JP2006308527A - Quantity-determining method of myocardial blood flow, blood flow quantity-determining program, and blood flow quantity determining system - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method of determining myocardial blood flow quantity using an SPECT image, and to provide a program and a system for executing the method. <P>SOLUTION: The SPECT image of the chest of a subject is acquired, an input function corresponding to the activity quantity in subject's arterial blood plasma is determined, temporary flow quantity in an interesting part is determined, based on the signal intensity in the interesting part in the acquired SPECT image using the determined input function, and the blood flow quantity is determined, by multiplying the temporary flow quantity by a correction coefficient represented by 1/(1-Hm)(where, Hm is a hematocrit value). <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

 The present invention relates to a method for determining myocardial blood flow using a single photon emission tomography (hereinafter referred to as SPECT) image, a program and a system for implementing the method.

 Heart disease such as ischemic heart disease such as myocardial infarction occupies the top causes of death, and since death rate is high when discovery is delayed, it is important to diagnose early. In addition to invasive left ventricular imaging and coronary angiography, diagnostic imaging methods in the heart region include echocardiography, X-ray computed tomography (X-ray CT), and magnetic resonance imaging (MRI). ), And nuclear medicine diagnosis such as positron emission tomography (PET) and single photon emission tomography (SPECT) are mainly used.

Thallium chloride-201 (manufactured by Nippon Mediphysics Co., Ltd.), which is one of myocardial perfusion diagnostic agents for SPECT examination that has been clinically applied, dissociates in aqueous solution and becomes a monovalent cation ( ²⁰¹ Tl ⁺ ) It is considered that the sodium-potassium pump actively ingests the myocardial cells, showing the same behavior as potassium ions. Therefore, there is a feature that the SPECT image reflecting the blood flow distribution of the myocardium is given with high uptake into the myocardium. Furthermore, since it has a high first-pass extraction rate (hereinafter referred to as FPEF), it has excellent features such as high blood flow linearity and high diagnostic accuracy.

Due to the above characteristics, it is considered that a chest SPECT image by administration of thallium chloride-201 gives an image reflecting myocardial blood flow (Non-patent Document 1). It is known that myocardial blood flow decreases due to stenosis or myocardial infarction. By using a chest SPECT image obtained by administration of thallium chloride-201, it is possible to recognize a part where blood flow is reduced as a defective part on the image when there is a part where blood flow is reduced in part. became.
However, this image does not reflect the absolute quantitative value of the myocardial blood flow, but displays the relative signal intensity, so it is difficult to recognize abnormalities when the blood flow is reduced as a whole. There is a case. There is also a problem that the size of the defective part may change depending on the image display conditions.
For these reasons, it is desirable to use an image reflecting the absolute quantitative value of the myocardial blood flow in the image diagnosis of heart disease.

 As a method for quantifying myocardial blood flow, a method using positron emission tomography (hereinafter referred to as PET) has been established. For example, a method for obtaining from a PET image by administration of oxygen-15 labeled water and a method for obtaining from a PET image by administration of ammonia labeled with nitrogen-13 are disclosed (Non-patent Document 2). However, oxygen-15 and nitrogen-13, which are nuclides used in this inspection, have extremely short half-lives of about 10 minutes and about 2 minutes, respectively, and are difficult to implement except in some facilities. Therefore, as the myocardial blood flow quantification method, it is desirable to use a method using SPECT images that can be performed in a wider facility.

On the other hand, various methods for obtaining cerebral blood flow from SPECT images have been proposed and are being studied for clinical application. For example, hydrochloric acid N- isopropyl-4-iodo ⁽¹²³ I) amphetamine (hereinafter, referred to as ¹²³ I-IMP) using SPECT images by administration, method of quantifying is disclosed by microsphere model or compartment model (Non-Patent Document 3, Non-Patent Document 4, Non-Patent Document 5, Non-Patent Document 6).
H. Iida & Stefan Eberl, “Quantitative assessment of regional myocardial blood flow with thallium-201 and SPECT.”, J. Nucl. Cardiol., (USA), The American Society of Nuclear Cardiology, 1998, May / June, p. 313-331 Steven R. Bergmann, “Cardiac Positron Emission Tomography.”, Seminars in Nuclear Medicine, (USA), WB Saunders Company, 1998, XXVIII, 4, p.320-340 Yoshiharu Yonekura et al., "Quantification of IMP cerebral blood flow SPECT by non-invasive microsphere method-Estimation of input function integral value by dynamic imaging-", Nuclear Medicine, Japanese Society of Nuclear Medicine, 1997, 34, p.901-908 Masatake Nakano et al., “Measurement of regional cerebral blood flow by non-invasive microsphere method using 123I-IMP: Comparison between modified fractional uptake method and continuous arterial blood method”, Nuclear Medicine, Nuclear Society of Japan, 1998, 35, p.209-218 Iida H., et al., “Quantitative mapping of regional cerebral blood flow using [123I] N-isopropyl-p-iodoamphetamine (IMP) and single photon emission tomography.”, J. Nucl. Med., (USA), Society of Nuclear Medicine, 1994, 35, p. 2019-2030 Hidehiro Iida et al., “Measurement of regional cerebral blood flow by one SPECT scan and one blood collection using 123I-IMP -Analysis of statistical error factors and optimal SPECT scan center time-”, Nuclear Medicine, 1995, 32, p.263-270

 As described above, with regard to cerebral blood flow, it is possible to obtain a quantitative value from a SPECT image. However, when the blood flow is quantified in the same procedure as this method using the chest SPECT image by thallium-201 administration, the obtained quantitative value is correlated with the value obtained by the microsphere method. The slope is significantly different from 1 (H. Iida & S. Eberl, J. Nucl. Cardiol., (USA), 1998, May / June, p.313-331). This result shows that accurate myocardial blood flow cannot be quantified from a chest SPECT image by thallium-201 administration by the method established as a method for quantifying cerebral blood flow by head SPECT. Therefore, in order to obtain a quantitative value of myocardial blood flow from a chest SPECT image by administration of a radiopharmaceutical such as thallium-201, it is necessary to use a method different from the blood flow quantitative method established in head SPECT. However, no such method has been disclosed so far.

 The present invention has been made in view of the above circumstances, and an object thereof is to provide a method for quantifying myocardial blood flow using a thallium-201-administered SPECT image, a program for implementing the method, and a system.

  As a result of intensive studies, the inventors obtained a temporary flow value using an input function corresponding to the amount of radioactivity in arterial blood plasma, and corrected the value by a correction term derived from a hematocrit value. Has been overcome, and it has been found that an absolute quantitative value of myocardial blood flow can be obtained from a chest SPECT image, and the present invention has been completed.

  A method for quantifying myocardial blood flow according to one aspect of the present invention includes a first step of acquiring a SPECT image of a chest in a subject, and a second step of obtaining an input function corresponding to the amount of radioactivity in arterial blood plasma of the subject. A third step of obtaining a temporary flow rate at the region of interest from the signal intensity at the region of interest in the acquired SPECT image using the obtained input function, and the following equation (1) for the temporary flow rate:

(Wherein Hm represents a hematocrit value) and a fourth step of obtaining a blood flow rate by multiplying by a correction coefficient.

In the myocardial blood flow quantification method, preferably, the first step is to acquire a series of SPECT data by imaging the chest of a subject who has been administered a radiopharmaceutical with a SPECT camera. Obtaining arterial blood collected from the subject at a plurality of times, and the second step comprises separating plasma from the arterial blood and measuring the amount of radioactivity per unit time unit mass in the plasma; Obtaining an input function C _a (t) representing the amount of radioactivity in plasma at time t from the measured values of the amount of radioactivity at the plurality of blood collection times.

  In the myocardial blood flow quantification method, preferably, the first step is to acquire a series of SPECT data by imaging the chest of a subject who has been administered a radiopharmaceutical with a SPECT camera. Obtaining arterial blood collected from the subject at a plurality of times, the second step separating plasma from the collected arterial blood and measuring the amount of radioactivity per unit time unit mass; and Obtaining an input function Ca (t) representing the amount of radioactivity in plasma at time t by obtaining an approximate curve for the measured values of the amount of radioactivity at a plurality of blood collection times.

In the myocardial blood flow quantification method, preferably, the first step is to acquire a series of SPECT data by imaging the chest of a subject who has been administered a radiopharmaceutical with a SPECT camera. Obtaining arterial blood collected from the subject at time t ₁ , and the second step is a step of calculating a radioactivity amount per unit time unit mass of the collected arterial blood with respect to a value at a time t ₁ of a standard input function. The standard input function is multiplied by the ratio of measured values, and the following equation (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t) multiplied by the correction factor given by time t An input function C _a (t) representing the amount of radioactivity in plasma at is obtained.

In the myocardial blood flow quantification method, preferably, the first step is to acquire a series of SPECT data by imaging the chest of a subject who has been administered a radiopharmaceutical with a SPECT camera. Obtaining arterial blood collected from the subject at a plurality of times, wherein the second step measures the amount of radioactivity per unit time unit mass in the arterial blood; and A step of obtaining an input function C _a ′ (t) representing a radioactivity amount of whole blood at time t from the measured value of the radioactivity amount, and the following equation (2) for the obtained input function C _a ′ (t):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t) multiplied by the correction factor given by time t And obtaining an input function C _a (t) corresponding to the amount of radioactivity in plasma.

In the myocardial blood flow quantification method, preferably, the first step is to acquire a series of SPECT data by imaging the chest of a subject who has been administered a radiopharmaceutical with a SPECT camera. Obtaining arterial blood collected from the subject at a plurality of times, wherein the second step includes measuring the amount of radioactivity per unit time unit mass of the collected arterial blood; and the plurality of blood collection times Obtaining an input function C _a ′ (t) representing the radioactivity amount of whole blood at time t by obtaining an approximate curve for the measured value of the radioactivity amount at, and the obtained input function C _a ′ (t) In contrast, the following formula (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t) multiplied by the correction factor given by time t And obtaining an input function C _a (t) corresponding to the amount of radioactivity in plasma.

In the method for quantifying myocardial blood flow, preferably, the first step has a step of acquiring a series of SPECT data by imaging a breast of a subject who has been administered a radiopharmaceutical with a SPECT camera. The step 2 includes the ratio of the dose of the radiopharmaceutical administered to the subject to the dose of the radiopharmaceutical administered when obtaining the standard input function, and the subject with respect to the weight of the specimen used when obtaining the standard input function. Is multiplied by the standard input function to obtain an input function C _a ′ (t) representing the amount of radioactivity of whole blood at time t, and the following equation (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t) multiplied by the correction factor given by time t And obtaining an input function C _a (t) corresponding to the amount of radioactivity in plasma.

In the myocardial blood flow quantification method, preferably, in the third step, an added image at different central scan times t ₁ and t ₂ is created from the series of SPECT data, and both images are designated identically. Obtaining the SPECT counts C _t (t ₁ ) and C _t (t ₂ ) of the region of interest and the measured SPECT counts C _t (t ₁ ) and C _t (t ₂ ) and the second step The input function C _a (t) is expressed by the following equation (3):

In assignment, and determining a value of k ₂ by table look-up, the second step the value of k ₂ obtained with the measured SPECT count C _t (t ₁₎ or C _t and (t ₂₎ to The obtained input function C _a (t) is expressed by the following equation (4):

And substituting for the provisional flow rate f.

In the myocardial blood flow quantification method, preferably, in the third step, an addition image at a center scan time t ₁ is created from the series of SPECT data, and a SPECT count C _t (t ₁ ), a distribution coefficient V _d given in advance, the input function C _a (t) obtained in the second step, and the measured SPECT count C _t (t ₁ ) are expressed by the following equation (5): :

And a provisional flow rate f is obtained by table lookup.

In the myocardial blood flow quantification method, preferably, the third step generates a plurality of images at a plurality of central scan times t from the series of SPECT data, and the same region of interest is designated for all the images. A step of obtaining a SPECT count C _t (t), a step of creating a time intensity curve representing the relationship between the obtained C _t (t) and the center scan time t, and the following equation (5):

And substituting the input function C _a (t) obtained in the second step and fitting with the time intensity curve to obtain a provisional flow rate f together with the distribution coefficient V _d .

In the myocardial blood flow quantification method, preferably, the third step generates a plurality of images at a plurality of central scan times t from the series of SPECT data, and the same region of interest is designated for all the images. A step of obtaining a SPECT count C _t (t), a step of creating a time intensity curve representing the relationship between the obtained C _t (t) and the center scan time t, and the following equation (5):

Substituting the value of the distribution coefficient V _d given in advance and the input function C _a (t) obtained in the second step and fitting with the time intensity curve to obtain the provisional flow rate f Steps.

 A program for quantifying myocardial blood flow according to another aspect of the present invention includes an input function creation process for obtaining an input function corresponding to the amount of radioactivity in arterial blood plasma in a subject, and interest from SPECT image data of a chest in the subject. A signal intensity extraction process for extracting the signal intensity of the part, a provisional flow rate calculation process for obtaining a provisional flow rate at the part of interest using the obtained input function and the extracted signal intensity at the part of interest, and the provisional flow rate In the following formula (1):

(Where Hm represents a hematocrit value) and a function for causing a computer to sequentially execute a blood flow calculation process for obtaining a blood flow by multiplying a correction coefficient given by
Here, the order in which the input function creation process for obtaining an input function corresponding to the amount of radioactivity in arterial blood plasma in the subject and the signal intensity extraction process for extracting the signal strength of the region of interest from the SPECT image data of the chest in the subject are as follows: , They may be interchanged.

  In the above-described program for quantifying myocardial blood flow, preferably, the input function creation processing is performed by obtaining an approximate curve for measured values of radioactivity in plasma at a plurality of times stored in the computer. An input function Ca (t) representing the amount of radioactivity in plasma at is obtained.

In the above-described program for quantifying myocardial blood flow, preferably, the input function creation processing is performed per unit time unit mass of arterial blood at time t ₁ stored in the computer with respect to a value at time t ₁ of a standard input function. Is multiplied by the standard input function, and the following equation (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t) multiplied by the correction factor given by time t An input function C _a (t) representing the amount of radioactivity in plasma at is obtained.

In the above-described program for quantifying myocardial blood flow, preferably, the input function creation processing represents the radioactivity amount of whole blood at time t from the measured values of the radioactivity amount at a plurality of blood collection times stored in the computer. An input function C _a '(t) is obtained, and the following equation (2) is obtained for the obtained input function C _a ' (t):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t) multiplied by the correction factor given by time t An input function C _a (t) corresponding to the amount of radioactivity in plasma at is obtained.

In the program for quantifying myocardial blood flow, preferably, the input function creation processing is performed at time t by obtaining an approximate curve for the measured values of the radioactivity at a plurality of blood collection times stored in the computer. An input function C _a ′ (t) representing the radioactivity level of whole blood is obtained, and the following equation (2) is obtained for the obtained input function C _a ′ (t):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t) multiplied by the correction factor given by time t An input function C _a (t) corresponding to the amount of radioactivity in plasma at is obtained.

In the above-mentioned program for quantifying myocardial blood flow, preferably, the input function creation processing is performed by the radioactivity administered to the subject stored in the computer with respect to the dose of the radiopharmaceutical administered when obtaining the standard input function. By multiplying the standard input function by the ratio of the weight of the medicinal product and the ratio of the weight of the subject stored in the computer to the weight of the specimen used when obtaining the standard input function, whole blood at time t is obtained. An input function C _a ′ (t) representing the amount of radioactivity of the following is obtained, and the following equation (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t) multiplied by the correction factor given by time t An input function C _a (t) corresponding to the amount of radioactivity in plasma at is obtained.

In the program for quantifying myocardial blood flow, preferably, the signal intensity extraction processing is performed at different center scan times t ₁ and t ₂ from a series of SPECT data constituting the SPECT image data stored in the computer. And the SPECT counts C _t (t ₁ ) and C _t (t ₂ ) of the region of interest designated identically for both images are obtained, and the provisional flow rate calculation process is performed using the calculated SPECT count C _t (t ₁ ) and C _t (t ₂ ) and the input function C _a (t) obtained in the second step are expressed by the following equation (3):

In assignment, and table determining a value of k ₂ by a look-up, the SPECT count was determined the value of k ₂ obtained C _{t (t 1)} or C _t (t ₂₎ and the second step in The obtained input function C _a (t) is expressed by the following equation (4):

To obtain a provisional flow rate f.

In the program for quantifying myocardial blood flow, preferably, the signal intensity extraction processing is performed by adding an addition image at a center scan time t ₁ from a series of SPECT data constituting the SPECT image data stored in the computer. The SPECT count C _t (t ₁ ) of the specified region of interest is created, and the provisional flow rate calculation process is performed by the distribution coefficient V _d given in advance and the input function C _a ( t) and the calculated SPECT count C _t (t ₁ ) are expressed by the following equation (5):

And a temporary flow rate f is obtained by table lookup.

In the program for quantifying myocardial blood flow, preferably, the signal intensity extraction processing includes a plurality of images at a plurality of central scan times t from a series of SPECT data constituting the SPECT image data stored in the computer. And SPECT count C _t (t) of the region of interest designated identically for all images, and a time intensity curve representing the relationship between the obtained C _t (t) and the central scan time t is created. The provisional flow rate calculation process is the following equation (5):

After substituting the input function C _a (t) obtained in the second step, the fitting with the time intensity curve is performed to obtain the provisional flow rate f together with the distribution coefficient V _d .

In the program for quantifying myocardial blood flow, preferably, the signal intensity extraction processing includes a plurality of images at a plurality of central scan times t from a series of SPECT data constituting the SPECT image data stored in the computer. And SPECT count C _t (t) of the region of interest designated identically for all images, and a time intensity curve representing the relationship between the obtained C _t (t) and the central scan time t is created. The provisional flow rate calculation process is the following equation (5):

Substituting the value of the distribution coefficient V _d given in advance and the input function C _a (t) obtained in the second step and fitting with the time intensity curve to obtain the provisional flow rate f .

 The blood flow rate quantification system according to another aspect of the present invention is a signal intensity extraction means for extracting a signal intensity of a region of interest from SPECT image data of a chest in a subject, and an input corresponding to the amount of radioactivity in arterial blood plasma in the subject. An input function creation means for obtaining a function, a provisional flow rate calculation means for obtaining a provisional flow rate at the region of interest using the obtained input function and the extracted signal intensity at the region of interest, and Formula (1):

A blood flow rate calculating means for determining a blood flow rate in the region of interest of the subject by multiplying a correction coefficient given by (where Hm represents a hematocrit value).

  In the blood flow rate quantification system, preferably, the input function creating means represents the amount of radioactivity in plasma at time t by obtaining an approximate curve for measured values of the amount of radioactivity in plasma at a plurality of given times. Find the input function Ca (t).

In the blood flow quantification systems, the ratio of preferably, the input function creating means, the measured value of the amount of radioactivity per unit time unit mass of the arterial blood at the standard input to the value at time t ₁ of the function, the time given t ₁ Is multiplied by the standard input function, and the following equation (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t) multiplied by the correction factor given by time t An input function C _a (t) representing the amount of radioactivity in plasma at is obtained.

In the blood flow rate quantification system, preferably, the input function creating means includes an input function C _a ′ (t) representing a radioactivity amount of whole blood at a time t from measured values of the radioactivity amount at a plurality of given blood collection times. And the following equation (2) for the obtained input function C _a ′ (t):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t) multiplied by the correction factor given by time t An input function C _a (t) corresponding to the amount of radioactivity in plasma at is obtained.

In the blood flow rate quantification system, preferably, the input function creating means is an input representing the radioactivity amount of whole blood at time t by obtaining an approximate curve for the measured values of the radioactivity amount at a plurality of given blood collection times. A function C _a '(t) is obtained, and the following equation (2) is obtained for the obtained input function C _a ' (t):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t) multiplied by the correction factor given by time t An input function C _a (t) corresponding to the amount of radioactivity in plasma at is obtained.

In the blood flow rate quantification system, preferably, the input function creation means includes a ratio of a dose of the radiopharmaceutical administered to the given subject to a dose of the radiopharmaceutical administered when obtaining a standard input function; By multiplying the standard input function by a given ratio of the subject's body weight to the weight of the specimen used when obtaining the standard input function, an input function C _a '( t), and the following equation (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t) multiplied by the correction factor given by time t An input function C _a (t) corresponding to the amount of radioactivity in plasma at is obtained.

In the blood flow rate quantification system, preferably, the signal intensity extraction unit creates an addition image at different center scan times t ₁ and t ₂ from a series of SPECT data constituting the given SPECT image data, The SPECT counts C _t (t ₁ ) and C _t (t ₂ ) of the region of interest designated identically for the image are obtained, and the temporary flow rate calculation means calculates the measured SPECT counts C _t (t ₁ ) and C _t (t ₂ ) and the input function C _a (t) obtained in the second step are expressed by the following equation (3):

In assignment, and determining a value of k ₂ by table look-up, the second step the value of k ₂ obtained with the measured SPECT count C _t (t ₁₎ or C _t and (t ₂₎ to The obtained input function C _a (t) is expressed by the following equation (4):

To obtain a provisional flow rate f.

In the blood flow rate quantification system, preferably, the signal intensity extraction unit creates an addition image at a center scan time t ₁ from a series of SPECT data constituting the given SPECT image data, and designates a specified region of interest. SPECT count C _t (t ₁ ) is calculated, and the provisional flow rate calculation means calculates the distribution coefficient V _d given in advance, the input function C _a (t) obtained in the second step, and the calculated SPECT count. C _t (t ₁ ) and the following equation (5):

And a temporary flow rate f is obtained by table lookup.

In the blood flow rate quantification system, preferably, the signal intensity extraction unit creates a plurality of images at a plurality of central scan times t from a series of SPECT data constituting the given SPECT image data, and the same for all the images. The SPECT count C _t (t) of the region of interest designated in the above is obtained, a time intensity curve representing the relationship between the obtained C _t (t) and the central scan time is created, and the provisional flow rate calculation means includes: Following formula (5):

After substituting the input function C _a (t) obtained in the second step, the fitting with the time intensity curve is performed to obtain the provisional flow rate f together with the distribution coefficient V _d .

In the blood flow rate quantification system, preferably, the signal intensity extraction unit creates a plurality of images at a plurality of central scan times t from a series of SPECT data constituting the given SPECT image data, and the same for all the images. The SPECT count C _t (t) of the region of interest designated in the above is obtained, a time intensity curve representing the relationship between the obtained C _t (t) and the central scan time is created, and the provisional flow rate calculation means includes: Following formula (5):

Substituting the value of the distribution coefficient V _d given in advance and the input function C _a (t) obtained in the second step and fitting with the time intensity curve to obtain the provisional flow rate f .

 By using the method, program and system according to the present invention, the myocardial blood flow in the region of interest can be quantified from the chest SPECT image.

Hereinafter, preferred embodiments of the method for quantifying myocardial blood flow according to the present invention will be described with reference to the drawings.
Various examination protocols can be used for performing the myocardial blood flow quantification method according to the present invention. FIG. 1 shows a typical protocol for quantifying myocardial blood flow according to the present invention.

As shown in FIG. 1, in the myocardial blood flow quantification method according to the present invention, first, a chest SPECT image is acquired (step S01). A chest SPECT image can be obtained by a known method in which a radiopharmaceutical is administered to a subject and imaged with a general-purpose SPECT camera.
The radiopharmaceutical is not particularly limited as long as it is for breast SPECT. For example, thallium chloride-201, technetium-99m-hexakis-2-methoxy-2-isobutyl-isonitrile (hereinafter referred to as MIBI) (Cardiolite, registered trademark, manufactured by Daiichi Radioisotope Laboratories), technetium-99m- Tetrofosmin (hereinafter referred to as Tetrofosmin) (Myoview, registered trademark, manufactured by Nippon Mediphysics Co., Ltd.) or the like can be used.

  The chest SPECT image can be acquired by various methods, and preferably, a method of collecting dynamic SPECT data can be taken over a certain period of time (for example, 10 minutes) immediately after administration. At this time, it is possible to obtain good image data by adding the collected data, but the data immediately after administration (for example, 2.5 minutes after administration) has a large temporal change in tissue radioactivity concentration. It is desirable not to use for this data addition. The center scan time of the dynamic SPECT data used for the addition (generally, the elapsed time from administration of the radiopharmaceutical is used) is used for later calculations as the SPECT image acquisition time.

Next, an input function corresponding to the radioactivity concentration in the arterial blood plasma is created (step S02). Various methods can be used as a method of creating the input function. 2 to 4 show an example of the input function creation protocol.
In order to obtain an input function according to the protocol described in FIGS. 3 and 4, it is necessary to obtain a standard input function and a correction term in advance. A method for acquiring the standard input function and the correction term will be described later.

 In the method shown in FIG. 2, first, arterial blood is collected at a plurality of times after administration of the radiopharmaceutical (step S11). The blood sampling time is selected so that the time interval and the number of measurements are sufficient to enable the calculation of the integral value in later calculations. For example, blood is collected at intervals of 15 seconds up to 2 minutes after administration, in which the change in the amount of radioactivity in the blood is large, and thereafter, blood is collected intermittently, for example, up to 90 minutes after administration, while gradually increasing the blood collection interval. Here, the amount of blood collected is sufficient to measure the amount of radioactivity in the blood (for example, 1.5 mL).

Next, with respect to the collected arterial blood, plasma is separated using a centrifuge (step S12), and the amount of radioactivity in the plasma is measured (step S13).
A known method can be used to measure the amount of radioactivity. For example, the blood count (corresponding to the amount of radioactivity) measured with a commercially available Well-type scintillation counter is expressed by the following formula (6):

Here, Counts is converted into a value per unit time unit mass according to the count number measured by the scintillation counter, T is the count collection time, and W is the mass of blood used for the count.
The obtained plasma count value is plotted against the arterial blood collection time, and an approximate curve is obtained to obtain an input function (step S14). In order to obtain the approximate curve, for example, curve fitting by a nonlinear least square method is performed.

On the other hand, when the standard input function is obtained in advance, it can be obtained by the method shown in the protocol of FIGS. In the method shown in FIG. 3, first, the amount of radioactivity (step S21) in the arterial blood of the subject is measured. This arterial blood is collected from a subject after a lapse of a certain time from administration of a radiopharmaceutical. The time for collecting arterial blood is preferably set to a time at which the time change of the blood radioactivity concentration is sufficiently small. This time can be determined from the shape of the standard input function. For example, in the case of a rat, the time may be about 10 minutes after the administration of the radiopharmaceutical.
The amount of arterial blood collected should be sufficient to measure the amount of radioactivity in the collected arterial blood, and usually 1.5 mL is sufficient.

 A known method can be used to measure the amount of radioactivity. For example, the blood count (corresponding to the amount of radioactivity) measured with a commercially available Well-type scintillation counter is expressed by the following formula (7):

(Here, Counts is a count number measured with a scintillation counter, T is a count collection time, and W is the mass of blood used for counting), and is converted into a value per unit time unit mass. The count per unit time unit mass (corresponding to the amount of radioactivity) is used as the value C _p (t ₁ ) of the arterial radioactivity amount at time t ₁ after administration of the radiopharmaceutical.

Next, an input function corresponding to the radioactivity of the whole blood is obtained by correcting the standard input function using the arterial radioactivity C _p (t ₁ ) obtained above (step S22). By multiplying the input function corresponding to the capacity by the correction term, conversion to an input function corresponding to the radioactivity level in the plasma is performed (step S23).

Correction of the standard input function, that is, creation of an input function corresponding to the amount of radioactivity of whole blood (step S22) can be performed by the following method.
First, the amount of radioactivity C _a (t ₁ ) at time t ₁ that is substantially equal to the time at which arterial blood was collected from the subject is extracted from the data constituting the standard input function, and the value C _p (t ₁ ) Ratio:

Ask for. The standard input function can be corrected by multiplying the data of the standard input function by the ratio value (step S22). This corrected standard input function becomes an input function corresponding to the radioactivity of whole blood.

 For the input function corresponding to the whole blood radioactivity, the following equation (2):

Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t), multiplied by the correction factor given by An input function corresponding to the amount of radioactivity in the medium can be obtained (step S23).

 In the input function creation method described with reference to FIG. 2, plasma is not separated from arterial blood in step S12, and the processing of steps S13 and S14 is performed on this arterial blood to cope with the radioactivity of whole blood. After obtaining the input function, an input function corresponding to the amount of radioactivity in plasma may be obtained in the same manner as in step S23.

The method shown in the protocol of FIG. 4 is different from the method shown in the protocol of FIG. 3 in that the input function is estimated from the dose of the radiopharmaceutical and the body weight of the subject without using the amount of radioactivity in the arterial blood of the subject. .
When estimating the input function using this protocol, first, the absolute sensitivity of the radiation detector used to create the standard input function is obtained. This is done using standard radioactive samples. On the other hand, the same sensitivity calibration is also performed in the radioactivity detector installed in each facility where the experiment is performed, and the relative sensitivity of this detector is calculated. Further, cross calibration is performed between the SPECT apparatus for performing the experiment and the radioactivity detector. These calibration conversion constants are used to determine the calibration factor of the standard input function in each experiment.

 Then, the input function is obtained as follows. First, the dose of the radiopharmaceutical administered to the subject and the body weight of the subject are obtained (step S31), and the ratio of the dose of radiopharmaceutical administered to the subject relative to the dose of radiopharmaceutical administered when obtaining the standard input function and Then, the ratio of the weight of the specimen and the weight of the subject used when obtaining the standard input function is multiplied by this standard input function to obtain an input function for each subject (step S32). Next, an input function corresponding to the amount of radioactivity in plasma is obtained in the same manner as in step S23 (step S33).

In FIG. 1, when the acquisition of the chest SPECT data and the creation of the input function corresponding to the amount of radioactivity in the arterial blood plasma shown in steps S01 and S02 are completed, the provisional flow rate at the site of interest on the SPECT image is calculated (step S03).
The calculation can be performed based on various models, for example, based on a three-compartment model or a two-compartment model. Below, the method based on the two-compartment model is taken as an example to explain the temporary flow rate calculation method.

 The two-compartment model is a model that assumes that the administered radiopharmaceutical is distributed between blood and tissue, and is represented by the following equation (5).

Here, t is the center scan time in the SPECT addition data, C _t (t) (cps / mL) is the SPECT count in the region of interest, C _a (t) is the input function (cps / mL), V _d (mL / g ) Is the distribution coefficient of radiopharmaceuticals in myocardial tissue and blood, and f (mL / mL / min) is a temporary flow rate. The SPECT count C _t (t) (cps / mL) in the region of interest can be designated as a region of interest on the SPECT image by specifying a portion for which the blood flow is to be obtained, and can be used as an average value of the count in that region. It is also possible to designate a portion for obtaining the flow rate in units of pixels and use it as a count in the pixels.

If the value of V _d is unknown, the flow rate of the provisional obtained, for example, by the following method.
First, an addition image at different center scan times t ₁ and t ₂ is created from a series of SPECT data, the same region of interest is specified in both images, and C _t (t ₁ ) and C _t (t ₂ ) are calculated. taking measurement.
Separately from this operation, two formulas are created by substituting t ₁ and t ₂ in the formula (5), respectively, and division is performed for both sides of these formulas. By this operation, the following formula (3) is obtained.

First, the value of k ₂ by table look-up as follows. By substituting arbitrary k ₂ into this equation (3), the calculated value of A is obtained. By repeating this operation while changing k ₂ little by little, a table representing the relationship between k ₂ and A can be created. Since the value of A can be calculated from the actual measurement values of C _t (t ₁ ) and C _t (t ₂ ), the value of k ₂ can be read from this table using A calculated based on the actual measurement values. .

The value of the read k ₂ , the measured C _t (t ₁ ) or C _t (t ₂ ), and the calculated C _a (t) are expressed by the following formula (4):

(T is the central scan time in the SPECT addition data, C _t (t) (cps / mL) is the SPECT count in the region of interest, C _a (t) is the input function (cps / mL), f (mL / mL / min) Is a provisional flow rate) to obtain a provisional flow rate f (step S03).

On the other hand, if the value of the distribution coefficient V _d is not significantly different for each subject, the distribution coefficient V _d was estimated from the measurement results stored from preliminary studies value, for example, accumulated from preliminary studies measurement results of the average value Can be used as a value of V _d given in advance.
In this case, the value of f is obtained by table lookup as follows. The above V _d , C _a (t) obtained above, and the center scan time t of the added data are substituted into the above equation (4), and an arbitrary f is substituted to obtain C _t (t ) Can be calculated. This operation is repeated while changing f little by little, and if a table showing the relationship between f and C _t (t) is created, it is a temporary flow rate using the table from the measured C _t (t). f can be read (step S03).

 For the obtained temporary flow rate, the following formula (1)

By multiplying the correction coefficient given by (where Hm represents a hematocrit value), the myocardial blood flow at the target region of interest is obtained (step S04).

Next, a method for acquiring the standard input function and the correction term used in the method shown in the protocol of FIGS. 3 and 4 will be described in detail.
The standard input function represents a standard value of blood radioactivity as a function of time, and can be obtained as an average value of blood radioactivity in a plurality of specimens.

To obtain the standard input function, first, a radiopharmaceutical is administered to a plurality of specimens, and arterial blood is collected at a plurality of times. At this time, the blood collection time is substantially aligned for each sample.
The blood sampling time is selected so that the time interval and the number of measurements are sufficient to enable the calculation of the integral value in later calculations. For example, blood is collected at intervals of 15 seconds up to 2 minutes after administration, in which the change in the amount of radioactivity in the blood is large, and thereafter, blood is collected intermittently, for example, up to 90 minutes after administration, while gradually increasing the blood collection interval. Here, the amount of blood collected is sufficient to measure the amount of radioactivity in the blood (for example, 1.5 mL).

 Next, the collected arterial blood is divided into two, and the count per unit time and unit mass is measured for one of them in the same manner as described above. For the obtained count per unit time per unit mass (corresponding to the amount of radioactivity), an average value between samples is calculated at each blood sampling time. A plot of this result versus blood collection time is the standard input function. An approximate curve obtained from this plot by curve fitting or the like may be used as the standard input function.

For the other arterial blood that was bisected, the blood cell component and the plasma component were separated using a centrifuge, and the count per unit time unit mass in the plasma was obtained in the same manner as in the case of whole blood. Calculate the average between samples.
For the count corresponding to each blood collection time, the ratio between the plasma radioactivity and the whole blood radioactivity was created, and the correction term:

(Where Cpla (t) is the amount of radioactivity in plasma at time t, and Ctot (t) is the amount of radioactivity of whole blood at time t).

  Next, a preferred embodiment of the quantitative program according to the present invention will be described with reference to the drawings. FIG. 5 is a diagram showing the configuration of the quantitative program according to the embodiment of the present invention, together with a recording medium. FIG. 6 is a flowchart showing the flow of processing in the most preferred embodiment of the program according to the present invention.

In the most preferred embodiment, the quantitative program 100 shown in FIG. 5 is provided by being stored in the recording medium 200. Examples of the recording medium 200 include a floppy (registered trademark) disk, a CD-ROM, a DVD, other recording media such as a ROM, a semiconductor memory, and the like.
By inserting the recording medium 200 storing the program 100 into a reader provided in the computer, the computer can access the program 100 and can operate as the quantitative system 300 by the quantitative program 100. .

As shown in FIG. 5, the quantification program 100 includes a main module 10 that supervises processing, an input module 20, an input function creation module 30, a SPECT count extraction module 40, a blood flow calculation module 50, and an output module 60. And.
The main module 10 causes the computer to sequentially execute processing by other modules. That is, the SPECT image information input process by the input module 20 (step S41), the input function generation process by the input function generation module 30 (step S42), the SPECT count extraction process by the SPECT count extraction module 40, and the temporary blood flow calculation module 50 The computer executes the flow rate calculation process (step S43), the blood flow rate calculation process (step S44), and the result output process (step S45) by the output module 60 in this order (see FIG. 6). Hereinafter, processing by each module will be described.

  The input module 20 causes the computer to execute an input operation of data necessary for quantifying the myocardial blood flow (step S41). Here, the necessary data is variously selected according to the model used for quantification and the input function creation method, but the SPECT image data of the subject is always included. As the SPECT image data, the data acquired in step S01 described above is input and stored in the storage device of the computer. The SPECT image data is composed of a series of SPECT data, and each SPECT data is composed of a value representing the signal intensity for each pixel. In addition, when the input function is created according to the protocol shown in FIG. 2 or 3, it is obtained in step S13 or step S21 as data relating to the measurement value of the radioactivity in plasma or arterial blood and the collection time of arterial blood. Values are entered and stored in a computer storage device. On the other hand, when the creation of the input function is performed according to the protocol shown in FIG. 4, the values obtained in step S31 described above are input as information relating to the body weight of the subject and the dose of the radiopharmaceutical, and are stored in the storage device of the computer. Remembered.

  The input function creation module 30 causes the computer to execute an input function creation operation corresponding to the amount of radioactivity in the arterial blood plasma (step S42). Specifically, depending on whether the protocol for creating the input function is any one of FIG. 2, FIG. 3, and FIG. 4, the computer performs step S14, step S22 to step S23, or step S32 to step S33. The processing related to is executed. Here, in the recording medium 200 in which the quantitative program 100 including the input function creation module 30 is stored, the standard input function used in each of the above steps, the standard plasma activity Cpla (t) at time t, For standard whole blood radioactivity Ctot (t) at time t, the time t given in a given range and increment, the value of the standard input function corresponding to this, the value of Cpla (t), Ctot (t) Table data consisting of the values of the radiopharmaceutical and the dose of the radiopharmaceutical administered when obtaining the standard input function and the weight of the specimen are stored in advance, and these are read out according to the processing contents and stored in the storage device of the computer. Is done.

  The processing for obtaining the input function in step S14 is performed by storing the measured values of the radioactivity at a plurality of blood sampling times in the storage means of the computer as table data, or by curve fitting or the like for the measured values of the radioactivity at the plurality of blood sampling times. An approximate curve is obtained, and the value of the corresponding approximate curve is stored in the storage means of the computer as table data for a given range and time given in steps.

When obtaining the value of the standard input function at time t ₁ in step S22, in the table data of the time given in the predetermined range and step and the value of the standard input function corresponding thereto, the time t ₁ is a predetermined value. If it does not match any of the time given in the range or step, the time closest to t ₁ is specified and the value of the standard input function corresponding to this is used. Further, when multiplying each data constituting the standard input function by the ratio value, the ratio value is added to each value of the standard input function corresponding to a predetermined time and given time in the table data. Multiply
The process of multiplying the correction coefficient in step S23 is the Cpla (t) for the standard input function value corrected in step S22 with respect to the time t given in the predetermined range and step, existing in the table data. And the value of Ctot (t).

The process of correcting the standard input function in step S32 is acquired and input in step S31 for each value of the standard input function corresponding to the time given in a predetermined range and step, which exists in the table data. The radiopharmaceutical dose and the subject's body weight stored in the storage device of the computer, and the radiopharmaceutical dose and the weight of the specimen administered when obtaining the standard input function stored in advance in the recording medium 200 are used. . The process of step S33 is performed in the same manner as the process of step S23 described above.
As described above, after separating the plasma from the arterial blood in step S12 and performing the processing of steps S13 and S14 on this arterial blood to obtain an input function corresponding to the amount of radioactivity of the whole blood, the same as in step S23 In addition, the processing in step S14 and step S23 when obtaining an input function corresponding to the amount of radioactivity in plasma is the same as described above.

The SPECT count extraction module 40 causes the computer to execute an operation of extracting the SPECT count number (signal intensity) at the site of interest on the chest SPET image. The region of interest may be designated as an arbitrarily selected region, but may be a region selected in units of one pixel. The SPECT count is obtained from the number of counts in the pixel when the region of interest is selected in units of one pixel. When the region of interest is designated as the selected region, the average number of counts in the designated region can be used.
The region of interest is selected using an input device provided in the computer.

  The SPECT count is obtained as follows. Of the series of collected SPECT data, SPECT data at a certain time before and after a specified time is added for each corresponding pixel to create an added image. Then, a value proportional to the signal intensity of each pixel is obtained in the region of interest selected as described above in the added image.

The blood flow rate quantification module 50 causes the computer to perform a calculation operation of a quantitative value of the myocardial blood flow, that is, a temporary flow rate calculation operation (step S43) and a myocardial blood flow calculation operation (step S44). Specifically, the computer is caused to execute the processes related to step S03 and step S04.
However, in the processing related to step S03, the calculation of the integral included in the equations (3) and (4), that is, the following equation (10):

When the predetermined time increment in the table data is Δt, the nearest integer not exceeding t / Δt is set to n, and the following equation (10) is an approximation of the above equation (10): 11):

Calculate even when performing the calculation of the integral in equation (5) by changing the f slightly, the value of f / V _d for a given f is substituted into k ₂ of the formula (11) is calculated similarly.

  The output module 60 outputs the obtained quantitative value of the myocardial blood flow to a display device such as a display (step S45). In a preferred embodiment, the quantitative value of the myocardial blood flow can be determined at a site of interest on the tomographic image displayed on the display device by brightness or color according to the myocardial blood flow. In this case, the SPECT data of the subject can be used as the tomographic image, but it may be displayed on an image obtained by another modality such as CT or MRI. Of course, the obtained myocardial blood flow value may be displayed numerically in a tabular format or the like.

  The quantitative program 100 according to the present invention may be provided via a network as a computer data signal superimposed on a carrier wave. In this case, the fixed amount program 100 is received by a communication device provided in the computer and stored in a memory provided in the computer, thereby being executed by the computer.

Next, the quantitative system 300 according to the present invention will be described.
FIG. 7 is a diagram showing the configuration of the image processing apparatus according to the present invention. As shown in FIG. 7, the quantitative system 300 functionally includes an input unit 310, an input function creation unit 320, a SPECT count extraction unit 330, a blood flow rate calculation unit 340, and an output unit 350.

  The input unit 310 performs the process related to step S41. The input function creation unit 320 performs the process related to step S42. The SPECT count extraction unit 330 performs the process according to step S43. The blood flow rate calculation unit 340 performs the process according to step S44. The output unit 350 performs the process according to step S45.

  Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited to the contents.

 In order to verify the myocardial blood flow quantification method according to the present invention, the following experiment using dogs was performed.

experimental method:
(1) SPECT imaging and measurement of radioactivity
20 beagle dogs were divided into 3 groups, 7 were resting conditions, 4 were beta blockers (dosage: 2-6 mg bolus followed by 2 or 4 mg / hr, continuous infusion, route of administration : Intravenous injection) conditions for reducing myocardial blood flow, and for 9 animals, conditions for increasing myocardial blood flow by injecting adenosine (dose: 140 mg / kg / hr to 700 mg / kg / hr, continuous administration via vein) The experiment below was conducted.

For each dog, 3 MBq of microsphere containing ¹⁴¹ Ce (purchased from the Japan Isotope Association) was injected into the left ventricle using a catheter, and arterial blood was collected from the aorta at a rate of 5 mL / min for 2 minutes (hereinafter, Arterial blood 1). Subsequently, thallium chloride-201 (manufactured by Nippon Mediphysics Co., Ltd.) was intravenously administered at 110 Bq / kg, and dynamic SPECT (use SPECT device: 7200A type 2 head gamma camera, manufactured by Toshiba Corporation) was imaged. This was continued for 1 hour from the start of administration. Imaging frame collection rate (rotation rate) is 10 x 1 min (10 times at 1 minute intervals), 6 x 2 min (6 times at 2 minute intervals), 3 x 4 min (3 times at 4 minute intervals). 5 x 5 min (5 times at 5 minute intervals). The energy window was 34% centered at 77 keV.
After the completion of a series of dynamic SPECT scans, for the purpose of confirming the fluctuation of the myocardial blood flow, 3 MBq containing ⁵¹ Cr was injected into the left ventricle using a catheter (purchased from the Japan Isotope Association).

Thereafter, each animal was sacrificed by administration of potassium chloride and the heart was removed. The heart was divided and the ²⁰¹ Tl radioactivity count was measured with a self-made well counter, and the radioactivity per unit time unit mass was determined using the following equation (6).

Here, Counts is a count number measured by a scintillation counter, T is a count collection time, and W is a mass of blood used for counting.
Further, after waiting for the decay of radioactivity derived from ²⁰¹ Tl, the radioactivity levels of ¹⁴¹ Ce and ⁵¹ Cr in the heart tissue and arterial blood 1 were determined in the same manner.

(2) Determination of input function In parallel with dynamic SPECT imaging, the input function was determined in the following manner.
First, after administration of thallium chloride-201, the interval is 20 seconds up to 6 minutes, 60 seconds up to 6-10 minutes, 2 minutes up to 10-20 minutes, 300 seconds up to 20-30 minutes, 30-60 minutes Until then, arterial blood was collected at 600 second intervals. In 6 of the 20 cases, some of the collected arterial blood samples were collected at a certain collection time point, and a part thereof was immediately centrifuged to separate the plasma. The amount of radioactivity was measured for the collected arterial blood and separated plasma using the well counter.

 Next, for the plasma-separated sample, the ratio of the amount of radioactivity between plasma and whole blood was calculated, and the value of the ratio was plotted against the collection time of arterial blood. The plotted data was subjected to curve fitting using IDL data analysis package (Research Systems, Inc.) to estimate the ratio of the radioactivity between plasma and whole blood at each time point (FIG. 8). The amount of radioactivity in plasma was determined by multiplying the amount of radioactivity in whole blood by the ratio of the amount of radioactivity in plasma and whole blood at each time point. By plotting the amount of radioactivity in the obtained plasma against the time of blood collection, an input function corresponding to the amount of radioactivity in plasma was obtained.

(3) Myocardial blood flow by microsphere method The value of myocardial blood flow by microsphere method was determined by the following method.
First, the myocardial blood flow (mL / min / g) was determined from the radioactivity levels of ¹⁴¹ Ce and ⁵¹ Cr in the heart tissue and arterial blood 1 measured above using the following formula (11).

Here, MBF _MS is the myocardial blood flow by the microsphere method, C _tiss is the radioactivity in the tissue, and C _blood is the radioactivity in the arterial _blood .

(4) Myocardial blood flow based on SPECT data On the obtained dynamic SPECT image, a circular region of interest is set for each of the front, tip, side, posterior and septum of the heart. The SPECT count was determined. By plotting the SPECT count value against the center scan time of each image, a time intensity curve in each region of interest was created.

Per time Intensity curve based on results of experiments performed at rest condition, performs fitting using the following equation (5) to determine the value of blood flow f and partition coefficient V _d provisional.

Here, t is the center scan time in the SPECT addition data, C _t (t) (cps / mL) is the SPECT count in the region of interest, C _a (t) is the input function (cps / mL), V _d (mL / g ) Is the distribution coefficient of radiopharmaceuticals in myocardial tissue and blood, and f (mL / mL / min) is a temporary flow rate.

On the other hand, for those administered beta blocker and adenosine, the average value of V _d obtained from the data of the resting example was previously substituted into the above formula (5), and then the time intensity curve based on each experimental result was obtained. To obtain a provisional flow rate f.
Myocardial blood flow was obtained by multiplying the calculated temporary flow rate by the coefficient obtained by the following equation (1). As the hematocrit value, a value measured for each specimen was used.

result:
Plot the calculated temporary flow values against the values of myocardial blood flow obtained by the microsphere method (the average value of the values obtained by microspheres containing ¹⁴¹ Ce and microspheres containing ⁵¹ Cr) The obtained graph is shown in FIG.
As is apparent from this figure, the value of the provisional flow rate obtained from the SPECT data shows a good correlation with the myocardial blood flow obtained by the microsphere method, but deviates greatly from the straight line with a slope of 1. It was. From this result, it was shown that the value of the provisional flow rate cannot be said to be a value that truly reflects the value of the myocardial blood flow.

FIG. 10 shows a graph in which the value of the myocardial blood flow obtained by multiplying the provisional flow rate by the correction term according to the equation (1) is plotted against the value of the myocardial blood flow obtained by the microsphere method. As is apparent from this figure, the value of the myocardial blood flow obtained by multiplying the provisional flow value by the correction term obtained by the equation (1) is between the myocardial blood flow obtained by the microsphere method. It was shown that there is a good correlation between the two and the distribution on a straight line with a slope of 1.
From this result, it was shown that the quantification method of the myocardial blood flow according to the present invention is a method capable of giving an actual measurement value reflecting the value of the myocardial blood flow.

  The present invention is used for quantifying myocardial blood flow in a region of interest based on a chest SPECT image.

It is a figure which shows an example of the protocol in the quantification method based on this invention. It is a figure which shows an example of the input function creation protocol in the fixed_quantity | assay method which concerns on this invention. It is a figure which shows an example of the input function creation protocol in the fixed_quantity | assay method which concerns on this invention. It is a figure which shows an example of the input function creation protocol in the fixed_quantity | assay method which concerns on this invention. It is a figure which shows an example of a structure of the fixed_quantity | quantitative_assay program which concerns on this invention. It is a figure which shows an example of the flow of the process in the program which concerns on this invention. It is a functional block diagram in the fixed_quantity | assay system which concerns on this invention. It is a figure which shows the time change of the ratio of the radioactivity amount in plasma, and the radioactivity amount of whole blood, and a fitting result. It is a figure which shows the relationship between the value of temporary flow volume, and the myocardial blood flow rate calculated | required with the microsphere method. It is a figure which shows the relationship between the myocardial blood flow calculated | required by the method which concerns on this invention, and the myocardial blood flow calculated | required by the microsphere method.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 ... Main module 20 ... Input module 30 ... Input function creation module 40 ... SPECT count extraction module 50 ... Blood flow rate calculation module 60 ... Output module 100 ... Determination program 200 ... Recording medium 300 ... Determination system 310 ... Input part 320 ... Input function Creation unit 330 ... SPECT count extraction unit 340 ... Blood flow rate calculation unit 350 ... Output unit

Claims (32)

A first step of acquiring a SPECT image of the chest in the subject;
A second step of determining an input function corresponding to the amount of radioactivity in the subject's arterial blood plasma;
A third step of obtaining a temporary flow rate at the site of interest from the signal intensity at the site of interest in the acquired SPECT image using the obtained input function;
In the temporary flow rate, the following formula (1):

(In the formula, Hm represents a hematocrit value)
A fourth step of determining the blood flow by multiplying the correction coefficient given by
A method for quantifying myocardial blood flow, comprising: The first step acquires a series of SPECT data by imaging a chest of a subject who has administered a radiopharmaceutical with a SPECT camera, and arterial blood collected from the subject at a plurality of times after the administration of the radiopharmaceutical. Having a step to obtain,
In the second step, plasma is separated from the arterial blood, the amount of radioactivity per unit time unit mass in the plasma is measured, and the plasma at time t is calculated from the measured values of the amount of radioactivity at the plurality of blood collection times. The method for determining myocardial blood flow according to claim 1, further comprising: obtaining an input function C _a (t) representing the amount of radioactivity in the myocardium. The first step acquires a series of SPECT data by imaging a chest of a subject who has administered a radiopharmaceutical with a SPECT camera, and arterial blood collected from the subject at a plurality of times after the administration of the radiopharmaceutical. Having a step to obtain,
In the second step, plasma is separated from the collected arterial blood and the amount of radioactivity per unit time unit mass is measured, and an approximate curve for the measured values of the amount of radioactivity at the plurality of blood collection times is obtained. The method for determining the myocardial blood flow according to claim 1, further comprising: obtaining an input function C _a (t) representing the amount of radioactivity in plasma at time t. The first step is to acquire a series of SPECT data by imaging the chest of a subject who has been administered a radiopharmaceutical with a SPECT camera, and arterial blood collected from the subject at time t ₁ after the radiopharmaceutical is administered. Having a step to obtain,
In the second step, the standard input function is multiplied by the ratio of the measured value of the amount of radioactivity per unit time of the collected arterial blood to the value at time t ₁ of the standard input function, and the following equation (2) :

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t)
The myocardial blood flow quantification method according to claim 1, wherein an input function C _a (t) representing the amount of radioactivity in plasma at time t is obtained by multiplying by a correction coefficient given by The first step acquires a series of SPECT data by imaging a chest of a subject who has administered a radiopharmaceutical with a SPECT camera, and arterial blood collected from the subject at a plurality of times after the administration of the radiopharmaceutical. Having a step to obtain,
The second step includes a step of measuring a radioactivity amount per unit time unit mass in the arterial blood, and an input function representing the radioactivity amount of whole blood at time t from the measured values of the radioactivity amount at the plurality of blood collection times For the step of obtaining C _a '(t) and the obtained input function C _a ' (t), the following equation (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t)
And determining an input function C _a (t) corresponding to the amount of radioactivity in plasma at time t by multiplying by the correction coefficient given by Law. The first step acquires a series of SPECT data by imaging a chest of a subject who has administered a radiopharmaceutical with a SPECT camera, and arterial blood collected from the subject at a plurality of times after the administration of the radiopharmaceutical. Having a step to obtain,
The second step includes a step of measuring a radioactivity amount per unit time unit mass of the collected arterial blood, and calculating an approximate curve for the measurement values of the radioactivity amount at the plurality of blood collection times to obtain a total curve at time t. A step of obtaining an input function C _a ′ (t) representing the amount of radioactivity of blood, and the following equation (2) for the obtained input function C _a ′ (t):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t)
And determining an input function C _a (t) corresponding to the amount of radioactivity in plasma at time t by multiplying by the correction coefficient given by Law. The first step has a step of acquiring a series of SPECT data by imaging the chest of a subject who has been administered a radiopharmaceutical with a SPECT camera,
In the second step, the ratio of the dose of the radiopharmaceutical administered to the subject to the dose of the radiopharmaceutical administered when obtaining the standard input function, and the weight of the specimen used when obtaining the standard input function By multiplying the standard input function by the weight ratio of the subject, an input function C _a ′ (t) representing the amount of radioactivity of whole blood at time t is obtained, and the following equation (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t)
And calculating an input function C _a (t) corresponding to the amount of radioactivity in plasma at time t by multiplying by the correction coefficient given in claim 1. Law. The third step creates an added image at different central scan times t ₁ and t ₂ from the series of SPECT data, and the SPECT count C _t (t ₁ ) of the region of interest designated identically for both images and The step of obtaining C _t (t ₂ ), the measured SPECT counts C _t (t ₁ ) and C _t (t ₂ ), and the input function C _a (t) obtained in the second step are expressed by the following formula ( 3):

In assignment, and determining a value of k ₂ by table look-up, the second step the value of k ₂ obtained with the measured SPECT count C _t (t ₁₎ or C _t and (t ₂₎ to The obtained input function C _a (t) is expressed by the following equation (4):

The method for determining the myocardial blood flow according to any one of claims 2 to 7, further comprising: calculating a provisional flow rate f by substituting into. In the third step, an addition image at a center scan time t ₁ is created from the series of SPECT data, and a SPECT count C _t (t ₁ ) of a designated region of interest is obtained. The coefficient V _d , the input function C _a (t) obtained in the second step, and the measured SPECT count C _t (t ₁ ) are expressed by the following equation (5):

The method of quantifying myocardial blood flow according to any one of claims 2 to 7, further comprising the step of calculating a provisional flow rate f by table lookup. The third step includes generating a plurality of images at a plurality of central scan times t from the series of SPECT data, and obtaining a SPECT count C _t (t) of a region of interest designated identically for all images; Creating a time intensity curve representing the relationship between the calculated C _t (t) and the center scan time t, and the following equation (5):

Substituting the input function C _a (t) obtained in the second step and fitting with the time intensity curve to obtain a provisional flow rate f together with a distribution coefficient V _d. The method for quantifying myocardial blood flow according to any one of claims 2 to 7. The third step includes generating a plurality of images at a plurality of central scan times t from the series of SPECT data, and obtaining a SPECT count C _t (t) of a region of interest designated identically for all images; Creating a time intensity curve representing the relationship between the calculated C _t (t) and the center scan time t, and the following equation (5):

Substituting the value of the distribution coefficient V _d given in advance and the input function C _a (t) obtained in the second step and fitting with the time intensity curve to obtain the provisional flow rate f The method for quantifying myocardial blood flow according to any one of claims 2 to 7, further comprising: a step. On the computer,
An input function creation process for obtaining an input function corresponding to the amount of radioactivity in arterial blood plasma in the subject;
A signal intensity extraction process for extracting the signal intensity of the region of interest from the SPECT image data of the chest in the subject;
Using the obtained input function and the extracted signal intensity at the region of interest, a provisional flow rate calculation process for obtaining a provisional flow rate at the region of interest;
In the temporary flow rate, the following formula (1):

(In the formula, Hm represents a hematocrit value)
Blood flow calculation processing to obtain the blood flow by multiplying the correction coefficient given in
Blood flow quantification program to execute sequentially. On the computer,
A signal intensity extraction process for extracting the signal intensity of the region of interest from the SPECT image data of the chest in the subject;
An input function creation process for obtaining an input function corresponding to the amount of radioactivity in arterial blood plasma in the subject;
Using the obtained input function and the extracted signal intensity at the region of interest, a provisional flow rate calculation process for obtaining a provisional flow rate at the region of interest;
In the temporary flow rate, the following formula (1):

(In the formula, Hm represents a hematocrit value)
Blood flow calculation processing to obtain the blood flow by multiplying the correction coefficient given in
Blood flow quantification program to execute sequentially. The input function creating process is an input function C _a (t) representing the amount of radioactivity in plasma at time t by obtaining an approximate curve for measured values of the amount of radioactivity in plasma at a plurality of times stored in the computer. The blood flow rate quantification program according to claim 12 or 13, characterized in that: The input function creating process, multiplied for the value at time t ₁ of the standard input function, the ratio of the measured value of the amount of radioactivity per unit time per unit mass of the arterial blood at time t ₁ stored in the computer to the standard input function Furthermore, the following formula (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t)
The blood flow rate quantification program according to claim 12 or 13, wherein an input function C _a (t) representing the amount of radioactivity in plasma at time t is obtained by multiplying by the correction coefficient given in (14). The input function creation processing obtains an input function C _a ′ (t) representing the radioactivity amount of whole blood at time t from the measurement values of the radioactivity amount at a plurality of blood collection times stored in the computer, and the obtained input For the function C _a '(t), the following equation (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t)
The blood flow rate quantification program according to claim 12 or 13, wherein an input function C _a (t) corresponding to the amount of radioactivity in plasma at time t is obtained by multiplying by the correction coefficient given by The input function creation process is an input function C _a ′ (t) representing the radioactivity of whole blood at time t by obtaining an approximate curve for the measured values of radioactivity at a plurality of blood collection times stored in the computer. And the following equation (2) for the obtained input function C _a ′ (t):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t)
The blood flow rate quantification program according to claim 12 or 13, wherein an input function C _a (t) corresponding to the amount of radioactivity in plasma at time t is obtained by multiplying by the correction coefficient given by In the input function creation process, the ratio of the radiopharmaceutical dose administered to the subject stored in the computer with respect to the radiopharmaceutical dose administered when obtaining the standard input function and the standard input function are obtained. By multiplying the standard input function by the ratio of the weight of the subject stored in the computer to the weight of the specimen used in step 1, an input function C _a ′ (t) representing the amount of radioactivity of whole blood at time t is obtained. The following formula (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t)
The blood flow rate quantification program according to claim 12 or 13, wherein an input function C _a (t) corresponding to the amount of radioactivity in plasma at time t is obtained by multiplying by the correction coefficient given by The signal intensity extraction process creates an added image at different center scan times t ₁ and t ₂ from a series of SPECT data constituting the SPECT image data stored in the computer, and is specified identically for both images. Find the SPECT counts C _t (t ₁ ) and C _t (t ₂ ) of the region of interest,
In the provisional flow rate calculation process, the obtained SPECT counts C _t (t ₁ ) and C _t (t ₂ ) and the input function C _a (t) obtained in the second step are expressed by the following equation (3):

In assignment, and table determining a value of k ₂ by a look-up, the SPECT count was determined the value of k ₂ obtained C _{t (t 1)} or C _t (t ₂₎ and the second step in The obtained input function C _a (t) is expressed by the following equation (4):

The temporary blood flow f is calculated by substituting into the blood flow volume quantification program according to any one of claims 14 to 18. In the signal intensity extraction process, an addition image at a center scan time t ₁ is created from a series of SPECT data constituting the SPECT image data stored in the computer, and a SPECT count C _t (t ₁ )
In the provisional flow rate calculation process, a distribution coefficient V _d given in advance, the input function C _a (t) obtained in the second step, and the obtained SPECT count C _t (t ₁ ) are expressed by the following equation (5). ):

The blood flow rate quantification program according to any one of claims 14 to 18, wherein the provisional flow rate f is obtained by table lookup. The signal intensity extraction process creates a plurality of images at a plurality of central scan times t from a series of SPECT data constituting the SPECT image data stored in the computer, and the same region of interest is designated for all the images. A SPECT count C _t (t) is obtained, and a time intensity curve representing the relationship between the obtained C _t (t) and the center scan time t is created,
The provisional flow rate calculation process is performed by the following equation (5):

Substituting the input function C _a (t) obtained in the second step for the fitting, the fitting with the time intensity curve is performed, and the provisional flow rate f is obtained together with the distribution coefficient V _d. Item 19. A blood flow determination program according to any one of items 14 to 18. The signal intensity extraction process creates a plurality of images at a plurality of central scan times t from a series of SPECT data constituting the SPECT image data stored in the computer, and the same region of interest is designated for all the images. A SPECT count C _t (t) is obtained, and a time intensity curve representing the relationship between the obtained C _t (t) and the center scan time t is created,
The provisional flow rate calculation process is performed by the following equation (5):

Substituting the value of the distribution coefficient V _d given in advance and the input function C _a (t) obtained in the second step and fitting with the time intensity curve to obtain the provisional flow rate f The blood flow rate quantification program according to any one of claims 14 to 18, characterized in that: A signal intensity extracting means for extracting the signal intensity of the region of interest from the SPECT image data of the chest in the subject;
An input function creating means for obtaining an input function corresponding to the amount of radioactivity in arterial blood plasma in the subject;
Using the obtained input function and the extracted signal intensity at the region of interest, a provisional flow rate calculation means for obtaining a provisional flow rate at the region of interest;
In the temporary flow rate, the following formula (1):

(In the formula, Hm represents a hematocrit value)
A blood flow rate calculating means for determining a blood flow rate in the region of interest of the subject by multiplying the correction coefficient given by
A blood flow rate determination system characterized by comprising: The input function creating means obtains an input function C _a (t) representing the amount of radioactivity in plasma at time t by obtaining an approximate curve for the measured value of the amount of radioactivity in plasma at a plurality of given times. The blood flow rate quantification system according to claim 23. The input function creating means multiplies the standard input function by the ratio of the measured value of the radioactivity per unit time unit mass of arterial blood at a given time t _{1 to} the value at the time t ₁ of the standard input function, and Following formula (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t)
The blood flow rate quantification system according to claim 23, wherein an input function C _a (t) representing the amount of radioactivity in plasma at time t is obtained by multiplying the correction coefficient given by The input function creating means obtains an input function C _a ′ (t) representing the radioactivity of whole blood at a time t from the measured values of the radioactivity at a plurality of given blood sampling times, and determines the input function C _a For '(t), the following formula (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t)
The blood flow rate quantification system according to claim 23, wherein an input function C _a (t) corresponding to the amount of radioactivity in plasma at time t is obtained by multiplying the correction coefficient given by The input function creating means obtains an input function C _a ′ (t) representing a radioactivity amount of whole blood at a time t by obtaining an approximate curve for the measured value of the radioactivity amount at a plurality of given blood collection times, For the obtained input function C _a ′ (t), the following equation (2):

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t)
The blood flow rate quantification system according to claim 23, wherein an input function C _a (t) corresponding to the amount of radioactivity in plasma at time t is obtained by multiplying the correction coefficient given by The input function creating means is used when obtaining the standard input function and the ratio of the dose of radiopharmaceutical administered to the given subject to the dose of radiopharmaceutical administered when obtaining the standard input function. By multiplying the standard input function by the ratio of the given subject's body weight to the body weight of the specimen, an input function C _a ′ (t) representing the radioactivity of whole blood at time t is obtained, and the following equation (2) :

(Where Cpla (t) is the standard plasma radioactivity at time t and Ctot (t) is the standard whole blood radioactivity at time t)
The blood flow rate quantification system according to claim 23, wherein an input function C _a (t) corresponding to the amount of radioactivity in plasma at time t is obtained by multiplying the correction coefficient given by The signal intensity extraction means creates an addition image at different center scan times t ₁ and t ₂ from a series of SPECT data constituting the given SPECT image data, and the same region of interest is designated for both images. Obtain SPECT counts C _t (t ₁ ) and C _t (t ₂ ),
The temporary flow rate calculation means uses the measured SPECT counts C _t (t ₁ ) and C _t (t ₂ ) and the input function C _a (t) obtained in the second step as the following formula (3):

In assignment, and determining a value of k ₂ by table look-up, the second step the value of k ₂ obtained with the measured SPECT count C _t (t ₁₎ or C _t and (t ₂₎ to The obtained input function C _a (t) is expressed by the following equation (4):

The blood flow rate quantification system according to any one of claims 24 to 28, wherein a provisional flow rate f is obtained by substituting into. The signal intensity extracting means creates an addition image at the center scan time t ₁ from a series of SPECT data constituting the given SPECT image data, and calculates a SPECT count C _t (t ₁ ) of the designated region of interest. Seeking
The temporary flow rate calculation means calculates a distribution coefficient V _d given in advance, the input function C _a (t) obtained in the second step, and the obtained SPECT count C _t (t ₁ ) from the following formula (5 ):

The blood flow rate quantification system according to any one of claims 24 to 28, wherein the provisional flow rate f is obtained by table lookup. The signal intensity extraction means creates a plurality of images at a plurality of central scan times t from a series of SPECT data constituting the given SPECT image data, and SPECT count C of the region of interest designated identically for all images _t (t) is determined, and a time intensity curve representing the relationship between the calculated C _t (t) and the central scan time is created,
The provisional flow rate calculation means is represented by the following formula (5):

Substituting the input function C _a (t) obtained in the second step for the fitting, the fitting with the time intensity curve is performed, and the provisional flow rate f is obtained together with the distribution coefficient V _d. Item 30. The blood flow rate determination system according to any one of items 24 to 28. The signal intensity extraction means creates a plurality of images at a plurality of central scan times t from a series of SPECT data constituting the given SPECT image data, and SPECT count C of the region of interest designated identically for all images _t (t) is determined, and a time intensity curve representing the relationship between the calculated C _t (t) and the central scan time is created,
The provisional flow rate calculation means is represented by the following formula (5):

Substituting the value of the distribution coefficient V _d given in advance and the input function C _a (t) obtained in the second step and fitting with the time intensity curve to obtain the provisional flow rate f The blood flow rate quantification system according to any one of claims 24 to 28, wherein:

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