Method for analyzing intravascular information, system for analyzing intravascular information, and method for collecting information regarding patency, occlusion, and stenosis of blood vessel

Abstract

Provided are a method for analyzing intravascular information, a system for analyzing intravascular information, and a method for collecting information regarding patency, stenosis, or occlusion of a blood vessel, which are capable of continuously monitoring intravascular state information, detecting an intravascular abnormality, and preventing an adverse event through early detection of and rapid intervention for the intravascular abnormality. The present invention is: a method for analyzing intravascular information for acquiring information about patency, stenosis, or occlusion of a blood vessel, in which the intravascular pressure of the blood vessel is measured and analyzed to obtain a pressure waveform while an electrocardiogram is recorded, an analysis segment in the pressure waveform is determined on the basis of the electrocardiogram, the total value of the amplitudes of the pressure waveform in the analysis segment is defined as the time frequency amplitude (TFA), and an increase in the TFA is determined to indicate an increase in the risk of vascular occlusion; a system for analyzing the intravascular information; and a method for collecting information regarding patency, stenosis, or occlusion of the blood vessel.

Description

Intravascular information analysis method, intravascular information analysis system, and method for collecting information related to vascular patency, occlusion, and stenosis

[0001] The present invention relates to a method for analyzing intravascular information mainly concerning cerebral blood vessels and the like, and a method for collecting the information. This application claims priority based on U.S. Patent Application No. 63 / 788,831 provisionally filed in the United States on April 15, 2025 and U.S. Patent Application No. 63 / 875,330 provisionally filed in the United States on September 4, 2025, the contents of which are incorporated herein by reference.

[0002] Endovascular treatment is a treatment using a catheter and is widely performed in clinical practice. On the other hand, particularly during endovascular treatment of the nervous system, indwelling a catheter in a blood vessel or the like may rarely cause thrombus formation, leading to vascular occlusion or stenosis. Such unexpected occlusion or stenosis events may lead to complications such as cerebral infarction.

[0003] Early detection of these vascular occlusions and stenoses is extremely important because rapid intervention can minimize adverse events. At present, evaluation by angiography is the standard method for such early detection.

[0004] As an angiography technique, for example, Patent Document 1 discloses an image processing apparatus including an image acquisition unit capable of acquiring an image that includes at least an intravascular examination or treatment device as a subject. Further, in the image processing apparatus, the image acquisition unit acquires an X-ray image created based on X-ray absorptivity, which includes at least a blood vessel and the intravascular examination or treatment device as subjects, the region of interest acquisition unit accepts one or a plurality of regions including at least a part of the device included in the X-ray image as regions of interest, the tracking unit tracks each of the regions of interest in the X-ray image, and the notification unit notifies the user of the image processing apparatus when at least any one of the regions of interest satisfies a condition defined for each region of interest, and this also includes recording intraoperative operations to create a summary. This technique aims to provide an image processing apparatus, an image processing method, a program, and an image processing system that can provide a technique for allowing medical personnel to concentrate on the work at the target site and support the judgment of the target site in catheter examination or treatment of blood vessels.

[0005] Japanese Patent Publication No. 2024-138391

[0006] On the other hand, when attempting to detect vascular occlusion or stenosis early using angiography, intravascular information can only be obtained during the short period of time during contrast agent administration and radiation exposure, which carries the risk of overlooking unexpected vascular occlusion or stenosis. In other words, because observation is necessarily limited to short, intermittent periods, occlusion or stenosis that occurs between imaging sessions may not be detected. Furthermore, repeated angiography is often necessary to monitor rapidly changing intravascular conditions, such as the transition between occluded and open states after a thrombotic event, which increases both radiation exposure and contrast agent usage.

[0007] Therefore, a continuous monitoring modality that provides up-to-date intravascular status information is desired. Furthermore, the use of such modalities during intentional occlusion or procedures such as parental artery occlusion with coils or intravascular balloon dilation could potentially reduce radiation dose and contrast agent usage by providing up-to-date intravascular status without additional imaging, making such monitoring modality technology highly desirable. In addition, in settings such as pre-transport, emergency departments, and ICUs, it is desirable to be able to continuously assess the risk of vascular occlusion and stenosis non-invasively through percutaneous pressure waveform measurement.

[0008] This invention has been made in view of the above background, and its purpose is to provide a method for analyzing intravascular information, an intravascular information analysis system, and a method for collecting information on the opening, stenosis, or occlusion of blood vessels, which can continuously monitor intravascular condition information, detect intravascular abnormalities, and prevent adverse events through early detection and rapid intervention of intravascular abnormalities.

[0009] The present invention includes the following embodiments: [1] A method for analyzing intravascular information to obtain information on the opening, stenosis, or occlusion of a blood vessel, comprising: measuring the intravascular pressure of the blood vessel, analyzing the intravascular pressure to obtain a pressure waveform, recording an electrocardiogram, determining an analysis interval in the pressure waveform based on the electrocardiogram, defining the sum of the amplitudes of the pressure waveform in the analysis interval as time frequency amplitude (TFA), and determining that an increase in the TFA indicates an increased risk of vascular occlusion. [2] The method for analyzing intravascular information according to [1], wherein the intravascular pressure is measured by a pressure sensor connected to a catheter in the blood vessel or by a transcutaneous pressure sensor. [3] The method for analyzing intravascular information according to [1] or [2], wherein time-frequency analysis is performed on the pressure waveform, and the time-frequency components obtained by the time-frequency analysis are summed in the analysis interval and a predetermined frequency band to calculate the TFA. [4] The method for analyzing intravascular information according to [3], wherein the time-frequency analysis is one of continuous or discrete wavelet transform, short-time Fourier transform (STFT), S transform, Wigner-Ville distribution, or Hilbert-Huang transform. [5] The method for analyzing intravascular information according to [1] or [2], wherein the R-R interval in the electrocardiogram is considered as one heartbeat, and the pressure waveform is divided into sections for each heartbeat, and the analysis section is defined as the section from the first negative peak in the fourth derivative waveform of the pressure waveform to 30% of the total length of the pressure waveform. [6] The method for analyzing intravascular information according to any one of [1] to [5], wherein after obtaining the TFA with the first 4 to 10 heartbeats in the electrocardiogram in a state where the blood vessel is open as the analysis section, the data is further standardized using the median value of the TFA as a reference and the percentage change relative to that value, and the cutoff value and accuracy suitable for each of the multiple blood vessels are verified. [7] A method for analyzing intravascular information according to any one of items [1] to [6], wherein if the TFA is greater than a reference value, it is determined that there is an increased risk of vascular occlusion or stenosis. [8] A method for analyzing intravascular information according to item [7], wherein the reference value is the median of the TFA obtained using the first 4 to 10 heartbeats of the electrocardiogram in a state in which the blood vessel is open as the analysis interval.[9] A method for analyzing intravascular information according to any one of [1] to [8], wherein TFA is acquired in a plurality of analysis intervals, and the risk of vascular occlusion is determined based on the TFA acquired in the plurality of analysis intervals.

[10] A method for analyzing intravascular information according to [9], wherein the plurality of analysis intervals are analysis intervals for 2 to 10 heartbeats.

[11] A method for analyzing intravascular information according to claim [9] or

[10] , wherein the plurality of analysis intervals are analysis intervals for a plurality of consecutive heartbeats.

[12] A method for analyzing intravascular information according to

[11] , wherein the plurality of analysis intervals are analysis intervals for a plurality of consecutive heartbeats.

[13] A method for analyzing intravascular information according to

[11] , wherein if all of the plurality of TFA acquired in the analysis intervals for the plurality of consecutive heartbeats are greater than a reference value, it is determined that the risk of vascular occlusion has increased.

[14] A method for analyzing intravascular information according to any one of [1] to

[13] , wherein the blood vessel is a cerebral blood vessel.

[15] An intravascular information analysis system for obtaining information on the opening, occlusion, or stenosis of a blood vessel, comprising: an intravascular pressure wave meter device equipped with a pressure sensor or percutaneous pressure sensor connected to an intravascular catheter to measure intravascular pressure, and an analysis unit that analyzes the intravascular pressure obtained from the pressure sensor to obtain a pressure waveform; and an electrocardiogram analysis device that records an electrocardiogram, wherein the analysis interval in the pressure waveform is determined by the electrocardiogram, the sum of the amplitudes of the pressure waveform in the analysis interval is defined as time frequency amplitude (TFA), and an increase in the TFA is judged to be an increase in the risk of vascular occlusion.

[16] The intravascular information analysis system according to

[15] , wherein when determining the sum of the amplitudes, the time frequency components obtained by time frequency analysis are summed in a predetermined frequency band to calculate the TFA, and the TFA is calculated for each of a plurality of subbands obtained by dividing the frequency band into predetermined bandwidths.

[17] The intravascular information analysis system according to

[15] , wherein the R-R interval in the electrocardiogram is considered as one heartbeat, and the pressure waveform is divided for each of the aforementioned heartbeats, and the analysis interval is defined as the section from the first negative peak in the fourth derivative waveform of the pressure waveform to 30% of the total length of the pressure waveform.

[18] An intravascular information analysis system according to any one of

[15] to

[17] , wherein the TFA is obtained using the first 4 to 10 heartbeats of the electrocardiogram in a state where the blood vessel is open as the analysis interval, the data is standardized using the median value of the TFA as a reference and the percentage change relative to that value, and a cutoff value and accuracy suitable for each of the multiple blood vessels is verified.

[19] An intravascular information analysis system according to any one of

[15] to

[18] , wherein if the TFA is greater than a reference value, it is determined that there is an increased risk of vascular occlusion.

[20] An intravascular information analysis system according to

[19] , wherein the reference value is the median value of the TFA obtained using the first 4 to 10 heartbeats of the electrocardiogram in a state where the blood vessel is open as the analysis interval.

[21] An intravascular information analysis system according to any one of

[15] to

[20] , wherein the TFA is obtained in multiple analysis intervals and the risk of vascular occlusion is determined based on the TFA obtained in the multiple analysis intervals.

[22] The intravascular information analysis system according to

[21] , wherein the plurality of analysis intervals are analysis intervals for 2 to 10 heartbeats.

[23] The intravascular information analysis system according to

[21] or

[22] , wherein the plurality of analysis intervals are analysis intervals for a plurality of consecutive heartbeats.

[24] The intravascular information analysis system according to

[23] , wherein the plurality of analysis intervals are analysis intervals for a plurality of consecutive heartbeats.

[25] The intravascular information analysis system according to

[23] , wherein if all of the plurality of TFAs obtained in the analysis intervals for the plurality of consecutive heartbeats are greater than the reference value, it is determined that there is an increased risk of vascular occlusion.

[26] A method for collecting information relating to the opening, stenosis, or occlusion of blood vessels, comprising: step A, a step of determining an analysis interval in a pressure waveform obtained by analyzing the intravascular pressure of an individual's blood vessels, based on an electrocardiogram measured simultaneously with the intravascular pressure in the individual; and step B, a step of obtaining the sum of the amplitudes of the pressure waveforms in the analysis interval as TFA, wherein an increase in TFA indicates an increased risk of vascular occlusion in the individual.

[0010] The present invention provides a method for analyzing intravascular information, an intravascular information analysis system, and a method for collecting information on the opening, stenosis, or occlusion of blood vessels, which enable continuous monitoring of intravascular status information, detection of intravascular abnormalities, and prevention of adverse events through early detection and rapid intervention of intravascular abnormalities.

[0011] This figure shows basic information about the patients in this embodiment. This is another figure showing basic information about the patients in this embodiment. This figure shows detailed characteristics of the arteries and segments collected from the patients in this embodiment. This is another figure showing detailed characteristics of the arteries and segments collected from the patients in this embodiment. This is yet another figure showing detailed characteristics of the arteries and segments collected from the patients in this embodiment. This is yet another figure showing detailed characteristics of the arteries and segments collected from the patients in this embodiment. This is a schematic diagram showing the flow for the participating patients in this embodiment. This is a schematic diagram showing the flow for the R-R interval in this embodiment. This figure shows dynamic modulation of time-frequency amplitude in the 6-18 Hz band in the patients in this embodiment. This figure shows a case of a patient who underwent balloon-assisted coil embolization for an unruptured intracranial aneurysm in this embodiment. This figure shows a mixed model analysis of TFA values ​​in this embodiment. This is another figure showing a mixed model analysis of TFA values ​​in this embodiment. This is yet another figure showing a mixed model analysis of TFA values ​​in this embodiment. This figure shows the detection performance of occlusion events in the 6-18 Hz frequency band in this embodiment. This is another figure showing the detection performance of blockage events in the 6-18 Hz frequency band of this embodiment. This is a figure showing the detection performance of blockage events in the 6-10 Hz frequency band of this embodiment. This is another figure showing the detection performance of blockage events in the 6-10 Hz frequency band of this embodiment. This is a figure showing the detection performance of blockage events in the 10-14 Hz frequency band of this embodiment. This is another figure showing the detection performance of blockage events in the 10-14 Hz frequency band of this embodiment. This is a figure showing the detection performance of blockage events in the 14-18 Hz frequency band of this embodiment. This is another figure showing the detection performance of blockage events in the 14-18 Hz frequency band of this embodiment. This is a graph showing the analysis results of ROC for receiver operating characteristics analysis of this embodiment. This is a graph showing the analysis results of PRC for receiver operating characteristics analysis of this embodiment. This is a figure showing the detection performance of blockage events in the 6-18 Hz frequency band based on post-analysis of this embodiment. This is another figure showing the detection performance of blockage events in the 6-18 Hz frequency band based on post-analysis of this embodiment.This schematic diagram shows the correlation between vascular patency, stenosis, or occlusion in the test of this embodiment, and the waveform and TFA. The graph shows an example of a carotid artery pressure waveform.

[0012] The following describes embodiments of the method for analyzing intravascular information, the system for analyzing intravascular information, and the method for collecting information on the opening, stenosis, or occlusion of blood vessels according to the present invention. However, the present invention is not limited to the following embodiments. In this specification, "intravascular pressure" is not limited to pressure directly measured within a blood vessel, but includes pressure waveforms (including estimated values) acquired percutaneously that reflect intravascular pressure. In this specification, "intravascular information" is not limited to information directly acquired within a blood vessel, but includes information acquired percutaneously that reflects the opening, occlusion, or stenosis of blood vessels. In this specification, "time-frequency analysis" refers to an analysis that expands a signal into time and frequency components to obtain amplitude components or energy components associated with time and frequency, and includes, but is not limited to, continuous or discrete wavelet transforms, short-time Fourier transforms (STFTs), S-transforms, Wigner-Ville distributions, Hilbert-Huang transforms, etc. In this specification, "time frequency amplification (TFA)" refers to the value obtained by summing (integrating) the time-frequency components obtained by the time-frequency analysis over a predetermined analysis interval and frequency band.

[0013] [Method for Analyzing Intravascular Information] The method for analyzing intravascular information of this embodiment is a method for analyzing intravascular information to obtain information on the opening, stenosis, or occlusion of a blood vessel, and includes the steps of measuring the intravascular pressure of the blood vessel, analyzing the intravascular pressure to obtain a pressure waveform, recording an electrocardiogram, determining an analysis interval in the pressure waveform based on the electrocardiogram, defining the sum of the amplitudes of the pressure waveform in the analysis interval as time frequency amplitude (TFA), and determining that an increase in the TFA indicates an increased risk of vascular occlusion. In this embodiment, for example, the method measures the intravascular pressure of the blood vessel, analyzes the intravascular pressure to obtain a pressure waveform, determines an analysis interval in the pressure waveform based on heart rate information corresponding to the pressure waveform, performs time-frequency analysis on the pressure waveform, defines the sum of the amplitude components or energy components associated with time and frequency as TFA, and determines vascular occlusion or stenosis based on the change in TFA.

[0014] In this embodiment, the method for analyzing intravascular information can be broadly used to obtain information on patency, stenosis, or occlusion of blood vessels. In particular, it is preferable that the blood vessels are cerebral blood vessels. Obtaining information on cerebral blood vessels is particularly effective because it allows for early and continuous acquisition of vascular information during treatment of blood vessels in the nervous system, thereby effectively suppressing the occurrence of unexpected occlusion or stenosis events such as thrombosis and the resulting serious complications. In this embodiment, cerebral blood vessels broadly refer to blood vessels related to the brain organs and the nervous system adjacent to the brain. In this specification, "patency of blood vessels" means a state in which blood flow is sufficiently maintained. "Stenosis of blood vessels" means a state in which the lumen of a blood vessel is partially narrowed and blood flow is reduced but not completely interrupted. "Occlusion of blood vessels" means a state in which the lumen of a blood vessel is substantially blocked and blood flow is significantly reduced or stopped. These states are not limited to morphological findings and can be evaluated based on hemodynamic indicators.

[0015] The intravascular information analysis method of this embodiment includes elements for measuring intravascular pressure, analyzing the intravascular pressure, and obtaining a pressure waveform. Any means capable of measuring intravascular pressure can be used as the means for measuring the intravascular pressure of a blood vessel. For example, the intravascular pressure may be measured using a pressure sensor connected to a catheter placed inside the blood vessel during intravascular catheterization. Any type of catheter is acceptable; various catheters used in intravascular catheterization can be used as appropriate. For example, if the blood vessel is a cerebral blood vessel, it is preferable to use a catheter designed to facilitate access to cerebral or peripheral blood vessels, particularly an intermediate catheter (distal access catheter, DAC). The pressure sensor can be appropriately selected to measure intravascular pressure. For example, one provided in a known blood pressure pulse wave analyzer may be used. The pressure sensor may be connected to either a guiding catheter or an angiography catheter. The pressure sensor may also be obtained percutaneously.

[0016] The transcutaneous pressure sensor may be, for example, a tonometry sensor, a piezoelectric sensor, or a cuff-type sensor that is in contact with the skin surface over the carotid artery. The signal obtained from the transcutaneous pressure sensor does not necessarily need to provide the absolute value of intravascular pressure; it is sufficient if a pressure waveform shape (pulse wave) synchronized with the pulsation is obtained. The signal from the transcutaneous pressure sensor may be subjected to, for example, bandpass filtering and artifact removal of a predetermined bandwidth, and then normalized by percentage change using the median of TFA of multiple heartbeats immediately after attachment or in an open state as the reference value.

[0017] Next, the intravascular pressure is analyzed to obtain a pressure waveform. It is preferable that the analysis of the intravascular pressure to obtain a pressure waveform is performed by an analysis unit equipped with certain analysis functions. The elements for obtaining the pressure waveform may also be an intravascular pressure wave meter device equipped with the pressure sensor and the analysis unit. The intravascular pressure wave meter device is a type of blood pressure pulse wave analyzer that has the function of measuring, processing, and displaying intravascular pressure information. It is preferable that the intravascular pressure wave meter device can collect and analyze information such as systolic blood pressure, diastolic blood pressure, mean blood pressure, heart rate, and blood flow reserve ratio. Furthermore, the intravascular pressure wave meter may also be capable of analyzing electrocardiogram information and calculating proximal and distal intravascular pressure.

[0018] The intravascular information analysis method of this embodiment includes elements for acquiring the pressure waveform and recording an electrocardiogram. The electrocardiogram can be recorded using an electrocardiogram analysis device. As the electrocardiogram analysis device, it may be appropriately selected from various conventionally used electrocardiogram testing devices and systems.

[0019] The intravascular information analysis method of this embodiment includes an element in which an analysis interval in the pressure waveform is determined based on the electrocardiogram, and the sum of the amplitudes of the pressure waveform in the analysis interval is defined as the time frequency amplitude (TFA). For example, time-frequency analysis is performed on the pressure waveform, and the time-frequency components obtained by the time-frequency analysis are summed up in the analysis interval and a predetermined frequency band to calculate the TFA. The intravascular information analysis method of this embodiment includes each of the above elements, and includes a step in which, with respect to the TFA obtained by the element for obtaining the TFA, an increase in the TFA indicates an increase in the risk of vascular occlusion.

[0020] The time-frequency analysis can preferably be a continuous or discrete wavelet transform, a short-time Fourier transform (STFT), an S-transform, a Wigner-Ville distribution, or a Hilbert-Huang transform. More preferably, it can be a wavelet transform. When calculating the sum of the amplitudes, it is also preferable to calculate the TFA by summing the time-frequency components obtained by the time-frequency analysis in a predetermined frequency band, and then calculating the TFA for each of the multiple subbands obtained by dividing the frequency band into predetermined bandwidths. When calculating the sum of the amplitudes, it is also preferable to perform the time-frequency analysis using a wavelet transform and calculate the sum for each range of 4 to 12 Hz. Multiple combinations of these ranges may be used for the target frequency band. For example, when the target frequency band is 6 to 18 Hz, and the sum is calculated for each 4 Hz range, the sum may be calculated for each range of 6 to 10 Hz, 10 to 14 Hz, and 14 to 18 Hz. As an example of combining multiple methods, if the target frequency band is 6 to 18 Hz, the sum can be calculated for each 4 Hz range: 6 to 10 Hz, 10 to 14 Hz, 14 to 18 Hz, and 18 to 22 Hz; for each 8 Hz range: 6 to 14 Hz, 10 to 18 Hz, and 14 to 22 Hz; and for each 12 Hz range: 6 to 18 Hz and 10 to 22 Hz.

[0021] When determining the analysis interval in the pressure waveform based on the electrocardiogram, it is also preferable to divide the pressure waveform into segments based on the R-R interval in the electrocardiogram, with each segment representing one heartbeat, and define the analysis interval as a certain percentage of the total length of the pressure waveform, starting from the first negative peak in the fourth derivative waveform of the pressure waveform. This certain percentage can be selected from, for example, 20-40%. It is particularly preferable that the certain percentage is up to 30%. Specifically, the analysis interval is defined as a segment up to 30% of the total length of each pressure waveform, and the sum of the amplitudes defined within that segment is defined as TFA. Even for pressure waveforms acquired transcutaneously, characteristic points corresponding to reflected waves can be identified using the extreme values ​​or zero crossings of the derivative waveform. Therefore, the analysis interval can be set as a segment from the first trough of the fourth derivative up to a predetermined percentage. Note that with pressure waveforms acquired transcutaneously, the calculation of the derivative waveform may be unstable due to body movement or fluctuations in wearing pressure. In this case, the analysis interval may be a predetermined time window set based on the R wave of the electrocardiogram (for example, 0.05 to 0.25 seconds after the R wave, or a predetermined percentage of the total waveform length). This allows the TFA to be calculated independently of the differential waveform.

[0022] The method for analyzing intravascular information in this embodiment may further include the step of obtaining the TFA using the first certain number of heartbeats in the electrocardiogram when the blood vessel is open as the analysis interval, standardizing the data using the median value of the TFA as a reference and the percentage change relative to that value, and verifying a cutoff value and accuracy suitable for each of the multiple blood vessels. The first certain number of heartbeats in the electrocardiogram may be, for example, 4 to 10 heartbeats. The first certain number of heartbeats in the electrocardiogram is more preferably 5 to 8 heartbeats, and particularly preferably 5 heartbeats.

[0023] The intravascular information analysis method of this embodiment includes a step of determining that an increase in TFA indicates an increased risk of vascular occlusion. Here, an increase in TFA may be determined by an increase in the TFA value over time for a given blood vessel. Alternatively, it may be determined by an increase compared to the TFA measured when the blood vessel was open. An increased risk of vascular occlusion means that there is a high probability that the blood vessel will become occluded in the near future. In the intravascular information analysis method of this embodiment, it is preferable to determine that there is an increased risk of vascular occlusion when the TFA is greater than a reference value. Here, the reference value is, so to speak, the TFA value when the blood vessel is recognized as open. As for how to determine this reference value, for example, TFA may be measured using an open blood vessel, and one or more measured values ​​may be used as the basis. For example, the median (intermediate value) or average value of multiple measured values ​​may be used.

[0024] It is more preferable that the reference value is the median of the TFA obtained using the first 4 to 10 heartbeats in the electrocardiogram with the blood vessels open as the analysis interval.

[0025] In the intravascular information analysis method of this embodiment, it is also preferable to acquire TFA in a plurality of analysis intervals and to determine the risk of vascular occlusion based on the TFA acquired in the plurality of analysis intervals. The plurality of analysis intervals can be appropriately selected. For example, it is also preferable that the plurality of analysis intervals consist of 2 to 10 heartbeats. It is also preferable that the plurality of analysis intervals consist of a plurality of consecutive heartbeats. As the plurality of consecutive heartbeats, it is also preferable that the plurality of consecutive heartbeats consist of an analysis interval of 5 consecutive heartbeats. Furthermore, it is also preferable to determine that the risk of vascular occlusion has increased if all of the plurality of TFAs acquired in the analysis interval of the plurality of consecutive heartbeats are greater than the reference value.

[0026] [Intravascular Information Analysis System] The intravascular information analysis system is an intravascular information analysis system for acquiring information on the opening, stenosis, or occlusion of blood vessels, and comprises an intravascular pressure wave meter device equipped with a pressure sensor or percutaneous pressure sensor connected to an intravascular catheter to measure intravascular pressure, and an analysis unit that analyzes the intravascular pressure obtained from the pressure sensor to obtain a pressure waveform, and an electrocardiogram analysis device that records an electrocardiogram, wherein the analysis interval in the pressure waveform is determined by the electrocardiogram, the sum of the amplitudes of the pressure waveform in the analysis interval is defined as time frequency amplitude (TFA), and an increase in the TFA is judged to be an increase in the risk of vascular occlusion.

[0027] Regarding the configuration of the pressure sensor, analysis unit, intravascular pressure wave meter device, and electrocardiogram analysis device, the methods described above for analyzing intravascular information may be used as appropriate.

[0028] In this embodiment, when determining the sum of the amplitudes in the intravascular information analysis system, it is also preferable to perform time-frequency analysis using Wavelet transformation and calculate the sum for each range of 4 to 12 Hz.

[0029] In this embodiment, the intravascular information analysis system may also divide the pressure waveform into segments based on the R-R interval in the electrocardiogram, with each segment representing one heartbeat. The analysis segment may be defined as the interval from the first negative peak in the fourth derivative waveform of the pressure waveform to a certain percentage of the total length of the pressure waveform. The certain percentage may, for example, be 30%.

[0030] In this embodiment, the intravascular information analysis system obtains the TFA using the first 4 to 10 heartbeats of the electrocardiogram in a state where the blood vessel is open as the analysis interval. It is also preferable to standardize the data using the median value of the TFA as a reference and the percentage change relative to that value, and to verify the appropriate cutoff value and accuracy for each of the multiple blood vessels.

[0031] In this embodiment, the intravascular information analysis system may also determine that there is an increased risk of vascular occlusion when the TFA is greater than a reference value. It is also preferable that the reference value is the median value of the TFA obtained using the first 4 to 10 heartbeats of the electrocardiogram in a state where the blood vessel is open as the analysis interval.

[0032] The intravascular information analysis system of this embodiment also preferably acquires TFA in a plurality of analysis intervals and determines the risk of vascular occlusion based on the TFA acquired in the plurality of analysis intervals. It is also preferable that the plurality of analysis intervals consist of 2 to 10 heartbeats.

[0033] In this embodiment, it is preferable that the plurality of analysis intervals are analysis intervals for multiple consecutive heartbeats. It is also preferable that the plurality of analysis intervals are analysis intervals for five consecutive heartbeats. In this embodiment, it is also preferable to use the intravascular information analysis system to determine an increased risk of vascular occlusion when all of the multiple TFAs obtained in the analysis intervals for multiple consecutive heartbeats are greater than the reference value.

[0034] [Method for collecting information on patency, stenosis, or occlusion of blood vessels] The method for collecting information on patency, stenosis, or occlusion of blood vessels according to this embodiment includes: step A, which determines an analysis interval in the pressure waveform obtained by analyzing the intravascular pressure of an individual, based on an electrocardiogram measured simultaneously with the intravascular pressure in the individual; and step B, which obtains the sum of the amplitudes of the pressure waveform in the analysis interval as TFA, and determines that an increase in TFA indicates an increased risk of vascular occlusion in the individual.

[0035] Regarding the configuration of the elements for acquiring the pressure waveform, recording the electrocardiogram, and determining the analysis interval from these in step A, the methods described above for analyzing intravascular information may be used as appropriate. Regarding the elements acquired as TFA in step B, the methods described above for analyzing intravascular information may be used as appropriate.

[0036] When the increase in TFA indicates an increased risk of vascular occlusion in the individual, the risk of vascular occlusion may be determined, for example, based on the TFA obtained in the multiple analysis intervals as described above. Alternatively, if all of the multiple TFAs obtained in the analysis intervals of the multiple consecutive heartbeats are greater than the reference value, an increased risk of vascular occlusion may be determined.

[0037] [Effects of this embodiment] This embodiment provides a method for analyzing intravascular information, an intravascular information analysis system, and a method for collecting information on the opening, stenosis, or occlusion of blood vessels, which enable continuous monitoring of intravascular state information, detection of intravascular abnormalities, and prevention of adverse events through early detection and rapid intervention of intravascular abnormalities.

[0038] A novel aspect of this embodiment is that, when used to obtain information on cerebral blood vessels, continuous monitoring of intracranial arterial pressure waveforms allows for accurate detection of arterial occlusion during neurovascular endovascular treatment. The clinical significance of this embodiment is that this method allows clinicians to evaluate the state of intracranial blood vessels without relying solely on intermittent angiographic images. Furthermore, because rapid changes in blood vessels can be detected in real time, surgical safety may be improved.

[0039] According to this embodiment, for example, intracranial arterial pressure (IAP) waveforms can be continuously measured through a catheter inserted during endovascular treatment of cerebrovascular disease. Characteristic changes in blood pressure waveforms are thought to fluctuate in response to factors such as peripheral resistance and stroke volume, and are therefore known to reflect the hemodynamic state within the blood vessels. When intravascular occlusion occurs, it can cause dramatic changes in these factors and alter the waveform. Such changes can be quantitatively captured by time-frequency analysis. Therefore, it may be possible to distinguish between occluded and open states by time-frequency analysis of the waveform in this embodiment.

[0040] As shown in the examples, the inventors verified whether quantifiable features obtained from time-frequency analysis of waveforms can reflect the state inside a blood vessel by comparing the features in occluded and open states. Furthermore, they aimed to develop a predictive tool for detecting occlusion using cutoff values.

[0041] As shown in the examples, this embodiment can reliably distinguish between occluded and open states of intracranial arteries by quantitative evaluation of IAP waveforms using time-frequency analysis. Furthermore, no conventional technology has been known to enable this.

[0042] The arterial blood pressure waveform consists of forward and reflected waves. The amplitude and velocity of the reflected wave are positively correlated with the reflection coefficient, which reflects peripheral vascular resistance. In occluded vessels, the amplitude of the reflected wave increases, and its arrival velocity increases due to the increased resistance. As a result, a distinct notch appears in the waveform corresponding to this enhancement of the reflected wave. In open vessels, this notch may be inconspicuous or not appear at all. This change in waveform morphology is reflected in an increase in CWT amplitude across various frequency bands. Furthermore, the width of the notch changes with heart rate. As heart rate increases, the entire waveform narrows, the notch narrows, and shifts to higher frequencies. Therefore, it is essential to carefully observe and compare the changes in CWT amplitude across multiple frequency bands. In this example, a significant increase in TFA value corresponding to occlusion was shown, particularly in the frequency band including frequencies below 18 Hz. Therefore, the frequency range below 18 Hz may be suitable for further analysis.

[0043] The results of the embodiment also show that subarachnoid hemorrhage (SAH) does not result in a significant change in TFA values ​​with respect to the intravascular state. Although increased intracranial pressure may affect IAP, it did not affect the difference in TFA values ​​between open and closed states. Therefore, the method of this embodiment can also be applied to SAH patients.

[0044] The use of an intermediate catheter (DAC) significantly reduced the TFA value compared to the group not using a DAC. The presence of the DAC within the guiding catheter reduces the effective lumen, inhibits the transmission of arterial pressure pulse waves, and lowers the waveform amplitude. Therefore, it was considered necessary to adjust the optimal cutoff value and frequency band between the DAC use group and the DAC non-use group. Although this effect was small, the waveform trial order showed a positive correlation with the TFA value in all frequency bands. As one explanation, since the waveforms were acquired immediately after endovascular interventions such as catheter and balloon operations, it is possible that they reflect the progression of vasospasm caused by these procedures. By conducting a test with a wider measurement period than in the present embodiment, it is expected that such induced spasm will likely subside over time.

[0045] In the examples described later, the intravascular state was evaluated based on angiographic findings. However, since angiography only allows intermittent evaluation, it is difficult to accurately capture variations in the vascular state between imaging sessions. On the other hand, in a certain patient, the rate of change of the TFA value fluctuated greatly beyond the cutoff value. Because this patient developed a thrombus during endovascular treatment, it is considered possible that thrombus instability altered the intravascular state between the two angiographic examinations that confirmed occlusion. After confirming the thrombotic event, fasudil hydrochloride and ozagrel sodium were administered to dissolve the thrombus, but subsequent angiography revealed a period of repeated patency and occlusion. Ultimately, the thrombus in this patient was completely resolved, and no neurological deficit remained.

[0046] These findings suggest that time-frequency analysis of IAP waveforms may enable dynamic detection of rapidly changing intravascular states that are difficult to monitor with angiography alone, which has intermittent observation intervals. Although angiography remains the reliable gold standard for intravascular evaluation, further results are expected to be obtained from larger-scale prospective cohort studies, in which time-frequency analysis of IAP waveforms provides an important real-time perspective.

[0047] The present inventors previously reported changes in the pressure waveform of a target vessel during an occlusion procedure for an abnormal vessel having a shunt path (Shimoda 2021 JNS case lessons). However, the description at that time was limited to changes in waveform shape, and quantitative evaluation using time-frequency analysis and comparison with normal vessels as in the present embodiment had not been performed. In addition, although pressure waveform analysis of the internal carotid artery by De Melis et al. reports that a characteristic change is observed around 3-6 Hz, no association with clinical information has been shown. The present embodiment provides novel findings that have not existed in the prior art in that the association between vascular occlusion and pressure waveform changes has been verified by time-frequency analysis.

[0048] [Other Embodiments] The present invention has the following aspects as other embodiments. One aspect of the present embodiment is a method for diagnosing a vascular-related disease using the aforementioned intravascular information analysis method. One aspect of the present embodiment is a method for diagnosing a cerebrovascular-related disease using the aforementioned intravascular information analysis method. One aspect of the present embodiment is a method for diagnosing a cerebrovascular nervous system disease using the aforementioned intravascular information analysis method. One aspect of the present embodiment is a method for diagnosing a vascular-related disease using the aforementioned intravascular information analysis system. One aspect of the present embodiment is a method for diagnosing a cerebrovascular-related disease using the aforementioned intravascular information analysis system. One aspect of the present embodiment is a method for diagnosing a cerebrovascular nervous system disease using the aforementioned intravascular information analysis system. One aspect of the present embodiment is use of the aforementioned intravascular information analysis system for diagnosing a vascular-related disease. One aspect of the present embodiment is a method for diagnosing a vascular-related disease using the method for collecting information related to patency, stenosis, or occlusion of the aforementioned blood vessel. One aspect of the present embodiment is a method for diagnosing a cerebrovascular-related disease using the method for collecting information related to patency, stenosis, or occlusion of the aforementioned blood vessel. One aspect of the present embodiment is a method for diagnosing a cerebrovascular nervous system disease using the method for collecting information related to patency, stenosis, or occlusion of the aforementioned blood vessel.

[0049] The present invention is described in detail below with reference to Examples, but the present invention is not limited to these Examples.

[0050] [Example of study] A retrospective analysis was conducted on cases that received endovascular treatment for cerebrovascular diseases at Konan Hospital (February-March 2022) and Iwaki Medical Center (April-December 2022). Patients who underwent endovascular treatment for cerebral aneurysms (ruptured and unruptured), internal carotid artery stenosis, and parental artery occlusion were included in the study. This study was approved by the ethics committees of Konan Hospital (2024-1120-07) and Iwaki Municipal Medical Center (R6-49) after completing the opt-out procedure.

[0051] Using pressure waveform data obtained from a pressure sensor connected to the parent catheter during surgery, the pressure waveforms at the point when "open" or "occluded" was determined based on angiographic findings were identified and extracted.

[0052] (Data Acquisition and Preprocessing) During each procedure, IAP was continuously recorded using a pressure monitoring kit (Merit Medical Systems Inc., Utah, USA) connected to a guiding catheter or angiography catheter. Periods containing artifacts caused by manual catheter manipulation were removed. The remaining data were segmented based on angiographic findings and labeled as open, stenotic, or occluded. More specifically, segments recorded between two angiographic evaluations confirming openness were labeled "open," and segments recorded between two evaluations confirming occlusion, or during the period from full balloon inflation to deflation, were labeled "occluded."

[0053] Each segment was processed with a 1–40 Hz bandpass filter and divided into individual waveform trials corresponding to each R-R interval obtained from the simultaneously recorded electrocardiogram (ECG). After processing the ECG signal with a 10–40 Hz bandpass filter, R peaks were detected at 5-second intervals.

[0054] Next, the MATLAB® findpeaks function was used with MinPeakHeight = 0.2, MinPeakProminence = 0.1, and MinPeakDistance = 0.15 seconds. R-R intervals containing ectopic pulses for which a corresponding IAP waveform could not be generated were excluded.

[0055] Next, time-frequency analysis was applied to each waveform by performing a continuous wavelet transform (CWT) over the entire R-R interval and obtaining the CWT amplitude value. An integration window was defined from the first bottom peak of the fourth derivative of each waveform to 30% of the total duration of the waveform. This window encompasses the second zero-crossing point of the fourth derivative, i.e., the starting point of the trailing wave (M). Within this time window, the CWT (continuous wavelet transform) amplitude values ​​were integrated over nine frequency bands (6–10 Hz, 10–14 Hz, 14–18 Hz, 18–22 Hz, 6–14 Hz, 10–18 Hz, 14–22 Hz, 6–18 Hz, 10–22 Hz).

[0056] On the other hand, frequencies below 6 Hz were excluded because they are greatly affected by the low-frequency components, which are the main components of the waveform. The CWT amplitude values ​​integrated from these bands were used as dependent variables in all subsequent analyses and are hereinafter referred to as TFA values.

[0057] (Mixed Model Analysis of TFA Values) Mixed model analysis was performed to evaluate the influence of several fixed factors on the combined TFA value for each frequency band. Fixed factors included age, subarachnoid hemorrhage (SAH) status (whether the patient had SAH), occlusion status (whether the artery was occluded), waveform trial order within each segment, use of an intermediate catheter (DAC), and effective lumen area of ​​the catheter.

[0058] The effective lumen area of ​​the outer catheter used for IAP monitoring was calculated by subtracting the total cross-sectional area of ​​all coaxially inserted inner catheters from the cross-sectional area of ​​the outer catheter. Specifically, the cross-sectional area of ​​the outer catheter was calculated using its inner diameter, and the cross-sectional area of ​​each inner catheter was calculated using its outer diameter. The total cross-sectional area is π * (d / 2) ２ The calculation was performed using the following formula, where d is determined by the manufacturer. Fixed-effect variables include the diagnosis of subarachnoid hemorrhage (because it can alter arterial dynamics and affect time-frequency amplitude due to increased intracranial pressure (ICP) and decreased cerebral perfusion) and effective lumen area (because it is expected to directly affect local arterial pressure and IAP waveform).

[0059] To account for interpersonal variability, both sampled arteries and sections were included as random effects. Statistical significance was set at a Bonferroni-corrected p-value < 0.05. SAH status was included as a factor because it can significantly alter intracranial dynamics, particularly through increased intracranial pressure and decreased cerebral perfusion, and thus potentially affect TFA values. Furthermore, the presence of DAC within the parent catheter reduces the effective lumen, which could potentially affect the transmission of pressure waveforms.

[0060] Subsequently, to facilitate comparison between the sampled arteries, the percentage change in TFA values ​​in each waveform test was calculated as follows: In the open-loop segment, the median TFA value of the first five tests was used as the baseline, and the percentage change relative to this baseline was calculated for each test from the sixth test onward. In the occluded-loop segment, the median TFA value of the last five tests in the preceding open-loop segment was used as the baseline, and the percentage change relative to each test from the first test onward was calculated. Subsequent analyses were performed separately for the DAC-treated group and the DAC-non-treated group.

[0061] (Detection Performance Analysis) Next, for each of the nine frequency bands, the area under the receiver operating characteristic curve (AUROC) and the area under the precision and recall curve (AUPRC) were calculated, and an occlusion was defined as positive. Occlusion (based on TFA value) was detected for each sample artery. In these detection performance analyses, sample arteries without occlusion events were excluded.

[0062] (Evaluation of cutoff and frequency band) The frequency band with the highest combined value of AUROC and AUPRC was selected. Within this band, among the optimal cutoff values ​​determined for each sample artery, the lowest cutoff value was selected as the final cutoff value, prioritizing sensitivity from the perspective of practical effectiveness. Finally, using this cutoff value in the selected frequency band, the median sensitivity, specificity, positive predictive value, and negative predictive value were calculated for all sample arteries.

[0063] (ECG R-peak detection parameters) Using the MATLAB findpeaks function, the R-peak was detected from each ECG segment (filtered at 10.40 Hz) with the parameters MinPeakHeight = 0.2, MinPeakProminence = 0.1, and MinPeakDistance = 0.15 seconds.

[0064] (Determination of the integration window) In each IAP waveform trial, the integration window was specifically defined from the first trough of the fourth derivative to 30% of the total duration of the trial.

[0065] (Evaluation of Diagnostic Performance of IAP Monitoring) Receiver Operating Characteristic (ROC) analysis was performed to evaluate how accurately IAP-based predictive variables could detect occlusions defined by angiography. The predictive variable was the percentage change from baseline in time-frequency amplitude, calculated using the median of the first five trials within each time segment as the baseline. If the effective lumen area of ​​the catheter changed (e.g., insertion or removal of a coaxial catheter), a new baseline was established. Diagnostic accuracy was evaluated using cross-validation excluding one artery, and the optimal cutoff value was determined by maximizing the Youden index within the training set.

[0066] The cross-validation procedure to exclude one artery was performed as follows: Data from each artery served sequentially as a test set, with the remaining arteries forming the training set. Within each training set, the optimal cutoff value for time-frequency amplitude (percentage change from baseline) was determined by maximizing the Youden index. This cutoff was then applied to the corresponding test artery. Classification performance metrics, including area under receiver operating characteristic curve (AUROC), area under accuracy recall curve (AUPRC), optimal cutoff value, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were recorded for each test set. The statistical significance of these metrics was tested against a defined baseline using a one-sample t-test (AUROC and AUPRC baseline: 0.5, sensitivity, specificity, PPV, and NPV baseline: 50%).

[0067] All analyses were performed using MATLAB R2024a (The MathWorks Inc., USA) and IBM SPSS Statistics version 30 (IBM, USA).

[0068] (Results) Sixty arteries from 52 patients were examined for eligibility, and ultimately, waveform trials were detected from 124 segments (88 open, 36 occluded) obtained from 43 arteries in 37 patients. The median age of the patients was 62 years (range: 40–81 years, interquartile range: 50.71 years), 23 were female, and 19 had subarachnoid hemorrhage (SAH). Thirty-four patients had received endovascular treatment for cerebral aneurysms (19 ruptured), two for internal carotid artery stenosis, and one for parental artery occlusion.

[0069] Basic patient information is shown in Figures 1A and 1B. Detailed characteristics of the arteries and segments collected from the patients are shown in Figures 2A to 2E. The abbreviations in the figures are as follows: Pt: Patient number. ACA: interior cerebral artery, Acom: interior communicating artery, AN: aneurysm, BA: basal artery, BAC: balloon assisted coil embolization, BTO: ballon test occlusion, CAS: carotid artery stenting, F: female, ICA: internal carotid artery, IC-Oph: internal carotid ophthalmic artery, IC-PC: internal carotid-posterior communicating artery, ICS: internal carotid artery stenosis, lat. wall: lateral wall, Lt: left, M: male, MCA: middle cerebral artery, MCB: middle cerebral artery bifurcation, PAO: parent artery occlusion, Pt: patient, Rt: right, SAH: subarachnoid hemorrhage, UIA: unruptured intracranial aneurysm, VA: vertical artery, VAO: vertical artery occlusion.

[0070] In the table, the occlusive events for patient Pt. 34 are indicated with "No. *". This patient had a history of left vertebral artery occlusion due to cervical dislocation fracture, and additional occlusion of the parent artery was performed during orthopedic reduction to prevent thrombosis. Therefore, only data for the right vertebral artery were included in the analysis.

[0071] Figure 3A is a schematic diagram showing the flow chart for this study and the participating patients. Figure 3B is a schematic diagram showing the flow chart for the R-R interval in this study.

[0072] During endovascular treatment, occlusion occurred in 14 of the 43 arteries. This included balloon-induced parental artery occlusion (n=9), coil-induced parental artery occlusion (n=3), and thrombotic occlusion (n=2). A total of 124 time segments were identified, and angiography classified 88 as open and 36 as occluded. Of the 6461 R-R intervals, 17, including premature contractions, were excluded, resulting in 6444 valid IAP measurement trials.

[0073] Figure 4 shows the dynamic modulation of time-frequency amplitude in the 6–18 Hz band in a patient. Patient Pt. 01 developed thrombosis during coil embolization for two left intracranial artery aneurysms. (a) The segments are labeled alphabetically, and the intravascular state is classified into pairs of open (A, B, E, F) and occluded (C, D, G, H, I, J, K). The broken line shows the dynamic modulation of time-frequency amplitude in the 6–18 Hz band. Large fluctuations in time-frequency were observed in some time segments (e.g., C, J, K). The amplitude occasionally exceeded the cutoff threshold +15.2% (red line). (b) are angiographic images taken at the start of segments B, C, F, J, and L. In the figure, the handwritten dashed lines represent the contours of the corresponding arteries (left anterior cerebral artery).

[0074] The median number of IAP measurement trials per time segment was 42.5 (interquartile range: 29.5–60.3). Further details are shown in the patient information in the previous figure. No adverse events related to continuous IAP monitoring were observed.

[0075] Figure 5 shows a case of a patient who underwent balloon-assisted coil embolization for an unruptured intracranial aneurysm. Columns A, B, and C in the figure show the balloon placement in the patient (described later), and the rows from top to bottom show angiographic images of the blood vessels, the R-R interval of the ECG (electrocardiogram), the waveform of intracranial artery pressure, the waveform of the fourth derivative of blood pressure, and a time-frequency plot. In the figure, CWT: Continuous Wavelet Transform, ECG: Electrocardiogram, IAP: Intracranial Artery Pressure.

[0076] In the figure, A shows the state immediately before balloon expansion, where the artery is open. B shows the state after the balloon has been fully expanded, where the artery is occluded. C shows the state after the balloon has been deflated, returning the artery to an open state. The yellow arrows in the angiographic images indicate the midpoint between the corresponding arterial region and the balloon placement. The purple region and red dashed line on the intracranial arterial pressure (IAP) waveform indicate the integration window used to calculate the continuous wavelet transform (CWT) time-frequency amplitude. The red circle on the fourth derivative of the IAP waveform indicates the first trough. In the time-frequency plot for the occluded state (B), a clear increase in CWT amplitude (light-colored region in the figure) was observed.

[0077] (Mixed Model Analysis of TFA Values) Figures 6A, 6B, and 6C show the mixed model analysis of TFA values ​​in this study. As shown in the figures, in this study, "occlusion state," "order of IAP measurement trials," and "effective lumen area" were independently associated with the increase in the time-frequency amplitude of the IAP waveform across all four frequency bands analyzed (P < 0.001). These associations were significant. After Bonferroni correction (α = 0.0125), all correlation coefficients were less than 0.7. No substantial multicollinearity was observed among these fixed-effect variables. Age and the diagnosis of subarachnoid hemorrhage did not have a significant effect on the time-frequency amplitude.

[0078] (Diagnostic performance of IAP monitoring) Figures 7A and 7B show the detection performance of obstruction events in the frequency band of 6 to 18 Hz. Figures 8A and 8B show the detection performance of obstruction events in the frequency band of 6 to 10 Hz. Figures 9A and 9B show the detection performance of obstruction events in the frequency band of 10 to 14 Hz. Figures 10A and 10B show the detection performance of obstruction events in the frequency band of 14 to 18 Hz.

[0079] The abbreviations in the table are as follows: AUPRC: area under the precision-recall curve, AUROC: area under the receiver operating characteristic curve, NPV: negative predictive value, PPV: positive predictive value.

[0080] Receiver operating characteristics analysis revealed that time-frequency amplitudes of 6–18 Hz showed the highest overall performance in detecting blockage trials. Specifically, across an average of 43 arteries in 37 patients, the mean Youden index was 0.67, AUROC was 0.881 (P<0.001; 95% CI 0.878.0.884), AUPRC was 0.772 (P<0.001; 95% CI 0.768.0.775), best cutoff was 113.9% (P<0.001; 95% CI 13.8.14.1) (13.9% increase), sensitivity was 88.5% (P<0.001; 95% CI 74.3.100), specificity was 87.5% (P<0.001; 95% CI 81.2.93.8), PPV was 36.1% (P=0.09), and NPV was 96.4% (P<0.001; The 95% CI was 93.0.99.8). The performance indicators of each time-frequency amplitude predictor for each artery are shown in the figure above. Figure 11A is a graph showing the analysis results of ROC from receiver operating characteristics analysis. Figure 11B is a graph showing the analysis results of PRC from receiver operating characteristics analysis.

[0081] To evaluate whether short-term fluctuations in time-frequency amplitude are the primary cause of false-positive detection in some occlusion tests, a post-hoc receiver operating characteristic analysis was performed. We hypothesized that a sustained increase in time-frequency amplitude exceeding the cutoff for five consecutive trials between 6 and 18 Hz would improve PPV without adversely affecting other classification indices. One time segment evaluating the left internal carotid artery in patient 37 was excluded because it contained only seven IAP measurement trials, making it impossible to assess sustained changes (0.5 trials).

[0082] Figures 12A and 12B show the detection performance of blockage events in the 6–18 Hz frequency band based on post-event analysis. Abbreviations are the same as in Figures 6–10.

[0083] Post-hoc analysis showed that a sustained increase in time-frequency amplitude reduced false positives, as evidenced by the improvement in PPV. Specifically, the mean Euden index was 0.75, the mean AUROC was 0.924 (P < 0.001; 95% CI 0.921, 0.926), AUPRC was 0.896 (P < 0.001; 95% CI 0.893, 0.899), the best cutoff increased by 14.3% (P < 0.001; 95% CI 14.2, 14.4%), sensitivity was 82.3% (P < 0.001; 95% CI 64.8, 99.9%), specificity was 96.8% (P < 0.001; 95% CI 92.9, 100%), and PPV was 75.5% (P = 0.027; 95% CI The percentages were 53.3.97.7%, and the NPV was 94.8% (P < 0.001; 95% CI 90.4.99.3).

[0084] (Discussion of Test Results) This study is the first to demonstrate that occlusive events during neurovascular intervention can be accurately detected by time-frequency analysis of IAP waveforms. Endovascular procedures typically take more than two hours for the entire patient. Generally, healthcare professionals are recommended to perform up to 40 angiography imaging sessions per procedure. Even under this simplified assumption, the average interval between imaging sessions exceeds three minutes. These intervals often last for several minutes, which means that transient vascular changes, such as sudden occlusions, may not be detected. Therefore, this embodiment is considered to provide complementary diagnostic value by enabling continuous monitoring during clinically important gaps in intermittent angiography.

[0085] Specifically, a sustained increase in the time-frequency amplitude of IAP predicted an occluding trial with an AUROC of 0.924. These findings suggest that continuous IAP monitoring is promising for detecting occluding events, but a prospective study with a larger sample size is needed to definitively confirm its diagnostic value. This study retrospectively investigated 37 consecutive cases that met the eligibility criteria. Importantly, the results of this study suggest that IAP monitoring has potential not so much to replace angiographic evaluation, but rather to be an auxiliary tool that provides timely warnings when angiographic confirmation of an occluding event is necessary. Given that most of the arteries analyzed were in the anterior circulation, further insights are needed to determine whether the reported diagnostic accuracy can be generalized to the posterior circulation or applied to other procedures such as blood flow diversion. Figure 13 is a schematic diagram illustrating the correlation between vascular patency, stenosis, or occlusion and waveforms and TFA in the trials of this embodiment.

[0086] Previous reports suggest that the IAP waveform reflects the dynamics of anterior blood flow and reflex blood flow. Figure 14 is a graph showing an example of a carotid artery pressure waveform. In the figure, Pf represents anterior blood flow and Pb represents reflex blood flow. The intensity and velocity of reflex blood flow are positively correlated with the reflex coefficient, suggesting that it effectively reflects peripheral vascular resistance. Therefore, the distinct notch observed in the IAP waveform, accompanied by an increase in time-frequency amplitude, is thought to reflect the early arrival of reflex blood flow due to increased vascular resistance caused by arterial occlusion.

[0087] The excellent performance in the 6–18 Hz band in this study may reflect differences in patient heart rates. Narrower bands may not effectively capture such variations. The notch width is heart rate dependent, with steeper notches at higher heart rates, and the increase in time-frequency amplitude associated with occlusion is more pronounced in the higher frequency band. Therefore, further prospective studies using time-frequency amplitudes of 6–18 Hz could more clearly evaluate the diagnostic usefulness of continuous IAP monitoring in detecting arterial occlusion events.

[0088] The results of the mixed model analysis suggest that capturing the relative increase in IAP time-frequency amplitude over time may be more important than capturing the absolute amplitude value. A decrease in effective lumen area significantly reduced the time-frequency amplitude. This suggests that inserting an additional coaxial catheter reduces the amplitude of the waveform. Therefore, if there is a change in effective lumen area, it is recommended to recalibrate the baseline IAP time-frequency amplitude to optimally detect occlusion events.

[0089] There is no evidence to suggest that IAP monitoring is difficult in patients with subarachnoid hemorrhage. No adverse events were observed in the study patients. Mixed model analysis did not show that the diagnosis of subarachnoid hemorrhage had a significant impact on IAP time-frequency amplitude. While it has been reported that elevated intracranial pressure (ICP) affects cerebral perfusion, this study performed continuous IAP monitoring and detected increases in time-frequency amplitude associated with transient arterial occlusion. In the later trials, an increase in time-frequency amplitude was observed within a predetermined time segment, but the effect was minor (0.003 mmHg·s per trial in the 6–18 Hz band). One possible cause is slowly progressing vasospasm caused by intravascular manipulation such as catheter or balloon adjustment. However, considering that the increase in time-frequency amplitude associated with arterial occlusion was 3.019 mmHg·s, ​​this trial effect is considered clinically negligible.

[0090] The low PPV (36.1%) reported in the trial-by-trial analysis was primarily due to false-positive detections unrelated to true occlusive events. These false positives are likely due to frequent and inherent fluctuations in the IAP waveform, which may mimic transient time-frequency amplitude increases that mimic true occlusive events. We also evaluated PPV using a more stringent detection criterion: an event was classified as occlusive only if the time-frequency amplitude increase persisted over at least five consecutive trials. This stricter threshold significantly reduced the false-positive rate, improving PPV to 75.5%, although sensitivity slightly decreased from 88.5% to 82.3%. Furthermore, the design of this study, in which no true occlusive events were observed in 29 of the 43 arteries tested, also contributed to the relatively low PPV. It has been reported that even when using highly sensitive and specific diagnostic tools, PPV may be reduced because a significant proportion of positive detections are false positives when including a considerable number of patients or evaluations without true positive events.

[0091] The validity of angiography as the gold standard for defining arterial occlusion events requires further discussion. Traditionally, angiography has only allowed for intermittent assessments, requiring the assumption that the intravascular state (occlusion or patency) remains stable between consecutive angiograms. Angiography may fail to detect transient thrombotic occlusions that occur between assessments, or temporary reopenings immediately after an occlusion has been recorded.

[0092] This case study shows dynamic modulation of IAP time-frequency amplitude in patient Pt. 01, who experienced a thrombotic event during neurovascular intervention. This patient was one of two patients in whom the accuracy of IAP-based occlusion detection was not optimal. This case study also shows that IAP time-frequency amplitude fluctuates even in occluded states defined by angiography. Arterial instability due to fluctuating thrombotic states cannot be ruled out. After confirming an occludative event by angiography, fasudil hydrochloride and ozagrel sodium were administered. Subsequent angiography showed alternating periods of openness and occlusion, supporting the suspicion of rapid intravascular changes. Ultimately, the thrombus completely disappeared without leaving neurological impairment. From this case observation, it can be predicted that continuous IAP time-frequency analysis can function as an auxiliary tool and provide real-time insights into rapidly changing intravascular states.

[0093] While preferred embodiments of the present invention have been described and illustrated above, it should be understood that these are illustrative and not limiting. Additions, omissions, substitutions, and other modifications can be made without departing from the spirit or scope of the invention. Therefore, the present invention is not limited by the foregoing description but is limited only by the scope of the appended claims.

[0094] According to the present invention, it is possible to obtain a method for analyzing intravascular information, an intravascular information analysis system, and a method for collecting information on the opening, stenosis, or occlusion of cerebral blood vessels, which can continuously monitor intravascular state information, detect intravascular abnormalities, and prevent adverse events through early detection and rapid intervention of intravascular abnormalities.

Claims

1. A method for analyzing intravascular information to obtain information on the opening, stenosis, or occlusion of a blood vessel, comprising: measuring the intravascular pressure of the blood vessel, analyzing the intravascular pressure to obtain a pressure waveform, recording an electrocardiogram, determining an analysis interval in the pressure waveform based on the electrocardiogram, defining the sum of the amplitudes of the pressure waveform in the analysis interval as time frequency amplitude (TFA), and determining that an increase in TFA indicates an increased risk of vascular occlusion.

2. The method for analyzing intravascular information according to claim 1, wherein the intravascular pressure is measured by a pressure sensor connected to a catheter inside the blood vessel, or by a transcutaneous pressure sensor.

3. A method for analyzing intravascular information according to claim 1 or 2, comprising performing a time-frequency analysis on the pressure waveform, and calculating the TFA by summing the time-frequency components obtained by the time-frequency analysis in the analysis interval and a predetermined frequency band.

4. The method for analyzing intravascular information according to claim 3, wherein the time-frequency analysis is any of the following: continuous or discrete wavelet transform, short-time Fourier transform (STFT), S-transform, Wigner-Ville distribution, or Hilbert-Huang transform.

5. The method for analyzing intravascular information according to claim 1 or 2, wherein the R-R interval in the electrocardiogram is considered as one heartbeat, the pressure waveform is divided for each heartbeat, and the section from the first negative peak in the fourth derivative waveform of the pressure waveform to 30% of the total length of the pressure waveform is defined as the analysis section.

6. The method for analyzing intravascular information according to claim 1 or 2, further comprising the steps of obtaining the TFA using the first 4 to 10 heartbeats in the electrocardiogram while the blood vessel is open as the analysis interval, standardizing the data using the median value of the TFA as a reference and the percentage change relative to that value, and verifying a cutoff value and accuracy suitable for each of the multiple blood vessels.

7. The method for analyzing intravascular information according to claim 1 or 2, wherein if the TFA is greater than a reference value, it is determined that there is an increased risk of vascular occlusion or stenosis.

8. The method for analyzing intravascular information according to claim 7, wherein the reference value is the median value of the TFA obtained using the first 4 to 10 heartbeats in the electrocardiogram when the blood vessel is open as the analysis interval.

9. A method for analyzing intravascular information according to claim 1 or 2, comprising acquiring TFA in a plurality of analysis intervals and determining the risk of vascular occlusion based on the TFA acquired in the plurality of analysis intervals.

10. The method for analyzing intravascular information according to claim 9, wherein the plurality of analysis intervals are analysis intervals for 2 to 10 heartbeats.

11. The method for analyzing intravascular information according to claim 9, wherein the plurality of analysis intervals are analysis intervals in a plurality of consecutive heartbeats.

12. The method for analyzing intravascular information according to claim 11, wherein the plurality of analysis intervals are analysis intervals of five consecutive heartbeats.

13. The method for analyzing intravascular information according to claim 11, wherein if all of the multiple TFAs obtained in the analysis intervals of multiple consecutive heartbeats are greater than the reference value, it is determined that there is an increased risk of vascular occlusion.

14. The method for analyzing intravascular information according to claim 1 or 2, wherein the blood vessel is a cerebral blood vessel.

15. An intravascular information analysis system for obtaining information on the opening, occlusion, or stenosis of blood vessels, comprising: an intravascular pressure wave meter device equipped with a pressure sensor or transcutaneous pressure sensor connected to an intravascular catheter to measure intravascular pressure, and an analysis unit that analyzes the intravascular pressure obtained from the pressure sensor to obtain a pressure waveform; and an electrocardiogram analysis device that records an electrocardiogram, wherein the analysis interval in the pressure waveform is determined by the electrocardiogram, the sum of the amplitudes of the pressure waveform in the analysis interval is defined as time frequency amplitude (TFA), and an increase in the TFA is judged to be an increase in the risk of vascular occlusion.

16. When determining the sum of the amplitudes, the time-frequency components obtained by time-frequency analysis are summed in a predetermined frequency band to calculate the TFA, and the TFA is calculated for each of the multiple subbands obtained by dividing the frequency band into predetermined bandwidths, as described in claim 15.

17. The intravascular information analysis system according to claim 15, wherein the R-R interval in the electrocardiogram is considered as one heartbeat, and the pressure waveform is divided for each of the aforementioned heartbeats, and the section from the first negative peak in the fourth derivative waveform of the pressure waveform to 30% of the total length of the pressure waveform is defined as the analysis section.

18. An intravascular information analysis system according to claim 15 or 16, wherein the first 4 to 10 heartbeats in the electrocardiogram while the blood vessel is open are used as the analysis interval to obtain the TFA, the data is standardized using the median value of the TFA as a reference and the percentage change relative to that value, and the cutoff value and accuracy suitable for each of the multiple blood vessels are verified.

19. The intravascular information analysis system according to claim 15 or 16, wherein if the TFA is greater than a reference value, it is determined that there is an increased risk of vascular occlusion.

20. The intravascular information analysis system according to claim 19, wherein the reference value is the median value of the TFA obtained using the first 4 to 10 heartbeats in the electrocardiogram when the blood vessel is open as the analysis interval.

21. An intravascular information analysis system according to claim 15 or 16, comprising acquiring TFA in a plurality of analysis intervals and determining the risk of vascular occlusion based on the TFA acquired in the plurality of analysis intervals.

22. The intravascular information analysis system according to claim 21, wherein the plurality of analysis intervals are analysis intervals for 2 to 10 heartbeats.

23. The intravascular information analysis system according to claim 21, wherein the plurality of analysis intervals are analysis intervals in a plurality of consecutive heartbeats.

24. The intravascular information analysis system according to claim 22, wherein the plurality of analysis intervals are analysis intervals of five consecutive heartbeats.

25. The intravascular information analysis system according to claim 23, wherein if all of the multiple TFAs obtained in the analysis intervals of multiple consecutive heartbeats are greater than the reference value, it is determined that there is an increased risk of vascular occlusion.

26. A method for collecting information relating to the opening, stenosis, or occlusion of blood vessels, comprising: step A, which determines an analysis interval in a pressure waveform obtained by analyzing the intravascular pressure of an individual's blood vessels, based on an electrocardiogram measured simultaneously with the intravascular pressure in the individual; and step B, which obtains the sum of the amplitudes of the pressure waveforms in the analysis interval as TFA, wherein an increase in TFA indicates an increased risk of vascular occlusion in the individual.

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