WO2021141135A1 - Functional ischemia detection technique by coronary artery ct4d flow imaging - Google Patents

Functional ischemia detection technique by coronary artery ct4d flow imaging Download PDF

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WO2021141135A1
WO2021141135A1 PCT/JP2021/000629 JP2021000629W WO2021141135A1 WO 2021141135 A1 WO2021141135 A1 WO 2021141135A1 JP 2021000629 W JP2021000629 W JP 2021000629W WO 2021141135 A1 WO2021141135 A1 WO 2021141135A1
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coronary artery
coronary
data
angiography
curve
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PCT/JP2021/000629
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French (fr)
Japanese (ja)
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充展 長尾
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学校法人東京女子医科大学
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
    • A61B6/02—Arrangements for diagnosis sequentially in different planes; Stereoscopic radiation diagnosis
    • A61B6/03—Computed tomography [CT]

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  • the present invention not only evaluates the degree of stenosis of coronary arteries, but also visualizes high-risk plaque (HRP) such as low-attenuation plaque (LAP), which is a predictor of acute coronary syndrome.
  • HRP high-risk plaque
  • LAP low-attenuation plaque
  • CCTA coronary computed tomography angiography
  • iFR is a hemodynamic index that evaluates coronary artery function at rest without requiring maximum hyperemia of the myocardium due to drugs.
  • CT-iFR the coronary angiography CT data
  • PCI percutaneous coronary intervention
  • AUC Appropriateness Use Criteria
  • Non-Patent Document 2 The necessity of PCI is judged by coronary angiography (CAG) and coronary CT (CCTA) based on the stenosis rate and lesion length.
  • CAG and CCTA are morphological evaluations, revascularization for stenosis without ischemia does not improve the prognosis.
  • functional evaluation before the enforcement of PCI has become mandatory in insurance medical care.
  • the coronary flow reserve ratio (FFR) which measures the pressure gradient before and after stenosis with a catheter, is recommended (Non-Patent Document 2).
  • FIG. 23 shows an outline of the functional ischemia detection method (Non-Patent Document 3).
  • blood pumped from the heart travels through the aorta to the entire body, it perfuse the heart itself to every corner through the coronary blood vessels (coronary arteries, coronary arteries) that branch off from the aorta immediately after part of it leaves the heart. doing.
  • the coronary arteries that pass around the heart become arteriosclerosis (for example, the blood vessels become stiff due to aging, and masses such as fat (plaques) accumulate on the walls of the blood vessels, causing a part of the walls of the blood vessels to rise and inside the blood vessels.
  • Quantify coronary blood flow by measuring changes in the concentration of contrast medium flowing through the coronary arteries before and after the stenosis site, changes in coronary artery pressure (coronary artery pressure), etc. It is possible to make it.
  • the measurement of changes in contrast medium concentration, pulse pressure, etc. before and after the stenotic site is performed in three dimensions of the coronary artery constructed from image data obtained by CT (Computed Tomography). It can be done using a 3D) model.
  • FIG. 24 shows an outline of a functional examination using a cardiac catheter.
  • a device called a pressure wire (outer diameter: about 0.36 mm) is inserted into the coronary artery while instilling a coronary artery dilator (ATP: adenosine), and the distal part before and after the stenosis site.
  • the coronary artery pressure Pd and the proximal coronary artery pressure Pa are measured.
  • the graph of FIG. 25 shows the change in pulse pressure between rest and maximal hyperemic reaction.
  • the vertical axis of the graph shows pulse pressure, and the horizontal axis shows time.
  • Coronary pressure (proximal) Pa (upper fold line in the graph) does not change significantly from rest to maximal red-eye reaction, but coronary pressure (distal) Pd (lower fold line in the graph) is Due to the effect of the stenosis site, the pulse pressure drops significantly during the maximal hyperemia reaction compared to at rest.
  • FFR is an index that quantitatively indicates such changes, and it is possible to know how severe the coronary artery stenotic lesion is.
  • FIG. 23 shows an example of a non-invasive coronary artery diagnostic method, a three-dimensional (3D) model of the heart (coronary artery) is constructed based on the data of a coronary artery CT scan, and computational fluid dynamics (computational) is constructed.
  • FFR values are visualized in a 3D model of coronary arteries by simulation with fluid dynamics) (see FIG. 26).
  • FIG. 26 shows an example of visualizing the FFR value by shade of color in a three-dimensional model of a coronary artery.
  • FFR-CT which analyzes CCTA anatomical information from computational fluid dynamics, has been developed by HeartFlow in the United States.
  • the instantaneous blood flow reserve ratio iFR which is a hemodynamic index for evaluating coronary artery function at rest, is adopted as an index without requiring maximum myocardial congestion by a drug.
  • the multi-phase CCTA data obtained by coronary angiography CT was reconstructed using predictive complement technology, and the time concentration curves of the proximal and distal coronary arteries were obtained from the reconstructed CCTA data.
  • iFR referred to as CT-iFR in the present invention
  • functional ischemia detection systems, methods, devices and programs hereinafter referred to as “functional ischemia detection systems, etc.” that can be calculated and can detect functional ischemia non-invasively. ..
  • IFR is an index for estimating how much blood flow is blocked by a stenotic lesion when there is a stenotic lesion in the coronary artery.
  • iFR Pd / Pa from the pressure Pa and Pd.
  • the present invention is based on the fact that the concentration in the coronary artery by CT reflects the blood flow.
  • Proximal and distal blood flow in the coronary artery stenosis is calculated using a time concentration curve and the maximum slope method (Non-Patent Document 7) or the convolution integral method (deconvolution method). If there is no energy loss such as functional stenosis, iFR will be close to 1.
  • the present invention of calculating iFR from blood flow is consistent with the original concept of iFR for estimating obstruction of blood flow.
  • the present invention is fundamentally different from the conventional catheter iFR in that it directly estimates blood flow rather than reproducing the pressure measurement of an invasive catheter.
  • the functional ischemia detection system includes a coronary angiography CT apparatus and Including an information processing device connected to the coronary angiography CT device.
  • the coronary angiography CT device integrates standard coronary angiography that requires a high dose and continuous low-dose imaging, CT scans the subject's chest in chronological order, and captures CT data of the heart in chronological order. Obtained to generate multi-phase coronary CT data,
  • the information processing apparatus reconstructs the multi-phase coronary angiography CT data by predictive complementation, and from the reconstructed multi-phase coronary angiography CT data, a time concentration curve of the proximal part of the coronary artery and a coronary artery.
  • the polyphasic coronary angiography by obtaining a time concentration curve of the distal part and quantifying the coronary flow of the region of interest in the distal part of the coronary artery and the proximal part of the coronary artery using the convolution integration method. It is characterized by calculating the instantaneous blood flow reserve ratio (CT-iFR) based on CT data.
  • CT-iFR instantaneous blood flow reserve ratio
  • the information processing apparatus moves the time concentration curve of the distal part of the coronary artery in parallel to the time concentration curve side of the proximal part of the coronary artery, and sets the rising point of the time concentration curve of the proximal part of the coronary artery and the distal part of the coronary artery.
  • Match By the convolution integral method, the value of the area under the proximal curve was obtained from the time concentration curve of the proximal part of the coronary artery, and the value of the area under the distal curve was obtained from the time concentration curve of the distal part of the coronary artery.
  • the instantaneous blood flow reserve ratio (CT-iFR) is calculated by dividing the value of the area under the distal curve by the value of the area under the proximal curve.
  • Each time concentration curve of the distal part of the coronary artery and the proximal part of the coronary artery is characterized in that it is a curve extracted from a part from the rising edge to the peak value.
  • the coronary angiography CT device is a 320-row CT device.
  • the 320-row CT apparatus is characterized in that the entire heart of the subject is covered by a single imaging, and continuous imaging of a contrast-enhanced first pass of the coronary artery is performed.
  • the predictive complement is characterized in that the number of predictive complementary images for reconstructing the coronary angiography CT data of the polychronous phase is increased or decreased according to the value of the predictive complement intensity input in the information processing apparatus. ..
  • the predictive complement increases the number of predictive complementary images for reconstructing the polyphasic coronary CT data and reduces the time interval of the images in the polyphasic coronary CT data. It is characterized by sequentially approximating and reconstructing the time-phase coronary angiography CT data to reduce image noise.
  • the region of interest is defined according to the range specified in the cross-sectional image of the coronary artery obtained from the multi-phase coronary angiography CT data displayed by the information processing apparatus.
  • the cross-sectional image of the coronary artery is characterized in that it is rotated at an angle substantially orthogonal to the direction of the coronary artery.
  • the region of interest is characterized by being a substantially spherical region at the center of the blood vessel in the cross-sectional image of the coronary artery.
  • the information processing apparatus automatically tracks the region of interest in the polyphasic coronary angiography CT data in a subsequent frame. It is characterized in that each time concentration curve of the distal part of the coronary artery and the proximal part of the coronary artery is measured.
  • the functional ischemia detection method is described. From a coronary angiography CT device that integrates standard coronary angiography that requires a high dose and continuous low-dose imaging, CT scans the subject's chest in chronological order, and acquires CT data of the heart in chronological order.
  • the stage of reconstructing the obtained multi-phase coronary angiography CT data by predictive complementation The stage of acquiring the time concentration curve of the proximal part of the coronary artery and the time concentration curve of the distal part of the coronary artery from the reconstructed multi-phase coronary angiography CT data, and By quantifying the coronary flow in the region of interest in the distal part of the coronary artery and the proximal part of the coronary artery using the convolutional integration method, the instantaneous blood flow reserve ratio (CT-) based on the multi-phase coronary angiography CT data. It is characterized by including a stage of calculating iFR).
  • the step of calculating the instantaneous blood flow reserve ratio is A step of moving the time concentration curve of the distal part of the coronary artery in parallel to the time concentration curve side of the proximal part of the coronary artery to match the rising and starting points of the time concentration curve of the proximal part of the coronary artery and the distal part of the coronary artery.
  • the value of the area under the proximal curve is obtained from the time concentration curve of the proximal part of the coronary artery
  • the value of the area under the distal curve is obtained from the time concentration curve of the distal part of the coronary artery. It is characterized by including a step of calculating the instantaneous blood flow reserve ratio (CT-iFR) by dividing the value of the area under the distal curve by the value of the area under the proximal curve.
  • Each time concentration curve of the distal part of the coronary artery and the proximal part of the coronary artery is characterized in that it is a curve extracted from a part from the rising edge to the peak value.
  • the coronary angiography CT device is a 320-row CT device.
  • the multi-phase coronary angiography CT data includes an image generated by continuously photographing the entire heart of the subject with a single imaging by the 320-row CT apparatus and performing continuous imaging of the contrast-enhanced first pass of the coronary artery. It is characterized by that.
  • the step of reconstructing by the prediction complement is It is characterized by including a step of increasing or decreasing the number of predictive complement images for reconstructing the multi-phase coronary angiography CT data according to a specified value of predictive complement intensity.
  • the step of reconstructing by the prediction complement is In order to reduce image noise, the number of predictive complementary images for reconstructing the multi-phase coronary CT data is increased, and the time interval of the images in the multi-phase coronary CT data is reduced. , The multi-phase coronary angiography CT data is sequentially approximated and reconstructed.
  • the step of calculating the instantaneous blood flow reserve ratio is The stage of determining the region of interest according to the range specified in the cross-sectional image of the coronary artery obtained from the multi-phase coronary angiography CT data, and
  • the cross-sectional image of the coronary artery is characterized by including a step of rotating the coronary artery at an angle orthogonal to the direction of the coronary artery.
  • the region of interest is characterized by being a substantially spherical region at the center of the blood vessel in the cross-sectional image of the coronary artery.
  • the step of calculating the instantaneous blood flow reserve ratio is When the region of interest in the distal coronary artery and the proximal coronary artery is designated, the region of interest in the polyphasic coronary angiography CT data is automatically tracked in a subsequent frame, and the distal coronary artery is distal. It is characterized by including a step of measuring each time concentration curve of the portion and the proximal portion of the coronary artery.
  • the functional ischemia detection device is Each step of the functional ischemia detection method according to any embodiment of the functional ischemia detection method is performed.
  • the functional ischemia detection program is executed by a computer to cause the computer to function as the functional ischemia detection device. To do.
  • the multi-phase CCTA data obtained by coronary angiography CT is reconstructed using predictive complement technology, and the reconstructed CCTA data is used to reconstruct the proximal part of the coronary artery and the proximal coronary artery.
  • CT-iFR can be calculated by acquiring the time concentration curve of the distal part of the coronary artery and quantifying the coronary artery flow using a quantitative analysis method, and non-invasively detecting functional ischemia. be able to.
  • the present invention can also be analyzed by a subject after coronary artery calcification or stent placement.
  • CT-iFR instantaneous blood flow reserve ratio
  • the functional ischemia detection system or the like it is possible to evaluate the function at the same time as the anatomical stenosis as compared with the conventional coronary CT, and it is possible to evaluate the contrast ability of the myocardium.
  • CT-FFR of HeartFlow, Inc. of the United States, which is one of the conventional examples, it is possible to analyze cases of coronary artery calcification and stent placement as described above. Data analysis is possible with an image analysis device, and the analysis results can be obtained about 1 hour after the inspection.
  • coronary CT data in Japan can be inspected with a domestic detection system, and coronary CT data can be transmitted overseas in order to use an overseas ischemia detection system (for example, FFR-CT of HeartFlow Inc. in the United States). It is not necessary to do so, and the risk of coronary CT data being used for other uses and research can be prevented.
  • an overseas ischemia detection system for example, FFR-CT of HeartFlow Inc. in the United States. It is not necessary to do so, and the risk of coronary CT data being used for other uses and research can be prevented.
  • the functional ischemia detection system and the like according to the present invention can shorten the time in an outpatient setting, are minimally invasive, and reduce the physical and economic burden on the patient (subject) as compared with cardiac catheterization. be able to.
  • a drug load such as a vasodilator, and the risk of cardiac accidents is low.
  • FIG. 8 is a diagram showing an example of a coronary artery CT image displayed to identify the distal portion of the right coronary artery, the left anterior descending artery, and the circumflex branch. It is a figure which shows an example of the cross section of a coronary artery displayed for setting a spherical interest area (Volume of Interest: VOI) on a coronary artery.
  • VOI spherical interest area
  • LMT left coronary artery main trunk
  • FIG. 1 It is a figure which shows the example which measured the area under the curve by the convolution integral about a part part of the time density curve shown in FIG. It is a figure which shows the outline of the functional ischemia detection method. It is a figure which shows the outline of the functional examination by a cardiac catheter. It is a graph which shows the change of the pulse pressure at rest and at the time of the maximum hyperemic reaction. It is a figure which shows an example which visualized the value of FFR by the shade of color in the three-dimensional model of a coronary artery.
  • FIG. 1 shows an outline of a functional ischemia detection system according to an embodiment of the present invention.
  • the functional ischemia detection system according to the present invention includes an image analysis device 100, a CT device (computed tomography device) 200, and a data processing device 210.
  • the CT apparatus 200 and the data processing apparatus 210 may be integrally configured to form one coronary angiography CT apparatus.
  • the image analysis device 100 and the data processing device 210 are connected via the network N.
  • the image analysis device 100 and the data processing device 210 include a hardware configuration of a general computer (information processing device), and, for example, a CPU (Central Processing Unit), a ROM (Read Only Memory), and a RAM. It includes hardware resources such as a memory composed of (Random Access Memory), a bus, an input / output interface, an input unit, an output unit, a storage unit, and a communication unit.
  • a CPU Central Processing Unit
  • ROM Read Only Memory
  • RAM random Access Memory
  • the CPU executes various processes according to the program recorded in the memory or the program loaded into the memory from the storage unit.
  • the CPU can, for example, execute a program for making the computer function as the image analysis device of the present invention.
  • at least a part of the functions of the image analysis apparatus can be implemented in hardware by an integrated circuit (ASIC) or the like for a specific application. The same applies to the other data processing device 210 of the present invention.
  • ASIC integrated circuit
  • the CPU and memory are connected to each other via a bus.
  • An input / output interface is also connected to this bus.
  • An input unit, an output unit, a storage unit, and a communication unit are connected to the input / output interface.
  • the input unit is composed of various buttons, a touch panel, a microphone, or the like, and inputs various information according to an instruction operation by a user or the like of the image analysis device 100 and the data processing device 210.
  • the output unit is composed of a display, a speaker, and the like, and outputs image data and audio data.
  • the storage unit is composed of a semiconductor memory such as DRAM (Dynamic Random Access Memory) or a hard disk, and stores various data.
  • the communication unit realizes communication with other devices.
  • the image analysis device 100 can acquire and store coronary contrast CT data (CCTA data) from, for example, a coronary contrast CT device including a CT device 200 and a data processing device 210.
  • CCTA data coronary contrast CT data
  • the image analysis device 100 can acquire CCTA data transferred from the data processing device 210 connected to the CT device 200 via a network N such as a dedicated line or a public line. ..
  • the image analyzer 100 reconstructs the CCTA data by predictive complementation, and acquires the time concentration curve of the proximal part of the coronary artery and the time concentration curve of the distal part of the coronary artery from the reconstructed CCTA data. can do.
  • the image analyzer 100 uses a quantitative analysis method such as the maximum slope method to quantify the coronary artery flow in the distal coronary artery and the proximal coronary artery (Volume of Interest: VOI).
  • the instantaneous blood flow reserve ratio (CT-iFR) can be calculated from CCTA data.
  • the data processing device 210 can be configured to perform the same processing as the image analysis device 100.
  • the CT device 200 which functions as a coronary angiography CT device, integrates standard coronary angiography that requires a high dose and continuous low-dose imaging, and CT scans the subject's chest in chronological order in chronological order. It is possible to acquire CT data of the heart and generate multi-phase coronary angiography CT data (CCTA data).
  • CCTA data multi-phase coronary angiography CT data
  • FIG. 2 shows a flowchart showing the flow of the functional ischemia detection method according to the embodiment of the present invention.
  • Each procedure of the functional ischemia detection method shown in FIG. 2 is performed by, for example, the functional ischemia detection system shown in FIG.
  • the data processing device 210 connected to the CT device 200 transfers the CT data (CCTA data) acquired in time series by the CT device 200 that CT scans the chest (heart) of the subject to the image analysis device 100. (Step S1).
  • the CCTA data is reconstructed using the predictive complement algorithm in the image analyzer 100 (step S2), and from the reconstructed image (reconstructed CCTA data), the aorta, the origin of the coronary artery (proximal part), Set the region of interest (VOI) such as the periphery (distal part of the coronary artery) and the myocardium (step S3).
  • VOI region of interest
  • the image analyzer 100 acquires a time contrast agent curve (hereinafter, also simply referred to as “time concentration curve”) of the region of interest of each site (step S4), and mathematically obtains a mathematical method (maximum slope) from the time concentration curve of each region of interest.
  • a time contrast agent curve hereinafter, also simply referred to as “time concentration curve”
  • a mathematical method maximum slope
  • FIG. 3 shows an example of an image of the entire heart generated by a 320-row CT device.
  • a 320-row CT apparatus can be mentioned.
  • the 320-row CT device is a 320-row CT that covers the entire heart of the subject (patient) with a single imaging, and performs continuous imaging of the contrast-enhanced first pass of the coronary artery.
  • the obtained CT data (image data) can be reconstructed by the predictive complement technology (predictive complement algorithm) in the image analysis apparatus 100, and the coronary artery flow can be imaged from the CT which is a conventional static image.
  • the image of the entire heart shown in FIG. 3 is an example imaged in this way.
  • a protocol that enables standard coronary angiography (boost scan) that requires a high dose by modulating the current during continuous imaging and continuous imaging of a low dose has been devised and adopted.
  • a large amount of contrast medium 50 to 60 ml
  • the coronary artery is imaged at a momentary timing when the contrast medium is sufficiently filled.
  • the diastolic phase is photographed by synchronizing with the electrocardiogram, and the injection amount and injection speed of the contrast medium are constant in terms of body weight, but the optimum imaging timing differs depending on the individual heart rate. ..
  • the conventional example requires the most complicated technique in CT imaging, and requires a high-voltage / high-current output device for rotating the X-ray tube at high speed.
  • CTDI CT dose index
  • DLP dose length product
  • the examination takes a long time, the exposure dose increases, and the burden on the patient increases.
  • the coronary artery morphology can be simultaneously performed by standard imaging, and the function evaluation can be performed simultaneously from CT-iFR by continuous imaging. Therefore, the examination in the present invention takes a shorter time than the conventional example, the exposure dose is reduced, and the burden on the patient can be reduced.
  • the entire series of data is used for the analysis in the low-dose continuous imaging, whereas in the conventional example, only the test scan is used for the analysis in the standard coronary artery imaging after the test scan.
  • a sufficient concentration gradient can be obtained in the time concentration curve of the coronary artery by using 50-70 ml of the contrast medium, which is smaller than that of the conventional example.
  • the time concentration curve of the coronary artery in the graph shown in FIG. 16 described later can be obtained, and the concentration (CT value) of the distal part of the coronary artery is sufficient as a contrast medium at 300 HU. It is in a filled state and is suitable for calculating the instantaneous blood flow reserve ratio (iFR).
  • the time concentration curve of the conventional example has a gentler gradient than the time concentration curve of the coronary artery in the graph shown in FIG. 16 described later, and the concentration (CT value) of the distal part of the coronary artery shows 300 HU in the present invention.
  • CT value concentration of the distal part of the coronary artery
  • FIG. 4 shows an example of a CT image in which noise is removed by performing predictive complementary reconstruction from a CT image taken at a low voltage to reduce radiation exposure.
  • the CT image taken at low voltage is very noisy like the image on the left side in FIG. 4 (the upper left is the cross section of the heart and the lower left is the side of the heart).
  • the coronary artery has not been sufficiently reproduced. Therefore, by predicting and complementing the CT images and reconstructing them so as to make the time interval (number of phases) of the CT images generated in time series (that is, multi-phase coronary angiography CT data) finer, the figure is shown.
  • the vortex of the image can be reduced and the image quality can be improved. That is, by making the time interval of the CT image finer, the CCTA data can be sequentially approximated and reconstructed, and noise can be removed as shown in the image on the right side in FIG. That is, the successive approximation reconstruction of CCTA data can contribute to the reduction of image noise.
  • Ziostation2 (Non-Patent Document 8) of Ziosoft's 3D medical image processing workstation can be used, and the predictive complement technology used in the image analysis device 100 is, for example, PhyZiodynamics used in Ziostation2.
  • the elemental technology of (Non-Patent Document 9) can be used. The outline of the prediction complementing technique will be described later with reference to FIGS. 13 and 14.
  • FIG. 5 shows an example of a coronary CT4D flow image with reduced noise and high spatial resolution.
  • the coronary CT4D flow image is a dynamic image that expresses the movement of the beating heart over time in real time.
  • the coronary CT4D flow image shown in FIG. 5 is an example of continuous 10 to 15 heartbeat imaging of the contrast medium first pass flowing from the pulmonary circulation to the systemic circulation using a 320-row CT device as the CT device 200 in the middle stage of expansion.
  • This is four-dimensional data obtained by reconstructing the captured data by increasing the number of phases by 3 to 5 times using predictive complementation.
  • Such four-dimensional data can be used to calculate CT-iFR, which is a blood flow index of coronary arteries.
  • CT-iFR which is an index of blood flow in the coronary arteries, is calculated by dividing the value of the slope of the time concentration curve in the distal part of the coronary artery by the value of the slope of the time concentration curve in the proximal part of the coronary artery.
  • the time concentration curve can be obtained by, for example, a dynamic measuring method as shown in FIG.
  • FIG. 6 shows an example of a dynamic measurement method for obtaining a time concentration curve of a coronary artery.
  • the time concentration curve of the region of interest set in the coronary artery can be dynamically measured by tracking the movement of the voxel (for example, the region of interest (region of interest) indicated by the arrow in FIG. 6) along the time series.
  • Such dynamic measurement makes it possible to automatically extract a cross-sectional view of a violently moving coronary artery over all phases (see FIG. 6). This makes it possible to obtain an accurate time concentration curve of the coronary arteries.
  • FIG. 7 shows an example of a coronary CT image displayed to identify the origin (proximal) of the left and right coronary arteries. From the front image (left in FIG. 7) and the image from above (right in FIG. 7) displayed on the output unit of the monitor or the like of the image analyzer 100, the origin (proximal portion) of the left and right coronary arteries. ) Can be specified.
  • FIG. 8 shows an example of a coronary CT image displayed to identify the distal part of the right coronary artery, the left anterior descending artery, and the circumflex branch. From the image of the entire heart displayed on the output unit such as the monitor of the image analyzer 100, the right coronary artery, the left anterior descending artery, the distal portion of the left circumflex branch, and a site having a blood vessel diameter of about 2 mm are identified.
  • FIG. 9 shows an example of a cross section of a coronary artery displayed to set a spherical region of interest (VOI) on the coronary artery.
  • To set the region of interest (VOI) first rotate the CT image at an arbitrary angle so that the cross section of the coronary artery (cross section orthogonal to the coronary artery) looks round (see FIG. 9A).
  • the region of interest can be determined according to the range specified in the cross-sectional image of the coronary artery obtained by the multi-phase coronary angiography CT data (CCTA data) displayed by the image analyzer, and the cross-sectional image of the coronary artery. Can be rotated at an angle substantially orthogonal to the direction of the coronary arteries.
  • CCTA data multi-phase coronary angiography CT data
  • a spherical VOI is set at the center of the blood vessel in the cross-sectional image of the coronary artery (see FIGS. 9 (b) and 9 (c)).
  • the region of interest (VOI) is set to match the diameter of the blood vessel at the origin (proximal) of the coronary artery and about 2 mm in diameter at the distal part of the coronary artery.
  • the region of interest is a substantially spherical region in the center of the vessel in the cross-sectional image of the coronary artery.
  • the image analyzer 100 automatically tracks the region of interest in the multi-phase coronary angiography CT data in the subsequent frame (cardiac cycle). , Each time concentration curve of the distal part of the coronary artery and the proximal part of the coronary artery can be measured. As a result, the image analysis apparatus 100 can automatically extract the change in coronary artery concentration with the passage of time in the region of interest (VOI), and can process the quantified data by the CT-iFR calculation algorithm.
  • VOI region of interest
  • FIG. 10 shows an example of a coronary artery CT image in which a region of interest is set and an example of a measurement result of a CT value (HU: Hounsfield unit) in the region of interest set in the coronary artery CT image.
  • HU Hounsfield unit
  • FIG. 10 (a) shows the site where the stenosis occurs in the coronary artery.
  • FIG. 10 (b) shows each interest obtained by the dynamic measurements described above when the regions of interest were set to the aorta, the origin (proximal) of the left anterior inferior branch (LAD) and the distal portion of the LAD.
  • This is an example of a graph (measurement result) in which the time concentration curve of the region is plotted.
  • the CT value (HU) is a black-and-white shading value (image density value) in a pixel or voxel representing a CT image.
  • the CT value is expressed by the lowest value of -1000, with water as the origin of zero and the state of empty air. And -1000 of air is set to be represented in black on the CT image.
  • FIG. 11 shows an example of a coronary artery time concentration curve focusing on the origin (proximal part) and the distal part before and after stenosis in the coronary artery.
  • the image analyzer 100 draws a time concentration curve of the coronary artery origin (proximal part) and the distal part based on the CT value (coronary artery concentration) obtained from the region of interest set on the coronary artery CT image. Can be done. It is also possible to input numerical data such as CT values to the computer for calculating CT-iFR by using a computer different from the image analysis device 100 for calculating CT-iFR.
  • FIG. 12 shows an example in which the inclination was calculated by extracting only the portion where the coronary artery concentration increased. From the time concentration curve as shown in FIG. 11, only the data in which the coronary artery concentration shows an ascending gradient is extracted (FIG. 12 (a)), a linear approximation straight line of two variables of time and concentration is drawn, and the origin (proximal) is drawn.
  • the inclination of the two straight lines of the portion) and the distal portion can be calculated.
  • the inclination of the starting portion (proximal portion) is 23.188
  • the inclination of the distal portion is 11.38.
  • the coronary flow in the region of interest (VOI) of the distal coronary artery and the origin (proximal) of the coronary artery can be quantified.
  • CT-iFR an index based on the instantaneous blood reserve ratio, divides the slope value of the time concentration curve at the distal part of the coronary artery by the slope value of the time concentration curve at the origin (proximal part) of the coronary artery (that is,).
  • CT-iFR was significantly lower in the ischemic region than in the non-ischemic region (0.68 vs. 0.89), and the ischemic region was detected in AUC 0.88, sensitivity 56%, and specificity 99%.
  • CT-iFR in the region with high-risk plaque was significantly lower than that in the region with calcified plaque and no plaque (0.71 vs. 0.94 vs. 0.93). From such evaluation experiments, it was confirmed that CT-iFR is a tool capable of detecting functional ischemia non-invasively, and that it is clear that coronary blood flow due to high-risk plaque is reduced.
  • FIG. 13 shows an outline of the prediction complementing technique.
  • An example of measuring the coronary CT4D flow image (FIG. 13 (a)) generated by the image analyzer 100 in 10 phases during the cardiac cycle is shown in FIG. 13 (b), and the coronary artery CT4D flow image (FIG. 13 (a)) is measured in 100 phases during the cardiac cycle.
  • An example of this is shown in FIG. 13 (c).
  • the measurement result shown in FIG. 13 (c) has a time resolution of 5 to 10 milliseconds, and can reproduce a high-quality coronary CT4D flow image as compared with the measurement result shown in FIG.
  • Predictive complement technology for example, PhyZiodynamics of Ziosoft (Non-Patent Document 9)
  • the multi-phase coronary angiography CT data is reconstructed so that the image data as shown in FIG. 13 (c) is approximately larger and the time resolution is higher. be able to.
  • Reconstructing the multi-phase coronary angiography CT data in this way is also referred to as successive approximation reconstruction of the multi-phase coronary angiography CT data.
  • the predictive complement can increase or decrease the number of predictive complementary images for reconstructing the multi-phase coronary angiography CT data according to the value of the predictive complement intensity input in the image analysis device 100.
  • FIG. 14 shows that the number of graph plots changes depending on the predicted complement strength.
  • the number of graph plots changes depending on the predicted complement strength.
  • the predictive complement strength is weak, the number of graph plots is small (FIG. 14 (a)), and when the predictive complement strength is strong (high), the number of graph plots is large (FIG. 14 (b)).
  • the slope of the time concentration curve and the area under the curve differ depending on the predicted complementary strength. Therefore, it is necessary to determine an appropriate predictive complement strength.
  • the image analysis device 100 can construct a coronary CT4D flow image and calculate CT-iFR by using such a prediction complementing technique.
  • FIG. 15 shows an example of calculating CT-iFR in the left coronary artery main trunk (LMT).
  • LMT left coronary artery main trunk
  • VOI region of interest
  • FIG. 15 (a) By setting the region of interest (VOI) to # 1, # 3, LMT, # 8 and # 13 (FIG. 15 (a)), each VOI is automatically tracked in the subsequent cardiac cycle, and each VOI is time-concentrated. You can get a curve.
  • CT-iFR can be calculated by dividing by the value.
  • the quantitative analysis method for calculating CT-iFR is based on the maximum slope method, but is not limited to this, and convolution using the entire graph of the time concentration curve is used. It may be an integration method or a method of calculating the area under the graph.
  • FIG. 16 shows an example of the time concentration curve of the coronary artery.
  • a sufficient concentration gradient can be obtained in the time concentration curve of the coronary artery by using a small amount of 50-70 ml of contrast medium.
  • the rise of concentration in the distal part of the coronary artery is delayed as compared with that in the proximal part. For this reason, when the maximum slope method is applied, there are cases where the measurement phase and interval of the upslope are different between the proximal part and the distal part.
  • the peak concentration (CT value) of the distal part of the coronary artery shows a value exceeding 300 HU, and the state is sufficiently filled with the contrast medium, but it is affected by the second circulation of the contrast medium over time 2 It becomes peak.
  • CT value peak concentration
  • FIG. 17 shows an example of analysis of the time concentration curve of the coronary artery by the convolution integration method.
  • the convolution integral is defined by the following equation. t and ⁇ are variables indicating time.
  • t and ⁇ are variables indicating time.
  • CT-iFR the convolution integral method
  • the time concentration curve is corrected by cross-correlation analysis.
  • the waveforms of the time concentration curves in the proximal and distal coronary arteries are similar and therefore cross-correlated. Therefore, the rising starting points of the two are made to match by translation, and the concentration (CT value) of the starting points is set to 0 point.
  • the time concentration curve of the distal part of the coronary artery is translated toward the proximal part of the coronary artery, and the rising points of the time concentration curves of the proximal part and the distal part of the coronary artery are matched. Then, in order to prevent the time concentration curve of the distal part of the coronary artery from becoming bimodal, only the initial circulation of the contrast medium is analyzed, so that the two graphs (time concentration curve) translated in parallel show the coronary artery. The data up to the peak in the proximal part is analyzed.
  • FIG. 18 shows an example of application of Bernoulli's theorem in the CT-iFR calculation method by the convolution integral method. Bernoulli's theorem states that for a steady flow of a non-viscous, incompressible fluid without external force, Is streamlined. However, v represents the speed of the fluid, p represents the pressure, and ⁇ represents the density. That is, the sum of the kinetic energy (kinetic energy, pressure, position) of the fluid in the cross section 1 (inflow) and the cross section 2 (outflow) of the flow pipe (corresponding to the blood vessel) shown in FIG. 18 is constant and equal.
  • Coronary blood flow is proportional to the intracoronary concentration (CT value), and the blood flow for a certain period of time can be estimated by the integral value of the time concentration curve (area under the curve). Then, based on Bernoulli's theorem, blood flow in the proximal and distal coronary arteries is kept constant in the absence of energy loss. However, it can be hypothesized that the presence of stenosis or atherosclerotic plaques that cause energy loss reduces distal blood flow.
  • FIG. 19 shows an example of measuring the area under the curve of the time concentration curve of the coronary artery by the convolution integration method.
  • the concentration in the coronary artery (CT value) is proportional to the coronary blood flow.
  • CT-iFR can be calculated as the ratio of the areas under the two curves.
  • the blood flow in the proximal portion is the area under the proximal curve (sum of the upper area and the lower area) calculated by the convolution integral method (3213 in the example of FIG. 19), and the distal portion.
  • FIG. 20 shows an example of a time concentration curve of a coronary artery in a functional ischemic region.
  • the example shown in FIG. 20 shows a case where there is an ischemic region in the distal part of the coronary artery.
  • CT value the peak value of the concentration
  • FIG. 21 shows an example in which a part from the rising edge of the time concentration curve shown in FIG. 20 to the peak value is extracted.
  • the time concentration curve is corrected by cross-correlation analysis. Since the waveforms of the temporal concentration curves of the proximal and distal coronary arteries are similar and cross-correlate, the rising starting points of both are made to match by translation, and the concentration (CT value) of the starting point is set to 0 point. And.
  • FIG. 22 shows an example in which the area under the curve is measured by convolution integration for a part of the time concentration curve shown in FIG.
  • the maximum slope method and the convolution integral method adopted when calculating CT-iFR are compared, and their functional ischemia detection diagnostic ability is compared.
  • the summarized table is shown below.
  • AUC area under the curve
  • AUC 0.9 to 1.0 is high accuracy
  • AUC 0.7 to 0.9 is medium accuracy
  • AUC 0.5 to 0.7 is low accuracy.
  • the calculation of CT-iFR by the convolution integral method shows an AUC of 0.9, and functional ischemia can be detected with high accuracy.
  • test scan low-dose continuous imaging
  • high-dose standard coronary imaging performed later
  • the test scan CT-iFR The optimal threshold for functional ischemia in the test scan is about 0.39, which is significantly lower than that of the iFR of the catheter.
  • a table summarizing the comparison between the maximum slope method and the convolution integral method for the calculation of CT-iFR for each region of the normal coronary artery is shown below.
  • the maximum slope method the left circumflex branch is lower than the left anterior lower branch.
  • the convolution integral method no difference is observed in the three coronary artery regions. From this result, it can be confirmed that the convolution integral method is easy to set the reference value and is not easily affected by the anatomical steering.
  • the multi-phase CCTA data obtained by coronary angiography CT is reconstructed by using predictive complement technology, and the reconstructed CCTA data is used to reconstruct the coronary artery.
  • CT-iFR can be calculated by acquiring time concentration curves of the proximal and distal coronary arteries and quantifying coronary flow using quantitative analysis techniques, non-invasively functional imagination. It can be expected to detect blood.
  • the functional ischemia detection system or the like according to the present invention can be used to support the diagnosis of heart disease or the like.

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Abstract

A conventional example (FFR-CT) regarding measurement of coronary fractional flow reserve (FFR) from a coronary artery 3D model by a simulation based on numerical fluid dynamics, has limitations such as the inability to perform analysis of a subject having coronary artery calcification or stent placement. In addition, FFR-CT is merely a calculation based on static information, and the hardness and the distensibility of the coronary artery wall are not taken into account.　The present invention provides a functional ischemia detection system or the like capable of calculating instantaneous flow reserve iFR (in the present invention, CT-iFR) and non-invasively detecting functional ischemia, by: reconstructing, by using a predictive interpolation technique, multi-time phase CCTA data obtained by coronary artery contrast CT; obtaining temporal concentration curves of a coronary artery proximal portion and a coronary artery distal portion from the reconstructed CCTA data; and quantifying coronary artery flow using a mathematical model (a maximum slope method, a convolution integral method, or the like).

Description

冠動脈ＣＴ４Ｄフローイメージによる機能的虚血検出技術Functional ischemia detection technology using coronary CT4D flow image
　本発明は、冠動脈の狭窄度を評価するだけでなく、急性冠症候群の予測因子となる低吸収プラーク（low attenuation plaque：LAP）等のハイリスクプラーク（high risk plaque：HRP）を可視化することができる冠動脈造影CT（以下、単に「冠動脈ＣＴ」ともいう）（coronary computed tomography angiography：CCTA）の時間造影剤濃度曲線から算出された冠血流量を用いて、非侵襲的に瞬時血流予備量比(instantaneous wave-free ratio：iFR)を測定する検査方法に関する。iFRとは、薬物による心筋の最大充血を必要とせず、安静時に冠動脈機能を評価する血行動態指標である。ここでは、CCTAから得られた冠動脈造影CTデータ（以下、「CCTAデータ」とも呼ぶ）に基づいて算出されたiFRを、ここでは、CT-iFRという。 The present invention not only evaluates the degree of stenosis of coronary arteries, but also visualizes high-risk plaque (HRP) such as low-attenuation plaque (LAP), which is a predictor of acute coronary syndrome. Non-invasive instantaneous blood flow reserve ratio using the coronary blood flow calculated from the time contrast agent concentration curve of coronary computed tomography angiography (CCTA) that can be performed. Regarding the inspection method for measuring (instantaneous wave-free ratio: iFR). iFR is a hemodynamic index that evaluates coronary artery function at rest without requiring maximum hyperemia of the myocardium due to drugs. Here, the iFR calculated based on the coronary angiography CT data (hereinafter, also referred to as “CCTA data”) obtained from CCTA is referred to as CT-iFR here.
　日本心臓血管外科手術データベース（Japan Cardiovascular Database）に登録された経皮的冠動脈形成術(Percutaneous Coronary Intervention；PCI)の適切性について、適切性基準（Appropriateness Use Criteria：AUC) に基づき分析した結果、慢性期冠動脈疾患（coronary artery disease：CAD）に対し適切と判断されたPCIは2009年版AUCで35.1%及び2012 年版AUC で24.8%に過ぎず、慢性期CADに対しPCIが不適切に実施されている（非特許文献１）。 As a result of analyzing the appropriateness of percutaneous coronary intervention (PCI) registered in the Japan Cardiovascular Database based on the Appropriateness Use Criteria (AUC), it is chronic. Only 35.1% of the 2009 AUC and 24.8% of the 2012 AUC were judged to be appropriate for coronary artery disease (CAD), and PCI is inappropriately implemented for chronic CAD. (Non-Patent Document 1).
　PCIの必要性は、冠動脈造影（coronary angiography：CAG）や冠動脈造影CT(CCTA)で狭窄率、病変長をもとに判断されている。しかしながら、CAGやCCTAはあくまで形態的評価であるから、虚血を伴わない狭窄に対して血行再建しても予後は改善しない。このような背景から、PCI施行前の機能的評価が保険診療において義務付けられるようになった。機能的評価として狭窄前後の圧較差をカテーテルで測定する冠血流予備量比（fractional flow reserve：FFR）が推奨されている（非特許文献２）。 The necessity of PCI is judged by coronary angiography (CAG) and coronary CT (CCTA) based on the stenosis rate and lesion length. However, since CAG and CCTA are morphological evaluations, revascularization for stenosis without ischemia does not improve the prognosis. Against this background, functional evaluation before the enforcement of PCI has become mandatory in insurance medical care. As a functional evaluation, the coronary flow reserve ratio (FFR), which measures the pressure gradient before and after stenosis with a catheter, is recommended (Non-Patent Document 2).
　図２３は、機能的虚血検出法の概要を示す（非特許文献３）。心臓から送り出された血液が大動脈を通って体全体に向かう際に、その一部が心臓を出た直後に大動脈から分岐する冠血管（冠状動脈、冠動脈）を通って心臓自身を隅々まで灌流している。心臓のまわりを通っている冠動脈が、動脈硬化（例えば、老化によって血管が硬くなったり、血管の壁に脂肪などの固まり（プラーク）が蓄積して血管の壁の一部が盛り上がり、血管の内腔が狭くなっている状態）などの原因で狭くなったり、閉塞したりして心筋に血液が行かなくなること（心筋虚血）が生じ得る。心筋虚血か否かの検査等を行うために、狭窄部位の前後で冠動脈を流れる造影剤の濃度の変化、冠動脈の圧力（冠動脈圧）の変化等を測定することで、冠血流を定量化することが可能である。狭窄部位の前後における造影剤濃度の変化、脈圧の変化等の測定は、後述するにように、CT（コンピュータ断層撮影、computed tomography）によって得られた画像データから構築された冠動脈の三次元（３Ｄ）モデルを用いて行うことができる。 FIG. 23 shows an outline of the functional ischemia detection method (Non-Patent Document 3). When blood pumped from the heart travels through the aorta to the entire body, it perfuse the heart itself to every corner through the coronary blood vessels (coronary arteries, coronary arteries) that branch off from the aorta immediately after part of it leaves the heart. doing. The coronary arteries that pass around the heart become arteriosclerosis (for example, the blood vessels become stiff due to aging, and masses such as fat (plaques) accumulate on the walls of the blood vessels, causing a part of the walls of the blood vessels to rise and inside the blood vessels. Blood cannot flow to the myocardium (myocardial ischemia) due to narrowing or obstruction due to (a state in which the cavity is narrowed) or the like. Quantify coronary blood flow by measuring changes in the concentration of contrast medium flowing through the coronary arteries before and after the stenosis site, changes in coronary artery pressure (coronary artery pressure), etc. It is possible to make it. As will be described later, the measurement of changes in contrast medium concentration, pulse pressure, etc. before and after the stenotic site is performed in three dimensions of the coronary artery constructed from image data obtained by CT (Computed Tomography). It can be done using a 3D) model.
　図２４は、心臓カテーテルによる機能的検査の概要を示す。心臓カテーテルによる機能的検査は、冠動脈拡張剤(ATP: アデノシン)を点滴投与しながら、プレッシャーワイヤーという装置(外径: 約0.36mm)を冠動脈に挿入して、狭窄部位の前後で遠位部の冠動脈圧Ｐｄと近位部の冠動脈圧Ｐａを測定する。ＦＦＲは、ＰｄをＰａで割ることで算出される（ＦＦＲ＝Ｐｄ／Ｐａ）。図２５のグラフは、安静時と最大充血反応時の脈圧の変化を示す。グラフの縦軸は脈圧を示し、横軸は時間を示す。冠動脈圧（近位部）Ｐａ（グラフ中の上方の折れ線）は、安静時から最大充血反応時の間で大きな変化はないが、冠動脈圧（遠位部）Ｐｄ（グラフ中の下方の折れ線）は、狭窄部位の影響で、安静時に比べて最大充血反応時では脈圧が大きく低下する。FFRは、このような変化を定量的に示す指標であり、冠動脈狭窄病変がどれくらい重度かを知ることができる。 FIG. 24 shows an outline of a functional examination using a cardiac catheter. For functional examination using a cardiac catheter, a device called a pressure wire (outer diameter: about 0.36 mm) is inserted into the coronary artery while instilling a coronary artery dilator (ATP: adenosine), and the distal part before and after the stenosis site. The coronary artery pressure Pd and the proximal coronary artery pressure Pa are measured. FFR is calculated by dividing Pd by Pa (FFR = Pd / Pa). The graph of FIG. 25 shows the change in pulse pressure between rest and maximal hyperemic reaction. The vertical axis of the graph shows pulse pressure, and the horizontal axis shows time. Coronary pressure (proximal) Pa (upper fold line in the graph) does not change significantly from rest to maximal red-eye reaction, but coronary pressure (distal) Pd (lower fold line in the graph) is Due to the effect of the stenosis site, the pulse pressure drops significantly during the maximal hyperemia reaction compared to at rest. FFR is an index that quantitatively indicates such changes, and it is possible to know how severe the coronary artery stenotic lesion is.
　FFRによる診断性能は、非常に良いが、侵襲的かつ煩雑な操作を要し、実臨床には普及していない。そこで、図２３に示されるように、非侵襲的な冠動脈診断方法の一例として、冠動脈ＣＴスキャンのデータに基づいて、心臓（冠動脈）の三次元（３Ｄ）モデルを構築し、数値流体力学（computational fluid dynamics）によるシミュレーションにより、冠動脈の３ＤモデルにおいてFFRの値を可視化することが行われている（図２６参照）。図２６は、冠動脈の三次元モデルにおいて色の濃淡でFFRの値を可視化した一例を示す。冠動脈３Ｄモデルを、FFRの値に応じで着色することで、色の濃淡でFFRの変化を容易に視認することができる。近年、CCTAの解剖学的情報を数値流体力学から解析するFFR-CTが米国HeartFlow社で開発されている。 The diagnostic performance by FFR is very good, but it requires invasive and complicated operations and is not widely used in clinical practice. Therefore, as shown in FIG. 23, as an example of a non-invasive coronary artery diagnostic method, a three-dimensional (3D) model of the heart (coronary artery) is constructed based on the data of a coronary artery CT scan, and computational fluid dynamics (computational) is constructed. FFR values are visualized in a 3D model of coronary arteries by simulation with fluid dynamics) (see FIG. 26). FIG. 26 shows an example of visualizing the FFR value by shade of color in a three-dimensional model of a coronary artery. By coloring the coronary artery 3D model according to the value of FFR, the change in FFR can be easily visually recognized by the shade of color. In recent years, FFR-CT, which analyzes CCTA anatomical information from computational fluid dynamics, has been developed by HeartFlow in the United States.
　しかしながら、数値流体力学によるシミュレーションによって冠動脈３ＤモデルからFFRを測定すること（例えば、米国HeartFlow社のFFR-CT）は、冠動脈石灰化やステント留置後の被検者で解析ができない等の大きな限界がある。また、FFR-CTは、あくまで静態情報に基づく計算であり、冠動脈壁の硬さや伸展性は考慮されていない（非特許文献４）。なお、米国HeartFlow社の要求する診療報酬は、日本国内の保健診療での画像管理加算とアンバランスで医療費を圧排するリスクがあり、広く普及に至っていない。 However, measuring FFR from a 3D model of coronary arteries by simulation by computational fluid dynamics (for example, FFR-CT of HeartFlow Co., Ltd. in the United States) has major limitations such as coronary artery calcification and inability to analyze by a subject after stent placement. is there. In addition, FFR-CT is a calculation based on static information to the last, and does not consider the hardness and extensibility of the coronary artery wall (Non-Patent Document 4). The medical fees required by HeartFlow in the United States have not become widespread because there is a risk of excluding medical expenses due to imbalance with image management addition in health care in Japan.
　そこで、上述の課題を解決するために、本発明では、薬物による心筋の最大充血を必要とせず、安静時に冠動脈機能を評価する血行動態指標である瞬時血流予備量比iFRを指標として採用し、冠動脈造影CTにより得られた多時相のCCTAデータを、予測補完技術を用いて再構成し、再構成されたCCTAデータから冠動脈近位部及び冠動脈遠位部の時間濃度曲線を取得し、定量的解析手法（maximum slope法（非特許文献５）、deconvolution法（非特許文献６）等）を用いて、冠動脈フローを定量化することで、iFR(本発明では、CT-iFRという)を算出することができ、非侵襲的に機能的虚血を検出することが可能な機能的虚血検出システム、方法、装置及びプログラム（以下、「機能的虚血検出システム等」という）を提供する。 Therefore, in order to solve the above-mentioned problems, in the present invention, the instantaneous blood flow reserve ratio iFR, which is a hemodynamic index for evaluating coronary artery function at rest, is adopted as an index without requiring maximum myocardial congestion by a drug. , The multi-phase CCTA data obtained by coronary angiography CT was reconstructed using predictive complement technology, and the time concentration curves of the proximal and distal coronary arteries were obtained from the reconstructed CCTA data. By quantifying coronary artery flow using a quantitative analysis method (maximum slope method (Non-Patent Document 5), deconvolution method (Non-Patent Document 6), etc.), iFR (referred to as CT-iFR in the present invention) can be obtained. Provided are functional ischemia detection systems, methods, devices and programs (hereinafter referred to as “functional ischemia detection systems, etc.”) that can be calculated and can detect functional ischemia non-invasively. ..
　iFRは、冠動脈内に狭窄病変があるとき、狭窄病変によってどのくらい血流が阻害されているかを推測する指標である。カテーテルを冠動脈に挿入し、プレッシャーワイヤーを用いて測定される（図２４参照）。冠動脈にプレッシャーワイヤーを挿入し、圧力Pa, PdからiFR=Pd/Paを求める。冠動脈拡張時に狭窄部位の影響でPdが低下する。冠動脈が最大拡張した状態では、末梢灌流圧が十分低下する。このため狭窄近位と遠位の血流比は、狭窄近位と遠位の圧力比に置換することができる。iFRはこの理論に基づいている。 IFR is an index for estimating how much blood flow is blocked by a stenotic lesion when there is a stenotic lesion in the coronary artery. A catheter is inserted into the coronary artery and measured using a pressure wire (see FIG. 24). Insert a pressure wire into the coronary artery and obtain iFR = Pd / Pa from the pressure Pa and Pd. When the coronary artery is dilated, Pd decreases due to the effect of the stenosis site. When the coronary arteries are maximally dilated, the peripheral perfusion pressure is sufficiently reduced. Therefore, the blood flow ratio between proximal and distal stenosis can be replaced by the pressure ratio between proximal and distal stenosis. iFR is based on this theory.
　本発明は、CTによる冠動脈内濃度が血流を反映することに基づいている。冠動脈狭窄部の近位と遠位の血流量を時間濃度曲線とmaximum slope法（非特許文献７）あるいは畳み込み積分法（deconvolution法）を用いて算出する。機能的狭窄などエネルギーロスがなければ iFR は１に近くなる。血流量からiFRを算出する本発明は、血流の阻害を推測するiFRの本来のコンセプトに合致している。本発明は、侵襲的カテーテルの圧力測定を再現するのではなく、血流量を直接推定する点で従来のカテーテルiFRとは根本的に異なる。 The present invention is based on the fact that the concentration in the coronary artery by CT reflects the blood flow. Proximal and distal blood flow in the coronary artery stenosis is calculated using a time concentration curve and the maximum slope method (Non-Patent Document 7) or the convolution integral method (deconvolution method). If there is no energy loss such as functional stenosis, iFR will be close to 1. The present invention of calculating iFR from blood flow is consistent with the original concept of iFR for estimating obstruction of blood flow. The present invention is fundamentally different from the conventional catheter iFR in that it directly estimates blood flow rather than reproducing the pressure measurement of an invasive catheter.
　本発明に係る機能的虚血検出システムの１つの実施形態として、機能的虚血検出システムは、冠動脈造影CT装置と、
　前記冠動脈造影CT装置に接続された情報処理装置と
を含み、
　前記冠動脈造影CT装置は、高線量を必要とする標準的冠動脈撮影と低線量の連続撮影を一体化し時系列的に被検者の胸部をCTスキャンして、時系列的に心臓のCTデータを取得して、多時相の冠動脈造影CTデータを生成し、
　前記情報処理装置は、前記多時相の冠動脈造影CTデータを、予測補完により再構成し、再構成された前記多時相の冠動脈造影CTデータから、冠動脈近位部の時間濃度曲線と、冠動脈遠位部の時間濃度曲線とを取得し、畳み込み積分法を用いて、前記冠動脈遠位部及び前記冠動脈近位部の関心領域の冠動脈フローを定量化することで、前記多時相の冠動脈造影CTデータによる瞬時血流予備量比（CT-iFR）を算出することを特徴とする。 As one embodiment of the functional ischemia detection system according to the present invention, the functional ischemia detection system includes a coronary angiography CT apparatus and
Including an information processing device connected to the coronary angiography CT device.
The coronary angiography CT device integrates standard coronary angiography that requires a high dose and continuous low-dose imaging, CT scans the subject's chest in chronological order, and captures CT data of the heart in chronological order. Obtained to generate multi-phase coronary CT data,
The information processing apparatus reconstructs the multi-phase coronary angiography CT data by predictive complementation, and from the reconstructed multi-phase coronary angiography CT data, a time concentration curve of the proximal part of the coronary artery and a coronary artery. The polyphasic coronary angiography by obtaining a time concentration curve of the distal part and quantifying the coronary flow of the region of interest in the distal part of the coronary artery and the proximal part of the coronary artery using the convolution integration method. It is characterized by calculating the instantaneous blood flow reserve ratio (CT-iFR) based on CT data.
　本発明に係る機能的虚血検出システムの好ましい実施形態として、
　前記情報処理装置は、前記冠動脈遠位部の時間濃度曲線を前記冠動脈近位部の時間濃度曲線側に平行移動させ、前記冠動脈近位部と前記冠動脈遠位部の時間濃度曲線の立ち上がり起点を一致させ、
　畳み込み積分法により、前記冠動脈近位部の時間濃度曲線から近位部曲線下面積の値を求め、前記冠動脈遠位部の時間濃度曲線から遠位部曲線下面積の値を求め、
　前記遠位部曲線下面積の値を、前記近位部曲線下面積の値で割ることで、前記瞬時血流予備量比（CT-iFR）を算出することを特徴とする。 As a preferred embodiment of the functional ischemia detection system according to the present invention,
The information processing apparatus moves the time concentration curve of the distal part of the coronary artery in parallel to the time concentration curve side of the proximal part of the coronary artery, and sets the rising point of the time concentration curve of the proximal part of the coronary artery and the distal part of the coronary artery. Match,
By the convolution integral method, the value of the area under the proximal curve was obtained from the time concentration curve of the proximal part of the coronary artery, and the value of the area under the distal curve was obtained from the time concentration curve of the distal part of the coronary artery.
The instantaneous blood flow reserve ratio (CT-iFR) is calculated by dividing the value of the area under the distal curve by the value of the area under the proximal curve.
　本発明に係る機能的虚血検出システムの好ましい実施形態として、
　前記冠動脈遠位部及び前記冠動脈近位部の各時間濃度曲線は、立ち上がりからピーク値までの一部部分を抽出した曲線であることを特徴とする。 As a preferred embodiment of the functional ischemia detection system according to the present invention,
Each time concentration curve of the distal part of the coronary artery and the proximal part of the coronary artery is characterized in that it is a curve extracted from a part from the rising edge to the peak value.
　本発明に係る機能的虚血検出システムの好ましい実施形態として、
　前記冠動脈造影CT装置は、320列CT装置であり、
　前記320列CT装置は、１回の撮影で前記被検者の心臓全体をカバーし、冠動脈の造影ファーストパスの連続撮影を行うことを特徴とする。 As a preferred embodiment of the functional ischemia detection system according to the present invention,
The coronary angiography CT device is a 320-row CT device.
The 320-row CT apparatus is characterized in that the entire heart of the subject is covered by a single imaging, and continuous imaging of a contrast-enhanced first pass of the coronary artery is performed.
　本発明に係る機能的虚血検出システムの好ましい実施形態として、
　前記予測補完は、前記情報処理装置において入力された予測補完強度の値に応じて、前記多時相の冠動脈造影CTデータの再構成のための予測補完画像の数を増減させることを特徴とする。 As a preferred embodiment of the functional ischemia detection system according to the present invention,
The predictive complement is characterized in that the number of predictive complementary images for reconstructing the coronary angiography CT data of the polychronous phase is increased or decreased according to the value of the predictive complement intensity input in the information processing apparatus. ..
　本発明に係る機能的虚血検出システムの好ましい実施形態として、
　前記予測補完は、前記多時相の冠動脈造影CTデータの再構成のための予測補完画像の数を増やし、前記多時相の冠動脈造影CTデータにおける画像の時間間隔を細かくすることで、前記多時相の冠動脈造影CTデータを逐次近似再構成し、画像ノイズを低減することを特徴とする。 As a preferred embodiment of the functional ischemia detection system according to the present invention,
The predictive complement increases the number of predictive complementary images for reconstructing the polyphasic coronary CT data and reduces the time interval of the images in the polyphasic coronary CT data. It is characterized by sequentially approximating and reconstructing the time-phase coronary angiography CT data to reduce image noise.
　本発明に係る機能的虚血検出システムの好ましい実施形態として、
　前記関心領域は、前記情報処理装置で表示される前記多時相の冠動脈造影CTデータにより得られる冠動脈の断面画像において指定された範囲に応じて定められ、
　前記冠動脈の断面画像は、冠動脈の方向に対して実質的に直交する角度になるように回転させられることを特徴とする。 As a preferred embodiment of the functional ischemia detection system according to the present invention,
The region of interest is defined according to the range specified in the cross-sectional image of the coronary artery obtained from the multi-phase coronary angiography CT data displayed by the information processing apparatus.
The cross-sectional image of the coronary artery is characterized in that it is rotated at an angle substantially orthogonal to the direction of the coronary artery.
　本発明に係る機能的虚血検出システムの好ましい実施形態として、
　前記関心領域は、前記冠動脈の断面画像の血管中心に実質的に球形の領域であることを特徴とする。 As a preferred embodiment of the functional ischemia detection system according to the present invention,
The region of interest is characterized by being a substantially spherical region at the center of the blood vessel in the cross-sectional image of the coronary artery.
　本発明に係る機能的虚血検出システムの好ましい実施形態として、
　前記情報処理装置は、前記冠動脈遠位部及び前記冠動脈近位部の前記関心領域が指定されると、前記多時相の冠動脈造影CTデータにおける前記関心領域をその後のフレームで自動的にトラッキングを行い、前記冠動脈遠位部及び前記冠動脈近位部の各時間濃度曲線を計測することを特徴とする。 As a preferred embodiment of the functional ischemia detection system according to the present invention,
When the region of interest in the distal portion of the coronary artery and the proximal portion of the coronary artery is designated, the information processing apparatus automatically tracks the region of interest in the polyphasic coronary angiography CT data in a subsequent frame. It is characterized in that each time concentration curve of the distal part of the coronary artery and the proximal part of the coronary artery is measured.
　本発明に係る機能的虚血検出方法の１つの実施形態として、機能的虚血検出方法は、
　高線量を必要とする標準的冠動脈撮影と低線量の連続撮影を一体化し時系列的に被検者の胸部をCTスキャンして、時系列的に心臓のCTデータを取得する冠動脈造影CT装置から得られた多時相の冠動脈造影CTデータを、予測補完により再構成する段階と、
　再構成された前記多時相の冠動脈造影CTデータから、冠動脈近位部の時間濃度曲線と、冠動脈遠位部の時間濃度曲線とを取得する段階と、
　畳み込み積分法を用いて、前記冠動脈遠位部及び前記冠動脈近位部の関心領域の冠動脈フローを定量化することで、前記多時相の冠動脈造影CTデータによる瞬時血流予備量比（CT-iFR）を算出する段階と
を含むことを特徴とする。 As one embodiment of the functional ischemia detection method according to the present invention, the functional ischemia detection method is described.
From a coronary angiography CT device that integrates standard coronary angiography that requires a high dose and continuous low-dose imaging, CT scans the subject's chest in chronological order, and acquires CT data of the heart in chronological order. The stage of reconstructing the obtained multi-phase coronary angiography CT data by predictive complementation,
The stage of acquiring the time concentration curve of the proximal part of the coronary artery and the time concentration curve of the distal part of the coronary artery from the reconstructed multi-phase coronary angiography CT data, and
By quantifying the coronary flow in the region of interest in the distal part of the coronary artery and the proximal part of the coronary artery using the convolutional integration method, the instantaneous blood flow reserve ratio (CT-) based on the multi-phase coronary angiography CT data. It is characterized by including a stage of calculating iFR).
　本発明に係る機能的虚血検出方法の好ましい実施形態として、
　前記瞬時血流予備量比（CT-iFR）を算出する段階は、
　前記冠動脈遠位部の時間濃度曲線を前記冠動脈近位部の時間濃度曲線側に平行移動させ、前記冠動脈近位部と前記冠動脈遠位部の時間濃度曲線の立ち上がり起点を一致させる段階と、
　畳み込み積分法により、前記冠動脈近位部の時間濃度曲線から近位部曲線下面積の値を求め、前記冠動脈遠位部の時間濃度曲線から遠位部曲線下面積の値を求める段階と、
　前記遠位部曲線下面積の値を、前記近位部曲線下面積の値で割ることで、前記瞬時血流予備量比（CT-iFR）を算出する段階と
を含むことを特徴とする。 As a preferred embodiment of the functional ischemia detection method according to the present invention,
The step of calculating the instantaneous blood flow reserve ratio (CT-iFR) is
A step of moving the time concentration curve of the distal part of the coronary artery in parallel to the time concentration curve side of the proximal part of the coronary artery to match the rising and starting points of the time concentration curve of the proximal part of the coronary artery and the distal part of the coronary artery.
By the convolution integral method, the value of the area under the proximal curve is obtained from the time concentration curve of the proximal part of the coronary artery, and the value of the area under the distal curve is obtained from the time concentration curve of the distal part of the coronary artery.
It is characterized by including a step of calculating the instantaneous blood flow reserve ratio (CT-iFR) by dividing the value of the area under the distal curve by the value of the area under the proximal curve.
　本発明に係る機能的虚血検出方法の好ましい実施形態として、
　前記冠動脈遠位部及び前記冠動脈近位部の各時間濃度曲線は、立ち上がりからピーク値までの一部部分を抽出した曲線であることを特徴とする。 As a preferred embodiment of the functional ischemia detection method according to the present invention,
Each time concentration curve of the distal part of the coronary artery and the proximal part of the coronary artery is characterized in that it is a curve extracted from a part from the rising edge to the peak value.
　本発明に係る機能的虚血検出方法の好ましい実施形態として、
　前記冠動脈造影CT装置は、320列CT装置であり、
　前記多時相の冠動脈造影CTデータは、前記320列CT装置により、１回の撮影で前記被検者の心臓全体をカバーし、冠動脈の造影ファーストパスの連続撮影を行い生成された画像を含むことを特徴とする。 As a preferred embodiment of the functional ischemia detection method according to the present invention,
The coronary angiography CT device is a 320-row CT device.
The multi-phase coronary angiography CT data includes an image generated by continuously photographing the entire heart of the subject with a single imaging by the 320-row CT apparatus and performing continuous imaging of the contrast-enhanced first pass of the coronary artery. It is characterized by that.
　本発明に係る機能的虚血検出方法の好ましい実施形態として、
　前記予測補完により再構成する段階は、
　指定された予測補完強度の値に応じて、前記多時相の冠動脈造影CTデータの再構成のための予測補完画像の数を増減させる段階を含むことを特徴とする。 As a preferred embodiment of the functional ischemia detection method according to the present invention,
The step of reconstructing by the prediction complement is
It is characterized by including a step of increasing or decreasing the number of predictive complement images for reconstructing the multi-phase coronary angiography CT data according to a specified value of predictive complement intensity.
　本発明に係る機能的虚血検出方法の好ましい実施形態として、
　前記予測補完により再構成する段階は、
　画像ノイズを低減するために、前記多時相の冠動脈造影CTデータの再構成のための予測補完画像の数を増やし、前記多時相の冠動脈造影CTデータにおける画像の時間間隔を細かくすることで、前記多時相の冠動脈造影CTデータを逐次近似再構成する段階を含むことを特徴とする。 As a preferred embodiment of the functional ischemia detection method according to the present invention,
The step of reconstructing by the prediction complement is
In order to reduce image noise, the number of predictive complementary images for reconstructing the multi-phase coronary CT data is increased, and the time interval of the images in the multi-phase coronary CT data is reduced. , The multi-phase coronary angiography CT data is sequentially approximated and reconstructed.
　本発明に係る機能的虚血検出方法の好ましい実施形態として、
　前記瞬時血流予備量比（CT-iFR）を算出する段階は、
　前記多時相の冠動脈造影CTデータにより得られる冠動脈の断面画像において指定された範囲に応じて、前記関心領域を定める段階と、
　前記冠動脈の断面画像を、冠動脈の方向に対して直交する角度になるように回転する段階とを含むことを特徴とする。 As a preferred embodiment of the functional ischemia detection method according to the present invention,
The step of calculating the instantaneous blood flow reserve ratio (CT-iFR) is
The stage of determining the region of interest according to the range specified in the cross-sectional image of the coronary artery obtained from the multi-phase coronary angiography CT data, and
The cross-sectional image of the coronary artery is characterized by including a step of rotating the coronary artery at an angle orthogonal to the direction of the coronary artery.
　本発明に係る機能的虚血検出方法の好ましい実施形態として、
　前記関心領域は、前記冠動脈の断面画像の血管中心に実質的に球形の領域であることを特徴とする。 As a preferred embodiment of the functional ischemia detection method according to the present invention,
The region of interest is characterized by being a substantially spherical region at the center of the blood vessel in the cross-sectional image of the coronary artery.
　本発明に係る機能的虚血検出方法の好ましい実施形態として、
　前記瞬時血流予備量比（CT-iFR）を算出する段階は、
　前記冠動脈遠位部及び前記冠動脈近位部の前記関心領域が指定されると、前記多時相の冠動脈造影CTデータにおける前記関心領域をその後のフレームで自動的にトラッキングを行い、前記冠動脈遠位部及び前記冠動脈近位部の各時間濃度曲線を計測する段階を含むことを特徴とする。 As a preferred embodiment of the functional ischemia detection method according to the present invention,
The step of calculating the instantaneous blood flow reserve ratio (CT-iFR) is
When the region of interest in the distal coronary artery and the proximal coronary artery is designated, the region of interest in the polyphasic coronary angiography CT data is automatically tracked in a subsequent frame, and the distal coronary artery is distal. It is characterized by including a step of measuring each time concentration curve of the portion and the proximal portion of the coronary artery.
　本発明に係る機能的虚血検出装置の１つの実施形態として、前記機能的虚血検出装置は、
　前記機能的虚血検出方法のいずれかの実施形態に記載の機能的虚血検出方法の各段階を実行することを特徴とする。 As one embodiment of the functional ischemia detection device according to the present invention, the functional ischemia detection device is
Each step of the functional ischemia detection method according to any embodiment of the functional ischemia detection method is performed.
　本発明に係る機能的虚血検出プログラムの１つの実施形態として、前記機能的虚血検出プログラムは、コンピュータによって実行させることで、前記コンピュータを前記機能的虚血検出装置として機能させることを特徴とする。 As one embodiment of the functional ischemia detection program according to the present invention, the functional ischemia detection program is executed by a computer to cause the computer to function as the functional ischemia detection device. To do.
　本発明に係る機能的虚血検出システム等は、冠動脈造影CTにより得られた多時相のCCTAデータを、予測補完技術を用いて再構成し、再構成されたCCTAデータから冠動脈近位部及び冠動脈遠位部の時間濃度曲線を取得し、定量的解析手法を用いて、冠動脈フローを定量化することで、CT-iFRを算出することができ、非侵襲的に機能的虚血を検出することができる。また、本発明は、冠動脈石灰化やステント留置後の被検者でも解析が可能である。さらに、本発明は、薬物による心筋の最大充血を必要とせず、安静時に冠動脈機能を評価する血行動態指標である瞬時血流予備量比iFRに基づいた指標（CT-iFR）を用いているので、静態情報に基づく計算とは異なり、冠動脈壁の硬さや伸展性も考慮される。 In the functional ischemia detection system and the like according to the present invention, the multi-phase CCTA data obtained by coronary angiography CT is reconstructed using predictive complement technology, and the reconstructed CCTA data is used to reconstruct the proximal part of the coronary artery and the proximal coronary artery. CT-iFR can be calculated by acquiring the time concentration curve of the distal part of the coronary artery and quantifying the coronary artery flow using a quantitative analysis method, and non-invasively detecting functional ischemia. be able to. The present invention can also be analyzed by a subject after coronary artery calcification or stent placement. Furthermore, since the present invention does not require maximum myocardial hyperemia due to a drug and uses an index (CT-iFR) based on the instantaneous blood flow reserve ratio iFR, which is a hemodynamic index for evaluating coronary artery function at rest. , Unlike the calculation based on static information, the hardness and extensibility of the coronary artery wall are also taken into consideration.
　そして、本発明に係る機能的虚血検出システム等を用いることで、従来の冠動脈CTに比べて、解剖学的狭窄と同時に機能的評価が可能となり、心筋の造影能を評価することができる。また、従来例の１つである米国HeartFlow社のCT-FFRに比べて、上述したように、冠動脈石灰化やステント留置症例でも解析可能である。データ解析は画像解析装置があれば可能であり、解析結果は検査後１時間程度で得ることができる。さらに、日本国内の冠動脈CTデータを国内の検出システムで検査することができ、海外の虚血検出システム等（例えば、米国HeartFlow社のFFR-CT）を用いるために、冠動脈CTデータを海外に送信する必要がなく、冠動脈CTデータが他の用途、研究に利用されるリスクを未然に防止することができる。 Then, by using the functional ischemia detection system or the like according to the present invention, it is possible to evaluate the function at the same time as the anatomical stenosis as compared with the conventional coronary CT, and it is possible to evaluate the contrast ability of the myocardium. In addition, as compared with CT-FFR of HeartFlow, Inc. of the United States, which is one of the conventional examples, it is possible to analyze cases of coronary artery calcification and stent placement as described above. Data analysis is possible with an image analysis device, and the analysis results can be obtained about 1 hour after the inspection. Furthermore, coronary CT data in Japan can be inspected with a domestic detection system, and coronary CT data can be transmitted overseas in order to use an overseas ischemia detection system (for example, FFR-CT of HeartFlow Inc. in the United States). It is not necessary to do so, and the risk of coronary CT data being used for other uses and research can be prevented.
　本発明に係る機能的虚血検出システム等は、上述した効果により、心臓カテーテル検査に比べて、外来で時間短縮でき、低侵襲で、患者（被検者）の肉体的・経済的負担軽減することができる。また、血管拡張剤などの薬剤負荷は必要なく、心事故発生のリスクが少ない。 Due to the above-mentioned effects, the functional ischemia detection system and the like according to the present invention can shorten the time in an outpatient setting, are minimally invasive, and reduce the physical and economic burden on the patient (subject) as compared with cardiac catheterization. be able to. In addition, there is no need for a drug load such as a vasodilator, and the risk of cardiac accidents is low.
本発明の一実施形態に係る機能的虚血検出システムの概要を示す図である。It is a figure which shows the outline of the functional ischemia detection system which concerns on one Embodiment of this invention. 本発明の一実施形態に係る機能的虚血検出方法の流れを示すフローチャートである。It is a flowchart which shows the flow of the functional ischemia detection method which concerns on one Embodiment of this invention. 320列CT装置により生成された心臓全体の画像の一例を示す図である。It is a figure which shows an example of the image of the whole heart generated by the 320-row CT apparatus. 放射線被曝低減のため低電圧撮影されたCT画像から、予測補完再構成を行うことでノイズを除去したCT画像の一例を示す図である。It is a figure which shows an example of the CT image which removed the noise by performing predictive complementation reconstruction from the CT image which was taken at low voltage to reduce radiation exposure. ノイズを低減して高い空間分解能を備えた冠動脈ＣＴ４Ｄフローイメージの一例を示す図である。It is a figure which shows an example of the coronary artery CT4D flow image which reduced noise and provided high spatial resolution. 冠動脈の時間濃度曲線を得るためのダイナミックな計測方法の一例を示す図である。It is a figure which shows an example of the dynamic measurement method for obtaining the time concentration curve of a coronary artery. 左右冠動脈の起始部（近位部）を特定するために表示される冠動脈CT画像の一例を示す図である。It is a figure which shows an example of the coronary artery CT image displayed for identifying the origin (proximal part) of the left and right coronary arteries. 図８は、右冠動脈、左前下行枝、回旋枝の遠位部を特定するために表示される冠動脈CT画像の一例を示す図である。FIG. 8 is a diagram showing an example of a coronary artery CT image displayed to identify the distal portion of the right coronary artery, the left anterior descending artery, and the circumflex branch. 冠動脈上に球形の関心領域（Volume of Interest: VOI）を設定するために表示される冠動脈の断面の一例を示す図である。It is a figure which shows an example of the cross section of a coronary artery displayed for setting a spherical interest area (Volume of Interest: VOI) on a coronary artery. 関心領域が設定された冠動脈CT画像の一例と、冠動脈CT画像において設定された関心領域におけるCT値（HU）の測定結果の一例を示す図である。It is a figure which shows an example of the coronary artery CT image in which a region of interest is set, and an example of the measurement result of the CT value (HU) in the region of interest set in a coronary artery CT image. 冠動脈の時間濃度曲線の一例を示す図である。It is a figure which shows an example of the time concentration curve of a coronary artery. 冠動脈濃度の上昇部分のみを抽出して傾きを算出した一例を示す図である。It is a figure which shows an example which calculated the inclination by extracting only the portion where the coronary artery concentration increased. 予測補完技術の概要を示す図である。It is a figure which shows the outline of the prediction complementing technique. 予測補完強度によりグラフプロット数が変化することを示す図である。It is a figure which shows that the graph plot number changes by the prediction complement strength. 左冠動脈主幹部（LMT）においてCT-iFRを算出する一例を示す図である。It is a figure which shows an example of calculating CT-iFR in the left coronary artery main trunk (LMT). 冠動脈の時間濃度曲線の一例を示す図である。It is a figure which shows an example of the time concentration curve of a coronary artery. 畳み込み積分法による冠動脈の時間濃度曲線の解析例を示す図である。It is a figure which shows the analysis example of the time concentration curve of a coronary artery by a convolution integral method. 畳み込み積分法によるCT-iFR算出法においてベルヌーイの定理の応用の一例を示す図である。It is a figure which shows an example of application of Bernoulli's theorem in the CT-iFR calculation method by a convolution integral method. 畳み込み積分法による冠動脈の時間濃度曲線の曲線下面積を測定する一例を示す図である。It is a figure which shows an example of measuring the area under the curve of the time concentration curve of a coronary artery by a convolution integral method. 機能的虚血領域の冠動脈の時間濃度曲線の一例を示す図である。It is a figure which shows an example of the time concentration curve of the coronary artery of a functional ischemic region. 図２０に示す時間濃度曲線の立ち上がりからピーク値までの一部部分を抽出した例を示す図である。It is a figure which shows the example which extracted a part part from the rise of the time density curve to the peak value shown in FIG. 図２１に示す時間濃度曲線の一部部分について畳み込み積分による曲線下面積を測定した例を示す図である。It is a figure which shows the example which measured the area under the curve by the convolution integral about a part part of the time density curve shown in FIG. 機能的虚血検出法の概要を示す図である。It is a figure which shows the outline of the functional ischemia detection method. 心臓カテーテルによる機能的検査の概要を示す図である。It is a figure which shows the outline of the functional examination by a cardiac catheter. 安静時と最大充血反応時の脈圧の変化を示すグラフである。It is a graph which shows the change of the pulse pressure at rest and at the time of the maximum hyperemic reaction. 冠動脈の三次元モデルにおいて色の濃淡でＦＦＲの値を可視化した一例を示す図である。It is a figure which shows an example which visualized the value of FFR by the shade of color in the three-dimensional model of a coronary artery.
　以下に図面を参照して、本発明の一実施形態について説明する。なお、実施の形態を説明するための全ての図において、同じものには原則として同一の符号を付し、その繰り返しの説明は省略する。本発明の個々の実施形態は、独立したものではなく、それぞれ組み合わせて適宜実施することができる。 An embodiment of the present invention will be described below with reference to the drawings. In addition, in all the figures for demonstrating the embodiment, in principle, the same reference numerals are given to the same ones, and the repeated description thereof will be omitted. The individual embodiments of the present invention are not independent and can be appropriately implemented in combination with each other.
　図１は、本発明の一実施形態に係る機能的虚血検出システムの概要を示す。本発明に係る機能的虚血検出システムは、画像解析装置１００と、CT装置（コンピュータ断層撮影装置）２００と、データ処理装置２１０とを含む。CT装置２００とデータ処理装置２１０とは、一体として構成し、１つの冠動脈造影CT装置とすることもできる。画像解析装置１００とデータ処理装置２１０とは、ネットワークＮを介して接続される。 FIG. 1 shows an outline of a functional ischemia detection system according to an embodiment of the present invention. The functional ischemia detection system according to the present invention includes an image analysis device 100, a CT device (computed tomography device) 200, and a data processing device 210. The CT apparatus 200 and the data processing apparatus 210 may be integrally configured to form one coronary angiography CT apparatus. The image analysis device 100 and the data processing device 210 are connected via the network N.
　画像解析装置１００及びデータ処理装置２１０は、一般的なコンピュータ（情報処理装置）のハードウェア構成を備えるものであり、例示的に、ＣＰＵ（Ｃｅｎｔｒａｌ　Ｐｒｏｃｅｓｓｉｎｇ　Ｕｎｉｔ）と、ＲＯＭ（Ｒｅａｄ　Ｏｎｌｙ　Ｍｅｍｏｒｙ）及びＲＡＭ（Ｒａｎｄｏｍ　Ａｃｃｅｓｓ　Ｍｅｍｏｒｙ）等からなるメモリと、バスと、入出力インターフェースと、入力部と、出力部と、記憶部と、通信部等のハードウェア資源を含む。 The image analysis device 100 and the data processing device 210 include a hardware configuration of a general computer (information processing device), and, for example, a CPU (Central Processing Unit), a ROM (Read Only Memory), and a RAM. It includes hardware resources such as a memory composed of (Random Access Memory), a bus, an input / output interface, an input unit, an output unit, a storage unit, and a communication unit.
　ＣＰＵは、メモリに記録されているプログラム、又は、記憶部からメモリにロードされたプログラムにしたがって各種の処理を実行する。ＣＰＵは、例えば、コンピュータを本発明の画像解析装置として機能させるためのプログラムを実行することができる。また、画像解析装置の少なくとも一部の機能を、特定用途向け集積回路（ＡＳＩＣ）等でハードウェア的に実装することも可能である。本発明のその他のデータ処理装置２１０についても同様である。 The CPU executes various processes according to the program recorded in the memory or the program loaded into the memory from the storage unit. The CPU can, for example, execute a program for making the computer function as the image analysis device of the present invention. Further, at least a part of the functions of the image analysis apparatus can be implemented in hardware by an integrated circuit (ASIC) or the like for a specific application. The same applies to the other data processing device 210 of the present invention.
　メモリには、ＣＰＵが各種の処理を実行する上において必要なデータ等も適宜記憶される。ＣＰＵ及びメモリは、バスを介して相互に接続されている。このバスには、入出力インターフェースも接続されている。入出力インターフェースには、入力部と、出力部と、記憶部と、通信部とが接続されている。入力部は、各種ボタン、タッチパネルあるいはマイク等で構成され、画像解析装置１００及びデータ処理装置２１０の利用者等の指示操作に応じて各種情報を入力する。出力部は、ディスプレイやスピーカ等で構成されており、画像データや音声データを出力する。記憶部は、ＤＲＡＭ（Ｄｙｎａｍｉｃ  Ｒａｎｄｏｍ  Ａｃｃｅｓｓ  Ｍｅｍｏｒｙ）等の半導体メモリまたはハードディスクで構成され、各種データを記憶する。通信部は、他の装置との間で行う通信を実現する。 Data and the like necessary for the CPU to execute various processes are also appropriately stored in the memory. The CPU and memory are connected to each other via a bus. An input / output interface is also connected to this bus. An input unit, an output unit, a storage unit, and a communication unit are connected to the input / output interface. The input unit is composed of various buttons, a touch panel, a microphone, or the like, and inputs various information according to an instruction operation by a user or the like of the image analysis device 100 and the data processing device 210. The output unit is composed of a display, a speaker, and the like, and outputs image data and audio data. The storage unit is composed of a semiconductor memory such as DRAM (Dynamic Random Access Memory) or a hard disk, and stores various data. The communication unit realizes communication with other devices.
　画像解析装置１００は、例えば、CT装置２００とデータ処理装置２１０とを含む冠動脈造影CT装置から、冠動脈造影CTデータ（CCTAデータ）を取得して記憶することができる。図１に示す実施形態では、画像解析装置１００は、CT装置２００に接続されたデータ処理装置２１０から、専用回線又は公衆回線等のネットワークＮを介して転送されたCCTAデータを取得することができる。 The image analysis device 100 can acquire and store coronary contrast CT data (CCTA data) from, for example, a coronary contrast CT device including a CT device 200 and a data processing device 210. In the embodiment shown in FIG. 1, the image analysis device 100 can acquire CCTA data transferred from the data processing device 210 connected to the CT device 200 via a network N such as a dedicated line or a public line. ..
　画像解析装置１００は、後述するように、CCTAデータを予測補完により再構成し、再構成されたCCTAデータから、冠動脈近位部の時間濃度曲線と、冠動脈遠位部の時間濃度曲線とを取得することができる。また、画像解析装置１００は、maximum slope法等の定量的解析手法を用いて、冠動脈遠位部及び冠動脈近位部の関心領域（Volume of Interest: VOI）の冠動脈フローを定量化することで、CCTAデータによる瞬時血流予備量比（CT-iFR）を算出することができる。なお、別の実施形態では、データ処理装置２１０において、画像解析装置１００と同様の処理を行えるように構成することもできる。 As will be described later, the image analyzer 100 reconstructs the CCTA data by predictive complementation, and acquires the time concentration curve of the proximal part of the coronary artery and the time concentration curve of the distal part of the coronary artery from the reconstructed CCTA data. can do. In addition, the image analyzer 100 uses a quantitative analysis method such as the maximum slope method to quantify the coronary artery flow in the distal coronary artery and the proximal coronary artery (Volume of Interest: VOI). The instantaneous blood flow reserve ratio (CT-iFR) can be calculated from CCTA data. In another embodiment, the data processing device 210 can be configured to perform the same processing as the image analysis device 100.
　冠動脈造影CT装置として機能するCT装置２００は、高線量を必要とする標準的冠動脈撮影と低線量の連続撮影を一体化し時系列的に被検者の胸部をCTスキャンして、時系列的に心臓のCTデータを取得して、多時相の冠動脈造影CTデータ（CCTAデータ）を生成することができる。 The CT device 200, which functions as a coronary angiography CT device, integrates standard coronary angiography that requires a high dose and continuous low-dose imaging, and CT scans the subject's chest in chronological order in chronological order. It is possible to acquire CT data of the heart and generate multi-phase coronary angiography CT data (CCTA data).
　図２は、本発明の一実施形態に係る機能的虚血検出方法の流れを示すフローチャートを示す。図２に示す機能的虚血検出方法の各手順は、例えば、図１に示す機能的虚血検出システムによって行われる。まず、CT装置２００に接続されたデータ処理装置２１０が、被験者の胸部（心臓）をCTスキャンするCT装置２００により時系列的に取得したCTデータ（CCTAデータ）を、画像解析装置１００に転送する（ステップS1）。次に、画像解析装置１００において予測補完アルゴリズムを用いてCCTAデータを再構成し（ステップS2）、再構成画像（再構成されたCCTAデータ）から、大動脈、冠動脈起始部（近位部）、末梢（冠動脈遠位部）、 心筋等の関心領域（VOI）をそれぞれ設定する（ステップS3）。 FIG. 2 shows a flowchart showing the flow of the functional ischemia detection method according to the embodiment of the present invention. Each procedure of the functional ischemia detection method shown in FIG. 2 is performed by, for example, the functional ischemia detection system shown in FIG. First, the data processing device 210 connected to the CT device 200 transfers the CT data (CCTA data) acquired in time series by the CT device 200 that CT scans the chest (heart) of the subject to the image analysis device 100. (Step S1). Next, the CCTA data is reconstructed using the predictive complement algorithm in the image analyzer 100 (step S2), and from the reconstructed image (reconstructed CCTA data), the aorta, the origin of the coronary artery (proximal part), Set the region of interest (VOI) such as the periphery (distal part of the coronary artery) and the myocardium (step S3).
　画像解析装置１００は、各部位の関心領域の時間造影剤曲線（以下、単に「時間濃度曲線」ともいう）を取得し（ステップS4）、各関心領域の時間濃度曲線から数学的手法（maximum slope法等の定量的解析手法）を用いてCT-iFRを算出する（ステップS5）。CT-iFRの具体的な算出方法については後述する。 The image analyzer 100 acquires a time contrast agent curve (hereinafter, also simply referred to as “time concentration curve”) of the region of interest of each site (step S4), and mathematically obtains a mathematical method (maximum slope) from the time concentration curve of each region of interest. Calculate CT-iFR using a quantitative analysis method such as a method (step S5). The specific calculation method of CT-iFR will be described later.
　図３は、320列CT装置により生成された心臓全体の画像の一例を示す。図１に示す実施形態において、CT装置２００の一例として、320列CT装置を挙げることができる。320列CT装置は、１回の撮影で被験者（患者）の心臓全体をカバーする320列CTで、冠動脈の造影ファーストパスの連続撮影を実施する。得られたCTデータ（画像データ）を、画像解析装置１００において予測補完技術（予測補完アルゴリズム）により再構成し、従来静態画像であるCTから冠動脈フローをイメージ化することができる。図３に示される心臓全体の画像は、このようにしてイメージ化された一例である。 FIG. 3 shows an example of an image of the entire heart generated by a 320-row CT device. In the embodiment shown in FIG. 1, as an example of the CT apparatus 200, a 320-row CT apparatus can be mentioned. The 320-row CT device is a 320-row CT that covers the entire heart of the subject (patient) with a single imaging, and performs continuous imaging of the contrast-enhanced first pass of the coronary artery. The obtained CT data (image data) can be reconstructed by the predictive complement technology (predictive complement algorithm) in the image analysis apparatus 100, and the coronary artery flow can be imaged from the CT which is a conventional static image. The image of the entire heart shown in FIG. 3 is an example imaged in this way.
　本発明では、連続撮影時電流を変調させ高線量が必要な標準的冠動脈撮影(boost scan)と低線量の連続撮影を可能となるプロトコールを考案して採用した。従来例（例えば、非特許文献７）の標準的冠動脈撮影は、大量の造影剤(50～60ml)を10秒程度で注入し、冠動脈を造影剤で十分に満たされた一瞬のタイミングに撮影している。また、従来例では、心電図同期をかけ拡張時相を撮影しており、造影剤の注入量、注入速度は体重換算で一定だが、至適な撮影タイミングは個々の心拍数に依存し異なってしまう。さら、従来例は、CT撮影において最も複雑な技術を要し、X線管球を高速で回転させるための高電圧・高電流の出力装置が必要である。 In the present invention, a protocol that enables standard coronary angiography (boost scan) that requires a high dose by modulating the current during continuous imaging and continuous imaging of a low dose has been devised and adopted. In the standard coronary artery imaging of the conventional example (for example, Non-Patent Document 7), a large amount of contrast medium (50 to 60 ml) is injected in about 10 seconds, and the coronary artery is imaged at a momentary timing when the contrast medium is sufficiently filled. ing. Further, in the conventional example, the diastolic phase is photographed by synchronizing with the electrocardiogram, and the injection amount and injection speed of the contrast medium are constant in terms of body weight, but the optimum imaging timing differs depending on the individual heart rate. .. Furthermore, the conventional example requires the most complicated technique in CT imaging, and requires a high-voltage / high-current output device for rotating the X-ray tube at high speed.
　このため本法で提案する連続撮影を標準的冠動脈撮影と同時に組み合わせることはできなかった。１つの従来例では、低線量の連続撮影（テストスキャン）を先に実施し、高線量の標準的冠動脈撮影を後に実施するといったように、２つの撮影を別々に実施している。 Therefore, it was not possible to combine the continuous imaging proposed by this method at the same time as standard coronary imaging. In one conventional example, two imagings are performed separately, such as a low-dose continuous imaging (test scan) first and a high-dose standard coronary imaging later.
　本発明に係る低線量連続撮影と、従来例のテストスキャン後の標準的冠動脈撮影との比較をまとめた表を以下に示す。
Figure JPOXMLDOC01-appb-T000001
 CTDI: CT 線量指標 (computed tomography dose index)
DLP：線量と長さの積 (dose length product)
CTDI, DLPは低線量連続撮影60例と標準的撮影85例の平均値 A table summarizing the comparison between the low-dose continuous radiography according to the present invention and the standard coronary artery radiography after the test scan of the conventional example is shown below.
Figure JPOXMLDOC01-appb-T000001
 CTDI: CT dose index
DLP: dose length product
CTDI and DLP are the average values of 60 low-dose continuous radiographs and 85 standard radiographs.
　従来例では、テストスキャン後に、高線量の標準的冠動脈撮影を実施しているため、検査は長時間となり、被ばく線量も増大し患者負担は増えてしまう。これに対して、本発明は、標準的撮影で冠動脈形態を、連続撮影でCT-iFRから機能評価を同時に実施することができる。このため、本発明での検査は、従来例に比べて短い時間となり、被ばく線量も少なくなり患者負担を軽減することができる。また、本発明では、低線量連続撮影において一連のデータ全てを解析に使用するのに対して、従来例では、テストスキャン後の標準的冠動脈撮影においてテストスキャンのみを解析に使用することになる。 In the conventional example, since a high-dose standard coronary angiography is performed after the test scan, the examination takes a long time, the exposure dose increases, and the burden on the patient increases. On the other hand, in the present invention, the coronary artery morphology can be simultaneously performed by standard imaging, and the function evaluation can be performed simultaneously from CT-iFR by continuous imaging. Therefore, the examination in the present invention takes a shorter time than the conventional example, the exposure dose is reduced, and the burden on the patient can be reduced. Further, in the present invention, the entire series of data is used for the analysis in the low-dose continuous imaging, whereas in the conventional example, only the test scan is used for the analysis in the standard coronary artery imaging after the test scan.
　本発明に係る低線量連続撮影では、従来例よりも少ない造影剤50-70mlを用いて、冠動脈の時間濃度曲線において十分な濃度勾配を得ることができる。例えば、本発明に係る低線量連続撮影では、後述する図１６に示すグラフにおける冠動脈の時間濃度曲線を得ることができり、冠動脈遠位部の濃度（CT値）は、300HUで十分造影剤に満たされた状態となり、瞬時血流予備量比(iFR)算出に適している。これに対して、テストスキャン後に、高線量の標準的冠動脈撮影を実施する従来例では、まず造影剤20mlと少ないテストスキャンでは、冠動脈の時間濃度曲線において十分な濃度勾配が得られない。従来例の時間濃度曲線は、例えば、後述する図１６に示すグラフにおける冠動脈の時間濃度曲線よりも緩やかな勾配となり、冠動脈遠位部の濃度（CT値）は、本発明では300HUを示すのに対して（図１６参照）、従来例では200HU前後となり造影効果に乏しい。 In the low-dose continuous imaging according to the present invention, a sufficient concentration gradient can be obtained in the time concentration curve of the coronary artery by using 50-70 ml of the contrast medium, which is smaller than that of the conventional example. For example, in the low-dose continuous imaging according to the present invention, the time concentration curve of the coronary artery in the graph shown in FIG. 16 described later can be obtained, and the concentration (CT value) of the distal part of the coronary artery is sufficient as a contrast medium at 300 HU. It is in a filled state and is suitable for calculating the instantaneous blood flow reserve ratio (iFR). On the other hand, in the conventional example in which a high-dose standard coronary angiography is performed after the test scan, a sufficient concentration gradient cannot be obtained in the time concentration curve of the coronary artery with a test scan as small as 20 ml of contrast medium. For example, the time concentration curve of the conventional example has a gentler gradient than the time concentration curve of the coronary artery in the graph shown in FIG. 16 described later, and the concentration (CT value) of the distal part of the coronary artery shows 300 HU in the present invention. On the other hand (see FIG. 16), in the conventional example, it is around 200 HU, and the contrast effect is poor.
　図４は、放射線被曝低減のため低電圧撮影されたCT画像から、予測補完再構成を行うことでノイズを除去したCT画像の一例を示す。被験者（患者）への放射線被曝を低減させるために、低電圧撮影されたCT画像は、図４中の左側の画像（左上は、心臓断面、左下は心臓側面）のようにノイズが非常に多く、冠動脈を十分に再現できていない。そこで、時系列的に生成されたCT画像（すなわち、多時相の冠動脈造影CTデータ）の時間間隔（フェーズ数）を細かくするように、CT画像を予測補完し、再構成することで、図４中の右側の画像（右上は心臓断面、左下は心臓側面）が示すように画像の渦を低減し画質を向上することができる。つまり、CT画像の時間間隔をより細かくすることで、CCTAデータを逐次近似再構成することができ、図４中の右側の画像のようにノイズを除去することができる。つまり、CCTAデータの逐次近似再構成は、画像ノイズの低減に寄与することができる。 FIG. 4 shows an example of a CT image in which noise is removed by performing predictive complementary reconstruction from a CT image taken at a low voltage to reduce radiation exposure. In order to reduce radiation exposure to the subject (patient), the CT image taken at low voltage is very noisy like the image on the left side in FIG. 4 (the upper left is the cross section of the heart and the lower left is the side of the heart). , The coronary artery has not been sufficiently reproduced. Therefore, by predicting and complementing the CT images and reconstructing them so as to make the time interval (number of phases) of the CT images generated in time series (that is, multi-phase coronary angiography CT data) finer, the figure is shown. As shown in the image on the right side of 4 (the upper right is the cross section of the heart and the lower left is the side surface of the heart), the vortex of the image can be reduced and the image quality can be improved. That is, by making the time interval of the CT image finer, the CCTA data can be sequentially approximated and reconstructed, and noise can be removed as shown in the image on the right side in FIG. That is, the successive approximation reconstruction of CCTA data can contribute to the reduction of image noise.
　画像解析装置１００は、例えば、Ziosoft社の３Ｄ医療画像処理ワークステーションのZiostation2（非特許文献８）を用いることができ、画像解析装置１００において用いられる予測補完技術は、例えば、Ziostation2で用いられるPhyZiodynamics（非特許文献９）の要素技術を用いることができる。予測補完技術の概要は、図１３及び図１４を参照して後述する。 As the image analysis device 100, for example, Ziostation2 (Non-Patent Document 8) of Ziosoft's 3D medical image processing workstation can be used, and the predictive complement technology used in the image analysis device 100 is, for example, PhyZiodynamics used in Ziostation2. The elemental technology of (Non-Patent Document 9) can be used. The outline of the prediction complementing technique will be described later with reference to FIGS. 13 and 14.
　図５は、ノイズを低減して高い空間分解能を備えた冠動脈CT4Dフローイメージの一例を示す。冠動脈CT4Dフローイメージとは、時間経過とともに拍動する心臓の動きをリアルタイムに表現した動的なイメージである。図５に示す冠動脈CT4Dフローイメージは、CT装置２００として320列CT装置を用いて肺循環から体循環へ流れる造影剤ファーストパスを拡張中期で連続１０～１５心拍撮影した一例である。撮影したデータを、予測補完を用いて３～５倍のフェーズ数を増加させて再構成した四次元データである。このような四次元データは、冠動脈の血流指標であるCT-iFRの算出に用いることができる。 FIG. 5 shows an example of a coronary CT4D flow image with reduced noise and high spatial resolution. The coronary CT4D flow image is a dynamic image that expresses the movement of the beating heart over time in real time. The coronary CT4D flow image shown in FIG. 5 is an example of continuous 10 to 15 heartbeat imaging of the contrast medium first pass flowing from the pulmonary circulation to the systemic circulation using a 320-row CT device as the CT device 200 in the middle stage of expansion. This is four-dimensional data obtained by reconstructing the captured data by increasing the number of phases by 3 to 5 times using predictive complementation. Such four-dimensional data can be used to calculate CT-iFR, which is a blood flow index of coronary arteries.
　冠動脈の血流指標であるCT-iFRは、冠動脈遠位部の時間濃度曲線の傾きの値を、冠動脈近位部の時間濃度曲線の傾きの値で割ることで算出される。時間濃度曲線は、例えば、図６に示すようなダイナミックな測定方法によって得ることができる。図６は、冠動脈の時間濃度曲線を得るためのダイナミックな計測方法の一例を示す。冠動脈において設定される関心領域の時間濃度曲線は、時系列に沿ったボクセル（例えば、図６中の矢印の部位（関心領域））の動きをトラッキングすることでダイナミックに計測することができる。このようなダイナミックな計測によって、激しく動く冠動脈の断面図を全時相にわたり自動的に抽出可能となる（図６参照）。これにより正確な冠動脈の時間濃度曲線を得ることができる。 CT-iFR, which is an index of blood flow in the coronary arteries, is calculated by dividing the value of the slope of the time concentration curve in the distal part of the coronary artery by the value of the slope of the time concentration curve in the proximal part of the coronary artery. The time concentration curve can be obtained by, for example, a dynamic measuring method as shown in FIG. FIG. 6 shows an example of a dynamic measurement method for obtaining a time concentration curve of a coronary artery. The time concentration curve of the region of interest set in the coronary artery can be dynamically measured by tracking the movement of the voxel (for example, the region of interest (region of interest) indicated by the arrow in FIG. 6) along the time series. Such dynamic measurement makes it possible to automatically extract a cross-sectional view of a violently moving coronary artery over all phases (see FIG. 6). This makes it possible to obtain an accurate time concentration curve of the coronary arteries.
　関心領域（VOI）の設定のために、まず、冠動脈CTから左右の冠動脈の起始部（近位部）を特定する。例えば、図７は、左右冠動脈の起始部（近位部）を特定するために表示される冠動脈CT画像の一例を示す。画像解析装置１００のモニター等の出力部に表示された心臓全体の正面像（図７中の左）と上からの像（図７中の右）から、左右冠動脈の起始部（近位部）を特定することができる。 To set the area of interest (VOI), first identify the origin (proximal part) of the left and right coronary arteries from the coronary artery CT. For example, FIG. 7 shows an example of a coronary CT image displayed to identify the origin (proximal) of the left and right coronary arteries. From the front image (left in FIG. 7) and the image from above (right in FIG. 7) displayed on the output unit of the monitor or the like of the image analyzer 100, the origin (proximal portion) of the left and right coronary arteries. ) Can be specified.
　次に、右冠動脈、左前下行枝、回旋枝の遠位部を特定する。図８は、右冠動脈、左前下行枝、回旋枝の遠位部を特定するために表示される冠動脈CT画像の一例を示す。画像解析装置１００のモニター等の出力部に表示された心臓全体の像から、右冠動脈、左前下行枝、左回旋枝の遠位部、血管径２ｍｍ程度の部位を特定する。 Next, identify the distal part of the right coronary artery, left anterior descending artery, and circumflex branch. FIG. 8 shows an example of a coronary CT image displayed to identify the distal part of the right coronary artery, the left anterior descending artery, and the circumflex branch. From the image of the entire heart displayed on the output unit such as the monitor of the image analyzer 100, the right coronary artery, the left anterior descending artery, the distal portion of the left circumflex branch, and a site having a blood vessel diameter of about 2 mm are identified.
　最後に、冠動脈CT画像の冠動脈上に実質的に球形の関心領域（VOI）を設定する。図９は、冠動脈上に球形の関心領域（VOI）を設定するために表示される冠動脈の断面の一例を示す。関心領域（VOI）の設定は、まず冠動脈横断（冠動脈に直交する断面）が丸くみえるように任意の角度にCT画像を回転させる（図９（ａ）参照）。つまり、関心領域は、画像解析装置で表示される多時相の冠動脈造影CTデータ（CCTAデータ）により得られる冠動脈の断面画像において指定された範囲に応じて定められることができ、冠動脈の断面画像は、冠動脈の方向に対して実質的に直交する角度になるように回転させることが可能である。 Finally, a substantially spherical region of interest (VOI) is set on the coronary artery of the coronary CT image. FIG. 9 shows an example of a cross section of a coronary artery displayed to set a spherical region of interest (VOI) on the coronary artery. To set the region of interest (VOI), first rotate the CT image at an arbitrary angle so that the cross section of the coronary artery (cross section orthogonal to the coronary artery) looks round (see FIG. 9A). That is, the region of interest can be determined according to the range specified in the cross-sectional image of the coronary artery obtained by the multi-phase coronary angiography CT data (CCTA data) displayed by the image analyzer, and the cross-sectional image of the coronary artery. Can be rotated at an angle substantially orthogonal to the direction of the coronary arteries.
　次に、冠動脈の断面画像において血管中心に球形VOIを設定する（図９（ｂ）及び（ｃ）参照）。関心領域（VOI）は、冠動脈起始部（近位部）は血管径に合わせて設定し、冠動脈遠位部は直径２ｍｍ程度に設定する。関心領域は、冠動脈の断面画像の血管中心に実質的に球形の領域である。画像解析装置１００は、冠動脈遠位部及び冠動脈近位部の関心領域が指定されると、多時相の冠動脈造影CTデータにおける関心領域をその後のフレーム（心周期）で自動的にトラッキングを行い、冠動脈遠位部及び冠動脈近位部の各時間濃度曲線を計測することができる。これにより、画像解析装置１００は、関心領域（VOI）において、時間経過による冠動脈濃度変化を自動抽出することができ、数値化したデータをCT-iFR算出アルゴリズムによって、処理することができる。 Next, a spherical VOI is set at the center of the blood vessel in the cross-sectional image of the coronary artery (see FIGS. 9 (b) and 9 (c)). The region of interest (VOI) is set to match the diameter of the blood vessel at the origin (proximal) of the coronary artery and about 2 mm in diameter at the distal part of the coronary artery. The region of interest is a substantially spherical region in the center of the vessel in the cross-sectional image of the coronary artery. When the region of interest in the distal part of the coronary artery and the proximal part of the coronary artery is specified, the image analyzer 100 automatically tracks the region of interest in the multi-phase coronary angiography CT data in the subsequent frame (cardiac cycle). , Each time concentration curve of the distal part of the coronary artery and the proximal part of the coronary artery can be measured. As a result, the image analysis apparatus 100 can automatically extract the change in coronary artery concentration with the passage of time in the region of interest (VOI), and can process the quantified data by the CT-iFR calculation algorithm.
　図１０は、関心領域が設定された冠動脈CT画像の一例と、冠動脈CT画像において設定された関心領域におけるCT値（HU：Hounsfield unit）の測定結果の一例を示す。図１０（ａ）では、冠動脈において狭窄が生じている部位を矢印で示す。図１０（ｂ）は、関心領域を大動脈、左前下枝（ＬＡＤ）の起始部（近位部）及びＬＡＤの遠位部に設定した際に、上述したダイナミックな計測によって得られた、各関心領域の時間濃度曲線をプロットしたグラフ（測定結果）の一例である。ここで、CT値（HU）とは、CT画像を表現するピクセルやボクセルにおける白黒の濃淡値（画像濃度値）のことである。CT値は水を原点のゼロとして、何もない空気の状態を最低の値である-1000で表現する。そして空気の-1000は、CT画像上では真っ黒に表現するように設定される。 FIG. 10 shows an example of a coronary artery CT image in which a region of interest is set and an example of a measurement result of a CT value (HU: Hounsfield unit) in the region of interest set in the coronary artery CT image. In FIG. 10 (a), the site where the stenosis occurs in the coronary artery is indicated by an arrow. FIG. 10 (b) shows each interest obtained by the dynamic measurements described above when the regions of interest were set to the aorta, the origin (proximal) of the left anterior inferior branch (LAD) and the distal portion of the LAD. This is an example of a graph (measurement result) in which the time concentration curve of the region is plotted. Here, the CT value (HU) is a black-and-white shading value (image density value) in a pixel or voxel representing a CT image. The CT value is expressed by the lowest value of -1000, with water as the origin of zero and the state of empty air. And -1000 of air is set to be represented in black on the CT image.
　簡略化のために、冠動脈における狭窄前後の起始部（近位部）と遠位部に着目した冠動脈時間濃度曲線の一例を図１１に示す。画像解析装置１００は、冠動脈CT画像上に設定された関心領域から得られたCT値（冠動脈濃度）に基づいて、冠動脈起始部（近位部）と遠位部の時間濃度曲線を描くことができる。なお、CT-iFR算出用に、画像解析装置１００とは別のコンピュータを用いて、CT値等の数値データをCT-iFR算出用のコンピュータに入力することもできる。 For simplification, FIG. 11 shows an example of a coronary artery time concentration curve focusing on the origin (proximal part) and the distal part before and after stenosis in the coronary artery. The image analyzer 100 draws a time concentration curve of the coronary artery origin (proximal part) and the distal part based on the CT value (coronary artery concentration) obtained from the region of interest set on the coronary artery CT image. Can be done. It is also possible to input numerical data such as CT values to the computer for calculating CT-iFR by using a computer different from the image analysis device 100 for calculating CT-iFR.
　冠動脈の各関心領域の時間濃度曲線を描いた後、冠動脈遠位部及び前記冠動脈近位部の各時間濃度曲線の傾きは、各時間濃度曲線の濃度上昇部分から線形近似直線を描き、線形近似直線の上り勾配（upslope）を計算することで求められる。図１２は、冠動脈濃度の上昇部分のみを抽出して傾きを算出した一例を示す。図１１に示すような時間濃度曲線から、冠動脈濃度が昇り勾配を呈すデータのみを抽出し（図１２（ａ））、時間と濃度の２変数の線形近似直線を描き、起始部（近位部）と遠位部の２直線の傾きを算出することができる。図１２（ｂ）に示すグラフでは、起始部（近位部）の傾きは２３．１８８であり、遠位部の傾きは１１．３８である。このようにして、冠動脈遠位部及び冠動脈起始部（近位部）の関心領域（VOI）の冠動脈フローを定量化することができる。 After drawing the time concentration curve of each region of interest of the coronary artery, the slope of each time concentration curve of the distal part of the coronary artery and the proximal part of the coronary artery is linearly approximated by drawing a linear approximation straight line from the concentration increasing part of each time concentration curve. It is obtained by calculating the upslope of a straight line. FIG. 12 shows an example in which the inclination was calculated by extracting only the portion where the coronary artery concentration increased. From the time concentration curve as shown in FIG. 11, only the data in which the coronary artery concentration shows an ascending gradient is extracted (FIG. 12 (a)), a linear approximation straight line of two variables of time and concentration is drawn, and the origin (proximal) is drawn. The inclination of the two straight lines of the portion) and the distal portion can be calculated. In the graph shown in FIG. 12B, the inclination of the starting portion (proximal portion) is 23.188, and the inclination of the distal portion is 11.38. In this way, the coronary flow in the region of interest (VOI) of the distal coronary artery and the origin (proximal) of the coronary artery can be quantified.
　瞬時血流予備量比に基づく指標CT-iFRは、冠動脈遠位部の時間濃度曲線の傾きの値を、冠動脈起始部（近位部）の時間濃度曲線の傾きの値で割ること（つまり、CT-iFR＝冠動脈遠位部の傾き／冠動脈起始部（近位部）で算出することができる。図１２（ｂ）に示す例では、CT-iFR=11.38/23.188=0.49である。 CT-iFR, an index based on the instantaneous blood reserve ratio, divides the slope value of the time concentration curve at the distal part of the coronary artery by the slope value of the time concentration curve at the origin (proximal part) of the coronary artery (that is,). , CT-iFR = inclination of distal coronary artery / origin of coronary artery (proximal). In the example shown in FIG. 12 (b), CT-iFR = 11.38 / 23.188 = 0.49.
　CT-iFRの機能的虚血検出能について、５０名の冠動脈疾患患者を対象とし、診断基準を負荷心筋血流SEPCT/SPECTとして評価実験を行った。結果として、CT-iFRは虚血領域で非虚血領域に比べ有意に低下し(0.68 vs. 0.89)、AUC 0.88, sensitivity 56%, specificity 99%で虚血領域を検出した。またハイリスクプラークを有する領域のCT-iFRは、石灰化プラークやプラーク無しの領域に比べ有意に低下していた（0.71 vs.0.94 vs.0.93）。このような評価実験により、CT-iFRは非侵襲的に機能的虚血を検出可能なツールであり、ハイリスクプラークによる冠血流が減少することを明らかであることを確認した。 An evaluation experiment was conducted on the functional ischemia detection ability of CT-iFR in 50 patients with coronary artery disease, using the diagnostic criteria as stress myocardial blood flow SEPCT / SPECT. As a result, CT-iFR was significantly lower in the ischemic region than in the non-ischemic region (0.68 vs. 0.89), and the ischemic region was detected in AUC 0.88, sensitivity 56%, and specificity 99%. In addition, CT-iFR in the region with high-risk plaque was significantly lower than that in the region with calcified plaque and no plaque (0.71 vs. 0.94 vs. 0.93). From such evaluation experiments, it was confirmed that CT-iFR is a tool capable of detecting functional ischemia non-invasively, and that it is clear that coronary blood flow due to high-risk plaque is reduced.
　CT-iFRを算出するアルゴリズムをより改善するためには、冠動脈造影CTデータ（CCTAデータ）を予測補完技術により適切に再構成する必要がある。図１３は、予測補完技術の概要を示す。画像解析装置１００によって生成された冠動脈CT4Dフローイメージ（図１３（ａ））を、心周期の間に１０フェーズで計測した例を図１３（ｂ）に示し、心周期の間に１００フェーズで計測した例を図１３（ｃ）に示す。図１３（ｃ）に示す計測結果は、５～１０ミリ秒の時間分解能であり、図１３（ｂ）に示す計測結果に比べて、高品質な冠動脈CT4Dフローイメージを再現することができる。予測補完技術（例えば、Ziosoft社のPhyZiodynamics（非特許文献９））は、例えば、図１３（ｂ）に示すように、心周期の間の画像データが少ない場合でも、画像間に予測補完画像を増やし、画像の時間間隔を細かくすることで、近似的に、図１３（ｃ）に示すような画像データが多く、時間分解能が高くなるように、多時相の冠動脈造影CTデータを再構成することができる。このように多時相の冠動脈造影CTデータを再構成することを、多時相の冠動脈造影CTデータを逐次近似再構成するともいう。 In order to further improve the algorithm for calculating CT-iFR, it is necessary to appropriately reconstruct the coronary angiography CT data (CCTA data) by predictive complement technology. FIG. 13 shows an outline of the prediction complementing technique. An example of measuring the coronary CT4D flow image (FIG. 13 (a)) generated by the image analyzer 100 in 10 phases during the cardiac cycle is shown in FIG. 13 (b), and the coronary artery CT4D flow image (FIG. 13 (a)) is measured in 100 phases during the cardiac cycle. An example of this is shown in FIG. 13 (c). The measurement result shown in FIG. 13 (c) has a time resolution of 5 to 10 milliseconds, and can reproduce a high-quality coronary CT4D flow image as compared with the measurement result shown in FIG. 13 (b). Predictive complement technology (for example, PhyZiodynamics of Ziosoft (Non-Patent Document 9)) produces predictive complementary images between images even when the image data during the cardiac cycle is small, as shown in FIG. 13 (b), for example. By increasing the number and making the time interval of the image finer, the multi-phase coronary angiography CT data is reconstructed so that the image data as shown in FIG. 13 (c) is approximately larger and the time resolution is higher. be able to. Reconstructing the multi-phase coronary angiography CT data in this way is also referred to as successive approximation reconstruction of the multi-phase coronary angiography CT data.
　予測補完は、画像解析装置１００において入力された予測補完強度の値に応じて、多時相の冠動脈造影CTデータの再構成のための予測補完画像の数を増減させることができる。例えば、図１４は、予測補完強度によりグラフプロット数が変化することを示す。予測補完強度により、グラフプロット数が変化する。予測補完強度が弱いとグラフプロットの数は少なく（図１４（ａ））、予測補完強度が強い（高い）とグラフプロットの数は多くなる（図１４（ｂ））。また、予測補完強度により、時間濃度曲線の傾きやカーブ下面積に違いが出てくる。このことから、適切な予測補完強度の決定が必要である。 The predictive complement can increase or decrease the number of predictive complementary images for reconstructing the multi-phase coronary angiography CT data according to the value of the predictive complement intensity input in the image analysis device 100. For example, FIG. 14 shows that the number of graph plots changes depending on the predicted complement strength. The number of graph plots changes depending on the predicted complement strength. When the predictive complement strength is weak, the number of graph plots is small (FIG. 14 (a)), and when the predictive complement strength is strong (high), the number of graph plots is large (FIG. 14 (b)). In addition, the slope of the time concentration curve and the area under the curve differ depending on the predicted complementary strength. Therefore, it is necessary to determine an appropriate predictive complement strength.
　画像解析装置１００は、このような予測補完技術を用いて、冠動脈CT4Dフローイメージを構築し、CT-iFRを算出することができる。例えば、図１５は、左冠動脈主幹部（LMT）においてCT-iFRを算出する一例を示す。関心領域（VOI）を＃１、＃３、LMT、＃８及び＃１３に設定すること（図１５（ａ））で、その後の心周期において各VOIを自動的にトラッキングして、それぞれ時間濃度曲線を得ることができる。＃８（冠動脈遠位部）の時間濃度曲線の上昇部分（上がり勾配）の線形近似直線の傾きの値と、ＬＭＴ（冠動脈起始部（近位部））の時間濃度曲線の上昇部分（上がり勾配）の線形近似直線の傾きの値を求め、＃８（冠動脈遠位部）の時間濃度曲線の傾きの値を、ＬＭＴ（冠動脈起始部（近位部））の時間濃度曲線の傾きの値で割ることで、CT-iFRを算出することができる。 The image analysis device 100 can construct a coronary CT4D flow image and calculate CT-iFR by using such a prediction complementing technique. For example, FIG. 15 shows an example of calculating CT-iFR in the left coronary artery main trunk (LMT). By setting the region of interest (VOI) to # 1, # 3, LMT, # 8 and # 13 (FIG. 15 (a)), each VOI is automatically tracked in the subsequent cardiac cycle, and each VOI is time-concentrated. You can get a curve. The slope value of the linear approximation straight line of the rising part (upward slope) of the time concentration curve of # 8 (distal part of the coronary artery) and the rising part (rising part) of the time concentration curve of the LMT (origin part of the coronary artery (proximal part)). Obtain the slope value of the linear approximation straight line of (gradient), and use the slope value of the time concentration curve of # 8 (distal part of the coronary artery) as the slope value of the time concentration curve of LMT (origin part of the coronary artery (proximal part)). CT-iFR can be calculated by dividing by the value.
　本発明の一実施形態では、CT-iFRを算出するための定量的解析手法は、maximum slope法を基準としているが、これに限定されるものではなく、時間濃度曲線のグラフ全体を用いた畳み込み積分法でもよく、グラフ下面積を算出する方法でもよい。 In one embodiment of the present invention, the quantitative analysis method for calculating CT-iFR is based on the maximum slope method, but is not limited to this, and convolution using the entire graph of the time concentration curve is used. It may be an integration method or a method of calculating the area under the graph.
　図１６は、冠動脈の時間濃度曲線の一例を示す。上述したとおり、本発明に係る低線量連続撮影では、少ない造影剤50-70mlを用いて、冠動脈の時間濃度曲線において十分な濃度勾配を得ることができる。しかしながら、冠動脈遠位部は濃度の立ち上がりは、近位部に比べ遅延している。このため、maximum slope法を適用した場合、上り勾配（upslope）の計測フェーズや間隔が、近位部と遠位部で異なる事例が生じている。また、冠動脈遠位部の濃度（CT値）のピークは300HUを超える値を示し、十分造影剤に満たされた状態となるが、時間経過により造影剤の２回目の循環に影響されてしまい２峰性となる。冠動脈遠位部の時間濃度曲線の上述した特徴は、上り勾配の計測の再現性や血流測定精度に悪影響となる。そこで、本発明の別の実施形態として、畳み込み積分法を用いた解析方法について以下に説明する。 FIG. 16 shows an example of the time concentration curve of the coronary artery. As described above, in the low-dose continuous radiography according to the present invention, a sufficient concentration gradient can be obtained in the time concentration curve of the coronary artery by using a small amount of 50-70 ml of contrast medium. However, the rise of concentration in the distal part of the coronary artery is delayed as compared with that in the proximal part. For this reason, when the maximum slope method is applied, there are cases where the measurement phase and interval of the upslope are different between the proximal part and the distal part. In addition, the peak concentration (CT value) of the distal part of the coronary artery shows a value exceeding 300 HU, and the state is sufficiently filled with the contrast medium, but it is affected by the second circulation of the contrast medium over time 2 It becomes peak. The above-mentioned characteristics of the time concentration curve in the distal part of the coronary artery adversely affect the reproducibility of uphill measurement and the accuracy of blood flow measurement. Therefore, as another embodiment of the present invention, an analysis method using the convolution integral method will be described below.
　図１７は、畳み込み積分法による冠動脈の時間濃度曲線の解析例を示す。なお、畳み込み積分は、次の式で定義される。t、τは時間を示す変数である。
Figure JPOXMLDOC01-appb-M000002
 畳み込み積分法によりCT-iFRを算出するために、まずは、相互相関解析による時間濃度曲線の補正を行う。冠動脈近位部と遠位部の時間濃度曲線の波形には、類似性があるため相互相関する。そこで、平行移動により両者の立ち上がり起点を一致させて、その起点の濃度（CT値）を０ポイントとする。例えば、冠動脈遠位部の時間濃度曲線を冠動脈近位部側に平行移動させ、冠動脈近位部と遠位部の時間濃度曲線の立ち上がり起点を一致させる。そして、冠動脈遠位部の時間濃度曲線が２峰性となることを回避するために、造影剤の初回循環のみを解析対象とするため、平行移動した２つのグラフ（時間濃度曲線）において、冠動脈近位部のピークまでのデータを解析対象とする。 FIG. 17 shows an example of analysis of the time concentration curve of the coronary artery by the convolution integration method. The convolution integral is defined by the following equation. t and τ are variables indicating time.
Figure JPOXMLDOC01-appb-M000002
 In order to calculate CT-iFR by the convolution integral method, first, the time concentration curve is corrected by cross-correlation analysis. The waveforms of the time concentration curves in the proximal and distal coronary arteries are similar and therefore cross-correlated. Therefore, the rising starting points of the two are made to match by translation, and the concentration (CT value) of the starting points is set to 0 point. For example, the time concentration curve of the distal part of the coronary artery is translated toward the proximal part of the coronary artery, and the rising points of the time concentration curves of the proximal part and the distal part of the coronary artery are matched. Then, in order to prevent the time concentration curve of the distal part of the coronary artery from becoming bimodal, only the initial circulation of the contrast medium is analyzed, so that the two graphs (time concentration curve) translated in parallel show the coronary artery. The data up to the peak in the proximal part is analyzed.
　図１８は、畳み込み積分法によるCT-iFR算出法においてベルヌーイの定理の応用の一例を示す。ベルヌーイの定理は、外力のない非粘性・非圧縮性流体の定常な流れに対して、
Figure JPOXMLDOC01-appb-M000003
 が流線上で成り立つ。ただし、ｖは流体の速さ、ｐは圧力、ρは密度を表す。つまり、図１８に示す流管（血管に相当）の断面１（流入）及び断面２（流出）における流体のエネルギー（運動、圧力、位置）の和は一定であり等しい。冠動脈への応用について検討すると、左室拡張期後半に撮影した冠動脈内圧は、末梢血管抵抗が一定かつ十分に低下している状態（圧力（ｐ）＝０）と仮定することができる。冠動脈血流は冠動脈内濃度（CT値）に比例し、一定時間の血流量は時間濃度曲線の積分値（曲線下面積）で推定することができる。そうすると、ベルヌーイの定理に基づいて、冠動脈近位部と遠位部の血流量は、エネルギーロスがなければ一定に保たれる。しかしながら、エネルギーロスの原因となる狭窄や動脈硬化プラークが存在すると、遠位部の血流量は低下すると仮説を立てることができる。 FIG. 18 shows an example of application of Bernoulli's theorem in the CT-iFR calculation method by the convolution integral method. Bernoulli's theorem states that for a steady flow of a non-viscous, incompressible fluid without external force,
Figure JPOXMLDOC01-appb-M000003
 Is streamlined. However, v represents the speed of the fluid, p represents the pressure, and ρ represents the density. That is, the sum of the kinetic energy (kinetic energy, pressure, position) of the fluid in the cross section 1 (inflow) and the cross section 2 (outflow) of the flow pipe (corresponding to the blood vessel) shown in FIG. 18 is constant and equal. When the application to the coronary artery is examined, it can be assumed that the intracoronary pressure taken in the latter half of the left ventricular diastole is a state in which the peripheral vascular resistance is constant and sufficiently reduced (pressure (p) = 0). Coronary blood flow is proportional to the intracoronary concentration (CT value), and the blood flow for a certain period of time can be estimated by the integral value of the time concentration curve (area under the curve). Then, based on Bernoulli's theorem, blood flow in the proximal and distal coronary arteries is kept constant in the absence of energy loss. However, it can be hypothesized that the presence of stenosis or atherosclerotic plaques that cause energy loss reduces distal blood flow.
　図１９は、畳み込み積分法による冠動脈の時間濃度曲線の曲線下面積を測定する一例を示す。冠動脈内濃度（CT値）は、冠血流に比例する。ベルヌーイの定理をもとに、末梢灌流圧が十分に低下した状態では、曲線下面積を冠動脈血流と推定することができる。そうすると、CT-iFRは２つの曲線下面積の比として算出することができる。例えば、図１９において、近位部の血流量は、畳み込み積分法により算出された近位部曲線下面積（上部エリアと下部エリアの和）であり（図１９の例では３２１３）、遠位部の血流量は、畳み込み積分法により算出された遠位部曲線下面積（下部エリア）であり（図１９の例では３０４７）、CT-iFR＝遠位血流量/近位血流量の式で求められる（図１９の例では、３０４７/３２１３＝０．９４８）。機能的狭窄などエネルギーロスの原因がなければCT-iFRは１に近い値となる。 FIG. 19 shows an example of measuring the area under the curve of the time concentration curve of the coronary artery by the convolution integration method. The concentration in the coronary artery (CT value) is proportional to the coronary blood flow. Based on Bernoulli's theorem, the area under the curve can be estimated as coronary blood flow when the peripheral perfusion pressure is sufficiently low. Then, CT-iFR can be calculated as the ratio of the areas under the two curves. For example, in FIG. 19, the blood flow in the proximal portion is the area under the proximal curve (sum of the upper area and the lower area) calculated by the convolution integral method (3213 in the example of FIG. 19), and the distal portion. Is the area under the distal curve (lower area) calculated by the convolution integral method (3047 in the example of FIG. 19), and is calculated by the formula CT-iFR = distal blood flow / proximal blood flow. (In the example of FIG. 19, 3047/3213 = 0.948). If there is no cause of energy loss such as functional stenosis, CT-iFR will be close to 1.
　冠動脈の時間濃度曲線から畳み込み積分法によるCT-iFRの算出手順を図２０から図２２に示す。図２０は、機能的虚血領域の冠動脈の時間濃度曲線の一例を示す。図２０に示す例は、冠動脈遠位部に虚血領域がある場合を示しており、虚血領域では、冠動脈遠位部の上り勾配はなだらかになり、濃度（CT値）のピーク値は200HUとなり冠動脈近位部に比べて低い値となる。 The calculation procedure of CT-iFR by the convolution integration method from the time concentration curve of the coronary artery is shown in FIGS. 20 to 22. FIG. 20 shows an example of a time concentration curve of a coronary artery in a functional ischemic region. The example shown in FIG. 20 shows a case where there is an ischemic region in the distal part of the coronary artery. In the ischemic region, the upslope of the distal part of the coronary artery becomes gentle, and the peak value of the concentration (CT value) is 200 HU. The value is lower than that of the proximal part of the coronary artery.
　図２１は、図２０に示す時間濃度曲線の立ち上がりからピーク値までの一部部分を抽出した例を示す。図１７の例で説明したとおり、相互相関解析による時間濃度曲線の補正を行う。冠動脈近位部と遠位部の時間濃度曲線の波形には、類似性があるため相互相関するため、平行移動により両者の立ち上がり起点を一致させて、その起点の濃度（CT値）を０ポイントとする。 FIG. 21 shows an example in which a part from the rising edge of the time concentration curve shown in FIG. 20 to the peak value is extracted. As described in the example of FIG. 17, the time concentration curve is corrected by cross-correlation analysis. Since the waveforms of the temporal concentration curves of the proximal and distal coronary arteries are similar and cross-correlate, the rising starting points of both are made to match by translation, and the concentration (CT value) of the starting point is set to 0 point. And.
　図２２は、図２１に示す時間濃度曲線の一部部分について畳み込み積分による曲線下面積を測定した例を示す。冠動脈において機能的虚血が生じた場合に、冠動脈遠位部の血流量が低下するため、CT-iFRが低下する。図２２に示す例では、CT-iFR=1545/2552=0.606であり、正常な値（1.0に近い値）よりも低下している。 FIG. 22 shows an example in which the area under the curve is measured by convolution integration for a part of the time concentration curve shown in FIG. When functional ischemia occurs in the coronary arteries, the blood flow in the distal part of the coronary arteries decreases, resulting in a decrease in CT-iFR. In the example shown in FIG. 22, CT-iFR = 1545/2552 = 0.606, which is lower than the normal value (value close to 1.0).
　本発明の低線量連続撮影によって得られた冠動脈CT画像から、CT-iFRを算出する際に採用したmaximum slope法と畳み込み積分法とを比較し、それらの機能的虚血検出の診断能を、まとめた表を以下に示す。
Figure JPOXMLDOC01-appb-T000004
 上記表中の非虚血について、侵襲的カテーテルの正常下限値は0.89であり、本手法の非虚血領域とほぼ一致することが分かる。AUC（area under the curve）は、 Reciever-Operating-Characteristics curve 解析の曲線下面積のことで、診断精度を表す。一般的には、AUC 0.9から1.0は高い精度であり、AUC 0.7から0.9が中程度の精度であり、AUC 0.5から0.7は低い精度である。上記表に示されるとおり、畳み込み積分法によるCT-iFRの算出は、AUCが0.9を示しており、高い精度で機能的虚血を検出することができる。 From the coronary CT images obtained by the low-dose continuous imaging of the present invention, the maximum slope method and the convolution integral method adopted when calculating CT-iFR are compared, and their functional ischemia detection diagnostic ability is compared. The summarized table is shown below.
Figure JPOXMLDOC01-appb-T000004
 For non-ischemia in the above table, the lower limit of normal for invasive catheters is 0.89, which is almost the same as the non-ischemic region of this method. AUC (area under the curve) is the area under the curve of the Reciever-Operating-Characteristics curve analysis and represents the diagnostic accuracy. In general, AUC 0.9 to 1.0 is high accuracy, AUC 0.7 to 0.9 is medium accuracy, and AUC 0.5 to 0.7 is low accuracy. As shown in the above table, the calculation of CT-iFR by the convolution integral method shows an AUC of 0.9, and functional ischemia can be detected with high accuracy.
　低線量の連続撮影（テストスキャン）を先に実施し、高線量の標準的冠動脈撮影を後に実施するといったように、２つの撮影を別々に実施している従来例では、テストスキャンのCT-iFRに関して、テストスキャンにおける機能的虚血の至適閾値は0.39程度であり、カテーテルのiFRと比較すると大きく低下する。 In the conventional example where two imagings are performed separately, such as low-dose continuous imaging (test scan) performed first and high-dose standard coronary imaging performed later, the test scan CT-iFR The optimal threshold for functional ischemia in the test scan is about 0.39, which is significantly lower than that of the iFR of the catheter.
　本発明の低線量連続撮影で用いるmaximum slope法と畳み込み積分法の解析特徴を、まとめた表を以下に示す。
Figure JPOXMLDOC01-appb-T000005
 The following is a table summarizing the analysis features of the maximum slope method and the convolution integral method used in the low-dose continuous imaging of the present invention.
Figure JPOXMLDOC01-appb-T000005
　正常冠動脈の領域ごとのCT-iFRの算出について、maximum slope法と畳み込み積分法との比較を、まとめた表を以下に示す。
Figure JPOXMLDOC01-appb-T000006
 maximum slope法では、左回旋枝が左前下枝に比べ低下する。一方、畳み込み積分法の場合、３つの冠動脈領域に差は認められない。この結果から、畳み込み積分法が基準値を設定しやすく、解剖学的な操向の影響を受けにくいことが確認できる。 A table summarizing the comparison between the maximum slope method and the convolution integral method for the calculation of CT-iFR for each region of the normal coronary artery is shown below.
Figure JPOXMLDOC01-appb-T000006
 In the maximum slope method, the left circumflex branch is lower than the left anterior lower branch. On the other hand, in the case of the convolution integral method, no difference is observed in the three coronary artery regions. From this result, it can be confirmed that the convolution integral method is easy to set the reference value and is not easily affected by the anatomical steering.
　このように、本発明に係る機能的虚血検出システム等は、冠動脈造影CTにより得られた多時相のCCTAデータを、予測補完技術を用いて再構成し、再構成されたCCTAデータから冠動脈近位部及び冠動脈遠位部の時間濃度曲線を取得し、定量的解析手法を用いて、冠動脈フローを定量化することで、CT-iFRを算出することができ、非侵襲的に機能的虚血を検出すること等が期待できる。 As described above, in the functional ischemia detection system and the like according to the present invention, the multi-phase CCTA data obtained by coronary angiography CT is reconstructed by using predictive complement technology, and the reconstructed CCTA data is used to reconstruct the coronary artery. CT-iFR can be calculated by acquiring time concentration curves of the proximal and distal coronary arteries and quantifying coronary flow using quantitative analysis techniques, non-invasively functional imagination. It can be expected to detect blood.
　本発明に係る機能的虚血検出システム等は、心臓疾患の診断の支援等に利用することができる。 The functional ischemia detection system or the like according to the present invention can be used to support the diagnosis of heart disease or the like.
１００　画像解析装置
２００　CT装置
２１０　データ処理装置
Ｎ　ネットワーク 100 Image analyzer 200 CT device 210 Data processing device N network

Claims (20)

  1. 　機能的虚血検出システムであって、
    　冠動脈造影CT装置と、
    　前記冠動脈造影CT装置に接続された情報処理装置と
    を含み、
    　前記冠動脈造影CT装置は、高線量を必要とする標準的冠動脈撮影と低線量の連続撮影を一体化し時系列的に被検者の胸部をCTスキャンして、時系列的に心臓のCTデータを取得して、多時相の冠動脈造影CTデータを生成し、
    　前記情報処理装置は、前記多時相の冠動脈造影CTデータを、予測補完により再構成し、再構成された前記多時相の冠動脈造影CTデータから、冠動脈近位部の時間濃度曲線と、冠動脈遠位部の時間濃度曲線とを取得し、畳み込み積分法を用いて、前記冠動脈遠位部及び前記冠動脈近位部の関心領域の冠動脈フローを定量化することで、前記多時相の冠動脈造影CTデータによる瞬時血流予備量比（CT-iFR）を算出することを特徴とする機能的虚血検出システム。     A functional ischemia detection system
    Coronary angiography CT device and
    Including an information processing device connected to the coronary angiography CT device.
    The coronary angiography CT device integrates standard coronary angiography that requires a high dose and continuous low-dose imaging, CT scans the subject's chest in chronological order, and captures CT data of the heart in chronological order. Obtained to generate multi-phase coronary CT data,
    The information processing apparatus reconstructs the multi-phase coronary angiography CT data by predictive complementation, and from the reconstructed multi-phase coronary angiography CT data, a time concentration curve of the proximal part of the coronary artery and a coronary artery. The polyphasic coronary angiography by obtaining a time concentration curve of the distal part and quantifying the coronary flow of the region of interest in the distal part of the coronary artery and the proximal part of the coronary artery using the convolution integration method. A functional ischemia detection system characterized by calculating the instantaneous blood flow reserve ratio (CT-iFR) based on CT data.
  2. 　前記情報処理装置は、前記冠動脈遠位部の時間濃度曲線を前記冠動脈近位部の時間濃度曲線側に平行移動させ、前記冠動脈近位部と前記冠動脈遠位部の時間濃度曲線の立ち上がり起点を一致させ、
    　畳み込み積分法により、前記冠動脈近位部の時間濃度曲線から近位部曲線下面積の値を求め、前記冠動脈遠位部の時間濃度曲線から遠位部曲線下面積の値を求め、
    　前記遠位部曲線下面積の値を、前記近位部曲線下面積の値で割ることで、前記瞬時血流予備量比（CT-iFR）を算出することを特徴とする請求項１に記載の機能的虚血検出システム。     The information processing apparatus moves the time concentration curve of the distal part of the coronary artery in parallel to the time concentration curve side of the proximal part of the coronary artery, and sets the rising point of the time concentration curve of the proximal part of the coronary artery and the distal part of the coronary artery. Match,
    By the convolution integral method, the value of the area under the proximal curve was obtained from the time concentration curve of the proximal part of the coronary artery, and the value of the area under the distal curve was obtained from the time concentration curve of the distal part of the coronary artery.
    The first aspect of claim 1, wherein the instantaneous blood flow reserve ratio (CT-iFR) is calculated by dividing the value of the area under the distal curve by the value of the area under the proximal curve. Functional ischemia detection system.
  3. 　前記冠動脈遠位部及び前記冠動脈近位部の各時間濃度曲線は、立ち上がりからピーク値までの一部部分を抽出した曲線であることを特徴とする請求項２に記載の機能的虚血検出システム。 The functional ischemia detection system according to claim 2, wherein each time concentration curve of the distal part of the coronary artery and the proximal part of the coronary artery is a curve extracted from a part from the rising edge to the peak value. ..
  4. 　前記冠動脈造影CT装置は、320列CT装置であり、
    　前記320列CT装置は、１回の撮影で前記被検者の心臓全体をカバーし、冠動脈の造影ファーストパスの連続撮影を行うことを特徴とする請求項１から３のいずれか１項に記載の機能的虚血検出システム。     The coronary angiography CT device is a 320-row CT device.
    The 320-row CT apparatus according to any one of claims 1 to 3, wherein the 320-row CT apparatus covers the entire heart of the subject with a single imaging, and continuous imaging of a contrast-enhanced first pass of the coronary artery is performed. Functional ischemia detection system.
  5. 　前記予測補完は、前記情報処理装置において入力された予測補完強度の値に応じて、前記多時相の冠動脈造影CTデータの再構成のための予測補完画像の数を増減させることを特徴とする請求項１から４のいずれか１項に記載の機能的虚血検出システム。 The predictive complement is characterized in that the number of predictive complement images for reconstructing the multi-phase coronary angiography CT data is increased or decreased according to the value of the predictive complement intensity input in the information processing apparatus. The functional ischemia detection system according to any one of claims 1 to 4.
  6. 　前記予測補完は、前記多時相の冠動脈造影CTデータの再構成のための予測補完画像の数を増やし、前記多時相の冠動脈造影CTデータにおける画像の時間間隔を細かくすることで、前記多時相の冠動脈造影CTデータを逐次近似再構成し、画像ノイズを低減することを特徴とする請求項１から５のいずれか１項に記載の機能的虚血検出システム。 The predictive complement increases the number of predictive complementary images for reconstructing the polyphasic coronary CT data and reduces the time interval of the images in the polyphasic coronary CT data. The functional ischemia detection system according to any one of claims 1 to 5, wherein the time-phase coronary angiography CT data is sequentially approximated and reconstructed to reduce image noise.
  7. 　前記関心領域は、前記情報処理装置で表示される前記多時相の冠動脈造影CTデータにより得られる冠動脈の断面画像において指定された範囲に応じて定められ、
    　前記冠動脈の断面画像は、冠動脈の方向に対して実質的に直交する角度になるように回転させられることを特徴とする請求項１から６のいずれか１項に記載の機能的虚血検出システム。     The region of interest is defined according to the range specified in the cross-sectional image of the coronary artery obtained from the multi-phase coronary angiography CT data displayed by the information processing apparatus.
    The functional ischemia detection system according to any one of claims 1 to 6, wherein the cross-sectional image of the coronary artery is rotated so as to be rotated at an angle substantially orthogonal to the direction of the coronary artery. ..
  8. 　前記関心領域は、前記冠動脈の断面画像の血管中心に実質的に球形の領域であることを特徴とする請求項７に記載の機能的虚血検出システム。 The functional ischemia detection system according to claim 7, wherein the region of interest is a substantially spherical region at the center of a blood vessel in a cross-sectional image of the coronary artery.
  9. 　前記情報処理装置は、前記冠動脈遠位部及び前記冠動脈近位部の前記関心領域が指定されると、前記多時相の冠動脈造影CTデータにおける前記関心領域をその後のフレームで自動的にトラッキングを行い、前記冠動脈遠位部及び前記冠動脈近位部の各時間濃度曲線を計測することを特徴とする請求項１から８のいずれか１項に記載の機能的虚血検出システム。 When the region of interest in the distal portion of the coronary artery and the proximal portion of the coronary artery is designated, the information processing apparatus automatically tracks the region of interest in the polyphasic coronary angiography CT data in a subsequent frame. The functional ischemia detection system according to any one of claims 1 to 8, wherein each time concentration curve of the distal part of the coronary artery and the proximal part of the coronary artery is measured.
  10. 　機能的虚血検出方法であって、
    　高線量を必要とする標準的冠動脈撮影と低線量の連続撮影を一体化し時系列的に被検者の胸部をCTスキャンして、時系列的に心臓のCTデータを取得する冠動脈造影CT装置から得られた多時相の冠動脈造影CTデータを、予測補完により再構成する段階と、
    　再構成された前記多時相の冠動脈造影CTデータから、冠動脈近位部の時間濃度曲線と、冠動脈遠位部の時間濃度曲線とを取得する段階と、
    　畳み込み積分法を用いて、前記冠動脈遠位部及び前記冠動脈近位部の関心領域の冠動脈フローを定量化することで、前記多時相の冠動脈造影CTデータによる瞬時血流予備量比（CT-iFR）を算出する段階と
    を含むことを特徴とする機能的虚血検出方法。     A functional ischemia detection method
    From a coronary angiography CT device that integrates standard coronary angiography that requires a high dose and continuous low-dose imaging, CT scans the subject's chest in chronological order, and acquires CT data of the heart in chronological order. The stage of reconstructing the obtained multi-phase coronary angiography CT data by predictive complementation,
    The stage of acquiring the time concentration curve of the proximal part of the coronary artery and the time concentration curve of the distal part of the coronary artery from the reconstructed multi-phase coronary angiography CT data, and
    By quantifying the coronary flow in the region of interest in the distal part of the coronary artery and the proximal part of the coronary artery using the convolutional integration method, the instantaneous blood flow reserve ratio (CT-) based on the multi-phase coronary angiography CT data. A functional ischemia detection method comprising the step of calculating iFR).
  11. 　前記瞬時血流予備量比（CT-iFR）を算出する段階は、
    　前記冠動脈遠位部の時間濃度曲線を前記冠動脈近位部の時間濃度曲線側に平行移動させ、前記冠動脈近位部と前記冠動脈遠位部の時間濃度曲線の立ち上がり起点を一致させる段階と、
    　畳み込み積分法により、前記冠動脈近位部の時間濃度曲線から近位部曲線下面積の値を求め、前記冠動脈遠位部の時間濃度曲線から遠位部曲線下面積の値を求める段階と、
    　前記遠位部曲線下面積の値を、前記近位部曲線下面積の値で割ることで、前記瞬時血流予備量比（CT-iFR）を算出する段階と
    を含むことを特徴とする請求項１０に記載の機能的虚血検出方法。     The step of calculating the instantaneous blood flow reserve ratio (CT-iFR) is
    The step of moving the time concentration curve of the distal part of the coronary artery in parallel to the time concentration curve side of the proximal part of the coronary artery and matching the rising point of the time concentration curve of the proximal part of the coronary artery and the distal part of the coronary artery
    By the convolution integral method, the value of the area under the proximal curve is obtained from the time concentration curve of the proximal part of the coronary artery, and the value of the area under the distal curve is obtained from the time concentration curve of the distal part of the coronary artery.
    A claim comprising the step of calculating the instantaneous blood flow reserve ratio (CT-iFR) by dividing the value of the area under the distal curve by the value of the area under the proximal curve. Item 10. The functional ischemia detection method according to Item 10.
  12. 　前記冠動脈遠位部及び前記冠動脈近位部の各時間濃度曲線は、立ち上がりからピーク値までの一部部分を抽出した曲線であることを特徴とする請求項１０又は１１に記載の機能的虚血検出方法。 The functional ischemia according to claim 10 or 11, wherein each time concentration curve of the distal part of the coronary artery and the proximal part of the coronary artery is a curve obtained by extracting a part from the rising edge to the peak value. Detection method.
  13. 　前記冠動脈造影CT装置は、320列CT装置であり、
    　前記多時相の冠動脈造影CTデータは、前記320列CT装置により、１回の撮影で前記被検者の心臓全体をカバーし、冠動脈の造影ファーストパスの連続撮影を行い生成された画像を含む特徴とする請求項１０から１２のいずれか１項に記載の機能的虚血検出方法。     The coronary angiography CT device is a 320-row CT device.
    The multi-phase coronary angiography CT data includes an image generated by continuously taking an angiography first pass of the coronary artery by covering the entire heart of the subject with one imaging by the 320-row CT apparatus. The functional ischemia detection method according to any one of claims 10 to 12, characterized in that.
  14. 　前記予測補完により再構成する段階は、
    　指定された予測補完強度の値に応じて、前記多時相の冠動脈造影CTデータの再構成のための予測補完画像の数を増減させる段階を含むことを特徴とする請求項１０から１３のいずれか１項に記載の機能的虚血検出方法。     The step of reconstructing by the prediction complement is
    Any of claims 10 to 13, comprising increasing or decreasing the number of predictive complementary images for reconstructing the polyphasic coronary angiography CT data according to a specified predictive complement intensity value. The functional ischemia detection method according to item 1.
  15. 　前記予測補完により再構成する段階は、
    　画像ノイズを低減するために、前記多時相の冠動脈造影CTデータの再構成のための予測補完画像の数を増やし、前記多時相の冠動脈造影CTデータにおける画像の時間間隔を細かくすることで、前記多時相の冠動脈造影CTデータを逐次近似再構成する段階を含むことを特徴とする請求項１０から１４のいずれか１項に記載の機能的虚血検出方法。     The step of reconstructing by the prediction complement is
    In order to reduce image noise, the number of predictive complementary images for reconstructing the multi-phase coronary CT data is increased, and the time interval of the images in the multi-phase coronary CT data is reduced. The functional ischemia detection method according to any one of claims 10 to 14, further comprising a step of sequentially approximating and reconstructing the multi-phase coronary angiography CT data.
  16. 　前記瞬時血流予備量比（CT-iFR）を算出する段階は、
    　前記多時相の冠動脈造影CTデータにより得られる冠動脈の断面画像において指定された範囲に応じて、前記関心領域を定める段階と、
    　前記冠動脈の断面画像を、冠動脈の方向に対して直交する角度になるように回転する段階とを含むことを特徴とする請求項１０から１５のいずれか１項に記載の機能的虚血検出方法。     The step of calculating the instantaneous blood flow reserve ratio (CT-iFR) is
    The stage of determining the region of interest according to the range specified in the cross-sectional image of the coronary artery obtained from the multi-phase coronary angiography CT data, and
    The functional ischemia detection method according to any one of claims 10 to 15, further comprising a step of rotating a cross-sectional image of the coronary artery at an angle orthogonal to the direction of the coronary artery. ..
  17. 　前記関心領域は、前記冠動脈の断面画像の血管中心に実質的に球形の領域であることを特徴とする請求項１６に記載の機能的虚血検出方法。 The functional ischemia detection method according to claim 16, wherein the region of interest is a substantially spherical region at the center of a blood vessel in a cross-sectional image of the coronary artery.
  18. 　前記瞬時血流予備量比（CT-iFR）を算出する段階は、
    　前記冠動脈遠位部及び前記冠動脈近位部の前記関心領域が指定されると、前記多時相の冠動脈造影CTデータにおける前記関心領域をその後のフレームで自動的にトラッキングを行い、前記冠動脈遠位部及び前記冠動脈近位部の各時間濃度曲線を計測する段階を含むことを特徴とする請求項１０から１７のいずれか１項に記載の機能的虚血検出方法。     The step of calculating the instantaneous blood flow reserve ratio (CT-iFR) is
    When the region of interest in the distal coronary artery and the proximal coronary artery is designated, the region of interest in the polyphasic coronary angiography CT data is automatically tracked in a subsequent frame, and the distal coronary artery is distal. The functional ischemia detection method according to any one of claims 10 to 17, wherein each time concentration curve of the portion and the proximal portion of the coronary artery is measured.
  19. 　請求項１０から１８のいずれか１項に記載の機能的虚血検出方法の各段階を実行することを特徴とする機能的虚血検出装置。 A functional ischemia detecting apparatus according to any one of claims 10 to 18, wherein each step of the functional ischemia detecting method is executed.
  20. 　コンピュータによって実行させることで、前記コンピュータを請求項１９に記載の機能的虚血検出装置として機能させることを特徴とする機能的虚血検出プログラム。 A functional ischemia detection program characterized in that the computer functions as the functional ischemia detection device according to claim 19 by being executed by a computer.
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