Patent Application
20230172575
The invention relates to a method for identifying an ischaemic region of an organ, a system for identifying an ischaemic region of an organ, a computer program for identifying an ischaemic region of an organ and a computer program product for identifying an ischaemic region of an organ based on arterial flow data, which provides clinically relevant information required for qualification for further surgical treatment.
A network of arteries encompasses the organ like an inverted river system, with the flow directed towards smaller vessels. The individual arteries split into smaller ones and supply the designated regions (volumes) of the organ like such an inverted river supply area. In the following description the term “supply area” corresponds to said region which is the inverse of the commonly understood definition of river supply region. The more distal (downstream, directed towards the end, as the blood flows) sections of the artery, or branches, cover correspondingly smaller regions of the organ corresponding to the location of an artery. For each point, on each artery, an area (a supply area) may be delineated that is supplied by the artery downstream said point, wherein the area comprises the supply area of an artery located directly downstream of a point at the artery, similar to an (inverted) river supply area.
The distribution of pressures in arteries results in flow towards smaller vessels, and thus distal pressures are lower than the pressure at the point where the artery leaves the aorta, with the difference being only minimal in normal vessels. If, due to a pathology, the diameter of the vessel does not match the size of the area supplied, for example as a result of arterial stenosis, said pressure difference increases. The pressure difference between the arterial outlet and the distal point may be gradual for less pronounced, but more extensive stenoses, or greater for tighter localised stenoses. It is assumed, for example for the cardiac arteries, that if the ratio between the pressure at the distal point (in practice downstream of the affected stenosis in the artery) and at the point where the artery leaves the aorta under conditions of maximum flow, the so-called fractional flow reserve (FFR), is less than or equal to 0.80, or less than or equal to 0.75, or less than or equal to 0.89 for the instantaneous wave-free ratio (iFR), this indicates ischaemia of the region supplied by the artery and is the basis for a decision to revascularise the artery.
Myocardial ischaemia is defined herein as a sufficiently important impairment of organ perfusion during hyperaemia (under conditions of minimal microcirculatory resistance) or stress that may be identified using established methods of assessing ischaemia such as: perfusion assessment using stress computed tomography or perfusion assessment using stress magnetic resonance or perfusion assessment using stress single-photon emission computed tomography (SPECT) or positron emission tomography (PET).
Attempts have been documented in the literature to determine, either in mass units, or, alternatively, as a percentage of the total heart mass, the region at risk of ischaemia of the myocardium based on the image of coronary arteries and the location of stenoses (paper “Incremental Value of Subtended Myocardial Mass for Identifying FFR-Verified Ischemia Using Quantitative CT Angiography: Comparison With Quantitative Coronary Angiography and CT-FFR”; doi.org/10.1016/j.jcmg.2017.10.027), where the region of myocardium supplied downstream of the stenosis is referred to for example as the “mass at risk” (region at risk), with the maximum stenoses corresponding to the minimum vessel lumen within the stenosis. In the studies available in the literature, the mass at risk thus defined is identified as an ischaemic region. However, it is not known whether a greater stenosis at a given point results in:
Document JP2018064967AA discloses a medical image processing device, a medical image processing method and a recording medium. In the solution, the occurrence of stenosis, with an associated ischaemic region is determined based on computed tomography (CT) data. The stenosis is then verified by measuring the flow in the vessel and determining values such as FFR. In this solution, the ischaemic region is estimated based on CT perfusion study, i.e., the ischaemic region is identified based on a test with additional contrast administration and additional scanning The results obtained allow for identifying the location to insert a bypass. The solution involves generating 2D and 3D heart images.
Document US20190318476A1 discloses a method and system for assessing vascular blockage based on machine learning. Methods and systems acquire, using coronary CT artery angiography (CCTA) method, a volumetric image dataset for the target organ that encompasses the vessel of interest. They extract the axial trajectory extending along the vessel of interest (VOI) in the volumetric image dataset and yield a three-dimensional (3D) multi-plane structured image based on the volumetric image dataset and the axial trajectory of the VOL Stenoses in vessels are classified accordingly based on the FFR value.
Patent description EP3041414B1 discloses a device, method, system and computer program for processing cardiac data for the purpose of imaging the heart of a living being. The processing device uses FFR values and myocardial perfusion values. The distribution of FFR values is identified based on 3D geometry of the coronary artery tree obtained from computed tomography angiography (CTA), and the perfusion value is determined based on spectral CT measurements. Both values are analysed for a match based on the distribution of FFR values and the distribution of myocardial perfusion values. The match, if found, confirms the reliability of the FFR data and allows for obtaining an accurate heart model. The display of combined FFR and perfusion information, performed as an additional test with contrast and additional scanning, allows the physician to better identify a critical stenosis. The systems and methods described can be used in CT angiography and myocardial perfusion imaging to evaluate patients with low to moderate risk ischaemic heart disease.
On the one hand, methods illustrating the distribution of arterial pressure that assess the pressure gradient across stenoses within an artery, in order to determine the presence or absence of ischaemia caused by the stenosis and to qualify the patient for revascularisation if the stenosis reaches a threshold gradient value are known from prior art. These methods include invasive methods that require additional arterial instrumentation to measure the fractional flow reserve (FFR) or iFR, as well as non-invasive methods based on simulations involving fluid mechanics or predicting (machine learning) pressure distributions based on images of the arteries and their stenoses obtained in a non-invasive test, such as computed tomography angiography (CT-FFR, FFR-CT) or invasive angiography (FFR-QCA).
On the other hand, methods for the so-called perfusion assessment of ischaemia, based on the evaluation of the ischaemic region of an organ, which do not require the knowledge of the anatomy of the coronary arteries, such as SPECT, PET, MRI, contrast echocardiography, which are based on imaging areas without contrast or radiotracer uptake usually under conditions of pharmacological or physiological stress (exercise) in the organ itself, such as the heart are also known. They allow an ischaemic region to be assessed in quantitative absolute terms (mass, volume) and relative terms (percentage of the volume or mass of the entire organ).
Using various techniques (either invasive or non-invasive), it is possible to determine the distribution of blood pressure in the arteries of various organs, such as the heart, taking into account the presence of arterial stenoses, and to identify at which point in the artery the pressure ratio between a particular point and the point where the artery leaves the aorta reaches the threshold value sufficient for the diagnosis of ischaemia. However, no methods are known for accurately identifying the region of organ ischaemia within the region at risk.
A method for identifying an ischaemic region of an organ based on anatomical data, comprising a step of acquiring data on the arterial tree of the organ and the shape of the organ and a step of identifying a threshold point in the artery at which a threshold indicative value is reached that corresponds to the ischaemia of the organ characterised in that it comprises the steps of:
Preferably, the step of identifying the arterial vessels of the organ and the volume of the organ is followed by the step of identifying the pressure distribution in the tested arteries relative to the pressure at a reference point.
Preferably, the ischaemic region is located at the most distal point relative to the threshold point in the artery.
Preferably, the measuring point is approx. 20 mm downstream of the threshold point.
Preferably, the ischaemic region represents 0.5 part of the stenosed region at risk downstream of the threshold point plus a ratio score of 0.1 to 0.05 of the difference between the indicating value at the threshold point and the indicating value at the measurement point.
Preferably, image data are acquired in the step of acquiring data.
Preferably, the step of acquiring data on the arterial tree and the shape of the target organ is performed by computed tomography angiography.
Preferably, the step of acquiring data on the arterial tree is performed by invasive angiography, and the shape of the target organ is reconstructed based on said data.
Preferably, the step of identifying the pressure distribution in the tested arteries is performed using an actual measurement.
Preferably, the step of identifying the pressure distribution in the tested arteries is performed using digital methods such as computer simulation.
Preferably, the reference point is the arterial outlet from the aorta or the reference point is the aortic sac.
Preferably, the indicative value is the flow fractional reserve value, and the threshold indicative value of the flow fractional reserve is equal to or less than 0.8.
Preferably, the flow fractional reserve value is obtained based on a computed tomography scan or a computer simulation.
Preferably, the indicative value is the ratio of the pressure at the threshold point to the pressure at the arterial outlet or the indicative value is the ratio of the pressure at the measuring point to the pressure at the arterial outlet.
Preferably, the step of qualifying an artery downstream of a threshold point of a stenosed region at risk is performed using at least one method from: a Voronoi diagram, a stem-and-crown model, an American Heart Association diagram.
Preferably, the step of identifying a stenosed region at risk is performed using a quantitative analysis of the volume of the stenosed region at risk.
Preferably, the step of identifying a stenosed region at risk is performed using a percentage analysis relative to total organ volume of the stenosed region at risk.
Preferably, the superimposing step is performed using a Voronoi diagram to visualise the ischaemic region.
A system for identifying ischaemic region of an organ based on anatomical data comprises a module for acquiring data on the arterial tree of the organ and the shape of the organ, and a module for identifying the threshold point in the artery at which the threshold indicative value corresponding to organ ischaemia is reached. The system comprises:
Preferably, the system further comprises a module for identifying the pressure distribution in the tested arteries, relative to the pressure at a reference point, located downstream of the module for identifying the arterial vessels of the organ and the volume of the organ.
Preferably, the module for acquiring data acquires image data.
Preferably, the module for acquiring data on the arterial tree and the shape of the target organ is performed by computed tomography angiography.
Preferably, the module for acquiring data on the arterial tree uses invasive angiography, and the shape of the target organ is reconstructed based on said data.
Preferably, the module for identifying the pressure distribution in the tested arteries uses actual measurements or uses digital methods, wherein preferably, the digital method is computer simulation.
Preferably, the module for qualifying an artery downstream of a threshold point of a stenosed region at risk uses at least one method from: a Voronoi diagram, a stem-and-crown model, an American Heart Association diagram.
Preferably, the module for identifying a stenosed region at risk uses quantitative analysis of the volume of the stenosed region at risk or uses a percentage analysis relative to the total organ volume of the stenosed region at risk.
Preferably, the superimposing module uses a Voronoi diagram to visualise the ischaemic region.
A computer program for identifying organ ischaemia, comprising instructions for performing the method according to any one of the steps of the method for identifying an ischaemic region of an organ.
A product of a computer program for identifying organ ischaemia, comprising a computer readable code performing the steps of the method according to any one of the steps of the method for identifying an ischaemic region of an organ.
The method according to the invention can be used to quantify the ischaemic region of an organ, such as the heart, based on recorded or simulated pressure distributions in the vessel tested and anatomical/geometrical data, i.e., images or simulated images of the organ tested. The added value of the method is the information on the size of organ ischaemia, which could constitute an important addition to the qualification for surgical treatment, such as of coronary artery disease.
According to the invention, the ischaemic region of an organ, such as the heart, extends in the supply area of a given artery downstream of the point where the pressure distribution reaches a threshold value diagnostic of ischaemia of the given organ, such as a value of 0.80 or 0.75 for invasive FFR measurement, FFR based on flow simulation or machine learning based on images of computed tomography of coronary arteries (CT FFR), or invasive angiography (QCA-FFR).
The method is innovative, as it introduces a new distinction, which is crucial for appropriate treatment, between the traditionally understood region at risk of ischaemia, i.e., downstream of the stenosis, and the stenosed region at risk downstream of the point where the value of pressure change exceeds the threshold value diagnostic of ischaemia of the organ in question, and the ischaemic region. Surprisingly, the Applicant found that in many cases the ischaemic region is much smaller than the region at risk, understood as both the region downstream of the stenosis and the region downstream of the point where the value of the pressure change exceeds the threshold value diagnostic of ischaemia of the organ in question (stenosed region at risk). The method allows for identifying the region of ischaemia of the organ tested, which, for example in the case of the heart, defines the indications for treatment by coronary revascularisation. Due to the anticipated widespread use of the virtual FFR in clinical practice, forming the basis of the described method, the solution according to the invention may be widely applicable. Additional analysis and identification of a smaller region of ischaemia may reduce the number of revascularisation procedures that will not be advantageous for the patient in terms of reducing the risk of myocardial infarction/death.
Approximately 5 million coronary revascularisation procedures are performed annually worldwide, and the trend is growing. If the recommendations of the cardiology societies regarding indications for revascularisation were followed, some of these procedures could be avoided. The method according to the invention can potentially reduce the indications for procedures given that, as regards stenoses in proximal sections of large vessels, it may indicate a smaller ischaemic region than is currently assumed. Showing the benefits of revascularisation in clinical trials only in patients with severe ischaemia as assessed by the method as above could result in the method as above being added to the guidelines.
In summary, the solution has the advantage of providing additional information that is clinically important for qualifying patients with arterial stenosis for further treatment.
The present description uses the following definitions:
The object of the invention is illustrated in the drawing, where:
In the embodiment illustrated in
The method then comprises extracting 20 the arterial vessels of the organ and identifying the volume of the organ. In another embodiment, the method also includes determining 21 the pressure distribution in the tested arteries, relative to the pressure at a reference point P0, wherein the reference point P0 is the point where the artery outlets from aorta, and in a further embodiment it is the aortic sac. The step of identifying 21 the distribution of pressures in the tested arteries is performed by means of actual measurement, and in another embodiment by digital methods such as computer simulation.
Then, following the step of extracting 20 the arterial vessels and optionally following the optional step of identifying 21 the pressure distribution, the method for identifying an ischaemic region On comprises identifying 30 the threshold point Pprog in the artery at which the threshold indicative value corresponding to organ ischaemia is reached, and the method comprises identifying the indicative value in the respective artery at the measuring point Ppom, such as approx. 20 mm downstream of the threshold point Pprog. In an embodiment, the indicative value corresponding to organ ischaemia is the fractional flow reserve, FFR, which has a threshold value equal to 0.8 or less. The FFR value is obtained based on the actual measurement and, in another embodiment, the FFR value is obtained from a computer simulation based on a computer tomography scan or invasive angiography scan. In another embodiment, the indicative value corresponding to organ ischaemia is the ratio of the pressure (or simulated pressure) at the threshold point Pprog to the pressure (or simulated pressure) at the arterial outlet, and in the following example, the indicative value is the ratio of the pressure (or simulated pressure) at the measuring point Ppom to the pressure (or simulated pressure) at the arterial outlet.
The subsequent step in the method is the step of qualifying 40 an artery downstream of the threshold point Pprog of the stenosed region at risk Oz being supplied, for example using the Voronoi diagram/method.
The method then comprises identifying 50 the stenosed region at risk Oz, for example using a quantitative analysis of the volume of the stenosed region at risk Oz, and in another embodiment by means of a percentage analysis relative to the total organ volume of the stenosed region at risk Oz.
Moreover, the present method involves calculating 60 the volume of the ischaemic region On as a part of the stenosed region at risk Oz. The ischaemic region On is located most distal to the threshold point Pprog in the artery and represents 0.2-1 part of the stenosed region at risk Oz downstream of the threshold point Pprog. The size of the ischaemic region On is proportional to the difference between the indicative value at the threshold point Pprog and at the measuring point Ppom. In an embodiment, the ischaemic region On represents 0.5 part of the stenosed region at risk Oz downstream of the threshold point Pprog plus a ratio score of 0.1 to 0.05 of the difference between the indicative value at the threshold point Pprog and the indicative value at the measuring point Ppom.
The final step of the present method is the step of superimposing 70 onto the image of the organ, acquired in the step of acquiring 10 data, the ischaemic region On of the muscle identified in the step of calculating 60. In one embodiment, the step of superimposing 70 is performed using a Voronoi diagram to visualise the ischaemic region On.
In another embodiment, the method can be used in practice as an additional imaging module overlay, such as CT-FFR, FFR-CT, FFR-QCA, invasive FFR, iFR.
For methods based on computed tomography (CT), the image of the heart acquired during the scan allows for accurate determination of its dimensions and the supply area of the individual arteries. Here, the method can further involve marking and identifying the ischaemic muscle including a calculation of its mass relative to that of the total organ. For FFR-QCA, or an invasive measurement such as FFR or iFR, in order to simulate an ischaemic region On, it is first required to create a virtual image of the left ventricle (based on ventriculography or the distribution of the coronary arteries alone) and then only to mark and identify the ischaemic muscle in the manner described above.
In another embodiment, the data of a CT coronary artery angiography scan in the form of DICOM files encoding spatial information on the shape and volume of the heart, including the myocardium and coronary arteries and their mutual spatial arrangement were transferred via external medium or network transfer to a station of a computational unit which:
volume of ischaemic region=(0.5+0.08)*OZ%,
where a factor of 0.58 was obtained as follows: the primary factor of 0.50 increases proportionally by 0.1 part for each 0.05 increase in the FFR value at the measuring point Ppom. Since the difference in FFR values at the threshold point Pprog and at the measuring point Ppom is 0.04, this means an increase of 0.08 in the primary factor to give a score of 20%. Then, in order to visualise the ischaemic region On, a point was sought on the stenosed artery for which the supply area corresponds to the calculated volume of the ischaemic region On. After marking this point using the Voronoi method, the software, such as CT Coronary Territories from Ziosoft identifies and displays the ischaemic region On.
In the embodiment wherein the step of identifying 20 the arterial vessels of an organ and the volume of an organ is followed by the step of identifying 21 the pressure distribution in the tested arteries, relative to the pressure at the reference point P0, the reference point P0 is identified at the arterial outlet from the aorta. The pressure distribution can be determined for example using computer simulation of the pressures, such as in the software “cFFR version 1.4, Siemens Healthcare GmbH”, or in conditions of actual measurement with a coronary artery pressure probe, such as Verrata® Pressure Guide Wire, placed at a given point in the artery, and the pressure at a reference point P0 identified at a guiding catheter, whose end is located at the arterial outlet.
In an embodiment wherein the step of identifying 50 a stenosed region at risk Oz is performed by quantifying the volume of the stenosed region at risk Oz, the myocardial volume is determined by visually identifying and extracting the myocardium based on three-dimensional images of the heart acquired using computer tomography, or by extraction using software such as CT Coronary Territories from Ziosoft.
The Applicant conducted an experiment in which 34 patients underwent coronary CT scanning, CT-FFR scanning/simulation, and CT (computed tomography) cardiac perfusion scanning using a vasodilator (adenosine or regadenoson). Based on the results, a reference ischaemic region On of the heart expressed as % of total myocardial mass was identified. In the patients studied, a number of points were marked on the stenosed coronary artery starting from the point of maximum stenosis (minimal lumen), in the distal direction of the artery, for which the corresponding “regions at risk” and the corresponding CT-FFR values were recorded. The results obtained were subjected to a proper analysis, which showed the following:
As an example, the results obtained show that the % (percentage) of the ischaemic muscle is equal to the % (percentage) of the stenosed area at risk Oz of the muscle (defined at the point where CT FFR assumes the value of 0.75) multiplied by a factor of 0.62 and to which a constant of 2.9 is added. In yet another embodiment, the % (percentage) of the ischaemic muscle is equal to the % (percentage) of the stenosed region at risk Oz of the muscle (defined at the point where CT FFR assumes the value 0.80) multiplied by a factor of 0.51 and to which a constant of 2.1 is added. In yet another embodiment, the % (percentage) of ischaemic muscle is equal to the averaged % (percentage) of the stenosed region at risk Oz of the muscle for a number of points, divided by the averaged FFR (CT FFR or iFR) value for said points (for values below the ischaemia threshold) multiplied by a factor of 0.49 to which a constant of 1.4 is added.
It generally follows from the embodiments above that the percentage of the ischaemic region On is on average a constant 0.50 (range 0.2-1) multiplied by the percentage (volume) of the stenosed muscle region, i.e., the stenosed region at risk Oz, identified for the point at which the FFR (or CT FFR or iFR) value varying along the vessel first takes at least the threshold value for the value diagnostic of organ ischaemia (for the heart≤0.80 or iFR≤0.89). Also, the volume of ischaemic muscle increases as the dynamics of the decrease in FFR (or CT FFR or iFR) value, i.e., the lower the FFR/CTFFR/iFR at the measuring point Ppom, the greater the percentage of ischaemic region On represents relative to the stenosed region at risk Oz identified downstream of the threshold point Pprog. The location of the ischaemic muscle represents the region having the volume (%) as calculated above and located most distally in the stenosed region at risk Oz.
In the embodiments, the Applicant has assumed that significant ischaemia is a region with at least 10% ischaemia, such as a stenosed region at risk Oz of muscle>11% downstream of the point for which the FFR (or CT FFR) is 0.75, or a stenosed region at risky Oz of muscle>17% downstream of the point for which the FFR (or CT FFR) is 0.80 (
In another embodiment, all of the steps of the method for identifying an ischaemic region On of an organ as described above may be performed by a computer programme for identifying ischaemia of an organ comprising instructions for performing said steps. In a further embodiment, all of the steps of the above-described method for identifying an ischaemic region On of an organ can be performed using a computer programme product comprising a computer readable code.
As shown in
In another embodiment, the system 100 further comprises module 21.1 for identifying the pressure distribution in the tested arteries relative to the pressure at a reference point P0, located downstream of the module 20.1 for identifying the arterial vessels of the organ and the volume of the organ.
In further embodiments of the system 100, module 10.1 for acquiring data on the arterial tree and target organ shape data acquires image data.
In other embodiments, module 10.1 for acquiring data on the arterial tree and target organ shape data uses computed tomography angiography or uses invasive angiography, wherein the target organ shape is reconstructed based on said data.
In another embodiment of the system 100, module 21.1 for identifying the pressure distribution in the tested arteries uses actual measurements.
In another embodiment of the system 100, module 21.1 for identifying the pressure distribution in the tested arteries uses digital methods, such as computer simulation.
In further embodiments of the system 100, module 40.1 for qualifying an artery downstream of a threshold point Pprog of a stenosed area at risk uses at least one method from: a Voronoi diagram, a stem-and-crown model, an American Heart Association diagram.
In another embodiment of the system 100, module 50.1 for identifying a stenosed region at risk Oz uses a quantitative analysis of the volume of the stenosed region at risk Oz, and in a further embodiment, module 50.1 for identifying the stenosed region at risk Oz uses a percentage analysis to the total organ volume of the stenosed region at risk Oz.
In another embodiment of the system 100, the superimposing module 70.1 uses the Voronoi diagram to visualise the ischaemic region On.
In one embodiment, the system 100 according to the invention is implemented on a processor in any server or PC type computing system.
In another embodiment, the system 100 comprises a processor and a memory for storing instructions that is coupled to the processor, wherein the execution of the instructions by the processor causes the processor to perform the steps of the above-described method for identifying an ischaemic region. The processor may be suitably configured to cause the software modules to perform the steps of the method for identifying an ischaemic region.
All embodiments of the method for identifying an ischaemic region of an organ On also refer to a system for identifying an ischaemic region of an organ, a computer program for identifying an ischaemic region of an organ, and a computer program product.
Each of the blocks of the diagram illustrating the method for identifying an ischaemic region and each of the blocks of the diagram of the system for identifying an ischaemic region can be implemented by computer program instructions. Such instructions may be provided to a processor of a general-purpose computer, a special purpose computer or another programmable data processing device, such that the instructions that are executed by the processor of the computer or another programmable data processing device allow for implementing the functions as defined in the method and system diagrams.
Aspects of the present invention may be implemented by a computer or devices such as a CPU (central processing unit) or MPU (memory protection unit) which read and execute a computer program product stored in a storage device for performing the functions of the embodiments described above. Aspects of the present invention may also be implemented by a method whose steps are performed by a computer of the system or device, such as by reading and executing a program stored on a storage device for performing the functions of the above-described embodiments. Accordingly, the computer program product is delivered to a computer, for example, via a network or another storage medium used as a storage device. The computer program product according to the invention further comprises a non-volatile machine-readable medium.
Embodiments herein are provided only as non-limiting guidelines for the invention and by no means do they limit the scope of protection as defined by the claims. It should be noted that any technical solution used in the invention can be implemented using equivalent technologies without departing from the scope of protection.
| Number | Date | Country | Kind |
|---|---|---|---|
| P.433612 | Apr 2020 | PL | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/PL2021/050028 | 4/21/2021 | WO |
