device that simulates physical forces applied by a curvature of the ascending aorta and the anatomy of the aortic valve that applies forces to position the aortic valve prosthesis device between the NCC and RCC.

[0099] Optionally, the parallax free pose is computed for each feature, and a respective SPFV is computed for each feature.

[0100] Optionally, the parallax free pose is computed using a s-curve. Optionally, the parallax free pose is computed for a cusp overlap view where the NCC is on the left side and the RCC overlaps the LCC and located on the right side.

[0101] Optionally, the parallax free pose is computed for a plurality of features, and a SPFV is computed for each feature.

[0102] Optionally, the parallax free pose is computed as an intersection of a plurality of s-curves, each s-curve for a respective feature.

[0103] Optionally, the SPFV of the at least one feature is presented as an overlay over the 2D fluoroscopy image.

[0104] Optionally, the SPFV of the at least one feature is presented separately from the 2D fluoroscopy image.

[0105] Optionally, the at least one feature includes at least one of: aortic annulus plane, membranous septum floor, and distal end of aortic valve prosthesis device.

[0106] Optionally, a safe zone is defined between the aortic annulus and the membranous septum. According to some embodiments of the present invention, there is provided a system for creating an image of at least one parallax free of at least one feature depicted in a 2D fluoroscopy image, comprising: at least one processor executing a code for: computing a registration for registering the 2D fluoroscopy image with a 3D image of a subject, wherein the 3D image comprises a CT scan, wherein the at least one feature is located within the 3D image, and associated with CT derived information (CDI) indicating coordinates of the location within the 3D image, detecting the at least one feature on the 2D fluoroscopy image, and extracting fluoroscopy derived information (FDI) indicating the location of the at least one feature on the 2D fluoroscopy image and a pose of a sensor that captured the 2D fluoroscopy image, computing a parallax free pose of the at least one feature depicted in the 3D image that is closest to the pose of the sensor, applying the registration for projecting the at least one feature of the 3D image defined by the CDI to a 2D plane corresponding to the FDI, according to the parallax free pose for generating a synthetic parallax free view (SPFV) of the at least one feature, and providing the SPFV of the at least one feature for presentation.

[0107] Optionally, further comprising: mapping the at least one feature from the 2D fluoroscopy image to the 3D image using a reversal of the registration, and wherein applying the registration comprises projecting the 3D image including the mapped at least one feature to the 2D plane, for generating a synthetic version of the 2D fluoroscopy image. Optionally, the at least one feature comprises a distal and of an aortic valve prosthesis device, and further comprising simulating a location of the aortic valve prosthesis device within the 3D image according to an anatomy of the ascending aorta and / or aortic valve, wherein the registration is applied to a location of the aortic valve prosthesis device within the 3D image corresponding to the location on the 2D fluoroscopy.

[0108] Optionally, the simulation is done according to a model of the aortic valve prosthesis device that simulates physical forces applied by a curvature of the ascending aorta and the anatomy of the aortic valve that applies forces to position the aortic valve prosthesis device between the NCC and RCC.

[0109] Optionally, the parallax free pose is computed for each feature, and a respective SPFV is computed for each feature.

[0110] Optionally, the parallax free pose is computed using a s-curve.

[0111] Optionally, the parallax free pose is computed for a cusp overlap view where the NCC is on the left side and the RCC overlaps the LCC and located on the right side.

[0112] Optionally, the parallax free pose is computed for a plurality of features, and a SPFV is computed for each feature.

[0113] Optionally, the parallax free pose is computed as an intersection of a plurality of s-curves, each s-curve for a respective feature.

[0114] Optionally, the SPFV of the at least one feature is presented as an overlay over the 2D fluoroscopy image.

[0115] Optionally, the SPFV of the at least one feature is presented separately from the 2D fluoroscopy image.

[0116] Optionally, the at least one feature includes at least one of: aortic annulus plane, membranous septum floor, and distal end of aortic valve prosthesis device.

[0117] Optionally, a safe zone is defined between the aortic annulus and the membranous septum.

[0118] According to some embodiments of the present invention, there is provided a computer implemented method for segmenting a membranous septum of a 3D image, comprising: identifying a left ventricle myocardium base rim, identifying a first point and a second point defining an anterior myocardial notch passing therebetween, identifying a first location spaced apart from the first point as a start of a cardiac conduction region between a perforating bundle and a branching point of the left branch bundle, passing through the membranous septum, defining a box having a predefined width, a predefined height and a length computed as a predicted length of the cardiac conduction region with margin of error, positioning the box parallel to and a preselected distance above the left ventricle myocardial base rim, wherein the box defines the location of the membranous septum.

[0119] Optionally, the predefined width is about 1 millimeter (mm), the predefined height is about 1 mm, the predefined length is obtained as an average of a length measured for a plurality of subjects and one standard deviation, and the preselected distance is about 0.5 mm.

[0120] According to some embodiments of the present invention, there is provided a system for segmenting a membranous septum of a 3D image, comprising:

[0121] At least one processor executing a code for: identifying a left ventricle myocardium base rim, identifying a first point and a second point defining an anterior myocardial notch passing therebetween, identifying a first location spaced apart from the first point as a start of a cardiac conduction region between a perforating bundle and a branching point of the left branch bundle, passing through the membranous septum, defining a box having a predefined width, a predefined height and a length computed as a predicted length of the cardiac conduction region with margin of error, positioning the box parallel to and a preselected distance above the left ventricle myocardial base rim, wherein the box defines the location of the membranous septum.

[0122] Optionally, the predefined width is about 1 millimeter (mm), the predefined height is about 1 mm, the predefined length is obtained as an average of a length measured for a plurality of subjects and one standard deviation, and the preselected distance is about 0.5 mm.

[0123] According to some embodiments of the present invention, there is provided a computer implemented method for locating a membranous septum on a 3D image, comprising: for each slice of a plurality of slices of a 3D image, segmenting a left ventricle, a right ventricle, and a muscular intraventricular septum, and identifying a tip of the muscular intraventricular septum, identifying a path denoted by a line connecting a superior point of the muscular intraventricular septum through the plurality of slices, and detecting a sub-segment that includes a His bundle within the path, wherein the membranous septum floor is defined at the location of the sub-segment.

[0124] Optionally, the sub-segment is defined between a first inferior about 10% of the membranous septum floor to an end of the conduction path located at about 90% of the length of the membranous septum floor.

[0125] Optionally, sub-segment of the path is defined between about 20% and about 70%, 80% or 85% of a total length of the membranous septum floor.

[0126] Optionally, the 3D image comprises a contrast enhanced cardiac CT.

[0127] According to some embodiments of the present invention, there is provided a system for locating a membranous septum on a 3D image, comprising: for each slice of a plurality of slices of a 3D image, segmenting a left ventricle, a right ventricle, and a muscular intraventricular septum, and identifying a tip of the muscular intraventricular septum, identifying a path denoted by a line connecting a superior point of the muscular intraventricular septum through the plurality of slices, and detecting a sub-segment that includes a His bundle within the path, wherein the membranous septum floor is defined at the location of the sub-segment.

[0128] Optionally, the sub-segment is defined between a first inferior about 10% of the membranous septum floor to an end of the conduction path located at about 90% of the length of the membranous septum floor.

[0129] Optionally, the sub-segment of the path is defined between about 20% and about 70%, 80% or 85% of a total length of the membranous septum floor.

[0130] Optionally, the 3D image comprises a contrast enhanced cardiac CT.

[0131] According to some embodiments of the present invention, there is provided a computer implemented method of locating an atrioventricular (AV) node on a 3D image, comprising: identification of a first set of hinges of an anterior cusp of the aortic valve, and a second set of hinges of a posterior cusp of the aortic valve, adjusting a plurality of parallel slice plane of the 3D image to the superior edge of the first set of hinges and the second set of hinges, localizing an area between a medial commissure of the mitral valve and the right atrium, and detecting a location of the AV node in close proximity to an atrial wall or an apex of the inferior pyramidal space. Optionally, the first and second set of hinges are identified in a two chamber and / or a three chamber view in NPR.

[0132] Optionally, the localizing of the area is performed in a short axis view.

[0133] According to some embodiments of the present invention, there is provided a system for locating an atrioventricular (AV) node on a 3D image, comprising: at least one processor executing a code for: identification of a first set of hinges of an anterior cusp of the aortic valve, and a second set of hinges of a posterior cusp of the aortic valve, adjusting a plurality of parallel slice plane of the 3D image to the superior edge of the first set of hinges and the second set of hinges, localizing an area between a medial commissure of the mitral valve and the right atrium, and detecting a location of the AV node in close proximity to an atrial wall or an apex of the inferior pyramidal space.

[0134] Optionally, the first and second set of hinges are identified in a two chamber and / or a three chamber view in NPR.

[0135] Optionally, the localizing of the area is performed in a short axis view.

[0136] According to some embodiments of the present invention, there is provided a computer implemented method of segmenting a floor of a membranous septum on a 3D image, comprising: detecting a posterior border of the floor of the membranous septum by: identifying an aortic annulus plane as a plane intersecting three nadirs of three cusps of the aortic valve, identifying of a roof of an inferoseptal recess in a short axis plane, wherein the roof denotes the posterior border of the membranous septum, identifying and annotating an inferior area of the membranous septum adjacent to the roof of the inferoseptal recess in long axis view, and detecting an anterior border of the floor of the membranous septum by: clockwise rotating each slice of a plurality of slices of a 3D image in a short axis until the anterior edge of the membranous septum is identified in the long axis view, and annotating the point between the inferior area of the membranous septum and the crest of the septum in long axis view.

[0137] According to some embodiments of the present invention, there is provided a system for segmenting a floor of a membranous septum on a 3D image, comprising: at least one processor executing a code for: detecting a posterior border of the floor of the membranous septum by: identifying an aortic annulus plane as a plane intersecting three nadirs of three cusps of the aortic valve, identifying of a roof of an inferoseptal recess in a short axis plane, wherein the roof denotes the posterior border of the membranous septum, identifying and annotating an inferior area of the membranous septum adjacent to the roof of the inferoseptal recess in long axis view, and detecting an anterior border of the floor of the membranous septum by: clockwise rotating each slice of a plurality of slices of a 3D image in a short axis until the anterior edge of the membranous septum is identified in the long axis view, and annotating the point between the inferior area of the membranous septum and the crest of the septum in long axis view.

[0138] According to some embodiments of the present invention, there is provided a computer implemented method of segmenting a floor of a membranous septum on a 3D image, comprising: segmenting a right ventricle endocardium (RV), a RV myocardium, a left ventricle (LV) endocardium, and a LV myocardium, identifying a region between the RV myocardium and the LV myocardium includes a minimum spatially consistent distance between the RV myocardium and the LV myocardium, wherein the membranous septum is segmented according to the region.

[0139] Optionally, further comprising: detecting a posterior down slope of a notch on the LV myocardium below an aortic root, and verifying that the region corresponds to the posterior down slope of the notch of the LV myocardium.

[0140] Optionally, further comprising: detecting a cardiac conduction region defined between a perforating bundle of a conduction system of the heart and a branching point of a left bundle branch (LBB) of the conduction system with the region, wherein the membranous septum is segmented according to the cardiac conduction region.

[0141] According to some embodiments of the present invention, there is provided a system for segmenting a floor of a membranous septum on a 3D image, comprising: at least one processor executing a code for: segmenting a right ventricle endocardium (RV), a RV myocardium, a left ventricle (LV) endocardium, and a LV myocardium, identifying a region between the RV myocardium and the LV myocardium includes a minimum spatially consistent distance between the RV myocardium and the LV myocardium, wherein the membranous septum is segmented according to the region.

[0142] Optionally, further comprising: detecting a posterior down slope of a notch on the LV myocardium below an aortic root, and verifying that the region corresponds to the posterior down slope of the notch of the LV myocardium.

[0143] Optionally, further comprising: detecting a cardiac conduction region defined between a perforating bundle of a conduction system of the heart and a branching point of a left bundle branch (LBB) of the conduction system with the region, wherein the membranous septum is segmented according to the cardiac conduction region.

[0144] According to some embodiments of the present invention, there is provided a method of treating a patient, comprising: delivering an aortic valve prosthesis device via a transcatheter approach in a contracted state to a heart of the patient, and deploying the aortic valve prosthesis device in the heart, such that a distal end of the aortic valve prosthesis device is positioned according to one of: (i) in response to a perforating bundle being located at or below an annulus plane of an aortic valve, deploying the distal end at a level of the annulus plane, (ii) in response to the perforating bundle being above the annulus plane and a branching point of a left branch bundle being located at or below the annulus plane, deploying the distal end within a range of about 0-1 millimeters (mm) above the perforating bundle, and (iii) in response to the perforating bundle being above the annulus plane and the branching point of the left branch bundle being located above the annulus plane, deploying the distal end within a range of about 1-2 mm above the perforating bundle and within a range of about 0- 1 mm above the branching point of the left branch bundle.

[0145] Optionally, the aortic valve prosthesis device includes inflow struts with sharp end regions.

[0146] Optionally, above is defined as proximally away from the heart and towards an operator delivering the aortic valve prosthesis device along a path of a guidewire and / or catheter used to deliver the aortic valve prosthesis device, and below is defined as distally to an interior of the heart and away from the operator.

[0147] Optionally, further comprising identifying the annulus plane, the perforating bundle, and the branching point of the left bundle branch. Optionally, further comprising identifying the annulus plane, the perforating bundle, and the branching point of the left bundle branch.

[0148] According to some embodiments of the present invention, there is provided a method of treating a patient, comprising: delivering an aortic valve prosthesis device via a transcatheter approach in a contracted state to a heart of the patient, and deploying the aortic valve prosthesis device in the heart, such that a distal end of the aortic valve prosthesis device is positioned within a personalized safe zone, wherein the personalized safe zone is between a location of the annulus plane of an aortic valve of the patient and a location of the conduction region of the heart of the patient.

[0149] Optionally, the location of the cardiac conduction region is identified as a floor of a membranous septum of the heart denoted as about 1-2 millimeters (mm) above a most inferior border of the membranous septum.

[0150] Optionally, the location of the cardiac conduction region is identified as between a perforating bundle and a branching point of the left branch bundle of the conduction system of the heart.

[0151] Optionally, the personalized safe zone is defined according to a conduction annulus depth (CAD) defined as distance between the annulus plane and the cardiac conduction region.

[0152] Optionally, when the CAD is greater than a threshold, the personalized safe zone is defined between the annulus plane and the cardiac conduction region.

[0153] Optionally, the threshold comprises about 2 millimeters.

[0154] Optionally, when the CAD is less than a threshold, the personalized safe zone is defined as greater than a defined distance from the annulus plane that is greater than the threshold.

[0155] Optionally, the personalized safe zone is defined as greater than about 3 millimeters from the annulus plane.

[0156] Optionally, the personalized safe zone denotes a region for placement of a defined portion of the aortic valve prosthesis device in a contracted state prior to expansion and deployment thereof. According to some embodiments of the present invention, there is provided a method of treating a patient, comprising: delivering an aortic valve prosthesis device via a transcatheter approach in a contracted state to a heart of the patient, and deploying the aortic valve prosthesis device in the heart, such that a distal end of the aortic valve prosthesis device is positioned as about 1-2 millimeters (mm) above a most inferior border of the membranous septum of the patient. Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

[0157] BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0158] Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.

[0159] In the drawings:

[0160] FIG. 1 is a pictorial illustration of an operating room equipped with a system for computing and / or using a safe zone for guiding a TAVI procedure, in accordance with some embodiments of the present invention;

[0161] FIG. 2 is a block diagram of components of a system 100 for computing a safe zone for guiding a TAVI procedure, in accordance with some embodiments of the present invention;

[0162] FIG. 3 is a flowchart of a method of computing a personalized safe zone for transcatheter deployment of an aortic valve prosthesis device in a subject, in accordance with some embodiments of the present invention;

[0163] FIG. 4 is a schematic to help understand anatomy of the cardiac conduction region, in accordance with some embodiments of the present invention;

[0164] FIG. 5 is a schematic of an aortic root depicting detected nadir points and points of a detected conduction system, in accordance with some embodiments of the present invention;

[0165] FIG. 6 is a schematic depicting foreshortening of an aortic valve prosthesis device, in accordance with some embodiments of the present invention;

[0166] FIG. 7 is a schematic depicting a possible mechanism of damage to a cardiac conduction region by foreshortening of an aortic valve prosthesis device during expansion from a contracted state to an expanded state, in accordance with some embodiments of the present invention;

[0167] FIG. 8 is a schematic depicting another possible mechanism of damage to a cardiac conduction region by distal displacement of an aortic valve prosthesis device in an expanded state, in accordance with some embodiments of the present invention; FIG. 9 is a schematic depicting exemplary locations of features within an anatomy, used for computing a personalized safe zone, in accordance with some embodiments of the present invention;

[0168] FIG. 10 is a schematic depicting a conduction annulus depth (CAD), in accordance with some embodiments of the present invention;

[0169] FIG. 11 is a schematic of a fluoroscopy image with an overlay depicting an annulus plane and portions of a cardiac conduction system, in accordance with some embodiments of the present invention;

[0170] FIG. 12 is a schematic depicting an exemplary approach for computing a conduction angle, in accordance with some embodiments of the present invention;

[0171] FIG. 13 is a schematic depicting another exemplary approach for computing the conduction angle, in accordance with some embodiments of the present invention;

[0172] FIG. 14A is a schematic depicting an exemplary user interface presenting a personalized safe zone, in accordance with some embodiments of the present invention;

[0173] FIG. 14B is another schematic depicting another exemplary user interface presenting the personalized safe zone, in accordance with some embodiments of the present invention;

[0174] FIG. 15 is a flowchart of an exemplary method of registering a 2D fluoroscopy image to a 3D image, in accordance with some embodiments of the present invention;

[0175] FIG. 16 includes schematics indicating computed distances between a membrane septum floor (MSF) to an annulus plane for defining the safe zone, in accordance with some embodiments of the present invention;

[0176] FIG. 17 is a schematic of a 3D image including automatically identified anatomical features of a heart of a subject for computing the location of the conduction system and / or the safe zone, in accordance with some embodiments of the present invention;

[0177] FIG. 18 is a schematic depicting a contour of an ascending aorta identified from a 2D fluoroscopy image, and a contour of the ascending aorta projected from a 3D image for computing a registration, in accordance with some embodiments of the present invention;

[0178] FIG. 19 is a schematic depicting an of example of processing features, in accordance with some embodiments of the present invention;

[0179] FIG. 20 is a flowchart of another method for registering a 2D fluoroscopy image to a 3D image, in accordance with some embodiments of the present invention;

[0180] FIG. 21 is a flowchart of a method of generating a parallax free image of one or more features depicted in a 2D fluoroscopy image, in accordance with some embodiments of the present invention; FIG. 22 is a schematic depicting an exemplary SPFV computed from a 2D fluoroscopy image, in accordance with some embodiments of the present invention;

[0181] FIG. 23 is a schematic depicting exemplary segmentations of a 3D image used for computing the safe zone, in accordance with some embodiments of the present invention;

[0182] FIG. 24 is a schematic depicting an example of a segmentation of a myocardium of a left ventricle, in accordance with some embodiments of the present invention;

[0183] FIG. 25 is a schematic depicting another exemplary approach for segmentation of a membranous septum from a 3D image, in accordance with some embodiments of the present invention;

[0184] FIG. 26 is a schematic depicting a first line at a distal end of an aortic valve prosthesis device within a safe zone in accordance with some embodiments of the present invention;

[0185] FIG. 27 is a decision tree depicting a method of treating a patient indicating where to place a distal end of an aortic valve prosthesis device being deployed in a heart of a subject, in accordance with some embodiments of the present invention;

[0186] FIG. 28 is a graph presenting measurements obtained during an experiment performed by the Inventor for evaluation of at least one embodiment;

[0187] FIG. 29 is a graph presenting odds of lower and increased risk for a pacemaker (PPM) post TAVR for the group of patients included in the experiment;

[0188] FIG. 30 includes graphs presenting incidences rates of requiring a pacemaker implant post TAVR for different locations within the personalized safe zone, computed as part of the experiment performed by Inventors;

[0189] FIG. 31 is a plot of predicted probability of requiring a pacemaker as a function of difference between point B and device depth, computed as part of the experiment performed by the Inventor; and

[0190] FIG. 32 includes additional graphs presenting incidences rates of requiring a pacemaker implant post TAVR for different locations within the personalized safe zone, computed as part of the experiment performed by the Inventor.

[0191] DETAILED DESCRIPTION

[0192] The present invention, in some embodiments thereof, relates to image processing and, more specifically, but not exclusively, to systems and methods for processing image for computation of features for supporting a transcatheter aortic valve implantation (TAVI) procedure. The aortic valve prosthesis device referred to herein is designed for transcatheter delivery. The aortic valve prosthesis device referred to herein is designed to be compressed for delivery within blood vessels (e.g., within a sheath and / or over a guidewire), and expanded for deployment.

[0193] An aspect of some embodiments of the present invention relates to systems, computing devices, methods, and / or code instructions (stored on a data storage device and executable by one or more processors) for computing a personalized safe zone for transcatheter deployment of an aortic valve prosthesis device in a subject. In some embodiments, the personalized safe zone represents a region where a distal end of the aortic valve prosthesis device is to be continuously maintained within during the transcatheter deployment and / or the personalized safe zone represents where the distal end of the aortic valve prosthesis device is to be positioned at an end of the transcatheter deployment (i.e., the deployed location of the distal end). The personalized safe zone may be computed per subject and / or per aortic valve prosthesis device. For example, different subjects may have different personalized safe zones according to their specific anatomies. In another example, the safe zone may be computed for different types of aortic valve prosthesis devices (e.g., model, manufacturer, size), which may enable the physician to select the best aortic valve prosthesis device to implant in the patient by comparing the different aortic valve prosthesis devices from the point of view of the different safe zones. A location of an annulus plane of an aortic valve is identified in at least one reference image of the subject, optionally a 3D images such as a volumetric CT scan. The annulus plane may be computed as a plane that intersects three nadirs of three cusps of the aortic valve. It is noted that other definitions of the annulus plane may be used. A location of a cardiac conduction region of a conduction system of the heart is identified in the reference image. Optionally, the cardiac conduction region is defined as between a perforating bundle and a branching point of the left branch bundle of the conduction system of the heart. Alternatively or additionally, the cardiac conduction system is defined as a floor of a membranous septum of the heart, which is about 1-2 millimeters (mm) above the most inferior border of the membranous septum. The personalized safe zone may be a distance away from the floor of the membranous septum, for example, about 0.5 mm, or about 1 mm, or about 1.5 mm away, or other values.

[0194] The cardiac conduction region represents the portion of the conduction system of the heart that may be at high risk of damage during deployment of the aortic valve prosthesis device in the aortic valve. The cardiac conduction region may be located close to a surface of the inner portion of the heart, such as on the floor of the membranous septum, a location which is vulnerable to be damaged, for example, by the distal end of the aortic valve prosthesis device during expansion and / or displacement. The personalized safe zone for transcatheter deployment of the aortic valve prosthesis device is computed as a function of (i.e., between) the location of the annulus plane and the location of the conduction region.

[0195] The personalized safe zone may further be computed according to one or more parameters of the aortic valve prosthesis device, such as foreshortening during expansion (i.e., reduction in length as a function of diameter (also referred to herein as width) of the aortic valve prosthesis device). The personalized safe zone may be defined as a target region within the heart for placement of a defined portion of the aortic valve prosthesis device in a contracted state, such that during expansion and deployment of the aortic valve prosthesis device, risk of damage to the cardiac conduction region by the aortic valve prosthesis device is reduced or prevented. The defined portion of the aortic valve prosthesis device may be, for example, the distal end of the aortic valve prosthesis device, and / or a radio-opaque marker on the aortic valve prosthesis device. The personalized safe zone may further be computed according to a target deployment range representing the desired location of deployment of the aortic valve prosthesis device (e.g., according to clinical guidelines and / or valve manufacturer guidelines) after expansion from an initial location. For example, to place the aortic valve prosthesis device at the target deployment range after expansion, the personalized safe zone may be selected as the location where the distal end of the aortic valve prosthesis device is to be placed prior to expansion taking into account the foreshortening of the aortic valve prosthesis device. The personalized safe zone may be selected to be more distal than the target deployment range, but before the cardiac conduction region, such that during expansion, as the aortic valve prosthesis undergoes foreshortening, the distal end of the aortic valve prosthesis device does not or is less likely to damage the cardiac conduction region (e.g., by scratching) for arrival at the target deployment range once fully expanded. The personalized safe zone may be identified in real time on fluoroscopy images captured during the procedure, for example, by registration of the 2D fluoroscopy images to the 3D CT reference image. An overlay indicating the location of the personalized safe zone may be dynamically generated and presented over the fluoroscopy images, for helping an operator to position the aortic valve prosthesis device where expansion and deployment will occur, while reducing or preventing damage to the cardiac conduction system.

[0196] An aspect of some embodiments of the present invention relates to a method of treating a patient based on or according to a computed personalized safe zone. The method of treating a patient, comprising: delivering an aortic valve prosthesis device via a transcatheter approach in a contracted state to a heart of the patient; and deploying the aortic valve prosthesis device in the heart, such that a distal end of the aortic valve prosthesis device is positioned within a personalized safe zone; wherein the personalized safe zone is between a location of the annulus plane of an aortic valve of the patient and a location of the conduction region of the heart of the patient.

[0197] An aspect of some embodiments of the present invention relates to a method of treating a patient, comprising: delivering an aortic valve prosthesis device via a transcatheter approach in a contracted state to a heart of the patient, and deploying the aortic valve prosthesis device in the heart, such that a distal end of the aortic valve prosthesis device is positioned according to one of: (i) in response to a perforating bundle being located at or below an annulus plane of an aortic valve, deploying the distal end at a level of the annulus plane, (ii) in response to the perforating bundle being above the annulus plane and a branching point of a left branch bundle being located at or below the annulus plane, deploying the distal end within a range of about 0-1 millimeters (mm) above the perforating bundle, and (iii) in response to the perforating bundle being above the annulus plane and the branching point of the left branch bundle being located above the annulus plane, deploying the distal end within a range of about 1-2 mm above the perforating bundle and within a range of about 0-1 mm above the branching point of the left branch bundle.

[0198] At least some embodiments described herein address the medical problem of reducing or preventing damage to the cardiac conduction system during a TAVI procedure. At least some embodiments described herein improve the medical field of TAVI procedures. At least some embodiments described herein improve upon prior approaches of performing a TAVI procedure.

[0199] At least some embodiments described herein address the technical problem of analyzing images of a heart of subject for guiding a TAVI procedure for reducing and / or preventing damage to the cardiac conduction system during the TAVI procedure. At least some embodiments described herein improve the technology of image processing. At least some embodiments described herein improve upon prior image processing approaches.

[0200] One of the potential risks during TAVI is damage to the conduction system of the heart, for example, the atrioventricular (AV) node or the bundle of His. The conduction system is responsible for coordinating the heart's rhythm and ensuring the proper sequence of contractions.

[0201] The potential risks to the conduction system during TAVI include:

[0202] • Conduction Block: TAVI procedures may cause conduction disturbances, such as heart block, where the electrical signals are delayed or blocked as they pass through the AV node. This can lead to a slower heart rate (bradycardia).

[0203] • Need for Pacemaker: In some cases, conduction abnormalities can be significant enough to require the implantation of a permanent pacemaker. This is especially true in patients who already have pre-existing conduction system issues. • Bundle Branch Block: TAVI can occasionally result in bundle branch block, which involves a delay or blockage in the electrical signals within the bundle branches of the heart's conduction system.

[0204] • Arrhythmias: The procedure may trigger arrhythmias, irregular heart rhythms, due to disruptions in the normal electrical pathways.

[0205] At least some embodiments described herein address the aforementioned technical problem, and / or improve the aforementioned technical field, and / or improve the aforementioned prior approaches, by computing a personalized safe zone for a subject. The personalized safe zone indicates a region where a target portion of the aortic valve prosthesis device is to be positioned in the compressed state, such that during expansion and / or after expansion, damage to the cardiac conduction system by the expanding and / or deployed aortic valve prosthesis device is reduced and / or prevented. The personalized safe zone is computed according to a location of a cardiac conduction region defined as between a perforating bundle (e.g., bundle of His) and a branching point of the left bundle branch. The cardiac conduction region usually lies close to the surface of the inner layer of the heart chambers (e.g., endocardium) and in proximity to the aortic valve, making it vulnerable to injury during transcatheter deployment of the aortic valve prosthesis device.

[0206] At least some embodiments described herein address the technical problem and / or the medical problem that is sometimes encountered during deployment of an aortic valve prosthesis device with significant foreshortening. When the operator (e.g., physician) tries to position the device too deeply (i.e., distally) into the aortic valve (i.e., towards and / or into the left ventricle) in view of a prediction of the eventual foreshortening, this may cause the device aortic valve prosthesis device in some patient to be partially open (i.e., expanded) and start moving upwards in the left ventricular outflow tract (LVOT) and may damage the cardiac conduction region between a perforating bundle and a branching point of the left branch bundle (also referred to herein as a BC segment) if the initial position of the aortic valve prosthesis device is lower than the BC segment. On the other hand, if the operator tries to position the aortic valve prosthesis device at a higher position when starting to open (i.e., expand) the aortic valve prosthesis device, the foreshortening may cause the aortic valve prosthesis device to pop out from the left ventricle (LV) into the aorta, which may cause the operator to move the device downward (i.e., distally) into the LV - a movement that can cause damage to the BC segment during the downward movement of the open device. At least some embodiments described herein provide a solution to the aforementioned technical and / or medical problem, and / or improve the technical field of image processing and / or the medical field of deployment of aortic valve prosthesis devices, by dynamically computing the personalized safe zone according to one or more momentary stage of delivery of the aortic valve prosthesis device which may be depicted in 2D fluoroscopy images. Multiple personalized safe zones may be computed, and / or the personalized safe zone may by dynamically adapted according to the current momentary state of delivery, i.e., the current diameter of the aortic valve prosthesis device. The personalized safe zone may be computed according to a foreshortening relationship between a current diameter of the aortic valve prosthesis device and length reduction. The currently computed personalized safe zone may be dynamically updated on the overlay, as described herein. Risk of damage to the BC segment may be decreased or eliminated during deployment of aortic valve prosthesis devices with significant shortening according to the dynamically computed personalized safe zone for one or more momentary stages of delivery.

[0207] Inventors discovered that the cardiac conduction region is located in different places in different patients, below or above an annulus plane (which may be used to guide where to deploy the aortic valve prosthesis device) and / or at different distances from the annulus plane. Computing the personalized safe zone for each subject may enable an operator to deploy the aortic valve prosthesis device in each subject, while reducing or avoiding damage to the cardiac conduction system in the subject.

[0208] Inventors analyzed data of multiple patents and discovered that:

[0209] The depth of the cardiac conduction region below the annulus plane is variable, as presented in Table 1 below:

[0210] The location of the cardiac conduction region is variable, as presented in Table 2 below (RCC=right coronary cusp, NNC = non-coronary cusp, LCC=left coronary cusp):

[0211] The location of different portions of the cardiac conduction system is variable, as presented in Table 3 below:

[0212] A conduction path angle (non-coronary cusp (NCC) midBC angle (between the penetrating bundle (denoted B) and the branching point of the left bundle branch (denoted C)) is variable, as presented in Table 4 below:

[0213] The depth of the cardiac conduction region (BC length) is variable, as presented in Table 5 below:

[0214] The variability of the location of the cardiac conduction system in different patients may lead to clinical complications in deployment of the aortic valve prosthesis device. For example, the same aortic valve prosthesis device deployed in the same anatomical location in two different patients may cause a conduction disturbance (e.g., AV block, left bundle branch block (LBBB)) requiring implantation of a pacemaker in one patient, while causing no problems in another patient. The uncertainty of the variability of the location of the cardiac conduction system in different patients may be overcome by computing the computing the personalized safe zone for each patient. The personalized safe zone may be computed by taking into account the actual location of portion of the cardiac conduction system of the patient, which may reduce or prevent damage to the cardiac conduction system during deployment of the aortic valve prosthesis device.

[0215] Moreover, different aortic valve prosthesis device may deform differently during deployment (e.g., foreshortening) and / or may have different manufacturer recommendations for a best deployment location. Taking the personalized safe zone of a subject into account with the specific parameters of the aortic valve prosthesis device which is to be deployed, may reduce or prevent damage to the cardiac conduction system in the subject. Damage to the cardiac conduction system may occur during TA VI, for example, by scratching and / or shear forces and / or friction applied to the conduction system and / or nearby tissues by dragging of a rough surface of the aortic valve prosthesis device during deployment. The scratching and / or shear forces and / or friction may be applied by the aortic valve prosthesis device to the cardiac conduction system due to foreshortening movement of a distal end of the aortic valve prosthesis device that occurs during expansion from a smaller contracted diameter during intravascular delivery, to a larger diameter for final deployment. Balloon expandable aortic valve prosthesis device may undergo significant foreshortening during deployment, during which the distal end thereof moves against the cardiac conduction system. The foreshortening may cause a dragging motion for a significant distance between the distal end of the device and the inner wall of the ventricle and / or septum where the conduction system lies, such as the membranous septum. The dragging motion may be at higher risk for damaging the cardiac conduction system when the device gets close to the inner wall of the ventricle and / or septum. The dragging motion against the floor of the membranous septum may damage the cardiac conduction system.

[0216] In some aortic valve prosthesis devices, cells of the stent housing the leaflets may undergo deformation during deployment to expand the diameter of the device based on foreshortening of a length of the device. The deformation of the cells may damage the cardiac conduction system. Foreshortening may be significant. For example, for one type of balloon expandable aortic valve prosthesis device, the following foreshortening occurs for different final diameters: 20 millimeter (mm) diameter incurs a foreshortening of 5.5 mm, 23 millimeter (mm) diameter incurs a foreshortening of 6.5 mm, 26 millimeter (mm) diameter incurs a foreshortening of 8 mm, and 29 millimeter (mm) diameter incurs a foreshortening of 8.5 mm.

[0217] In at least some embodiments described herein, the personalized safe zone is computed for deploying the aortic valve prosthesis device at a location such that the dragging movement of the distal end of the aortic valve prosthesis device against the conduction system (e.g., membranous septum) is reduced or prevented. The parameters of the valve indicating amount of foreshortening and / or target deployment location relative to the annulus plane may be taken into account for computing the personalized safe zone.

[0218] The personalized safe zone may be selected when the cardiac conduction system is well below the area of apposition of dragging motion between aortic valve prosthesis device and the cardiac conduction system, and still be enough below the annulus plane of the aortic annulus.

[0219] An aspect of some embodiments of the present invention relates to systems, methods, computing device, and / or code, for registering an anatomical structure (e.g., ascending aorta) depicted in a 3D image (e.g., pre-procedure CT scan) to a 2D fluoroscopy image (obtained during the projection). The registration enables mapping anatomical landmarks detected in the 3D image to the fluoroscopy image, optionally in real time during the procedure. For example, annulus line (e.g., plane) and / or conduction system and / or membranous septum, for computing and presenting the safe zone. The registration may be performed by identifying the anatomical structure (e.g., ascending aorta) and the anatomical landmark(s) in the 3D image. The contour of the anatomical structure (e.g., ascending aorta) is detected in the fluoroscopy image, which may depict contrast injected into the anatomical structure (e.g., ascending aorta). A pose of the sensor that captured the fluoroscopy image (e.g., C-arm of an x-ray machine) is obtained. The contour of the anatomical structure (e.g., ascending aorta) detected in the 3D image is projected to a 2D plane according to the pose, representing what the anatomical structure (e.g., ascending aorta) looks like as viewed from the sensor at the pose. The contour projected from the 3D image is registered to the contour detected in the fluoroscopy image. A registration (e.g., function) is computed. The registration may applied for registering (e.g., mapping) the anatomical landmarks detected in the 3D image to the fluoroscopy image, e.g., during the medical procedure. The anatomical landmarks are presented on the fluoroscopy image, such as using an overlay, for example, for depicting the safe zone in real time and / or the conduction system.

[0220] Inventors discovered that the best location for deployment is within the safe zone, as close as possible to the membranous septum floor, which is the lower end of the safe zone, and above it. At least some embodiments described herein generate an image depicting the safe zone, optionally overlaid on a fluoroscopy image, which may be obtained and / or updated in real time during the procedure, for aiding deployment of the aortic valve prosthesis device. The safe zone cannot be directly visualized on fluoroscopy images. The implant location may be as close as possible to the membranous septum floor without contacting the membranous septum floor. For example, implanting about 1 millimeter away from the membranous septum floor. It is noted that the safe zone may be wider than 1 millimeter, providing a larger safe implant range if needed. Moreover, the floor of the safe zone, defined by the membranous septum, is often slanted. The overlay of the safe zone helps visualize the trapezoidal like shape of the safe zone, for assisting in accurate and safe deployment. The distal end of the aortic valve replacement device is to be maintained as close as possible to the lower end of the membranous septum floor throughout deployment and at final deployment. The best location for deployment reduces risk of damage to the conduction system of the heart, which passes within the membranous septum floor. Moreover, the best location may reduce risk of coronary blockage and / or pop-out of the aortic valve replacement device, which may occur with higher likelihood when deployment is above the annulus line (the upper line of the safe zone). The deployment within the safe zone, close to the membranous septum floor is in contrast to current aortic valve replacement implantation guidelines, which recommend implanting the aortic valve prosthesis device about 2-3 millimeters below the native annulus (defined as zero), or in some cases closer. Implanting at zero is meant to reduce risk of damage to the conduction system, but provides the disadvantage of blocking entrance to the coronary arteries and / or increases risk of pop-out of the aortic valve prosthesis device. Moreover, implanting close to zero often prevents a future valve in valve procedure, since the next valve will be too high, thereby blocking entrance to the coronaries. Implanting within the safe zone, optionally close to the membranous septum floor as described herein, may prevent or reduce risk of conduction disturbances, while also enabling a future valve in valve procedure since the next valve can be implanted lower without blocking the coronaries.

[0221] As used herein, the term “without parallax” or “parallax free” refers to a 2D projection of a 3D structure, such as on a 2D image (e.g., fluoroscopy) that is “face-on”, such as an aortic annulus plane appearing as a line rather than a plane or circle-like shape, and a distal end of an aortic valve prosthesis device (during deployment) appearing as a line rather than approximately as a circle-like shape.

[0222] An aspect of some embodiments of the present invention relates to systems, methods, computing devices, and / or code instructions, for generating a parallax free presentation of one or more features depicted in a 2D fluoroscopy image, optionally for depicting the safe zone and / or a distal end of an aortic valve prosthesis device within the safe zone. The safe zone may be defined between an aortic annulus line / plane and aortic and a membranous septum floor, as described herein. A registration (e.g., function) for registering a 2D fluoroscopy image with a 3D image (e.g., pre-procedure cardiac CT) of a subject is computed. One or more features are located within the 3D image, for example, the aortic annulus plane, membranous septum floor, and / or a simulation of a location of the aortic valve prosthesis device. The features are associated with CT derived information (CDI) indicating coordinates of the location within the 3D image. The features are detected on the 2D fluoroscopy image. Fluoroscopy derived information (FDI) is extracted. The FDI includes the location of the feature(s) on the 2D fluoroscopy image and a pose of a sensor that captured the 2D fluoroscopy image. A parallax free pose of the feature(s) depicted in the 3D image is computed. The parallax free pose may be the pose that is closest to the pose of the sensor that captured the 2D fluoroscopy image. The registration is applied for projecting the feature(s) of the 3D image defined by the CDI to a 2D plane corresponding to the FDI, according to the parallax free pose for generating a synthetic parallax free view (SPFV) of the feature(s). Alternatively, the whole 3D image is projected to the 2D plane to generate a synthetic fluoroscopy image. The SPFV of the feature(s) is provided for presentation, for example, as an overlay over the fluoroscopy image and / or as a separate presentation.

[0223] At least some embodiments address the technical problem of generating a presentation for helping accurately guide an aortic valve prosthesis device for implantation, optionally for more accurately depicting and / or computing the safe zone and location of a distal end of the aortic valve prosthesis device within the safe zone. At least some embodiments improve the technology of image processing, by generating a presentation for helping accurately guide an aortic valve prosthesis device for implantation, optionally for more accurately depicting and / or computing the safe zone and location of a distal end of the aortic valve prosthesis device within the safe zone.

[0224] During TAVR the operator uses fluoroscopy to help navigate through the vascular system and implant an aortic valve prosthesis device to replace the malfunctioning native valve. While fluoroscopy is a 2D imaging technique, the implant as well as the heart anatomy are 3D, making it challenging to guide the 3D aortic valve prosthesis device within the 3D heart using 2D fluoroscopy images. Guidelines were developed to suggest to the operator to place the fluoroscopy machine with such angulation relative to the patient body to allow the operator to see the anatomy and the aortic valve prosthesis device with a view that assure that the projection is without parallax. Achieving the angulation target from a practical perspective is too time consuming and the operators in practice perform the implantation procedure without securing a parallax free view of the heart anatomy (especially the aortic valve) and the aortic valve prosthesis device. In a clinical study, Inventors demonstrated that the vast majority of the fluoroscopy throughout the TAVR procedure was contaminated with parallax for the annulus and the device. The result complications are multiple, based on the inability to assess device depth within the heart relative to the annulus of the aortic valve.

[0225] United States Provisional Patent application No. 63 / 532,995, having at least one Inventor in common with the present disclosure, and incorporated herein by reference in its entirety, relates to calculating the parallax free fluoroscopy positions the operator should achieve to help capture images that are parallax free. At least some embodiments described herein provide an alternative approach.

[0226] At least some embodiments described herein address the technical problem of segmenting and / or identifying on a 3D image and / or on a fluoroscopy image, the location of the membranous septum, floor of the membranous septum, and / or other features for computing the safe zone, such as an annulus line. The membranous septum in particular cannot be seen on a CT scan and / or on a fluoroscopy image, making it technically challenging to identify on the CT scan and / or fluoroscopy image. At least some embodiments described herein improve the technical field of image processing, by detecting a 3D image and / or on a fluoroscopy image, the location of the membranous septum, floor of the membranous septum, and / or other features for computing the safe zone, such as an annulus line. When the membranous septum is located on the 3D image, its location may be mapped to the fluoroscopy image using approaches described herein.

[0227] Interventional procedure on the heart that relate to implanting and / or that relate to interacting with cardiac tissue benefit in many cases by pre procedure anatomical imaging of the heart of the patient undergoing the procedure. For example, a pre-procedure cardiac CT is performed. Procedure pre-planning is performed in the field of cardiology, especially for structural heart disease procedures. Generally, existing software packages for pre-planning of a structural heart disease procedure, are divided according to the specific procedure that they are designed to support. Some existing software packages may be used for pre-planning trans-catheter aortic valve replacement procedures, which may use measurement made from an anatomical imaging modality such as a cardiac CT scan. However, measurements that are done for trans-catheter aortic valve replacement procedures are standard measurements, for example, aortic valve dimensions, sinotubular dimensions, aorta dimensions. Standard dimensions include for example, the long and the short axis, the cross-sectional areas. Other examples of measurements include locations of the commissioners, and measurement of the distance to the aortic plane from the origin of the right and the left coronary arteries. These standard dimensions cannot be used to compute the safe zone described herein.

[0228] Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details of construction and the arrangement of the components and / or methods set forth in the following description and / or illustrated in the drawings and / or the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

[0229] The present invention may be a system, a method, and / or a computer program product. The computer program product may include a computer readable storage medium (or media) having computer readable program instructions thereon for causing a processor to carry out aspects of the present invention.

[0230] The computer readable storage medium can be a tangible device that can retain and store instructions for use by an instruction execution device. The computer readable storage medium may be, for example, but is not limited to, an electronic storage device, a magnetic storage device, an optical storage device, an electromagnetic storage device, a semiconductor storage device, or any suitable combination of the foregoing. A non-exhaustive list of more specific examples of the computer readable storage medium includes the following: a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), a static random access memory (SRAM), a portable compact disc read-only memory (CD-ROM), a digital versatile disk (DVD), a memory stick, a floppy disk, and any suitable combination of the foregoing. A computer readable storage medium, as used herein, is not to be construed as being transitory signals per se, such as radio waves or other freely propagating electromagnetic waves, electromagnetic waves propagating through a waveguide or other transmission media (e.g., light pulses passing through a fiber-optic cable), or electrical signals transmitted through a wire.

[0231] Computer readable program instructions described herein can be downloaded to respective computing / processing devices from a computer readable storage medium or to an external computer or external storage device via a network, for example, the Internet, a local area network, a wide area network and / or a wireless network. The network may comprise copper transmission cables, optical transmission fibers, wireless transmission, routers, firewalls, switches, gateway computers and / or edge servers. A network adapter card or network interface in each computing / processing device receives computer readable program instructions from the network and forwards the computer readable program instructions for storage in a computer readable storage medium within the respective computing / processing device.

[0232] Computer readable program instructions for carrying out operations of the present invention may be assembler instructions, instruction-set-architecture (ISA) instructions, machine instructions, machine dependent instructions, microcode, firmware instructions, state-setting data, or either source code or object code written in any combination of one or more programming languages, including an object oriented programming language such as Smalltalk, C++ or the like, and conventional procedural programming languages, such as the "C" programming language or similar programming languages. The computer readable program instructions may execute entirely on the user's computer, partly on the user's computer, as a stand-alone software package, partly on the user's computer and partly on a remote computer or entirely on the remote computer or server. In the latter scenario, the remote computer may be connected to the user's computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider). In some embodiments, electronic circuitry including, for example, programmable logic circuitry, field-programmable gate arrays (FPGA), or programmable logic arrays (PLA) may execute the computer readable program instructions by utilizing state information of the computer readable program instructions to personalize the electronic circuitry, in order to perform aspects of the present invention. Aspects of the present invention are described herein with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the invention. It will be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer readable program instructions.

[0233] These computer readable program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks. These computer readable program instructions may also be stored in a computer readable storage medium that can direct a computer, a programmable data processing apparatus, and / or other devices to function in a particular manner, such that the computer readable storage medium having instructions stored therein comprises an article of manufacture including instructions which implement aspects of the function / act specified in the flowchart and / or block diagram block or blocks.

[0234] The computer readable program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other device to cause a series of operational steps to be performed on the computer, other programmable apparatus or other device to produce a computer implemented process, such that the instructions which execute on the computer, other programmable apparatus, or other device implement the functions / acts specified in the flowchart and / or block diagram block or blocks.

[0235] The flowchart and block diagrams in the Figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to various embodiments of the present invention. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of instructions, which comprises one or more executable instructions for implementing the specified logical function(s). In some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and / or flowchart illustration, and combinations of blocks in the block diagrams and / or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts or carry out combinations of special purpose hardware and computer instructions.

[0236] Reference is now made to FIG. 1, which is a pictorial illustration of an operating room equipped with a system for computing and / or using a safe zone for guiding a TAVI procedure, in accordance with some embodiments of the present invention. Reference is also made to FIG. 2, which is a block diagram of components of a system 100 for computing a safe zone for guiding a TAVI procedure, in accordance with some embodiments of the present invention. Reference is also made to FIG. 3, which is a flowchart of a method of computing a personalized safe zone for transcatheter deployment of an aortic valve prosthesis device in a subject, in accordance with some embodiments of the present invention. Reference is also made to FIG. 4, which is a schematic to help understand anatomy of the cardiac conduction region, in accordance with some embodiments of the present invention. Reference is also made to FIG. 5, which is a schematic of an aortic root depicting detected nadir points and points of a detected conduction system, in accordance with some embodiments of the present invention. Reference is also made to FIG. 6, which is a schematic 602 depicting foreshortening of an aortic valve prosthesis device, in accordance with some embodiments of the present invention. Reference is also made to FIG. 7, which is a schematic depicting a possible mechanism of damage to a cardiac conduction region by foreshortening of an aortic valve prosthesis device during expansion from a contracted state to an expanded state, in accordance with some embodiments of the present invention. Reference is also made to FIG. 8, which is a schematic depicting another possible mechanism of damage to a cardiac conduction region by distal displacement of an aortic valve prosthesis device in an expanded state, in accordance with some embodiments of the present invention. Reference is also made to FIG. 9, which is a schematic depicting exemplary locations of features within an anatomy, used for computing a personalized safe zone, in accordance with some embodiments of the present invention. Reference is now made to FIG. 10, which is a schematic depicting a conduction annulus depth (CAD), in accordance with some embodiments of the present invention. Reference is also made to FIG. 11, which is a schematic of a fluoroscopy image with an overlay depicting an annulus plane and portions of a cardiac conduction system, in accordance with some embodiments of the present invention. Reference also made to FIG. 12, which is a schematic 1202 depicting an exemplary approach for computing a conduction angle 1250, in accordance with some embodiments of the present invention. Reference is also made to FIG. 13, which is a schematic 1302 depicting another exemplary approach for computing the conduction angle, in accordance with some embodiments of the present invention. Reference is also made to FIG. 14A, which is a schematic depicting an exemplary user interface 1402 presenting the personalized safe zone, in accordance with some embodiments of the present invention. Reference is also made to FIG. 14B, which is another schematic depicting another exemplary user interface 1452 presenting the personalized safe zone, in accordance with some embodiments of the present invention. Reference is also made to FIG. 15, which is a flowchart of an exemplary method of registering a 2D fluoroscopy image to a 3D image, in accordance with some embodiments of the present invention. Reference is also made to FIG. 16, which includes schematics 1602 and 1612 indicating computed distances between a membrane septum floor (MSF) to an annulus plane for defining the safe zone, in accordance with some embodiments of the present invention. Reference is also made to FIG. 17, which is a schematic 1702 of a 3D image including automatically identified anatomical features of a heart of a subject for computing the location of the conduction system and / or the safe zone, in accordance with some embodiments of the present invention. Reference is also made to FIG. 18, which is a schematic 1802 depicting a contour 1804 of an ascending aorta identified from a 2D fluoroscopy image, and a contour 1806 of the ascending aorta projected from a 3D image for computing a registration, in accordance with some embodiments of the present invention. Reference is also made to FIG. 19, which is a schematic depicting an of example of processing features, in accordance with some embodiments of the present invention. Reference is also made to FIG. 20, which is a flowchart of another method for registering a 2D fluoroscopy image to a 3D image, in accordance with some embodiments of the present invention. Reference is also made to FIG. 21, which is a flowchart of a method of generating a parallax free image of one or more features depicted in a 2D fluoroscopy image, in accordance with some embodiments of the present invention. Reference is also made to FIG. 22, which is a schematic depicting an exemplary SPFV 2202 computed from a 2D fluoroscopy image 2204, in accordance with some embodiments of the present invention. Reference is also made to FIG. 23, which is a schematic 2302 depicting exemplary segmentations of a 3D image used for computing the safe zone, in accordance with some embodiments of the present invention. Reference is also made to FIG. 24, which is a schematic depicting an example of a segmentation of a myocardium of a left ventricle 2404, in accordance with some embodiments of the present invention. Reference is also made to FIG. 25, which is a schematic 2502 depicting another exemplary approach for segmentation of a membranous septum from a 3D image, in accordance with some embodiments of the present invention. Reference is also made to FIG. 26, which is a schematic 2602 depicting a first line 2604 at a distal end of an aortic valve prosthesis device 2606 within a safe zone 2608, in accordance with some embodiments of the present invention. Reference is also made to FIG. 27, which is a decision tree 2702 depicting a method of treating a patient indicating where to place a distal end of an aortic valve prosthesis device being deployed in a heart of a subject, in accordance with some embodiments of the present invention. Reference is also made to FIG. 28, which is a graph 2802 presenting measurements obtained during an experiment performed by the Inventor for evaluation of at least one embodiment. Referring is also made to FIG. 29, which is a graph 2902 presenting odds of lower and increased risk for a pacemaker (PPM) post TAVR for the group of patients included in the experiment. Reference is also made to FIG. 30, which includes graphs presenting incidences rates of requiring a pacemaker implant post TAVR for different locations within the personalized safe zone, computed as part of the experiment performed by Inventor. Reference is also made to FIG. 31, which is a plot of predicted probability of requiring a pacemaker as a function of difference between point B and device depth, computed as part of the experiment performed by Inventor. Reference is also made to FIG. 32, which includes additional graphs presenting incidences rates of requiring a pacemaker implant post TAVR for different locations within the personalized safe zone, computed as part of the experiment performed by Inventor.

[0237] Referring now back to FIG. 1, system 300 is depicted as being used for computing and / or using a personalized safe zone for guiding (e.g., automated tools, medical devices) a TAVI procedure. An exemplary environment for system 300 is now described. A catheter 15 may be percutaneously inserted into a living body 17 of a patient lying on a gurney 19. Catheter 15 may be controlled and manipulated by operator 70 (e.g., a surgeon). An imaging system 30 may be used to obtain an image of the inside of the body of the patient for guiding the aortic valve prosthesis device. For example, an image of the heart in which the prosthetic valve is located. Imaging system 30 is shown to optionally include an image source 32, which may be implemented as, for example, fluoroscopy (i.e., 2D x-rays) machine, magnetic resonance imaging (MRI) machine, X-ray computed tomography (CT) machine, and / or any suitable imaging technique to obtain the image(s) of the interior of the body for pre-procedure processing and / or in real-time during the procedure, for computation of the personalized safe zone and / or for using the personalized safe zone. An image 18 (e.g., a fluoroscopy image of the heart with an overlay of the personalized safe zone may be displayed to operator 70 on an output display 50, and / or a copy of the image may be sent to system 300 for processing and / or generating an overlay of the safe zone (e.g., in a GUI 60).

[0238] Referring now back to FIG. 2, system 100 may implement the acts of the methods described herein optionally by one or more hardware processor(s) 102 of a computing device 104 executing code instructions stored in a memory 106.

[0239] Computing device 104 may be implemented as, for example, a client terminal, a server, a virtual server, a radiology workstation, a catheterization laboratory workstation, a virtual machine, a computing cloud, a mobile device, a desktop computer, a thin client, a Smartphone, a Tablet computer, a laptop computer, a wearable computer, glasses computer, and a watch computer. Computing device 104 may include an advanced visualization process that sometimes is add-on to a catheterization laboratory workstation and / or other devices for computing the personalized safe zone and / or for presenting the personalized safe zone as an overlay on fluoroscopy images, e.g., as described herein.

[0240] Computing device 104 may include locally stored software that performs one or more of the acts of the method described herein and / or may act as one or more servers (e.g., network server, web server, a computing cloud, virtual server) that provides services (e.g., one or more of the acts of the method described herein) to one or more client terminals 108 (e.g., remotely located catheterization laboratory workstation) over a network 110, for example, providing software as a service (SaaS) to the client terminal(s) 108, providing an application for local download to the client terminal(s) 108, as an add-on to a web browser and / or a medical imaging viewer application, and / or providing functions using a remote access session to the client terminals 108, such as through a web browser.

[0241] Different architectures based on system 100 may be implemented. In one example, computing device 104 provides centralized services. Computing device 104 may obtain images from an image repository 122A (e.g., fluoroscopy images captured during a procedure and / or a pre-procedure image such as a CT scan) storing images from each of multiple different imaging devices 112 (e.g., fluoroscopy machines and / or CT scanners). Each imaging device 112 includes an image sensor that captures the images. The images 122 A may be provided to computing device 104 for centralized analysis, for example for computation of the safe zone and / or generating an overlay of the safe zone, as described herein. The images (e.g. pre-procedure and / or intraprocedure) may be provided to computing device 104, for example, via an application programming interface (API), software development kit (SDK), and / or other local application, over a network 110, and / or transmitted using a suitable transmission protocol. The outcome of the analysis may be provided, for example, to client terminal(s) 108 for presentation on a display such as within a GUI and / or other indications (e.g., audio and the like) and / or local storage, stored in an electronic medical record (e.g., hosted by server 118), and / or stored by computing device 104.

[0242] In another architecture, computing device 104 provides localized services, by locally analyzing the images (e.g., pre-procedure and / or intra-procedure). For example, computing device 104 is implemented as code executed by a processor of a catheterization laboratory workstation that analyses pre-procedure CT scans for computing the personalized safe zone, and / or generates an overlay of the personalized safe zone for presentation over fluoroscopy image captured by a fluoroscopy machine of the catheterization laboratory. System 100 and / or computing device 104 described with reference to FIG. 2. may include and / or be implemented as system 300 described with reference to FIG. 1.

[0243] Imaging device 112 provides the medical images, optionally the pre-procedure image used to compute the personalized safe zone and / or intra-procedure image on which the safe zone may be presented. Imaging device(s) 112 may include a pre-procedure imaging device such as a 3D scanner, for example, a CT and / or MRI machine. Imaging device(s) 112 may include an intra- procedure imaging device for capturing image during the procedure, for example, a 2D fluoroscopy and / or x-ray machine, as commonly used in catheterization labs (e.g., cardiac).

[0244] Imaging device(s) 112 described with reference to FIG. 2 may include and / or be implemented as imaging system 30 and / or imaging source 32 described with reference to FIG. 1.

[0245] The pre-procedure images and / or intra-procedures images may be stored in image repository 122A. Image repository 122A may be stored in a data repository 114 and / or data storage device 122, for example, a storage server, a computing cloud, virtual memory, and a hard disk. It is noted that the pre-procedure images and / or intra-procedure images may be stored by a server 118, accessible by computing device 104 over network 110.

[0246] Computing device 104 may receive the pre-procedure images and / or intra-procedure images using one or more data interfaces 120, for example, a wire connection (e.g., physical port), a wireless connection (e.g., antenna), a local bus, a port for connection of a data storage device, a network interface card, other physical interface implementations, and / or virtual interfaces (e.g., software interface, virtual private network (VPN) connection, application programming interface (API), software development kit (SDK)), and / or a network interface 124.

[0247] Processor(s) 102 may be implemented, for example, as a central processing unit(s) (CPU), a graphics processing unit(s) (GPU), field programmable gate array(s) (FPGA), digital signal processor(s) (DSP), and application specific integrated circuit(s) (ASIC). Processor(s) 102 may include one or more processors (homogenous or heterogeneous), which may be arranged for parallel processing, as clusters and / or as one or more multi core processing units.

[0248] Memory 106 (also referred to herein as a program store, and / or data storage device) may store code instruction for execution by hardware processor(s) 102, for example, a random access memory (RAM), read-only memory (ROM), and / or a storage device, for example, non-volatile memory, magnetic media, semiconductor memory devices, hard drive, removable storage, and optical media (e.g., DVD, CD-ROM). For example, memory 106 may store code 106A that implement one or more acts and / or features of the methods described herein.

[0249] Computing device 104 may include a data storage device 122 for storing data, for example, image repository 122A set for storing pre-procedure and / or intra-procedure images (e.g., 2D, 3D), a personalized safe zone repository 122B set for storing computing personalized safe zones for different patients, device parameter repository 122C set for storing different parameters of different aortic valve prosthesis devices used to compute the personalized safe zones, and / or other code for other features, as described herein. Data storage device 122 may be implemented as, for example, a memory, a local hard-drive, a removable storage device, an optical disk, a storage device, and / or as a remote server and / or computing cloud (e.g., accessed over network 110).

[0250] Computing device 104 may include network interface 124 for connecting to network 110, for example, one or more of, a network interface card, a wireless interface to connect to a wireless network, a physical interface for connecting to a cable for network connectivity, a virtual interface implemented in software, network communication software providing higher layers of network connectivity, and / or other implementations. Computing device 104 may access one or more remote servers 118 using network 110.

[0251] It is noted that data interface 120 and network interface 124 may exist as two independent interfaces (e.g., two network ports), as two virtual interfaces on a common physical interface (e.g., virtual networks on a common network port), and / or integrated into a single interface (e.g., network interface). Computing device 104 may communicate using network 110 (or another communication channel, such as through a direct link (e.g., cable, wireless) and / or indirect link (e.g., via an intermediary computing device such as a server, and / or via a storage device) with one or more of:

[0252] * Client terminal(s) 108, for example, when computing device 104 acts as a server providing image analysis services (e.g., SaaS) to remote catheterization laboratory workstations, for analyzing remotely obtained images 122A (e.g., CT scans, fluoroscopy images) for computing of the personalized safe zone and / or for generating an overlay of the personalized safe zone.

[0253] * Server 118, for example, implemented in association with a PACS, which may store captured pre-procedure images used to compute the personalized safe zone and / or intra-procedure images on which the personalized safe zone is overlaid.

[0254] * Imaging device 112 and / or data repository 114 that store images acquired by imaging device 112.

[0255] Computing device 104 and / or client terminal(s) 108 and / or server(s) 118 may include and / or may be in communication with a user interface(s) 126 that includes a mechanism designed for a user to enter data (e.g., parameter of an aortic valve prosthesis device used to compute the personalized safe zone) and / or to view data (e.g., overlay of the personalized safe zone). Exemplary user interfaces 126 include, for example, one or more of, a touchscreen, a display, a keyboard, a mouse, and voice activated software using speakers and microphone. Referring now back to FIG. 3, features described with reference to 302-312 may be performed as part of a pre-procedure planning process. Features described with reference to 314- 324 may be performed during the procedure.

[0256] At 302, one or more reference images are accessed. The reference image depicts at least the aortic valve and tissues in proximity that include at least the perforating bundle and branching point of the left bundle branch and optionally the AV node, such as the membranous septum.

[0257] The reference image may be a pre-procedure image, obtained prior to the transcatheter procedure for implantation of the aortic valve prosthesis device.

[0258] The reference image may be a 3D images, such as a CT scan and / or MRI scan and / or 3D ultrasound scan.

[0259] Alternatively, the reference image may be a 2D image, such as a fluoroscopy image. The reference image may be obtained during the procedure, for example, prior to delivery of the aortic valve prosthesis device to the aortic valve or proximally to it, such that the reference image excludes the aortic valve prosthesis device. Alternatively or additionally, the reference image may depict the aortic valve prosthesis device.

[0260] At 304, a location of an annulus plane of the aortic valve may be detected on the reference image.

[0261] The annulus plane may be detected by identifying a nadir of each respective cusp of the aortic valve. I.e., in an aortic valve with three cusps, three nadirs are identified, for the right coronary cusp, the left coronary cusp, and the non-coronary cusp. The aortic valve and / or cusps and / or nadirs may be detected, for example, by a machine learning model trained on a training dataset of images labelled with ground truths indicating the aortic valve and / or cusps and / or nadirs. Alternatively, image processing approaches may be applied. For example, the lower boundary of the aortic valve may be determined. In a contrast image where contrast is injected into the aortic root, the lower boundary is the boundary between the lower contrast enhanced aortic root and the left ventricle without contrast. The cusps may be detected as local curvatures of the boundary. For each cusp, the nadir may be computed as a local minimum, for example, using image processing approaches. The annulus plane may be detected by drawing a circle or other planar shape, intersecting the three nadirs.

[0262] Alternatively or additionally, one or more other anatomical features used to compute the personalized safe zone may be identified on the reference image, for example, shape and / or dimensions of a proximal aorta and / or a left ventricular outflow tract. The identification may be performed, for example, using a trained machine learning model, and / or using image processing approaches. At 306, locations of components of a cardiac conduction system may be detected on the reference image.

[0263] The perforating bundle may be detected on the reference image.

[0264] The branching point of the left branch bundle of may be detected on the reference image.

[0265] The cardiac conduction region may be defined between the location of the perforating bundle and the location of the branching point of the left branch bundle, for example, as a line drawn between them.

[0266] Optionally, a location of an atrioventricular (AV) node is detected the reference image, and Optionally, a conduction angle relative to the aortic valve right trigone location may be computed, or the nadir of the NCC. The conduction path angle (also referred to herein as conduction angle) may be related to a typical path a guidewire and / or aortic valve prosthesis device is introduced to the left ventricle from the aorta will be in contact with. The conduction angle may be defined as either the rotational angle between the center of the cardiac conduction region between a perforating bundle and a branching point of the left branch bundle (also referred to herein as a BC segment) to either the nadir of the NCC or the right trigone. The conduction angle may provide an indication of the personal variation of the aorta to the left ventricle and conduction system rotational position. Due to the aorta curvature in the proximal ascending part, the guidewire(s) tend to follow the outer curve of the aorta - which usually positions the guidewire(s) on the right trigone (i.e., the area of the apposition between the NCC and the right coronary cusp (RCC)). If the mid BC segment (which is the highly exposed segment of the cardiac conduction region as described herein), usually in the left ventricle lumen, is just under the right trigone, the likelihood of damage to the cardiac conduction region is higher. However when the rotation of the left ventricle (LV) and the cardiac conduction region is either clockwise or counter clockwise - the likelihood of damage to the cardiac conduction region is lower. The measurement of the conduction angle may be done on the reference image (e.g., pre -procedure CT scan of the patient). The conduction angle may be highly variable, as well as the BC depth relative to the virtual aortic plane, for example, as presented in tables of measurements performed by the Inventor during actual cases.

[0267] The preceding refers to the conduction angle from the trigone (the highest likelihood of damage from the guidewire(s) will be related to a conduction angle close to / about zero degree rotation). If the conduction angle is calculated relative to the nadir of the NCC then the highest likelihood of damage from the guidewire(s) may be between about 30-55 degree rotation.

[0268] Referring now back to FIG. 12, schematic 1202 depicts a nadir of a non-coronary cusp (NCC) 1204, a nadir of a right coronary cusp (RCC) 1206, and a nadir of a left coronary cusp (LCC) 1208. A virtual aortic annulus 1210 is computed as a circle or oval shaped plane having an outer circumference that intersects the nadirs of NCC 1204, RCC 1206, and LCC 1208. Schematic 1202 further depicts a middle 1212 of a BC segment (referred to herein as mid BC) of a line 1240 between a B location 1214 and a C location 1216. B location 1214 denotes the perforating bundle, and C location 1216 denotes the branching point of the left branch bundle. Conduction angle 1250 is computed between a first line 1230 and a second line 1232. First line 1230 is defined from a center 1234 of virtual aortic annulus 1210 and mid BC segment 1212. Second line 1232 is defined from center 1234 to nadir of NCC 1204.

[0269] Referring now back to FIG. 13, anatomical features of schematic 1302 are as described with reference to FIG. 12. Conduction angle 1230 is computed between first line 1230 and a second line 1332 defined from center 1234 to a right trigone 1360 (i.e., the area of the apposition between the NCC and the RCC).

[0270] The location of the components of the cardiac conduction system may be computed from a subject anatomical image, e.g., based on one of more rules and / or identification of anatomical structures in the heart. The anatomical structures in the heart may be computing by ML methods and / or computer vision.

[0271] Optionally, the location of AV node is estimated to be the middle of the infra- septal recess. Alternatively or additionally, the location of AV node is estimated to be within the intraventricular septum adjacent to the septal commissure between the posterior and the anterior leaflets of the mitral valve.

[0272] Alternatively or additionally, the location of AV node is estimated to be within the intraventricular septum at the left most proximal left proximal part of the posterior leaflet adjacent to the septal commissure between the posterior and the anterior leaflets of the mitral valve.

[0273] Optionally, the location of the penetrating bundle, is estimated to be between the most posterior part of the floor of the membranous septum to the most anterior part of the floor of the membranous septum tracking over the floor of the membranous septum.

[0274] Optionally, the location of the bifurcating bundle, is estimated to be toward the left ventricle next to the most anterior part of the floor of the membranous septum.

[0275] Optionally, the location of the floor of the membranous septum is detected. The cardiac conduction region may be on the floor of the membranous septum.

[0276] The location of the membranous septum may be detected, for example, by obtaining orientation of a NRL and / or depth of the aorta. Using this data the membranous septum may be detected, for example, according to the calculations described with reference to Figs. 7A-C of the paper “Vulnerability of the ventricular conduction axis during transcatheter aortic valvar implantation: A translational pathologic study” by Tretter et al. dated Jan 2023, incorporated herein in its entirety. The location of the membranous septum may be computed, for example, according to the publication “The atrioventricular conduction axis and the aortic root — Inferences for transcatheter replacement of the aortic valve”, by Yolanda Macias et at., Clinical Anatomy. 2022;35:143-154, incorporated herein by reference in its entirety.

[0277] The location of one or more components of the cardiac conduction system may be computed, for example, according to the following exemplary process, using the 3D image (e.g., CT) which may be obtained pre-procedure:

[0278] 1. Identification of the nadir of each of the aortic cusps (the right coronary cusp, the left coronary cusp, and the non-coronary cusp)- which may be used for defining the annulus plane.

[0279] 2. Identifying the location of the right and the left fibrous trigones, which are fibrous connective tissue regions near the aortic cusps.

[0280] 3. Identifying the triangular attachment of the atrial septum. The triangular attachment of the atrial septum may serve as an anatomical reference point.

[0281] 4. Drawing a first line in a posterior anterior direction from step #3 (e.g., across the Aortic Root).

[0282] 5. Drawing a second line connecting the center of the non-coronary cusp to the area of apposition of apposition (e.g., where the left and right coronary cusps meet).

[0283] 6. Measuring the rotation angle of the aorta by recording the angle between the center of non- coronary cusp to apposition area (step #5) and the atrial septum to posterior-anterior direction (step# 4).

[0284] 7. Comparing the angle of rotation (of step #6) to nomograms and / or guideline indicating normal and / or expected values.

[0285] 8. Identifying the width of the roof of the infero-spetal recess at the level of the virtual aortic valve plane.

[0286] 9. Identifying the location of the apex of the infero-septal recess in section of the preprocedure CT that are parallel and lower (toward the apex of the left ventricle) than the apex.

[0287] 10. Measuring the virtual aortic valve plane.

[0288] Embodiments described herein which may be used for computing the location of components of the cardiac conduction system may simplify the aforementioned process, which may be complex, and the result of which may still not necessarily show the location of the cardiac conduction region between the perforating bundle and branching point of the left branch bundle. The detection of the floor of the membranous septum and / or the estimated location on the AV node may be relatively simple computational tasks for image vision technologies and / or NRL. The outcome generated by at least some embodiments described herein, i.e., the location of the cardiac conduction region and / or other components of the conduction system, may be in a format that is ready to be converted into 2D image (s) that can be presented to the operator on a fluoroscopy screen, for example, as an overlay on the fluoroscopy images.

[0289] Referring now back to FIG. 4, a membranous septum 402 is depicted. The septum is a structure within the heart that separates the two lower chambers, or ventricles: the right ventricle and the left ventricle. The heart is divided into four chambers — two atria (upper chambers) and two ventricles (lower chambers) — and the septum serves to keep the oxygenated blood on the left side of the heart from mixing with the deoxygenated blood on the right side. There are two main components of the septum: the membranous septum and the muscular septum. The membranous septum is a thin, fibrous partition that lies between the two ventricles. FIG. 4 depicts a location of a cardiac conduction system 412 relative to membranous septum. Cardiac conduction system 412 includes AV node (indicated by A) 414, perforating bundle (indicated by B) 416, and a branching point of the LBB (indicated by C) 418. A cardiac conduction region 420 may be indicated as a line between perforating bundle 416 and branching point 418. Cardiac conduction region 420 may run along the floor of membranous septum 402. Usually, cardiac conduction region 420 is superficially located. Usually, cardiac conduction region 420 is located on the left ventricle since of membranous septum 402. The location of cardiac conduction region 420 within membranous septum 402 makes cardiac conduction region 420 vulnerable to damage by the aortic valve prosthesis device, such as by scratching and / or shear forces applied by the aortic valve prosthesis device to the floor of the membranous septum 402 where cardiac conduction region 420 is located. For example, displacement (e.g., proximally and / or distally) of the expanded aortic valve prosthesis device in proximity to membranous septum 402 may damage the floor of the membranous septum 402. In another example, the distal end of the aortic valve prosthesis device may move proximally due to the aortic valve prosthesis device undergoing foreshortening during expansion of the aortic valve prosthesis device from the contracted state to the expanded state. Damage to perforating bundle 416 may lead to AV block. Damage to branching point 418 may lead to a left bundle branch block (LBBB). In general, damage to cardiac conduction system 412 may require implantation of a pacemaker.

[0290] Referring now back to FIG. 5, a 3D aortic root 502 is depicted. 3D aortic root 502 may be extracted (e.g., segmented) from a 3D image, optionally obtained prior to the procedure (also referred to herein as a pre-procedure image), for example, a CT scan and / or MRI scan. It is noted that other anatomical regions depicted in the 3D image may be presented and / or used. The aortic root is depicted for clarity and simplicity of explanation, and it not necessarily limiting. The annulus plane of the aortic valve may be identified by detecting three nadir points 504 A-C. Each nadir point may be determined as the lowest point on a cusp of the aortic valve (for aortic valves with three cusps). Regions of the cardiac conduction system may be identified, for example, a perforating bundle 506 and / or branching point 508 of the left bundle branch (which may be used to define the cardiac conduction region, as described herein). A distance 510 between the aortic annulus and the cardiac conduction region (or points therein) may be computed, as described herein. For example, as shown distance 510 between the annulus plane and the closest point of the cardiac conduction region is about 3 millimeters (mm). Distance 510 varies between subjects, due to anatomical variations in the locations of the cardiac conduction region, for example, as described herein with reference to experimental data obtained by Inventors. Distance 510 may be used for computing the location of the personalized safe zone, as described herein.

[0291] At 308, one or more parameters of the aortic valve prosthesis device for deployment in the subject may be obtained. The parameters may be obtained, for example, when the operator (e.g., physician) pre-selects the aortic valve prosthesis device to implant.

[0292] Alternatively, the parameters of the aortic valve prosthesis device are not obtained. Rather, the parameters for a suitable aortic valve prosthesis device may be computed according to the computed personalized safe zone, for example, as described with reference to 310-312. The aortic valve prosthesis device that conforms to the computed parameters may then be selected.

[0293] Optionally, the parameter(s) of the aortic valve prosthesis include a deployment range within the heart for positioning of the defined portion of the aortic valve prosthesis device when deployed. The deployment range may be determined, for example, by the manufacturer, such as based on testing and / or empirical data. For example, selected to improve performance and / or selected to reduce likelihood of dislodgement after implantation.

[0294] Alternatively or additionally, the parameter(s) of the aortic valve prosthesis include an amount of foreshortening of a length of the aortic valve prosthesis device in the expanded state compared to the contracted state (also referred to as the aortic valve prosthesis device when crimped). Different aortic valve prosthesis devices experience undergo different amounts of foreshortening, for example, from no foreshortening, or about 20%, or about 21-24%, or about 26- 27%, or about 40-45%, or other values. The amount of foreshortening may be, for example, according to the deployment method (e.g., balloon expandable valves may undergo more foreshortening than self-expanding valve), the design of the scaffold and / or stent housing the leaflets, and the like. The amount of foreshortening may be dynamic, changing according to different momentary stages of delivery in which the aortic valve prosthesis device undergoes expansion, i.e., increase in diameter. The reduction in length may vary with the increase in diameter, for example, according to a predefined function. The foreshortening may be determined for each type, model, and / or size of aortic valve prosthesis devices.

[0295] Alternatively or additionally, the parameter(s) of the aortic valve prosthesis include one or more dimensions of the aortic valve prosthesis device in the expanded state. For example, a diameter and / or length of the aortic valve prosthesis device in the expanded state. In another example, a location of the leaflets within the scaffold, such as distance of the nadir of the leaflets from the edge of the scaffold.

[0296] Alternatively or additionally, the parameter(s) of the aortic valve prosthesis includes a type and / or model of the aortic valve prosthesis device, for example, shape, materials, and the like. The type may be, for example, balloon expandable or self-expanding, general shape of scaffold, and the like. The impact of the type and / or model of the aortic valve prosthesis device on the personalized safe zone may be predefined and / or computed, for example, based on empirical data obtained during procedures, mathematical models, simulations, and the like.

[0297] Referring now back to FIG. 6, a stent 602 of an aortic valve prosthesis device in a compressed state is depicted. The compressed state is used for delivery of the aortic valve prosthesis device via the blood vessels for deployment at the native aortic valve (or within a previously deployed aortic valve prosthesis device, also referred to as a valve-in-valve deployment). In the compressed state, stent 602 has a compressed diameter 604 (also denoted Dc) and a length 606 (also denoted he). Stent 602 is designed to expand from the compressed state to an expanded state 608. For example, stent 602 includes struts designed to change orientation for enabling changing from the compressed state to the expanded state. Stent 602 may be designed for balloon expansion (e.g., made from stainless steel, such as laser cut from a tube), and / or designed for self-expansion (e.g., made from a memory material such as Nitinol). In the expanded state, a length 610 (also denoted ho) of stent 608 undergoes foreshortening in comparison to length 606 of stent 602 in the compressed state. A diameter 612 (also denoted Do) of stent 608 in the expanded state is increased in comparison to diameter 604 of stent 602 in the compressed state.

[0298] Optionally, the length and / or diameter of the stent in the expanded state may be computed as a function of the length and / or diameter of the stent in the compressed state, for example mathematically represented as: Do, ho = f(Dc, hc). The function may enable predicting the length of the aortic valve prosthesis device for deployment. The function may be determined for different aortic valve prosthesis devices of different manufacturers, different models, and / or of different diameters.

[0299] Referring now back to FIG. 7, schematic 702 depicts a possible mechanism of damage to a cardiac conduction region 720 (also referred to herein as “BC line”) by foreshortening of an aortic valve prosthesis device during expansion from a contracted state 704 to an expanded state 706. The length of aortic valve prosthesis devices changes from hcto ho, as described herein. For example, when aortic valve prosthesis device is balloon expanded. In the contracted state 704, a distal end 708 of the aortic valve prosthesis device is positioned distal to cardiac conduction region 720, which may be located on a floor of a membranous septum (MS) 710. During expansion, the aortic valve prosthesis device undergoes foreshortening, which causes distal end 708 to move proximally across cardiac conduction region 720. The movement of distal end 702 across cardiac conduction region 720 may damage cardiac conduction region 720, for example, by scratching. Taking the foreshortening of the aortic valve prosthesis device into account when computing the personalized safe zone may prevent or reduce risk of damage to the cardiac conduction region during deployment by expansion of the aortic valve prosthesis device.

[0300] Referring now back to FIG. 8, schematic 802 depicts a possible mechanism of damage to a cardiac conduction region 820 by distal displacement of an aortic valve prosthesis device 804 in an expanded state. Cardiac conduction region 820 may be defined as a line between a perforating bundle 806 (denoted B) and a branching point of the LBB 808 (denoted C). Cardiac conduction region 820 may be located on a floor of a membranous septum (MS) 810. A distal end 812 of aortic valve prosthesis device 804 in the expanded state may scratch membranous septum 810 during distal displacement, which may damage cardiac conduction region 820. Taking the possibility of distal displacement of the distal end of the aortic valve prosthesis device in the expanded state when computing the personalized safe zone may prevent or reduce risk of damage to the cardiac conduction region during deployment.

[0301] Referring now back to FIG. 3, at 310, the personalized safe zone is computed.

[0302] The personalized safe zone may be defined as a target region within the heart for placement of a defined portion of the aortic valve prosthesis device in a contracted state, such that during expansion and deployment of the aortic valve prosthesis device from the personalized safe zone, risk of damage to the cardiac conduction region by the aortic valve prosthesis device is reduced or prevented, and / or the personalized safe zone represents where the distal end of the aortic valve prosthesis device is to be positioned at an end of the transcatheter deployment (i.e., the deployed location of the distal end). Expansion of the aortic valve prosthesis device from the personalized safe zone may be predicted to deploy the aortic valve prosthesis device at a target deployment range. The deployment range may be defined, for example, based on clinical guidelines, operator experience, and / or manufacture recommendations. The personalized safe zone is selected for reducing or preventing damage to the conduction region from expansion and / or displacement and / or deployment of the aortic valve prosthesis device, by providing a safety margin of the aortic valve prosthesis device away from the conduction region and within a deployment range of the aortic valve.

[0303] The personalized safe zone denotes a region for placement of a defined portion of the aortic valve prosthesis device in a contracted state prior to expansion and deployment thereof. The defined portion of the aortic valve prosthesis device for placement within the personalized safe zone, from where expansion will occur, may be, for example, the distal end of the aortic valve prosthesis device, and / or one or more (e.g., radio-opaque) markers on the aortic valve prosthesis device. The markers may be located at the distal end or in proximity to the distal end of the aortic valve prosthesis device.

[0304] The personalized safe zone for transcatheter deployment of the aortic valve prosthesis device is computed at least as a function of the location of the annulus plane and the location of the conduction region. The personalized safe zone may further be computed to one or more parameters of the aortic valve prosthesis device, such as foreshortening during expansion (i.e., reduction in length) and / or final deployment diameter. The personalized safe zone may further be computed according to the target deployment range representing the desired location of deployment of the aortic valve prosthesis device (e.g., according to clinical guidelines and / or valve manufacturer guidelines) after expansion from an initial location.

[0305] For example, to place the aortic valve prosthesis device at the target deployment range after expansion, the personalized safe zone may be selected as the location where the distal end of the aortic valve prosthesis device is to be placed prior to expansion taking into account the foreshortening of the aortic valve prosthesis device. The personalized safe zone may be selected to be more distal than the target deployment range, but before the cardiac conduction region, such that during expansion, as the aortic valve prosthesis undergoes foreshortening, the distal end of the aortic valve prosthesis device does not or is less likely to damage the cardiac conduction region (e.g., by scratching) for arrival at the target deployment range once fully expanded.

[0306] Alternatively or additionally, the personalized safe zone may be computed according to one or more momentary stage of delivery of the aortic valve prosthesis device which may be depicted in 2D fluoroscopy images. Multiple personalized safe zones may be computed, and / or the personalized safe zone may by dynamically adapted according to the current momentary state of delivery, i.e., the current diameter of the aortic valve prosthesis device. The personalized safe zone may be computed according to a foreshortening relationship between a current diameter of the aortic valve prosthesis device and length reduction. The currently computed personalized safe zone may be dynamically updated on the overlay, as described herein. For example, for an initial momentary stage of delivery where the aortic valve prosthesis device is fully compressed the diameter / length is 9 / 75mm. An initial personalized safe zone is computed for the compressed aortic valve prosthesis device, and optionally presented as an overlay as described herein. In a subsequent image, a second momentary state of delivery is depicted where the aortic valve prosthesis device is partially expanded, having diameter / length of 12 / 70mm, i.e., note reduction in length of 5 mm in response to an increase in diameter of 2 mm. A second personalized safe zone is dynamically computed for the second momentary state of delivery and optionally presented as an overlay. In yet another subsequent image, a third momentary state of delivery is depicted where the aortic valve prosthesis device is further expanded, having diameter / length of 14 / 60mm, i.e., note further reduction in length of 10 mm in response to a further increase in diameter of 2 mm. A third personalized safe zone is dynamically computed for the third momentary state of delivery and optionally presented as an overlay. The dynamic computation of multiple personalized safe zones may be iteratively computed. Alternatively or additionally, the personalized safe zone may be computed according to the conduction angle for reducing likelihood of damage to the cardiac conduction region. A lower conduction angle may be associated with higher risk of damage to the conduction system. A lower conduction angle may indicate that the cardiac conduction region of the conduction system is located along a typical path of insertion of the aortic valve prosthesis device, increasing likelihood for conduction damage. A higher conduction angle may indicate that the cardiac conduction region of the conduction system is located further away along the typical path of insertion of the aortic valve prosthesis device, lowering likelihood for conduction damage. The conduction angle may be evaluated according to a threshold, for example about 5, 10, 20, 30, 40, or 50 degrees, or other values. A conduction angle above the threshold indicates lower likelihood of damage. A conduction angle above the threshold indicates higher likelihood of damage. In another example, likelihood of damage is inversely related to the conduction angle by a predefined function / curve.

[0307] Alternatively or additionally, the personalized safe zone may be defined according to a conduction annulus depth (CAD), which may be defined as a distance between the annulus plane and the cardiac conduction region. The CAD may be sufficiently large to reduce or prevent popping of the aortic valve prosthesis device out of the left ventricle outflow tract, for example, at least about 1-2 mm. When the CAD is greater than a threshold, the personalized safe zone may be defined between the annulus plane and the cardiac conduction region. The threshold may be, for example, about 1 millimeter (mm), or about 2 mm, or about 3 mm, or other values. The threshold may be preset, or computed for the subject, for example, based on analysis of anatomical landmarks of the heart on the CT scan. When the CAD is less than the threshold, the personalized safe zone may be defined as greater than a defined distance from the annulus plane that is greater than the threshold. For example, the personalized safe zone may be defined as greater than about 3 mm, or 4 mm (or other values) from the annulus plane, which is greater than the threshold of 2 mm.

[0308] Alternatively or additionally, the safe zone may be computed according to the anatomical data including shape and / or dimensions of a proximal aorta and / or a left ventricular outflow tract obtained from the reference image.

[0309] Alternatively or additionally, the safe zone may be computed according to a set of rules. The safe zone may be computed to satisfy a combination of the set of rules and other constraints described herein. Examples of rules which may be included in the set of rules:

[0310] • Implanting the aortic valve prosthesis device as close as possible to the annulus plane.

[0311] • Reducing or preventing scratching and / or shear forces applied by the aortic valve prosthesis device to the cardiac conduction region by predicting extent of downward or upward movement of the aortic valve prosthesis device in a partially expanded or fully expanded state.

[0312] • Implanting the aortic valve prosthesis device sufficiently below the annulus plane for preventing or reducing likelihood of migration and / or pop-out, optionally at the deployment range. The deployment range may be, for example, at least about 1 mm or 2 mm below the annulus plane.

[0313] • A final target placement of leaflets of the aortic valve prosthesis device to corresponding to a location of the native leaflets when the aortic valve prosthesis device is expanded from the personalized safe zone.

[0314] • Considering the relative axial device-tissue movement (e.g., either downward movement of the open aortic valve prosthesis device or an upward movement during expansion of the aortic valve prosthesis device (such as for a balloon expandable (BEV) device) or an open aortic valve prosthesis device downward movement in the case of SEV (Self Expandable Valves) to reduce or eliminate the potential scratching movement of the aortic valve prosthesis device over the cardiac conduction region (also referred to herein as BC segment) of the conduction system.

[0315] • Optimize the depth of the aortic valve prosthesis device to approximate native leaflet height as similar as possible to the aortic valve prosthesis device leaflets height. Referring now back to FIG. 9, schematic depicts a simplified diagram of an anatomy 900 of a heart of a subject, for example, as would appear on a 2D fluoroscopy image during deployment of an aortic valve prosthesis device. The simplified anatomy 900 includes a left ventricle (LV) 902, an ascending aorta 904, and an aortic valve 906 are depicted. A location of an annulus plane 910 is indicated. A location of a cardiac conduction system 912 is indicated. Cardiac conduction system 912 includes AV node (indicated by A) 914, perforating bundle (indicated by B) 916, and a branching point of the LBB (indicated by C) 918. A cardiac conduction region 920 may be indicated as a line between perforating bundle 916 and branching point 918. A location of the deployed aortic valve prosthesis device in the expanded state (i.e., open) within anatomy 900 is depicted, by indicating a proximal end 922 and a distal end 924. The location indicates a desired location when the aortic valve prosthesis device is deployed. It is noted that a length of the aortic valve prosthesis device in the expanded state is marked ho, and a diameter is marked Do, as described with reference to FIG. 6. The safe zone may be computed, according to the location of annulus plane 910, portions of cardiac conduction system 912 (e.g., cardiac conduction region 920), by taking into account foreshortening of the aortic valve prosthesis device, the desired location of the aortic valve prosthesis device when deployed and / or considerations described herein. The safe zone may be computed to reduce or prevent damage to one or more components of the cardiac conduction system 912 during deployment of the aortic valve prosthesis device, in order to reach the desired deployment location as shown, as described herein.

[0316] Referring now back to FIG. 10, schematic 1002 depicts a conduction annulus depth 1004, which is defined as a distance between an annulus plane 1008 of the native aortic valve, and a cardiac conduction region 1020. Cardiac conduction region 1020 may be defined as a line between a perforating bundle 1006 (denoted B) and a branching point of the LBB 1022 (denoted C). Cardiac conduction region 1020 may be located on a floor of a membranous septum (MS) 1010. There may be multiple computed CADs, computing as a distance between annulus plane 1008 and different parts of cardiac conduction region 1020. For example, one CAD 1012 denoted Hcl may be computed as a distance between annulus plane 1008 and perforating bundle 1006. Another CAD 1014 denoted Hc2 may be computed as a distance between annulus plane 1008 and branching point 1022. When cardiac conduction region 1020 is non-parallel with annulus plane 1008, CAD 1004 may be defined, for example, as the average distance, or distance to the closest point. The length of CAD 1004 and / or CAD 1012 and / or CAD 1014 may be used for determining the location of the personalized safe zone, as described herein.

[0317] At 312, when the aortic valve prosthesis device has not been selected prior to computing the personalized safe zone (e.g., as described with reference to 308), the aortic valve prosthesis having one or more parameters (e.g., as described with reference to 308) satisfying and / or enabling deployment of the aortic valve prosthesis at the personalized safe zone computed for the subject, may be selected. The aortic valve prosthesis device may be selected for placement of the defined portion of the selected aortic valve prosthesis (e.g., distal end thereof) at the personalized safe zone computed for the subject.

[0318] At 314, another image may be obtained.

[0319] The image may be obtained during a TA VI procedure for deployment of the aortic valve prosthesis device. The image may depict the aortic valve prosthesis device within or in proximity to the aortic valve.

[0320] The other image may be a 2D image, optionally a fluoroscopy image.

[0321] As used herein, the term 2D image and / or fluoroscopy image refers to the other image.

[0322] The other image may be different than the reference image. For example, the reference image is a 3D pre-procedure CT scan, and the other image is a 2D intra-procedure fluoroscopy image. Alternatively, the other image is the same as the reference image and / or of the same time as the reference image. For example, both images are fluoroscopy images.

[0323] At 316, the other image obtained with reference to 314 may be registered to the reference image obtained as described with reference to 302.

[0324] Optionally, the 2D fluoroscopy image is registered to the pre-procedure 3D image.

[0325] Registration may be performed, for example, by matching anatomical features detected on the fluoroscopy image to corresponding features detected on the pre-procedure image. The anatomical features may include, for example, calcification deposits, a pattern of calcification deposits, the aortic valve, cusps of the aortic valve, the ascending aorta, the septum, the left ventricle, and the like.

[0326] Optionally, the 3D pre-procedure image is projected to a 2D plane. The projection may include the annulus plane, nadir points, and / or components of the cardiac conduction system detected on the 3D image. The angle of the 2D plane may correspond to a viewing angle of the image sensor of the fluoroscopy machine that captured the fluoroscopy image. The projection of the 3D pre-procedure image to the 2D plane may be registered to the fluoroscopy image.

[0327] Alternatively, when the other image described with reference to 314 is the same as the reference image, no registration is needed.

[0328] Alternatively, when the other image described with reference to 314 is of the same type as the reference image, for example, both images are fluoroscopy images, where the other image is obtained an amount of time after the reference image, registration may be performed. The registration may be simpler when the two image are obtained from the same viewing orientation of the image sensor that captured the images.

[0329] At 318, an overlay over the fluoroscopy image may be generated.

[0330] The overlay may include features identified in the pre-procedure image, which are mapped to the intra-procedure image (e.g., the 2D fluoroscopy image), such as the nadirs of cusps of the aortic valve, and / or portions of the conduction system, which were identified on the pre-procedure 3D image (e.g., CT scan).

[0331] Optionally, the location of the computed personalized safe zone is presented in the overlay.

[0332] Referring now back to FIG. 11, a fluoroscopy image 1102 is depicted with an overlay. The overlay may include one or more of: nadirs 1104A-C of the three cusps of the aortic valve, an annulus plane 1106 (shown as a circle) that intersects nadirs 1104A-C, an AV node 1108, a penetrating bundle 1110, a branching point of the left bundle branch 1112, and a cardiac conduction region 1114 (between penetrating bundle 1110 and branching point 1112). The overlay may include other detected features, for example, a bounding box 1116 indicating a pigtail catheter.

[0333] At 320, the fluoroscopy image may be further analyzed.

[0334] Optionally, the fluoroscopy image is analyzed for identifying a location of a defined portion of the aortic valve prosthesis device. The defined portion may be the distal end of the aortic valve prosthesis device. The defined portion that is detected may be used to position the aortic valve prosthesis device within the personalized safe zone.

[0335] The detected defined portion may be presented on the display, optionally within the overlay. For example, the detected defined portion may be visually enhanced by the overlay, such as colored, bolded, and / or within a bounding box. Presenting the defined portion of the aortic valve prosthesis device within the overlay may help the operator determine whether the defined portion is within the personalized safe zone.

[0336] Alternatively or additionally, the fluoroscopy image may presented within a user interface, which may be adjusted according to a certain view. The adjustment may be done, for example, manually based on user selection, and / or automatically according to an analysis of the stage of the procedure and / or features in the image. Examples of views include:

[0337] • Cardiac and breathing filtered image. Motion components due to the beating heart and / or breathing may be removed. The beating heart frequency and / or breathing frequency may be obtained by Kalman filter which may be filtered from the image. Motion due to the operator may be maintained. Additional exemplary details are for example, as described herein. • Annulus centric view. The image is repositioned by centering at the annulus.

[0338] • Centering on the conduction system and / or components thereof such as conduction system within the membranous septum.

[0339] • Annulus and conduction centric view.

[0340] • Zoom in of the distal end of the aortic valve prosthesis device with annulus centric view and cardiac filtered conduction axis.

[0341] At 322, an indication of whether the location of the detected defined portion of the aortic valve prosthesis device is within the personalized safe zone may be generated. The indication may be, for example, presented on the display and / or played as an audio message.

[0342] Referring now back to FIG. 14A, user interface 1402 may be created by overlaying one or more visual elements automatically detected and / or computed as described herein, over a fluoroscopy image 1404. The fluoroscopy image 1404 is obtained during the procedure and displayed to the user. The visual elements which may be identified and / or computed, and presented include:

[0343] • Nadir 1406A-C of the three cusps of the aortic valve.

[0344] • Virtual annulus 1408, which is intersects the three nadirs 1406A-C. Virtual annulus 1408, shown as a circle, may be represent a plane.

[0345] • Membranous septum floor 1410.

[0346] • Conduction system 1412 within the membranous septum.

[0347] • Safe zone 1414 defined between the virtual annulus 1408 and the membranous septum floor 1410. It is noted that safe zone 1414 may look approximately like a trapezoid.

[0348] • Distal end 1416 of the aortic valve prosthesis device. The distal end 1416 may be dynamically tracked during deployment. The distal end 1416 is to be maintained within the boundaries of safe zone 1414 throughout deployment, for minimizing or reducing risk to conduction system 1412, as described herein.

[0349] Referring now back to FIG. 14B, another user interface 1452 is presented. User interface 1452 may be created as an overlay over another fluoroscopy image 1454, for example, at a later stage of deployment where the aortic valve prosthesis device shown in FIG. 14A has been further expanded. Exemplary visual elements which may be identified and / or computed, and presented include:

[0350] • A virtual annulus 1458, which may be shown face-on, without parallax, appearing as a straight line.

[0351] • Membranous septum floor 1460.

[0352] • Conduction system 1462 within the membranous septum. • Safe zone 1464 defined within between virtual annulus 1458 and a line 1468 denoting a location that is about 1 millimeter (mm) above cardiac conduction system 1462 (in the fluoroscopic projection used in the fluoroscopic view of fluoroscopy image 1454). It is noted that safe zone 1464 may look approximately like a trapezoid.

[0353] • Distal end 1466 of the aortic valve prosthesis device. The distal end 1466 which may be dynamically tracked during deployment. Distal end 1466 of FIG. 14B is longer than distal end 1416 of FIG. 14A, indicating that the aortic valve prosthesis device has been expanded more in FIG. 14B than in FIG. 14A.

[0354] • The optimal location for implantation of the aortic valve prosthesis device may be such that the distal end 1466 is as close as possible to line 1468 (above line 1468), within the boundaries of safe zone 1464, for minimizing or reducing risk to conduction system 1462, as described herein.

[0355] Referring now back to FIG. 16, schematics 1602 and 1612 indicate computed distances between a MSF to an annulus plane (also referred to as MSF height) for defining the safe zone. Schematic 1602 depicts a MSF height 1604 of 7.06 millimeters (mm). MSF height 1604 is defined an annulus line 1606 and membranous septum floor 1608. Annulus line 1606 may be defined as a plane / line that inserts three nadirs of the leaflets of the aortic valve. MSF 1608 may be defined as a line between two conduction points (B and C as described herein), and / or between anterior position on membranous septum floor and posterior position on membranous septum floor. Schematic 1612 depicts a MSF height 1614 of -0.92 mm. It is noted that in schematic 1612, annulus line 1616 is below membrane septum floor 1618, in contrast to schematic 1602 where annulus line 1606 is above membranous septum floor 1608.

[0356] Referring now back to FIG. 3, at 324, features described with reference to 314-322 may be dynamically iterated for subsequent fluoroscopy images. For example, for each new image, or at a certain sampling rate (e.g., one image per second, or 3 images per second).

[0357] The iterations may dynamically update the overlay for real-time guidance of the aortic valve prosthesis device for deployment according to personalized safe zone.

[0358] Approaches described herein for computing the personalized safe zone for deployment of an aortic valve prosthesis device (i.e., delivered via a trans-catheter approach, for deployment by expansion) may be adapted for other devices inserted into the heart in proximity to and / or through the aortic valve. For example, for insertion of a guidewire. In another example, for performing a transseptal procedure in which the inter-atrial and / or inter-ventricular septum is punctured. For example, computing a personalized safe zone for a transseptal procedure is different than for the aortic valve prosthesis device. The personalized safe zone for the transseptal procedure may include two different regions. The first region being the area that is recommended to puncture for a specific case, and the second region is an area of risk that is not allowed to be punctured. The areas that are recommended to puncture may be based on procedure specific and / or patient specific requirements. The areas to puncture may be determined from the reference image, optionally in a preplanning step. For example, in a patient that is going for mitral clipping, the recommended area to puncture may be at a certain height above the area of the fossil valley and it may be predicted. The optimal puncturing area may be predicted in the preplanning step from the reference image and / or as part of the preplanning procedure process. For example, for a procedure for atrial appendage occlusion, the recommended area may be determined from the reference image during the preplanning step for a personalized planning of a procedure in a specific patient for using a specific device. The areas that are not recommended to puncture may be determined based on anatomical consideration. The area that is the number one risk factor during a transseptal procedure may be the area of the opposition of the alter with the right atrium. This area is considered very dangerous if punctured, since the patient may die during the procedure due to the puncture.

[0359] Referring now back to FIG. 15, the method enables mapping anatomical landmarks detected in the 3D image to the fluoroscopy image, optionally in real time during the procedure. For example, for computing and presenting the safe zone. The method may compensate for the subject’s breathing, heart rate, physician movements, and / or change in C-arm position, such that the presentation of the safe zone over the fluoroscopy image remains substantially constant.

[0360] The anatomical structure of the ascending aorta is exemplary and not necessarily limiting. Other anatomical structures may be used in addition to, or instead of, the ascending aorta.

[0361] At 1502, a reference 3D image of a subject is accessed. The 3D image depicts at least the ascending aorta. The 3D image may be a CT scan, optionally a cardiac CT scan. The reference 3D image may be obtained pre-procedure. The 3D image may be captured with contrast injected into the vasculature, to aid in detection of the ascending aorta.

[0362] Referring now back to FIG. 17, schematic 1702 may be computed from a 3D image, such as a pre-procedure CT scan. Schematic 1702 depicts a LV myocardium 1704, a non-coronary cusp (NCC) 1706 (of the aortic valve), and a right coronary cusp (RCC) 1708 of the aortic valve.

[0363] The following anatomical features may be automatically identified on the 3D image: NCC- RCC commissure 1710, AV node 1712, membranous septum 1714, anterior position on membranous septum floor 1716, and posterior position on membranous septum floor 1718. The membranous septum floor lies on the myocardium. The location of the conduction system and / or safe zone may be computed based on the detected anatomical features. Since the conduction system is not shown in a CT scan, the conduction system may be computed, identified and / or imaged using known correlation between gross anatomical structures (detected from CT scan) and the conduction system. The conduction system may be computed, identified and / or imaged by a trained machine learning model and / or heuristic models.

[0364] Referring now back to FIG. 15, at 1504, the ascending aorta is detected in the 3D image. The ascending aorta may be detected, for example, manually by a user, automatically by a trained machine learning model, and / or automatically by image processing approaches. A contour of the ascending aorta may be identified, such as the outer border defining the ascending aorta.

[0365] The detected ascending aorta may include the aortic root with aortic valve.

[0366] At 1506, one or more anatomical landmark are detected and / or computed on the 3D image. The anatomical landmarks may be used for computing the safe zone. Examples of the anatomical landmarks include: aortic annulus plane (e.g., plane intersecting three aortic valve leaflet nadirs), membranous septum, membranous septum floor (MSF), conduction system passing through the membranous septum, AV node location.

[0367] The 3D image may include a multi-series 3D imaging session, where multiple 3D images depicting at least the native aortic valve are captured at different phases of a cardiac cycle. A location of at least one of the following anatomical landmarks is detected in the 3D images depicting the different phases of the cardiac cycle: the membranous septum, commissures of the native aortic valve, nadirs of the native aortic valve, and a cardiac conduction region defined between a perforating bundle of a conduction system of the heart and a branching point of a left bundle branch (LBB) of the conduction system. The safe zone may be computed for each of the 3D images depicting the different phases of the cardiac cycle. The smallest safe zone may represent the safest safe zone over the cardiac cycle. The anatomical landmark(s) registered to the fluoroscopy image for presentation may include the smallest safe zone.

[0368] At 1508, a 2D fluoroscopy image is accessed. The fluoroscopy image depicts at least the ascending aorta. The fluoroscopy image is captured during the procedure, optionally while the aortic valve prosthesis device is located in the ascending aorta.

[0369] The fluoroscopy image may be analyzed to determine whether contrast is present in the ascending aorta or not (e.g., no contrast, or insufficient contrast such as contrast that has dissipated after the initial injection). The analysis may be done, for example, using image processing approaches based on pixel intensity values and / or by a trained machine learning model.

[0370] At 1510, for the fluoroscopy image with contrast, a contour of the ascending aorta is detected in the 2D fluoroscopy image. The contour may be detected, for example, by a trained machine learning model such as a neural network. The neural network may be trained on a training dataset of images with contrast in the ascending aorta, labelled with ground truth indications of the contour of the ascending aorta.

[0371] At 1514, a pose of a sensor that captured the 2D fluoroscopy image is obtained. The pose may be of the C-arm that includes the x-ray detector for capturing fluoroscopy images. The pose may be extracted from the fluoroscopy image, for example, by applying optical character recognition (OCR) to the fluoroscopy image. Alternatively or additionally, the pose is obtained to sensors and / or controllers that adjust the C-arm.

[0372] The pose may include, for example, current fluoroscopy camera angulation (C,L), position (L), zoom (Z), table height (T) relative to the fluoroscopy iso-center, and / or variations thereof.

[0373] At 1516, the ascending aorta depicted in the 3D image may be projected to a 2D plane according to the pose of the sensor. The 2D plane may represent the view of the ascending aorta depicted in the 3D image as seen from the pose of the sensor.

[0374] At 1518, a registration (e.g., function) for registering between the contour of the aorta of the 2D fluoroscopy image and the projection of the contour from the 3D image on the 2D plane, is computed.

[0375] The registration may be a mapping (e.g., function) from a 3D location (e.g., x,y,z) in the 3D image (e.g., CT scan) to a 2D location (e.g., x,y) within the fluoroscopy image.

[0376] Referring now back to FIG. 18, schematic 1802 depicts contour 1804 of an ascending aorta identified from the 2D fluoroscopy image of the subject, where the ascending aorta may include contrast. Contour 1806 of the ascending aorta is computed by projecting the contour of the ascending aorta identified in the 3D image (e.g., pre-procedure CT scan) to a 2D plane according to a pose of the image sensor (e.g., fluoroscopy imager) that captured the 2D fluoroscopy image. A registration may be computed between contour 1804 and 1806 for mapping other visual features of the 3D image to the 2D fluoroscopy image. The visual feature may include one or more of: an accessory catheter positioned in the heart, a medical tool (e.g., pacing wire), a pigtail catheter positioned in the heart, at least one calcification external to the heart, and at least one bone feature of a spine of the subject.

[0377] Referring now back to FIG. 19, in a fluoroscopy image 1902, a visual feature, such as a pigtail catheter or pacing wire, is automatically detected as indicated by detected box 1904. In another fluoroscopy image 1906 (or the same fluoroscopy image as image 1902), a contour 1908 of the aorta is detected. Fluoroscopy image 1906 includes injected contrast, for assisting with detection of contour 1908. A 3D rendering of aorta 1910 is created from the 3D image (e.g., preprocedure CT scan). Other anatomical features such as annulus line 1912 may be detected on the 3D image. The contour of the 3D rendering may be registered with contour 1908, for mapping the anatomical features such as annulus line 1912 to the fluoroscopy image, as described herein.

[0378] Referring now back to FIG. 15, at 1520, the registration is applied to the anatomical landmarks identified on the 3D image, for registering (e.g., mapping) the anatomical landmark(s) from the 3D image to the 2D fluoroscopy image. Examples of the anatomical landmarks include: aortic annulus plane (e.g., plane intersecting three aortic valve leaflet nadirs), membranous septum, membranous septum floor (MSF), and conduction system passing through the membranous septum, AV node location.

[0379] At 1522, the anatomical landmark(s) registered to the 2D fluoroscopy image may be presented, for example, a visual indication representing the anatomical landmarks(s) (e.g., dot, line, icon) is overlaid on the fluoroscopy image.

[0380] Optionally, the safe zone is computed and presented as an overlay over the fluoroscopy image.

[0381] Other features may be presented within the fluoroscopy image, for example, the distal end of the aortic valve prosthesis device may be dynamically tracked and marked over the fluoroscopy image, optionally with reference to the safe zone. In another example, the pigtail and / or pacing wire and / or other catheter may be detected and / or presented, for example, within a bounding box and / or visually marked using another marking.

[0382] The presented fluoroscopy image with overlays and / or markings enables the operator to view one or more of: the annulus line, the membranous septum floor, conduction system components, the safe zone, the distal end of the aortic valve prosthesis device, and / or other anatomical landmarks registered to the fluoroscopy image.

[0383] A region of interest of the fluoroscopy image may be zoomed in, for example, more than 2, or 5, or 10, or 20 times. The region of interest that is zoomed in may include the safe zone.

[0384] At 1524, one or more features described with respect to 1508 are iterated, for subsequent fluoroscopy images. The iterations may be dynamically performed for maintaining the presentation of the safe zone (or other presented features). Changes in c-arm position may be detected, and accommodated by re-computing the registration using the current pose.

[0385] Optionally, iterations are performed for a first 3D image captured at diastole and a second 3D image captured at systole. The anatomical landmark may include an aortic annulus plane and at least one of: membranous septum and a cardiac conduction region between a perforating bundle and a branching point of the left branch bundle. The safe zone may be defined between a location of the aortic annulus plane selected as a most inferior location of the first 3D image and the second 3D image, and a location of the membranous septum and / or cardiac conduction region selected as a most superior location of the first 3D image and the second 3D image.

[0386] Referring now back to FIG. 15, when no contrast or insufficient contrast is detected in the ascending aorta of the fluoroscopy image, the method follows 1512, and other features are adapted according.

[0387] At 1512, a pacing wire is detected in the fluoroscopy image. The pacing wire is located within the heart depicted in the fluoroscopy image. The pacing wire may pass through the inferior vena cava, to the right atrium, and into the right ventricle.

[0388] The pacing wire is selected as representing a visible object within the heart that is stable, serving as an anchor point for calculating the location of the contour of the ascending aorta when no contrast is present.

[0389] The pacing wire may be detected, for example, by trained machine learning model (e.g., neural network trained on images labelled with an indication of the pacing wire) and / or based on image processing approaches (e.g., pixel intensities, edge detection, and the like).

[0390] It is noted that the pacing wire is an example, and not necessarily limiting, as other objects may be used.

[0391] The presence of the pacing wire within the heart of the subject depicted in the 3D image may be simulated. The simulation may performed by simulating curvature of a resilient straight line due to the inferior vena cava, right atrium, and right ventricle.

[0392] Features described with reference to 1516-1518 are adapted accordingly.

[0393] At 1516, the pacing wire simulated within the 3D image is projected to a 2D plane according to the pose of the sensor.

[0394] At 1518, a registration (e.g., function_ for registering between the pacing wire detected in the 2D fluoroscopy image and the pacing wire projected from the 3D image to the 2D plane, is computed.

[0395] At 1520, the registration is used for registering the anatomical landmark(s) on the 3D image to the 2D fluoroscopy image, as described herein.

[0396] Alternatively or additionally to 1512, when lack of sufficient contrast in the ascending aorta in the 2D fluoroscopy image, is detected, a visual feature(s) is detected in the 2D fluoroscopy image. The visual feature(s) may exclude anatomical features of the native heart of the subject, such that the visual feature(s) are not impacted or less impacted by beats of the heart, for example, a pacing wire, a pigtail (or other accessory catheter) catheter positioned in the heart, at least one calcification external to the heart, and at least one bone feature of a spine of the subject. A location of the visual feature(s) is tracked over subsequent 2D fluoroscopy images, for computing a movement (e.g., vector, optical flow) of the visual feature in the subsequent 2D fluoroscopy images. The movement is applied to the anatomical landmark(s) in the subsequent 2D fluoroscopy images without contrast, to track the location of the anatomical landmarks when there is no contrast.

[0397] The movement of the location of the visual feature may be tracked over a time interval sufficiently long to include multiple cardiac cycles and / or multiple respiratory cycles. One or more of the following may be extracted: a first parameter indicating motion due to the cardiac cycles, a second parameter indicating motion due to the respiratory cycles, and a third parameter indicating motion due to the operator. The component of motion due to the cardiac cycles and / or due to the respiratory cycles may be removed from the anatomical landmarks presented in the fluoroscopy image. The motion due to the operator may be maintained. This may help the operator maneuver the aortic valve prosthesis device more accurately, without distractions from the motion due to the heart beating and / or breathing.

[0398] In the case of using a pigtail located in one of the aortic cusps, the following mathematical relationship may be used to compute the first, second, and / or third parameters:

[0399] Pigioc(t)= Al*Card(t)+A2*Resp(t)+A3*Opera(t)+Noise

[0400] Where:

[0401] Al A2 and A3 denote the first, second, and third model parameters,

[0402] Card(t), Restp(t) and Opera(t) denote function describing the cardiac motion, respiratory motion, and operator motion, and

[0403] Pigioc (t) denotes the predicted pigtail location computed by tracking the movement of the pigtail catheter over multiple fluoroscopy images.

[0404] Referring now back to FIG. 20, at 2002, a 3D image, such as pre-procedure CT image (e.g., CT cardiac scan) is obtained.

[0405] One or more visible features are detected within a 3D image (i.e., reference image) of a subject. The visible features may be detected within a detected region of interest (ROI), for example, the heart and / or a box defined around the heart. The visible features are selected to be visible on a 2D fluoroscopy image of the subject, for example, calcifications within the heart, calcifications external to the heart, calcifications external to the aorta, and bone (e.g., spine, ribs, sternum).

[0406] One or more anatomical landmarks are detected within the 3D image. The anatomical landmarks are different than the visible features. The anatomical landmarks may be used for computing the safe zone, for example, annulus line, membranous septum, and the like, as described herein. At 2004, for the 3D image, a signature is computed based on the visible features. The signature may be computed based on relative locations between the visible features and / or relative pixel intensities of the visible features. The pixel intensities may be Hounsfield units (HU). The relative location may be mathematically denotes as R(I,H)(x,y,z) where R denotes the reference image, i denotes the index number of the visible feature, and H denotes the relative HU of the visible feature. The relative location may be defined, for example, from a reference point in the 3D image (e.g., middle), as a first angle along the coronal- sagittal plane, and a second angle along the coronal-axial plane. For example, the signature may be represented as a graph, where nodes represent visible features, values of nodes represent the pixel values and / or location within the 3D image, and edges may represent relative locations between the visible features.

[0407] At 2006, visible features are detected on a 2D fluoroscopy image of the subject. The visible features detected on the fluoroscopy image may be selected to correspond to the visible features detected on the 3D image.

[0408] At 2008, a signature is computed for the 2D image. The signature of the 2D image is selected to correspond to the signature computed for the 3D image. The signature of the 2D image may be computed based on relative locations between the visible features and relative pixel intensities (e.g., relative opacifications). The pixel intensities may be mathematically defined as F(I, O)(a,b) where F denotes the fluoroscopy image, I denotes the visible feature index number, O denotes the average relative opacity of i visible feature.

[0409] At 2010, a transformation (e.g., function, matrix) is computed for transforming the signature of the 3D image to the signature of the 2D image (fluoroscopy image).

[0410] The transformation may include a conversion between the pixel intensities of the 3D image (e.g., HU) and the pixel intensities of the 2D image.

[0411] The transformation may be represented as G, such as G defines as the 2D projection of R at the first and second angles. G may be defined as G(a,b)= T(a,b)){R(I,H)(x,y,z)}. An optimization calculation process may be performed to find the best fit between G(a,b) and I(a,b).

[0412] At 2012, the transformation is applied for registering the anatomical landmarks from the 3D image to the 2D fluoroscopy image.

[0413] At 2014, the anatomical landmark(s) registered to the 2D fluoroscopy image may be presented, for example, a visual indication representing the anatomical landmarks(s) (e.g., dot, line, icon) is overlaid on the fluoroscopy image.

[0414] At 2016, one or more features described with reference to 2006-2014 may be iterated, for subsequent fluoroscopy images. The iterations may be dynamically performed for maintaining the presentation of the safe zone (or other presented features). Referring now back to FIG. 21, the method of generating a parallax free image of one or more features depicted in a 2D fluoroscopy image may be used for presenting a parallax free image of the safe zone and / or a distal end of an aortic valve prosthesis device, for real time guidance and / or deployment.

[0415] At 2102, a 3D image is access, optionally a CT scan, such as a pre-procedure cardiac CT scan.

[0416] One or more features are located within the 3D image. The features may be segmented. Each feature may be associated with CT derived information (CDI) indicating coordinates (e.g., x,y,z) of the location within the 3D image. Features may be automatically detected, for example, using machine learning models, image processing approaches, and / or other approaches as described herein for example, for detecting the MSF. The features may be for defining the safe zone between the aortic annulus and the membranous septum.

[0417] The features located within the 3D image may include an aortic valve prosthesis device, optionally a distal end thereof. The term aortic valve prosthesis device may refer to other objects which may be located, for example, a pigtail catheter, pacing wire, and the like. Such features are not part of the human anatomy, and may not be depicted in the 3D image. The location of such features may be simulated within the 3D image. A location of the aortic valve prosthesis device may be simulated within the 3D image according to an anatomy of the ascending aorta and / or aortic valve. This enables registering and / or projecting from the location of the aortic valve prosthesis device within the 3D image corresponding to the location on the 2D fluoroscopy, for creating the parallax free image.

[0418] The simulation may be done according to a model of the aortic valve prosthesis device that simulates physical forces applied by a curvature of the ascending aorta and the anatomy of the aortic valve that applies forces to position the aortic valve prosthesis device between the NCC and RCC. The simulation may be based on a simulated path of the aortic valve prosthesis device for arrival at the aortic annulus via the ascending aorta, given the aorta has a curvature which makes the path of the aortic valve prosthesis device to prefer to progress in contact with the lateral wall of the ascending aorta (i.e., the outer surface that have the least curvature of the many possible orientations of the implant while going through aorta). The simulation may include the path for aortic valve prosthesis device to cross a stenotic, usually calcified cusp. The simulation may be based on the observation that the aortic valve prosthesis device would usually try and keep its curvature when entering through the valve into the left ventricular outflow tract (EVOT). The aortic valve prosthesis device may be simulated for finding a space between two adjacent leaflets that are the closest to its path on the ascending aorta. The space is usually at a commissure between the NCC and RCC, that we may be located on the 3D image.

[0419] The simulated path (e.g., from outer curvature of aorta through near the space into the LVOT) may resolve a possible ambiguity in calculating an “inverse transform” from a 2D fluoroscopy image back to the 3D CT, making it possible to generate a synthetic view of the 3D volume from any selected angle.

[0420] At 2104, a 2D fluoroscopy image is accessed. The 2D fluoroscopy image is captured during the procedure, depicting at least the aortic valve and optionally the aortic valve prosthesis device.

[0421] It may be assumed that the 2D fluoroscopy image depicts parallax, since obtaining a parallax view is difficult, as discussed herein.

[0422] At 2106, the feature(s) corresponding to the features located on the 3D image, are located on the 2D fluoroscopy image.

[0423] At 2108, fluoroscopy derived information (FDI) may be extracted from the 2D fluoroscopy image. The FDI indicates the location of the feature(s) on the 2D fluoroscopy image and a pose of a sensor that captured the 2D fluoroscopy image. The pose may be of the C-arm. The pose may refer to angulation of the C-arm.

[0424] At 2110, a registration (e.g., function) for registering the 2D fluoroscopy image with the 3D image of a subject is computed. The registration may be based on the exemplary registration process described herein.

[0425] At 2112, a parallax free pose of the feature(s) depicted in the 3D image is computed.

[0426] The parallax free pose may be computed using a s-curve computed for the 3D image.

[0427] The s-curve may represent an amount of parallax as a function of pose (e.g., angulation) of the sensor.

[0428] There may be multiple parallax free poses that may be computed for the 3D image. The parallax free pose that is computed may be for the parallax free pose that is closest to the pose of the sensor (e.g., C-arm). The parallax free pose closest to the pose of the sensor may be computed based on a s-curve computed for the 2D fluoroscopy image.

[0429] The parallax free pose may be computed for each feature, optionally using a respective s- curve for each feature. Alternatively, the parallax free pose may be computed for multiple features, optionally, as an intersection of multiple s-curves, where each s-curve is for a respective feature.

[0430] Alternatively, the parallax free pose may be computed for a cusp overlap view where the NCC is on the left side and the RCC overlaps the LCC and located on the right side. At 2114, the registration is applied for projecting the feature(s) of the 3D image defined by the CDI to a 2D plane corresponding to the FDI, according to the computed parallax free pose. The registration is applied for generating a synthetic parallax free view (SPFV) of the features.

[0431] A synthetic version of the 2D fluoroscopy image may be generated. The feature(s) may be are mapped from the 2D fluoroscopy image to the 3D image using a reversal of the registration (e.g., function). The registration may be applied by projecting the 3D image including the mapped feature(s) to the 2D plane, for generating the synthetic version of the 2D fluoroscopy image.

[0432] A respective SPFV may be computed for each feature. Alternatively, a single SPFV is computed for multiple features.

[0433] The SPFV may be created for one or more cardiac phases of the cardiac cycle, such as diastole and / or systole.

[0434] The SPFV may be created for depicting a pigtail centric view.

[0435] At 2116, the SPFV of the feature(s) is provided for presentation.

[0436] The SPFV of the features may be presented as an overlay over the 2D fluoroscopy image, and / or presented separately from the 2D fluoroscopy image (e.g., on a different screen, and / or on a different window on the same screen).

[0437] Alternatively or additionally, the CDI and / or the FDI are presented, for example, on the same display as the SPFV and / or on a separate display, showing real time device depth relative to the location of the aortic annulus line (e.g., during systole) and the MSF (e.g., during diastole).

[0438] Referring now back to FIG. 22, SPFV 2202 is computed from a 2D fluoroscopy image 2204, as described herein. The features aortic annulus 2206, distal end 2208 of an aortic valve prosthesis device, and MSF 2210 are detected and / or otherwise computed on 2D fluoroscopy image 2204. SPFV 2202 depicting parallax free views is generated, as described herein. SPFV 2202 depicts parallax free views of aortic annulus 2216 corresponding to 2206, distal end 2218 corresponding to 2208, and MSF 2220 corresponding to 2210.

[0439] Referring now back to FIG. 21, at 2118, features described with reference to 2104-2116 may be iterated. The iterations may be in response to changes, for example, a change of the C- arm, displacement of the aortic valve prosthesis device, change of patient position, and the like.

[0440] Motion components due to cardiac and / or breathing may be removed, and / or motion due to the operator may be maintained, for example, as described herein.

[0441] An exemplary approach for automatic segmentation of the membranous septum from a 3D image is now described. The exemplary approach is based on segmenting the posterior border of the membranous septum and the anterior border (e.g., point) of the membranous septum. The AV node not may be segmented. The membranous septum sits between the tip of the septal muscle and connects to the aortic root. The floor of the membranous septum includes part of the conduction axis (His Bundle and / or perforating bundle).

[0442] The AV node may be segmented using the following exemplary approach: Identification of both hinges of the anterior cusps of the aortic valve and posterior cusps of the aortic valve, in a two chamber and / or three chamber view in NPR. Adjusting the parallel slice planes of the 3D image (e.g., CT scan that includes the parallel slice planes) to the superior edge of the hinges. Locating an area between the medial commissure of the mitral valve and the right atrium, optionally in a short axis view. The AV node may be annotated in close proximity to the atrial wall or the apex of the inferior pyramidal space (if clearly visible).

[0443] The posterior border of the floor of the membranous septum may be segmented using the following exemplary approach: Identification of the aortic annulus plane, such as by intersecting nadirs of the three cusps of the aortic valve (i.e., NCC, LCC, RCC). Identification of the membranous septum posterior border by identification of the roof of the inferoseptal recess in the short axis plane. Identification and optional annotation of an inferior area of the membranous septum adjacent to the roof of the inferoseptal recess, optionally in a long axis view.

[0444] The anterior point of the floor of the membranous septum may be segmented using the following exemplary approach: Performing clockwise rotation of each slice plane of the 3D image, optionally in a short axis, until the anterior edge of the membranous septum is identified, optionally in a long axis view. Annotation of a point between the inferior area of the membranous septum and the crest of the septum, optionally in the long axis view.

[0445] An exemplary approach for automatic segmentation of the membranous septum from a 3D image is now described. The 3D image may be a contrast enhanced cardiac CT scan. The 3D image may be segmented to identify the left and the right ventricles and the muscular ventricular septum between the ventricles. A tip of the muscular ventricular septum is identified and optionally marked for each slice of multiple slices of the 3D image, such as CT scan. A line connecting the superior point of the ventricular septal muscle through all the slices may be defined as the membranous septum floor. A sub-region within the line that includes the His bundle is identified within the membranous septum floor. The sub-segment may be defined between a first inferior about 10% or 20% or other percentage of the membranous septum floor to an end of the conduction path located at about 70%, or 80%, or 85%, or 90% of the length of the membranous septum floor.

[0446] Referring now back to FIG. 23, schematic 2302 depicts exemplary segmentations of a 3D image used for computing the safe zone. Segmentation 2304 represents the endocardium of the left ventricle. Segmentation 2306 represents the right ventricle, in particular, the endocardium. Segmentation 2308 represents the myocardium of the left ventricle. AV node 2310, penetrating bundle 2312, and branching bundle 2314, of the conduction system, are identified. The membranous septum used to compute the safe zone may be defined as a region 2316 between penetrating bundle 2312 and branding bundle 2314, where segmentation 2308 is minimal between segmentation 2304 and segmentation 2306, and is in the posterior slope of the LV myocardium notch shown with reference to FIG. 24. 2316 may represent an area of apposition of the right ventricle (RV) and the left ventricle (LV).

[0447] The membranous septum may be segmented, for example, using the following exemplary approach: identifying a region between the RV myocardium segmentation and the LV myocardium segmentation that includes a minimum spatially consistent distance between the RV myocardium and the LV myocardium. A length of a base of the region may be, for example, greater than about 0.8 mm, or 1mm, or 1.2 mm, and / or shorter than about 10 mm, or 12mm, or 14 mm, or other values. The thickness of membranous septum may be on the lower (possibly the lowest) percentile of distance between the segmentations of the LV and RV. Identifying an area defined as the edge of the LV myocardial segmentation that corresponds to the region of the left and right ventricles segmentation. Verifying that the identified area substantially matches a posterior down slope, optionally the notch, of the LV myocardium segmentation. Marking the path of the membranous septum floor that is included in the region of the LV myocardium segmentation apposition of the right ventricle to the left ventricle. Marking on the identified area the posterior down slope of left ventricle myocardium segmentation.

[0448] Referring now back to FIG. 24, the segmentation of the myocardium of left ventricle 2404 from a 3D image may is presented, optionally on a display. A notch in the left ventricle wall is indicated by dashed line 2406. The notch may be on the left ventricle myocardium segmentation, below the aortic root. The posterior down slope of the notch may be marked, for example, using a straight line with thickness and / or using a thick line (e.g., thickness is a function of the CT resolution and quality). AV node 2410, penetrating bundle 2412, and branching bundle 2414, are shown.

[0449] Referring now back to FIG. 25, schematic 2502 depicts another exemplary approach for segmentation of a membranous septum from a 3D image. A left ventricle myocardium base rim 2504 is identified. A first point 2506 and a second point 2508 are identified. An anterior myocardial notch 2510 is defined as passing between points 2506 and 2508. A space 2512 apart from first point 2506 is used to defined a start of a cardiac conduction 2514 region (also referred to as BC length) between a perforating bundle and a branching point of the left branch bundle. The cardiac conduction region 2514 passes through the membranous septum. Space 2512 may be, for example, about 0.8 mm, or 1 mm, or 1.2 mm, or other values. A box 2516 is defined. The dimensions of box 2516 may be a predefined width (e.g., about 0.8 mm, or 1 mm, or 1.2 mm), a predefined height (e.g., about 0.8 mm, or 1 mm, or 1.2 mm) and a length. The length may be computed as a predicted length of the cardiac conduction region with margin of error, for example, average of multiple subjects plus a standard deviation (e.g., about 0.5, 1, 1.5, or 2 standard deviations). Box 2516 may be positioned parallel to and a preselected distance (e.g., above 0.3 mm, or 0.5 mm, or 0.7 mm) above the left ventricle myocardial base rim. Box 2516 defines the location of the membranous septum.

[0450] Referring now back to FIG. 26, schematic 2602 depicts first line 2604 at the distal end of aortic valve prosthesis device 2606 within safe zone 2608. Aortic valve prosthesis device 2606 is passed through an aorta 2620. Schematic 2602 may be presented to a user on a display, optionally within a user interface, for assisting in deployment of the aortic valve prosthesis device 2606. The presentation on the display may be dynamically updated in real time. Schematic 2602 may help the reader understand relationships between different measurements which may be computed in real time, and / or used to generate alerts which may be presented on the display and / or played over speakers, and / or used to instruct a robot for automatically deploying .

[0451] Safe zone 2608 is defined between a second line 2610 denoting the location of the aortic annulus line / plane, and a third line 2612 defining the bottom of safe zone 2608, according to a location of the membranous septum, membranous septum floor, and / or a cardiac conduction region between a perforating bundle and a branching point of the left branch bundle. H 2614 denotes the thickness of safe zone 2608 between second line 2610 and third line 2612. It is noted that H may vary across the safe zone, when the safe zone is viewed as a trapezoid, as described herein. L 2616 denotes the distance between first line 2604 and second line 2610. D 2618 denotes the distance between first line 2604 and third line 2612. H = L+D when measured across a same axis at a same location.

[0452] The following exemplary instructions may be generated based on real time values of H, L, and D:

[0453] • Real time values of one or more of H, L, and D.

[0454] • Generating an alert when D below is below a threshold, for example, about 0.5 mm, or 0.7 mm, or 1mm, or 1.3 mm, or other values.

[0455] • Generating an alert when L is below a threshold, for example, about 1 mm, or 1.5mm, or 2 mm, or other values.

[0456] • Instructing to activate a mechanical brake (e.g., robot) to prevent further insertion of the aortic valve prosthesis device. • Instructing an operator and / or robot to insert the aortic valve prosthesis device such that D is within a range, for example, about 1 mm < D < about 2 mm.

[0457] • Instructing an operator and / or robot to insert the aortic valve prosthesis device such that about 1 mm (or other value) < D and maintain within the range of about 1.5 mm (or other value) < L < maximum { 1.5 mm (or other value), L}.

[0458] Referring now back to FIG. 27, decision tree 2702 depicting a method of treating a patient indicating where to place a distal end of an aortic valve prosthesis device being deployed in a heart of a subject, is presented. FIG. 27 may represent a set of rules for where to implant the distal end of the aortic valve prosthesis device according to the location of the perforating bundle and the branching point of the left bundle branch relative to the annulus plane.

[0459] At 2704, the decision tree begins. An aortic valve prosthesis device is delivered via a transcatheter approach in a contracted state to a heart of the patient, for example, over a guidewire. The aortic valve prosthesis device may include inflow struts with sharp end regions, which may pose an increased risk of damaging the cardiac conduction system.

[0460] The annulus plane, the perforating bundle, and the branching point of the left bundle branch, may be identified, for example, as described herein.

[0461] The annulus plane may be set as 0.

[0462] As used herein, “B” or “point B” may refer to the perforating bundle. Alternatively or additionally, “point B” may refer to The posterior inferior point where the His bundle reaches the membranous septum floor.

[0463] As used herein, “C” or “point C” may refer to the branching point of the left bundle branch. Alternatively or additionally, “point C” may refer to the anterior superior point on the membranous septum floor, where the His bundle branches.

[0464] Midpoint (mBC, or midpoint BC) refers to the middle between point B and point C.

[0465] As used herein, the term “above”, or <, is defined as proximally away from the heart (i.e., from the aortic valve towards the aorta) and / or towards an operator delivering the aortic valve prosthesis device along a path of a guidewire and / or catheter used to deliver the aortic valve prosthesis device. The term “below” or <, is defined as distally to an interior of the heart (i.e., from the aortic valve towards the interior of the left ventricle) and away from the operator.

[0466] The aortic valve prosthesis device is deployed in the heart, such that a distal end of the aortic valve prosthesis device is positioned according to the decision tree. The distal end may be maintained in position according to the decision tree during expansion of the aortic valve prosthesis device, and the distal end is deployed in the expanded state according to the decision tree. At 2706, the perforating bundle is determined to be located at or below the annulus plane.

[0467] At 2708, the distal end of the aortic valve prosthesis device is deployed at a level of the annulus plane.

[0468] Alternatively to 2706, at 2710, the perforating bundle is determined to be located above the annulus plane.

[0469] At 2712, the branching point of the left branch bundle is determined to be located at or below the annulus plane.

[0470] At 2714, the distal end is deployed within a range of about 0-1 millimeters (mm) above the perforating bundle.

[0471] Alternatively to 2712, at 2716, the branching point of the left branch bundle is determined to be located above the annulus plane.

[0472] At 2718, the distal end is deployed within a range of about 1-2 mm above the perforating bundle and within a range of about 0-1 mm above the branching point of the left branch bundle.

[0473] Various embodiments and aspects of the present disclosure as delineated hereinabove and as claimed in the claims section below find experimental support in the following examples.

[0474] EXAMPLES

[0475] Reference is now made to the following examples, which together with the above descriptions illustrate some embodiments in a not necessarily limiting fashion.

[0476] Inventor analyzed data of 229 patients that underwent TAVR to evaluate whether deployment in the personalized safe zone reduced risk of damage to the cardiac conduction system. An indication of whether a pacemaker was implanted post TAVR was used as a surrogate to indicate whether the cardiac conduction system was damaged or not during TAVR.

[0477] Referring now back to FIG. 28, graph 2802 presents a location of point B 2804 (i.e., perforating bundle), a location of point C 2806 (i.e., branching point of the left bundle branch), a location of a midpoint between BC 2808, and a device depth 2810 (i.e., location of a distal end of the aortic valve prosthesis device relative to an annulus plane 2812). The location is along an x- axis 2814 indicating distance from annulus plane 2812 marked as zero. An indication of whether a pacemaker was required or not (used as a surrogate indicating whether the cardiac conduction system was damaged or not) was recorded.

[0478] Following TAVR, 51 of the 229 patients (22.2%) developed AV block necessitating a pacemaker.

[0479] Table 6 below indicates that the pacemaker requirement odds were significantly lower if TAVR was implanted above the cardiac conduction system over the membranous septum than lower down the cardiac conduction system. Pacemaker requirement odds for implants below and above point B were 0.67 (95% CI [0.21-2.05]) and 0.152 (95% CI [0.09-0.24]), with below over above odds ratio of 4.45 (95% CI [2.33-8.68]); while absolute odds below and above point C were 0.41 (95% CI [0.08-1.92]) and 0.11 (95% CI [0.05-0.21]), with odds ratio of 3.74 (95% CI [1.74- 9.00]).

[0480] Table 6

[0481] Referring now back to FIG. 29, a graph 2902 presenting odds of lower and increased risk for a pacemaker (PPM) post TAVR for the group of patients included in the experiment.

[0482] Patients with the implanted device positioned above the conduction system landmarks (point B or C) experienced significantly lower odds of requiring a pacemaker (for each 1 mm above points B, C, and their midpoint: OR = 0.80, 95% CI [0.72-0.88], OR = 0.81, 95% CI [0.72- 0.89], and OR = 0.79, 95% CI [0.70-0.87], respectfully. Conversely, patients with the implanted device positioned below the conduction system landmarks (point B or C) experienced significantly higher odds of requiring a pacemaker (for each 1 mm below points B, C, and their midpoint: OR = 1.26 (95% CI [1.14-1.40], OR = 1.24 (95% CI [1.12-1.38]), and OR = 1.27 (95% CI [1.15-1.42]), respectfully).

[0483] Following the set of rules described with reference to FIG. 27, the 229 patient cohort data will look like as presented in Table 7: Adherence to the rules described with reference to FIG. 27 would have led to a significantly shallower device implantation (4.05 [SD 2.76] v 2.50 [SD 1.45], p = 0.0017), l-2mm (4.18 [SD 2.68) v 1.34 [SD 0.29], p < 0.0001), and 2-3mm rules (4.10 [SD 2.81] v 2.40 [SD 0.26], p < 0.0001), but not for the 3-4mm rule (3.97 [SD 2.89] v 3.34 [SD 0.31], p = 0.129). However, a deployment strategy based on the rules described herein with reference to FIG. 27 offered significantly deeper device implantation (at 2.50 [SD 1.45]) compared to l-2mm strategy (1.34 [SD 0.29]; p = 0.005429), similar device depth compared to 2-3mm strategy (2.40 [SD 0.26]; p = 0.7087); and shallowed device depth compared to 3-4mm strategy (3.34 [SD 0.31]; p = 0.03787).

[0484] Referring now back to FIG. 30, graphs 3002, 3004, 3006, and 3008 present incidences rates (%) of requiring a pacemaker implant post TAVR for different locations within the personalized safe zone. Regions 3010 indicate that a PPM was required post TAVR. Regions 3012 indicate that a PPM was not required post TAVR.

[0485] Referring now back to FIG. 31, a plot 3102 of predicted probability of requiring a pacemaker as a function of difference between point B and device depth, is presented. Plot 3102 indicates reduced risk of requiring a pacemaker with increasing difference between point B and device depth.

[0486] Referring now back to FIG. 32, graphs 3202, 3204, 3206, 3208, 3210, and 3212 present incidences rates (%) of requiring a pacemaker implant post TAVR for different locations within the personalized safe zone. Regions 3020 indicate that a PPM was required post TAVR. Regions 3022 indicate that a PPM was not required post TAVR.

[0487] The descriptions of the various embodiments of the present invention have been presented for purposes of illustration, but are not intended to be exhaustive or limited to the embodiments disclosed. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The terminology used herein was chosen to best explain the principles of the embodiments, the practical application or technical improvement over technologies found in the marketplace, or to enable others of ordinary skill in the art to understand the embodiments disclosed herein.

[0488] It is expected that during the life of a patent maturing from this application many relevant aortic valve prosthesis device will be developed and the scope of the term aortic valve prosthesis device is intended to include all such new technologies a priori.

[0489] As used herein the term “about” refers to ± 10 %.

[0490] The terms "comprises", "comprising", "includes", "including", “having” and their conjugates mean "including but not limited to". This term encompasses the terms "consisting of" and "consisting essentially of". The phrase "consisting essentially of" means that the composition or method may include additional ingredients and / or steps, but only if the additional ingredients and / or steps do not materially alter the basic and novel characteristics of the claimed composition or method.

[0491] As used herein, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" may include a plurality of compounds, including mixtures thereof.

[0492] The word “exemplary” is used herein to mean “serving as an example, instance or illustration”. Any embodiment described as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments and / or to exclude the incorporation of features from other embodiments.

[0493] The word “optionally” is used herein to mean “is provided in some embodiments and not provided in other embodiments”. Any particular embodiment of the invention may include a plurality of “optional” features unless such features conflict.

[0494] Throughout this application, various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0495] Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases “ranging / ranges between” a first indicate number and a second indicate number and “ranging / ranges from” a first indicate number “to” a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.

[0496] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements. Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. It is the intent of the applicant(s) that all publications, patents and patent applications referred to in this specification are to be incorporated in their entirety by reference into the specification, as if each individual publication, patent or patent application was specifically and individually noted when referenced that it is to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting. In addition, any priority document(s) of this application is / are hereby incorporated herein by reference in its / their entirety.

Claims

WHAT IS CLAIMED IS:

1. A computer implemented method of computing a personalized safe zone for transcatheter deployment of an aortic valve prosthesis device in a heart of a subject, comprising: identifying a location of an annulus plane of an aortic valve in at least one reference image; identifying a location of a cardiac conduction region of the heart in the at least one reference image; and computing the personalized safe zone for transcatheter deployment of the aortic valve prosthesis device, the personalized safe zone is between the location of the annulus plane and the location of the conduction region, wherein the personalized safe zone defines where a distal end of the aortic valve prosthesis device is at least one of: to be maintained during transcatheter deployment, and to be positioned at an end of the transcatheter deployment.

2. The computer implemented method of claim 1, wherein the location of the cardiac conduction region is identified as a floor of a membranous septum of the heart denoted as about 1-2 millimeters (mm) above a most inferior border of the membranous septum.

3. The computer implemented method of claim 1, wherein the location of the cardiac conduction region is identified as between a perforating bundle and a branching point of the left branch bundle of the conduction system of the heart.

4. The computer implemented method of claim 1, wherein the personalized safe zone is defined according to a conduction annulus depth (CAD) defined as distance between the annulus plane and the cardiac conduction region.

5. The computer implemented method of claim 4, wherein when the CAD is greater than a threshold, the personalized safe zone is defined between the annulus plane and the cardiac conduction region.

6. The computer implemented method of claim 5, wherein the threshold comprises about 2 millimeters.

7. The computer implemented method of any one of claims 4-6, wherein when the CAD is less than a threshold, the personalized safe zone is defined as greater than a defined distance from the annulus plane that is greater than the threshold.

8. The computer implemented method of any one of the preceding claims, wherein the personalized safe zone is defined as greater than about 3 millimeters from the annulus plane.

9. The computer implemented method of any one of the preceding claims, wherein the personalized safe zone denotes a region for placement of a defined portion of the aortic valve prosthesis device in a contracted state prior to expansion and deployment thereof.

10. The computer implemented method of any one of the preceding claims, wherein the personalized safe zone is further computed according to at least one parameter of the aortic valve prosthesis device for deployment in the subject.

11. The computer implemented method of claim 10, wherein the at least one parameter of the aortic valve prosthesis device includes a deployment range within the heart for positioning of the defined portion of the aortic valve prosthesis device when deployed.

12. The computer implemented method of claim 10 or claim 11, wherein the at least one parameter of the aortic valve prosthesis device includes an amount of foreshortening of a length of the aortic valve prosthesis device in the expanded state compared to the contracted state.

13. The computer implemented method of claim 1, wherein a plurality of safe zones are computed according to a plurality of momentary stages of delivery based on the foreshortening of the aortic valve prosthesis device as a function of a diameter of the aortic valve prosthesis device.

14. The computer implemented method of any one of claims 10-12, wherein the at least one parameter of the aortic valve prosthesis device includes at least one of: at least one dimension of the aortic valve prosthesis device in the expanded state, at least one dimension of the aortic valve prosthesis device in the compressed state, type and / or model of the aortic valve prosthesis device.

15. The computer implemented method of any one of the preceding claims, further comprising selecting an aortic valve prosthesis device having at least one parameter enabling placement of the defined portion of the selected aortic valve prosthesis device at the personalized safe zone computed for the subject.

16. The computer implemented method of any one of the preceding claims, further comprising: identifying a location of a defined portion of the aortic valve prosthesis device in at least one 2D fluoroscopy image captured during a TAVI procedure; and presenting an indication of whether the location of the defined portion of the aortic valve prosthesis device is within the personalized safe zone.

17. The computer implemented method of any one of the preceding claims, wherein the safe zone is selected according to a set of rules.

18. The computer implemented method of claim 17, wherein the set of rules define implanting the aortic valve prosthesis device as close as possible to the annulus plane.

19. The computer implemented method of claim 17 or claim 18, wherein the set of rules define reducing or preventing scratching and / or shear forces applied by the aortic valve prosthesis device to the cardiac conduction region by predicting extent of downward or upward movement of the aortic valve prosthesis device in a partially expanded or fully expanded state.

20. The computer implemented method of any one of claims 17-19, wherein the set of rules define implanting the aortic valve prosthesis device sufficiently below the annulus plane for preventing or reducing likelihood of migration and / or pop-out.

21. The computer implemented method of any one of claims 17-20, wherein the set of rules define a final target placement of leaflets of the aortic valve prosthesis device to corresponding to a location of native leaflets when the aortic valve prosthesis device is expanded from the personalized safe zone.

22. The computer implemented method of any one of the preceding claims, wherein the defined portion of the aortic valve prosthesis device for placement within the personalized safe zone comprises at least one of: a distal end of the aortic valve prosthesis device, and at least one marker disposed at or in proximity to the distal end of the aortic valve prosthesis device.

23. The computer implemented method of any one of the preceding claims, wherein the personalized safe zone is selected for reducing or preventing damage to the conduction region from expansion of the aortic valve prosthesis device and / or from deployment of the aortic valve prosthesis device, by providing a safety margin of the aortic valve prosthesis device away from the conduction region and within a deployment region of the aortic valve.

24. The computer implemented method of any one of the preceding claims, wherein the at least one reference image comprises a pre-procedure 3D image.

25. The computer implemented method of claim 24, further comprising: accessing at least one 2D fluoroscopy image during a TAVI procedure; registering the at least one 2D fluoroscopy image to the pre-procedure 3D image; and dynamically presenting the personalized safe zone as an overlay over the at least one 2D fluoroscopy image.

26. The computer implemented method of claim 25, further comprising dynamically adapting the personalized safe zone according to a momentary stage of delivery depicted in the at least one 2D fluoroscopy image, according to a foreshortening relationship between a current diameter of the aortic valve prosthesis device and length reduction.

27. The computer implemented method of any one of the preceding claims, further comprising: computing a conduction angle of the cardiac conduction region, relative to an aortic valve trigone location, wherein the personalized safe zone is further computed according to the conduction angle for reducing likelihood of damage, wherein when the conduction angle is below a threshold or lower, risk to the cardiac conduction region is increased, and when the conduction angle is above the threshold or higher, risk to the cardiac conduction region is decreased.

28. The computer implemented method of claim 27, wherein the conduction angle is computed between a first line and a second line, the first line is defined from a center of a virtual aortic annulus and a middle of a third line connecting a perforating bundle and branching point of a left branch bundle, the second line is measured from the center of the virtual aortic annulus to a nadir of the non-coronary cusp (NCC), and the virtual aortic annulus is defined as a circle or oval shaped plane having an outer circumference that intersects the nadirs of the NCC, the right coronary cusp (RCC), and the left coronary cusp (LCC).

29. The computer implemented method of claim 27, wherein the conduction angle is computed between a first line and a second line, the first line is defined from a center of a virtual aortic annulus and a middle of a third line connecting a perforating bundle and branching point of a left branch bundle, the second line is measured from the center of the virtual aortic annulus to a right trigone, and the virtual aortic annulus is defined as a circle or oval shaped plane having an outer circumference that intersects the nadirs of the NCC, the right coronary cusp (RCC), and the left coronary cusp (LCC).

30. The computer implemented method of any of the preceding claims, wherein the personalized safe zone is further computed according to anatomical data including shape and / or dimensions of a proximal aorta and / or a left ventricular outflow tract obtained from the at least one reference image.

31. A system for computing a personalized safe zone for transcatheter deployment of an aortic valve prosthesis device in a subject, comprising: at least one processor executing a code for: identifying a location of an annulus plane of an aortic valve in at least one reference image; identifying a location of a cardiac conduction region of the heart in the at least one reference image; and computing the personalized safe zone for transcatheter deployment of the aortic valve prosthesis device, the personalized safe zone is between the location of the annulus plane and the location of the conduction region, wherein the personalized safe zone defines where a distal end of the aortic valve prosthesis device is at least one of: to be maintained during transcatheter deployment, and to be positioned at an end of the transcatheter deployment.

32. The system of claim 31, wherein the location of the cardiac conduction region is identified as a floor of a membranous septum of the heart denoted as about 1-2 mm above a most inferior border of the membranous septum.

33. The system of claim 31, wherein the location of the cardiac conduction region is identified as between a perforating bundle and a branching point of the left branch bundle of the conduction system of the heart.

34. The system of claim 31, wherein the personalized safe zone is defined according to a conduction annulus depth (CAD) defined as distance between the annulus plane and the cardiac conduction region.

35. The system of claim 34, wherein when the CAD is greater than a threshold, the personalized safe zone is defined between the annulus plane and the cardiac conduction region.

36. The system of claim 35, wherein the threshold comprises about 2 millimeters.

37. The system of any one of claims 34-36, wherein when the CAD is less than a threshold, the personalized safe zone is defined as greater than a defined distance from the annulus plane that is greater than the threshold.

38. The system of any one of claims 31-37, wherein the personalized safe zone is defined as greater than about 3 millimeters from the annulus plane.

39. The system of any one of claims 31-38, wherein the personalized safe zone denotes a region for placement of a defined portion of the aortic valve prosthesis device in a contracted state prior to expansion and deployment thereof.

40. The system of any one of claims 31-39, wherein the personalized safe zone is computed according to at least one parameter of the aortic valve prosthesis device for deployment in the subject.

41. The system of claim 40, wherein the at least one parameter of the aortic valve prosthesis device includes a deployment range within the heart for positioning of the defined portion of the aortic valve prosthesis device when deployed.

42. The system of any one of claim 40 or claim 41, wherein the at least one parameter of the aortic valve prosthesis includes an amount of foreshortening of a length of the aortic valve prosthesis device in the expanded state compared to the contracted state.

43. The system of any one of claims 39-42, wherein a plurality of safe zones are computed according to a plurality of momentary stages of delivery based on the foreshortening of the aortic valve prosthesis device as a function of a diameter of the aortic valve prosthesis device.

44. The system of any one of claims 40-42, wherein the at least one parameter of the aortic valve prosthesis device includes at least one of: at least one dimension of the aortic valve prosthesis device in the expanded state, at least one dimension of the aortic valve prosthesis device in the compressed state, type and / or model of the aortic valve prosthesis device.

45. The system of any one of claims 31-44, further comprising code for selecting an aortic valve prosthesis device having at least one parameter enabling placement of the defined portion of the selected aortic valve prosthesis device at the personalized safe zone computed for the subject.

46. The system of any one of claims 31-45, further comprising code for: identifying a location of a defined portion of the aortic valve prosthesis device in at least one 2D fluoroscopy image captured during a TAVI procedure; and presenting an indication of whether the location of the defined portion of the aortic valve prosthesis device is within the personalized safe zone.

47. The system of any one of claims 31-46, wherein the safe zone is selected according to a set of rules.

48. The system of claim 47, wherein the set of rules define implanting the aortic valve prosthesis device as close as possible to the annulus plane.

49. The system of any one of claim 47 or claim 48, wherein the set of rules define reducing or preventing scratching and / or shear forces applied by the aortic valve prosthesis device to the cardiac conduction region by predicting extent of downward or upward movement of the aortic valve prosthesis device in a partially expanded or fully expanded state.

50. The system of any one of claims 47-49, wherein the set of rules define implanting the aortic valve prosthesis device sufficiently below the annulus plane for preventing or reducing likelihood of migration and / or pop-out.

51. The system of any one of claims 47-50, wherein the set of rules define a final target placement of leaflets of the aortic valve prosthesis device to corresponding to a location of native leaflets when the aortic valve prosthesis device is expanded from the personalized safe zone.

52. The system of any one of claims 31-51, wherein the defined portion of the aortic valve prosthesis device for placement within the personalized safe zone comprises at least one of: a distal end of the aortic valve prosthesis device, and at least one marker disposed at or in proximity to the distal end of the aortic valve prosthesis device.

53. The system of any one of claims 31-52, wherein the personalized safe zone is selected for reducing or preventing damage to the conduction region from expansion of the aortic valve prosthesis device and / or from deployment of the aortic valve prosthesis device, by providing a safety margin of the aortic valve prosthesis device away from the conduction region and within a deployment region of the aortic valve.

54. The system of any one of claims 31-53, wherein the at least one reference image comprises a pre-procedure 3D image.

55. The system of claim 54, further comprising code for: accessing at least one 2D fluoroscopy image during a TAVI procedure; registering the at least one 2D fluoroscopy image to the pre-procedure 3D image; and dynamically presenting the personalized safe zone as an overlay over the at least one 2D fluoroscopy image.

56. The system of claim 55, further comprising code for dynamically adapting the personalized safe zone according to a momentary stage of delivery depicted in the at least one 2D fluoroscopy image, according to a foreshortening relationship between a current diameter of the aortic valve prosthesis device and length reduction.

57. The system of any one of claims 31-56, further comprising code for: computing a conduction angle of the cardiac conduction region, relative to an aortic valve trigone location, wherein the personalized safe zone is further computed according to the conduction angle for reducing likelihood of damage, wherein when the conduction angle is below a threshold or lower, risk to the cardiac conduction region is increased, and when the conduction angle is above the threshold or higher, risk to the cardiac conduction region is decreased.

58. The system of claim 57, wherein the conduction angle is computed between a first line and a second line, the first line is defined from a center of a virtual aortic annulus and a middle of a third line connecting a perforating bundle and branching point of a left branch bundle, the second line is measured from the center of the virtual aortic annulus to a nadir of the non-coronary cusp (NCC), and the virtual aortic annulus is defined as a circle or oval shaped plane having an outer circumference that intersects the nadirs of the NCC, the right coronary cusp (RCC), and the left coronary cusp (LCC).

59. The system of claim 57, wherein the conduction angle is computed between a first line and a second line, the first line is defined from a center of a virtual aortic annulus and a middle of a third line connecting a perforating bundle and branching point of a left branch bundle, the second line is measured from the center of the virtual aortic annulus to a right trigone, and the virtual aortic annulus is defined as a circle or oval shaped plane having an outer circumference that intersects the nadirs of the NCC, the right coronary cusp (RCC), and the left coronary cusp (LCC).

60. The system of any of claims 31-59, wherein the personalized safe zone is further computed according to anatomical data including shape and / or dimensions of a proximal aorta and / or a left ventricular outflow tract obtained from the at least one reference image.

61. A computer implemented method of registering a 2D fluoroscopy image to a 3D image, comprising: accessing a 2D fluoroscopy image and a 3D image of a subject; identifying an anatomical structure in the 3D image, including a contour of the anatomical structure; identifying at least one anatomical landmark on the 3D image; identifying a contour of the anatomical structure in the 2D fluoroscopy image depicting injected contrast within the anatomical structure; extracting a pose of a sensor that captured the 2D fluoroscopy image; projecting the contour of the anatomical structure of the 3D image to a 2D plane according to the pose of the sensor; computing a registration for registering between the contour of the anatomical structure of the 2D fluoroscopy image and the projection of the contour on the 2D plane; applying the registration for registering the at least one anatomical landmark on the 3D image to the 2D fluoroscopy image; and presenting the at least one anatomical landmark registered to the 2D fluoroscopy image.

62. The computer implemented method of claim 61, wherein the anatomical structure includes an ascending aorta.

63. The computer implemented method of claim 61 , wherein the at least one anatomical landmark is used for computing the safe zone.

64. The computer implemented method of claim 61 , wherein the at least one anatomical landmark is used for displaying the safe zone.

65. The computer implemented method of claim 61, wherein the 3D image comprises a first 3D image captured at diastole and a second 3D image captured at systole, wherein the at least one anatomical landmark comprises an aortic annulus plane and at least one of: membranous septum and a cardiac conduction region between a perforating bundle and a branching point of the left branch bundle, and further comprising defining a safe zone between a location of the aortic annulus plane selected as a most inferior location of the first 3D image and the second 3D image, and a location of the membranous septum and / or cardiac conduction region selected as a most superior location of the first 3D image and the second 3D image.

66. The computer implemented method of claim 61, wherein the 3D image comprises a multi-series 3D imaging session, wherein a plurality of 3D images depicting at least the native aortic valve are captured at different phases of a cardiac cycle, further comprising: detecting a location of at least one of the following in the plurality of 3D images depicting the different phases of the cardiac cycle: the membranous septum, commissures of the native aortic valve, nadirs of the native aortic valve, and a cardiac conduction region defined between a perforating bundle of a conduction system of the heart and a branching point of a left bundle branch of the conduction system; computing a safe zone for each of the plurality of 3D images depicting the different phases of the cardiac cycle; computing a smallest safe zone using the plurality of 3D images, wherein the at least one anatomical landmark comprises the smallest safe zone.

67. The computer implemented method of claim 61, further comprising: detecting a medical tool located within the heart of the subject depicted in the 2D fluoroscopy image; simulate presence of the medical tool within the heart of the subject depicted in the 3D image; extracting a pose of a sensor that captured the 2D fluoroscopy image; projecting the medical tool of the 3D image to a 2D plane according to the pose of the sensor; compute a registration for registering between the medical tool of the 2D fluoroscopy image and the medical tool of the 2D plane; applying the registration for registering the at least one anatomical landmark on the 3D image to the 2D fluoroscopy image; and presenting the at least one anatomical landmark registered to the 2D fluoroscopy image.

68. The computer implemented method of claim 67, wherein the medical tool is located within the inferior vena cava, right atrium and right ventricle.

69. The computer implemented method of claim 61, further comprising: detecting a visual feature in the 2D fluoroscopy image, wherein the visual feature excludes anatomical features of the native heart of the subject;tracking a location of the visual feature in subsequent 2D fluoroscopy images; computing a movement of the visual feature in the subsequent 2D fluoroscopy images; and applying the movement to the at least one anatomical landmark in the subsequent 2D fluoroscopy images.

70. The computer implemented method of claim 69, further comprising detecting lack of sufficient contrast in the ascending aorta in the 2D fluoroscopy image.

71. The computer implemented method of claim 69, wherein the visual feature is selected from: an accessory catheter positioned in the heart, a pacing wire, a pigtail catheter positioned in the heart, at least one calcification external to the heart, and at least one bone feature of a spine of the subject.

72. The computer implemented method of claim 69, wherein the movement of the location of the visual feature is tracked over a time interval sufficiently long to include a plurality of cardiac cycles and / or a plurality of respiratory cycles, and further comprising at least one of: extracting a first parameter indicating motion due to the plurality of cardiac cycles, extracting a second parameter indicating motion due to the plurality of respiratory cycles, and extracting a third parameter indicating motion due to the operator; and removing the component of motion due to the plurality of cardiac cycles and / or due to the plurality of respiratory cycles from the at least one anatomical landmark presented in the fluoroscopy image, and maintaining the motion due to the operator.

73. A system for registering a 2D fluoroscopy image to a 3D image, comprising: at least one processor executing a code for: accessing a 2D fluoroscopy image and a 3D image of a subject; identifying an anatomical structure in the 3D image, including a contour of the anatomical structure; identifying at least one anatomical landmark on the 3D image; identifying a contour of the anatomical structure in the 2D fluoroscopy image depicting injected contrast within the anatomical structure; extracting a pose of a sensor that captured the 2D fluoroscopy image;projecting the contour of the anatomical structure of the 3D image to a 2D plane according to the pose of the sensor; computing a registration for registering between the contour of the anatomical structure of the 2D fluoroscopy image and the projection of the contour on the 2D plane; applying the registration for registering the at least one anatomical landmark on the 3D image to the 2D fluoroscopy image; and presenting the at least one anatomical landmark registered to the 2D fluoroscopy image.

74. The system of claim 73, wherein the anatomical structure includes an ascending aorta.

75. The system of claim 73, wherein the at least one anatomical landmark is used for computing a personalized safe zone for transcatheter deployment of an aortic valve prosthesis device in a heart of a subject.

76. The system of claim 75, wherein the at least one anatomical landmark is used for displaying the personalized safe zone.

77. The system of claim 73, wherein the 3D image comprises a first 3D image captured at diastole and a second 3D image captured at systole, wherein the at least one anatomical landmark comprises an aortic annulus plane and at least one of: membranous septum and a cardiac conduction region between a perforating bundle and a branching point of the left branch bundle, and further comprising defining a safe zone between a location of the aortic annulus plane selected as a most inferior location of the first 3D image and the second 3D image, and a location of the membranous septum and / or cardiac conduction region selected as a most superior location of the first 3D image and the second 3D image.

78. The system of claim 73, wherein the 3D image comprises a multi-series 3D imaging session, wherein a plurality of 3D images depicting at least the native aortic valve are captured at different phases of a cardiac cycle, further comprising: detecting a location of at least one of the following in the plurality of 3D images depicting the different phases of the cardiac cycle: the membranous septum, commissures of the native aorticvalve, nadirs of the native aortic valve, and a cardiac conduction region defined between a perforating bundle of a conduction system of the heart and a branching point of a left bundle branch of the conduction system; computing a safe zone for each of the plurality of 3D images depicting the different phases of the cardiac cycle; computing a smallest safe zone using the plurality of 3D images, wherein the at least one anatomical landmark comprises the smallest safe zone.

79. The system of claim 73, further comprising: detecting a medical tool located within the heart of the subject depicted in the 2D fluoroscopy image; simulating presence of the medical tool within the heart of the subject depicted in the 3D image; extracting a pose of a sensor that captured the 2D fluoroscopy image; projecting the medical tool of the 3D image to a 2D plane according to the pose of the sensor; computing a registration for registering between the medical tool of the 2D fluoroscopy image and the medical tool of the 2D plane; applying the registration for registering the at least one anatomical landmark on the 3D image to the 2D fluoroscopy image; and presenting the at least one anatomical landmark registered to the 2D fluoroscopy image.

80. The system of claim 79, wherein the medical tool is located within the inferior vena cava, right atrium and right ventricle.

81. The system of claim 73, further comprising: detecting a visual feature in the 2D fluoroscopy image, wherein the visual feature excludes anatomical features of the native heart of the subject; tracking a location of the visual feature in subsequent 2D fluoroscopy images; computing a movement of the visual feature in the subsequent 2D fluoroscopy images; and applying the movement to the at least one anatomical landmark in the subsequent 2D fluoroscopy images.

82. The system of claim 81, further comprising detecting lack of sufficient contrast in the ascending aorta in the 2D fluoroscopy image.

83. The system of claim 81, wherein the visual feature is selected from: an accessory catheter positioned in the heart, a pacing wire, a pigtail catheter positioned in the heart, at least one calcification external to the heart, and at least one bone feature of a spine of the subject.

84. The system of claim 81, wherein the movement of the location of the visual feature is tracked over a time interval sufficiently long to include a plurality of cardiac cycles and / or a plurality of respiratory cycles, and further comprising at least one of: extracting a first parameter indicating motion due to the plurality of cardiac cycles, extracting a second parameter indicating motion due to the plurality of respiratory cycles, and extracting a third parameter indicating motion due to the operator; and removing the component of motion due to the plurality of cardiac cycles and / or due to the plurality of respiratory cycles from the at least one anatomical landmark presented in the fluoroscopy image, and maintaining the motion due to the operator.

85. A computer implemented method of registering a 2D fluoroscopy image to a 3D image, comprising: identifying a plurality of visible features within a 3D image of a subject, wherein the plurality of visible features are selected to be visible on a 2D fluoroscopy image of the subject; for the 3D image, computing a first signature comprising relative locations between the plurality of visible features and relative pixel intensities; detecting the plurality of visible features on a 2D fluoroscopy image of the subject; for the 2D image, computing a second signature comprising relative locations between the plurality of visible features and relative pixel intensities; computing a transformation for transforming the first signature to the second signature; applying the transformation for registering at least one anatomical landmark on the 3D image to the 2D fluoroscopy image; and presenting the at least one anatomical landmark registered to the 2D fluoroscopy image.

86. The computer implemented method of claim 85, wherein the transformation further comprises converting between the pixel intensities of the 3D image and the pixel intensities of the2D image.

87. The computer implemented method of claim 85, wherein the 3D image comprises a CT scan and the relative pixel intensities of the 3D image comprise Hounsfield units (HU).

88. A system for registering a 2D fluoroscopy image to a 3D image, comprising: at least one processor executing a code for: identifying a plurality of visible features within a 3D image of a subject, wherein the plurality of visible features are selected to be visible on a 2D fluoroscopy image of the subject; for the 3D image, computing a first signature comprising relative locations between the plurality of visible features and relative pixel intensities; detecting the plurality of visible features on a 2D fluoroscopy image of the subject; for the 2D image, computing a second signature comprising relative locations between the plurality of visible features and relative pixel intensities; computing a transformation for transforming the first signature to the second signature; applying the transformation for registering at least one anatomical landmark on the 3D image to the 2D fluoroscopy image; and presenting the at least one anatomical landmark registered to the 2D fluoroscopy image.

89. The system of claim 88, wherein the transformation further comprises converting between the pixel intensities of the 3D image and the pixel intensities of the 2D image.

90. The system of claim 88, wherein the 3D image comprises a CT scan and the relative pixel intensities of the 3D image comprise Hounsfield units (HU).

91. A computer implemented method of creating an image of at least one parallax free of at least one feature depicted in a 2D fluoroscopy image, comprising: computing a registration for registering the 2D fluoroscopy image with a 3D image of a subject, wherein the 3D image comprises a CT scan;wherein the at least one feature is located within the 3D image, and associated with CT derived information (CDI) indicating coordinates of the location within the 3D image; detecting the at least one feature on the 2D fluoroscopy image, and extracting fluoroscopy derived information (FDI) indicating the location of the at least one feature on the 2D fluoroscopy image and a pose of a sensor that captured the 2D fluoroscopy image; computing a parallax free pose of the at least one feature depicted in the 3D image that is closest to the pose of the sensor; applying the registration for projecting the at least one feature of the 3D image defined by the CDI to a 2D plane corresponding to the FDI, according to the parallax free pose for generating a synthetic parallax free view (SPFV) of the at least one feature; and providing the SPFV of the at least one feature for presentation.

92. The computer implemented method of claim 91, further comprising: mapping the at least one feature from the 2D fluoroscopy image to the 3D image using a reversal of the registration, and wherein applying the registration comprises projecting the 3D image including the mapped at least one feature to the 2D plane, for generating a synthetic version of the 2D fluoroscopy image.

93. The computer implemented method of claim 91, wherein the at least one feature comprises a distal and of an aortic valve prosthesis device, and further comprising simulating a location of the aortic valve prosthesis device within the 3D image according to an anatomy of the ascending aorta and / or aortic valve, wherein the registration is applied to a location of the aortic valve prosthesis device within the 3D image corresponding to the location on the 2D fluoroscopy.

94. The computer implemented method of claim 93, wherein the simulation is done according to a model of the aortic valve prosthesis device that simulates physical forces applied by a curvature of the ascending aorta and the anatomy of the aortic valve that applies forces to position the aortic valve prosthesis device between the NCC and RCC.

95. The computer implemented method of claim 91, wherein the parallax free pose is computed for each feature, and a respective SPFV is computed for each feature.

96. The computer implemented method of claim 91, wherein the parallax free pose is computed using a s -curve.

97. The computer implemented method of claim 91, wherein the parallax free pose is computed for a cusp overlap view where the NCC is on the left side and the RCC overlaps theLCC and located on the right side.

98. The computer implemented method of claim 91, wherein the parallax free pose is computed for a plurality of features, and a SPFV is computed for each feature.

99. The computer implemented method of claim 91, wherein the parallax free pose is computed as an intersection of a plurality of s-curves, each s-curve for a respective feature.

100. The computer implemented method of claim 91, wherein the SPFV of the at least one feature is presented as an overlay over the 2D fluoroscopy image.

101. The computer implemented method of claim 91, wherein the SPFV of the at least one feature is presented separately from the 2D fluoroscopy image.

102. The computer implemented method of claim 91, wherein the at least one feature includes at least one of: aortic annulus plane, membranous septum floor, and distal end of aortic valve prosthesis device.

103. The computer implemented method of claim 91, wherein a safe zone is defined between the aortic annulus and the membranous septum.

104. A system for creating an image of at least one parallax free of at least one feature depicted in a 2D fluoroscopy image, comprising: at least one processor executing a code for: computing a registration for registering the 2D fluoroscopy image with a 3D image of a subject, wherein the 3D image comprises a CT scan; wherein the at least one feature is located within the 3D image, and associated with CT derived information (CDI) indicating coordinates of the location within the 3D image; detecting the at least one feature on the 2D fluoroscopy image, and extracting fluoroscopy derived information (FDI) indicating the location of the at least one feature on the 2D fluoroscopy image and a pose of a sensor that captured the 2D fluoroscopy image;computing a parallax free pose of the at least one feature depicted in the 3D image that is closest to the pose of the sensor; applying the registration for projecting the at least one feature of the 3D image defined by the CDI to a 2D plane corresponding to the FDI, according to the parallax free pose for generating a synthetic parallax free view (SPFV) of the at least one feature; and providing the SPFV of the at least one feature for presentation.

105. The system of claim 104, further comprising: mapping the at least one feature from the 2D fluoroscopy image to the 3D image using a reversal of the registration, and wherein applying the registration comprises projecting the 3D image including the mapped at least one feature to the 2D plane, for generating a synthetic version of the 2D fluoroscopy image.

106. The system of claim 104, wherein the at least one feature comprises a distal and of an aortic valve prosthesis device, and further comprising simulating a location of the aortic valve prosthesis device within the 3D image according to an anatomy of the ascending aorta and / or aortic valve, wherein the registration is applied to a location of the aortic valve prosthesis device within the 3D image corresponding to the location on the 2D fluoroscopy.

107. The system of claim 106, wherein the simulation is done according to a model of the aortic valve prosthesis device that simulates physical forces applied by a curvature of the ascending aorta and the anatomy of the aortic valve that applies forces to position the aortic valve prosthesis device between the NCC and RCC.

108. The system of claim 104, wherein the parallax free pose is computed for each feature, and a respective SPFV is computed for each feature.

109. The system of claim 104, wherein the parallax free pose is computed using a s- curve.

110. The system of claim 104, wherein the parallax free pose is computed for a cusp overlap view where the NCC is on the left side and the RCC overlaps the LCC and located on the right side.

111. The system of claim 104, wherein the parallax free pose is computed for a plurality of features, and a SPFV is computed for each feature.

112. The system of claim 104, wherein the parallax free pose is computed as an intersection of a plurality of s-curves, each s-curve for a respective feature.

113. The system of claim 104, wherein the SPFV of the at least one feature is presented as an overlay over the 2D fluoroscopy image.

114. The system of claim 104, wherein the SPFV of the at least one feature is presented separately from the 2D fluoroscopy image.

115. The system of claim 104, wherein the at least one feature includes at least one of: aortic annulus plane, membranous septum floor, and distal end of aortic valve prosthesis device.

116. The system of claim 104, wherein a safe zone is defined between the aortic annulus and the membranous septum.

117. A computer implemented method for segmenting a membranous septum of a 3D image, comprising: identifying a left ventricle myocardium base rim; identifying a first point and a second point defining an anterior myocardial notch passing therebetween; identifying a first location spaced apart from the first point as a start of a cardiac conduction region between a perforating bundle and a branching point of the left branch bundle, passing through the membranous septum; defining a box having a predefined width, a predefined height and a length computed as a predicted length of the cardiac conduction region with margin of error; positioning the box parallel to and a preselected distance above the left ventricle myocardial base rim; wherein the box defines the location of the membranous septum.

118. The method of claim 117, wherein the predefined width is about 1 millimeter (mm), the predefined height is about 1 mm, the predefined length is obtained as an average of a length measured for a plurality of subjects and one standard deviation, and the preselected distance is about 0.5 mm.

119. A system for segmenting a membranous septum of a 3D image, comprising: at least one processor executing a code for: identifying a left ventricle myocardium base rim; identifying a first point and a second point defining an anterior myocardial notch passing therebetween; identifying a first location spaced apart from the first point as a start of a cardiac conduction region between a perforating bundle and a branching point of the left branch bundle, passing through the membranous septum; defining a box having a predefined width, a predefined height and a length computed as a predicted length of the cardiac conduction region with margin of error; positioning the box parallel to and a preselected distance above the left ventricle myocardial base rim; wherein the box defines the location of the membranous septum.

120. The system of claim 119, wherein the predefined width is about 1 millimeter (mm), the predefined height is about 1 mm, the predefined length is obtained as an average of a length measured for a plurality of subjects and one standard deviation, and the preselected distance is about 0.5 mm.

121. A computer implemented method for locating a membranous septum on a 3D image, comprising: for each slice of a plurality of slices of a 3D image; segmenting a left ventricle, a right ventricle, and a muscular intraventricular septum; and identifying a tip of the muscular intraventricular septum; identifying a path denoted by a line connecting a superior point of the muscular intraventricular septum through the plurality of slices; and detecting a sub-segment that includes a His bundle within the path, wherein the membranous septum floor is defined at the location of the sub-segment.

122. The computer implemented method of claim 121, wherein the sub-segment is defined between a first inferior about 10% of the membranous septum floor to an end of the conduction path located at about 90% of the length of the membranous septum floor.

123. The computer implemented method of claim 121, wherein sub-segment of the path is defined between about 20% and about 70%, 80% or 85% of a total length of the membranous septum floor.

124. The computer implemented method of claim 121, wherein the 3D image comprises a contrast enhanced cardiac CT.

125. A system for locating a membranous septum on a 3D image, comprising: for each slice of a plurality of slices of a 3D image; segmenting a left ventricle, a right ventricle, and a muscular intraventricular septum; and identifying a tip of the muscular intraventricular septum; identifying a path denoted by a line connecting a superior point of the muscular intraventricular septum through the plurality of slices; and detecting a sub-segment that includes a His bundle within the path, wherein the membranous septum floor is defined at the location of the sub-segment.

126. The system of claim 125, wherein the sub-segment is defined between a first inferior about 10% of the membranous septum floor to an end of the conduction path located at about 90% of the length of the membranous septum floor.

127. The system of claim 125, wherein sub-segment of the path is defined between about 20% and about 70%, 80% or 85% of a total length of the membranous septum floor.

128. The system of claim 125, wherein the 3D image comprises a contrast enhanced cardiac CT.

129. A computer implemented method of locating an atrioventricular (AV) node on a 3D image, comprising:identification of a first set of hinges of an anterior cusp of the aortic valve, and a second set of hinges of a posterior cusp of the aortic valve; adjusting a plurality of parallel slice plane of the 3D image to the superior edge of the first set of hinges and the second set of hinges; localizing an area between a medial commissure of the mitral valve and the right atrium; and detecting a location of the AV node in close proximity to an atrial wall or an apex of the inferior pyramidal space.

130. The computer implemented method of claim 129, wherein the first and second set of hinges are identified in a two chamber and / or a three chamber view in NPR.

131. The computer implemented method of claim 129, wherein the localizing of the area is performed in a short axis view.

132. A system for locating an atrioventricular (AV) node on a 3D image, comprising: at least one processor executing a code for: identification of a first set of hinges of an anterior cusp of the aortic valve, and a second set of hinges of a posterior cusp of the aortic valve; adjusting a plurality of parallel slice plane of the 3D image to the superior edge of the first set of hinges and the second set of hinges; localizing an area between a medial commissure of the mitral valve and the right atrium; and detecting a location of the AV node in close proximity to an atrial wall or an apex of the inferior pyramidal space.

133. The system of claim 132, wherein the first and second set of hinges are identified in a two chamber and / or a three chamber view in NPR.

134. The system of claim 132, wherein the localizing of the area is performed in a short axis view.

135. A computer implemented method of segmenting a floor of a membranous septum on a 3D image, comprising: detecting a posterior border of the floor of the membranous septum by: identifying an aortic annulus plane as a plane intersecting three nadirs of three cusps of the aortic valve; identifying of a roof of an inferoseptal recess in a short axis plane, wherein the roof denotes the posterior border of the membranous septum; identifying and annotating an inferior area of the membranous septum adjacent to the roof of the inferoseptal recess in long axis view; and detecting an anterior border of the floor of the membranous septum by: clockwise rotating each slice of a plurality of slices of a 3D image in a short axis until the anterior edge of the membranous septum is identified in the long axis view; and annotating the point between the inferior area of the membranous septum and the crest of the septum in long axis view.

136. A system for segmenting a floor of a membranous septum on a 3D image, comprising: at least one processor executing a code for: detecting a posterior border of the floor of the membranous septum by: identifying an aortic annulus plane as a plane intersecting three nadirs of three cusps of the aortic valve; identifying of a roof of an inferoseptal recess in a short axis plane, wherein the roof denotes the posterior border of the membranous septum; identifying and annotating an inferior area of the membranous septum adjacent to the roof of the inferoseptal recess in long axis view; and detecting an anterior border of the floor of the membranous septum by: clockwise rotating each slice of a plurality of slices of a 3D image in a short axis until the anterior edge of the membranous septum is identified in the long axis view; and annotating the point between the inferior area of the membranous septum and the crest of the septum in long axis view.

137. A computer implemented method of segmenting a floor of a membranous septum on a 3D image, comprising:segmenting a right ventricle endocardium (RV), a RV myocardium, a left ventricle (LV) endocardium, and a LV myocardium; identifying a region between the RV myocardium and the LV myocardium includes a minimum spatially consistent distance between the RV myocardium and the LV myocardium, wherein the membranous septum is segmented according to the region.

138. The computer implemented method of claim 137, further comprising: detecting a posterior down slope of a notch on the LV myocardium below an aortic root; and verifying that the region corresponds to the posterior down slope of the notch of the LV myocardium.

139. The computer implemented method of claim 137, further comprising: detecting a cardiac conduction region defined between a perforating bundle of a conduction system of the heart and a branching point of a left bundle branch (LBB) of the conduction system with the region, wherein the membranous septum is segmented according to the cardiac conduction region.

140. A system for segmenting a floor of a membranous septum on a 3D image, comprising: at least one processor executing a code for: segmenting a right ventricle endocardium (RV), a RV myocardium, a left ventricle (LV) endocardium, and a LV myocardium; identifying a region between the RV myocardium and the LV myocardium includes a minimum spatially consistent distance between the RV myocardium and the LV myocardium, wherein the membranous septum is segmented according to the region.

141. The system of claim 140, further comprising: detecting a posterior down slope of a notch on the LV myocardium below an aortic root; and verifying that the region corresponds to the posterior down slope of the notch of the LV myocardium.

142. The system of claim 140, further comprising: detecting a cardiac conduction region defined between a perforating bundle of a conduction system of the heart and a branching point of a left bundle branch (LBB) of the conduction system with the region, wherein the membranous septum is segmented according to the cardiac conduction region.

143. A method of treating a patient, comprising: delivering an aortic valve prosthesis device via a transcatheter approach in a contracted state to a heart of the patient; and deploying the aortic valve prosthesis device in the heart, such that a distal end of the aortic valve prosthesis device is positioned according to one of:(i) in response to a perforating bundle being located at or below an annulus plane of an aortic valve, deploying the distal end at a level of the annulus plane,(ii) in response to the perforating bundle being above the annulus plane and a branching point of a left branch bundle being located at or below the annulus plane, deploying the distal end within a range of about 0- 1 millimeters (mm) above the perforating bundle, and(iii) in response to the perforating bundle being above the annulus plane and the branching point of the left branch bundle being located above the annulus plane, deploying the distal end within a range of about 1-2 mm above the perforating bundle and within a range of about 0-1 mm above the branching point of the left branch bundle.

144. The method of claim 143, wherein the aortic valve prosthesis device includes inflow struts with sharp end regions.

145. The method of claim 143, wherein the distal end is maintained within (i), (ii), or (iii), during expansion of the aortic valve prosthesis device and the distal end is deployed within (i), (ii), or (iii).

146. The method of claim 143, wherein above is defined as proximally away from the heart and towards an operator delivering the aortic valve prosthesis device along a path of a guidewire and / or catheter used to deliver the aortic valve prosthesis device, and below is defined as distally to an interior of the heart and away from the operator.

147. The method of claim 143, further comprising identifying the annulus plane, the perforating bundle, and the branching point of the left bundle branch.

148. A method of treating a patient, comprising: delivering an aortic valve prosthesis device via a transcatheter approach in a contracted state to a heart of the patient; and deploying the aortic valve prosthesis device in the heart, such that a distal end of the aortic valve prosthesis device is positioned within a personalized safe zone; wherein the personalized safe zone is between a location of the annulus plane of an aortic valve of the patient and a location of the conduction region of the heart of the patient.

149. The method of claim 148, wherein the location of the cardiac conduction region is identified as a floor of a membranous septum of the heart denoted as about 1-2 millimeters (mm) above a most inferior border of the membranous septum.

150. The method of claim 149, wherein the location of the cardiac conduction region is identified as between a perforating bundle and a branching point of the left branch bundle of the conduction system of the heart.

151. The method of claim 149, wherein the personalized safe zone is defined according to a conduction annulus depth (CAD) defined as distance between the annulus plane and the cardiac conduction region.

152. The method of claim 151, wherein when the CAD is greater than a threshold, the personalized safe zone is defined between the annulus plane and the cardiac conduction region.

153. The method of claim 152, wherein the threshold comprises about 2 millimeters.

154. The method of any one of claims 151-153, wherein when the CAD is less than a threshold, the personalized safe zone is defined as greater than a defined distance from the annulus plane that is greater than the threshold.

155. The method of any one of claims 148-154, wherein the personalized safe zone is defined as greater than about 3 millimeters from the annulus plane.

156. The method of any one of claims 148-155, wherein the personalized safe zone denotes a region for placement of a defined portion of the aortic valve prosthesis device in a contracted state prior to expansion and deployment thereof.

157. A method of treating a patient, comprising: delivering an aortic valve prosthesis device via a transcatheter approach in a contracted state to a heart of the patient; and deploying the aortic valve prosthesis device in the heart, such that a distal end of the aortic valve prosthesis device is positioned as about 1-2 millimeters (mm) above a most inferior border of the membranous septum of the patient.

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