JP4701406B2 - Image quantification apparatus, method, program by PET imaging, and computer-readable recording medium recording the image quantification program - Google Patents

Description

  The present invention relates to quantitative image evaluation of cerebral blood flow, cerebral oxygen metabolism, and cerebral oxygen uptake rate by positron emission tomography (PET).

Examination by positron emission tomography using O-15 labeled oxygen (ie, ¹⁵ O) has been put to practical use in the following amounts. Cerebral local oxygen metabolism ( ¹⁵ O ₂ gas), cerebral local blood volume (C ¹⁵ O gas). Cerebral local blood flow (C ¹⁵ O ₂ gas), cerebral local blood flow (H ₂ ¹⁵ O). Here, a labeled compound containing 0-15 labeled oxygen shown in parentheses is used for each amount of examination. Inspection by PET imaging has the following advantages.
(1) Since the labeled drug to be administered is originally an isotope of an element constituting a molecule present in the living body, the function of the living body can be observed as a labeled drug without modifying the molecule present in the living body.
(2) Since the half-life is short, there is little exposure of the living body. Therefore, it is easy to perform repetitive inspection and non-inspection.
(3) Since the half-life is short, the specific radioactivity is high and diagnosis is possible with a very small amount of nuclide.

  Quantitative image evaluation of cerebral blood flow, cerebral oxygen metabolism, and cerebral oxygen uptake rate is possible by PET examination, and examinations such as stroke are performed. This test is performed by administering O-15 labeled oxygen. Although 0-15 labeled oxygen is a diagnostic probe that traces the behavior of oxygen molecules in the body, its kinetics in the brain depend not only on tissue oxygen metabolism but also on washing out metabolized water molecules, ie, blood flow. Furthermore, since the oxygen uptake rate is as low as about 40% under normal conditions, the radioactive concentration in the blood vessel contributes to the oxygen metabolism image. For this reason, in PET examination, not only examination based on inhalation of O-15 labeled oxygen gas but also blood flow examination using O-15 labeled water and blood volume examination based on 0-15 labeled carbon monoxide inhalation are performed. These three tests for cerebral oxygen metabolism, cerebral blood flow, and cerebral oxygen uptake rate are performed independently, but wait for radioactive decay during the test. In the routine method that is widely used, it was necessary to continue to administer the drug continuously until the distribution of radioactivity concentration in the body became constant for each test (see the following paper. (1) Correia JA, Alpert NM, Buxton RB, Ackerman RH (1985) Analysis of some errors in the measurement of oxygen extraction and oxygen consumption by the equilibrium inhalation method, J Cereb Blood Flow Metab 5: 591-9, (2) Frackowiak RS, Jones T, Lenzi GL, Heather JD ( 1980a) Regional cerebral oxygen utilization and blood flow in normal man using oxygen-15 and positron emission tomography, Acta Neurol Scand 62: 336-344, (3) Frakkowiak RS, Lenzi GL, Jones T, Heather JD (1980) Quantitative measurement of regional cerebral blood flow and oxygen metabolism in man using 15O and positron emission tomography theory, procedure, and normal values, J Comput Assist Tomogr. 4: 727-36, and (4) Lammertsma AA, Heather JD, Jones T, Frackowiak RS , Lenzi GL, (1982) A statistical study of the steady state technique for measuring regional cerebral blood flow and oxygen utilization using 150, J Comput Assist Tomogr 6: 566-573).

  In contrast, a method based on short-term administration of three kinds of labeled compounds was developed, and the test time was reduced to about 1 hour (see the following paper. (5) Mintun MA, Raichle ME, Martin WR, Herscovitch P, (1984) J Nucl Med 25: 177-187, (6) Hatazawa J, Fujita H, Kanno I, Satoh T, Iida H, Miwa S, Murakami M, Okudera T, Inugami A, Ogawa T, et al. , (1995) Regional cerebral blood flow, blood volume, oxygen extraction fraction, and oxygen utilization rate in normal volunteers measured by the autoradiographic technique and the single breath inhalation method, Ann Nucl Med. 9: 15-21, (7) Shidahara M , Watabe H, Kim KM, Oka H, Sago M, Hayashi T, Miyake Y, Ishida Y, Hayashida K, Nakamura T, Iida H, (2002) Evaluation of a commercial PET tomograph-based system for the quantitative assessment of rCBF, rOEF and rCMRO2 by using sequential administration of 15O-labeled compounds, Ann Nucl Med. 16: 317-327). FIG. 1 shows the time course of PET imaging by this method. First, for blood volume examination, PET imaging is performed for 6 minutes after inhalation of 0-15 labeled carbon monoxide. Further, after waiting for 15 to 20 minutes for radioactive decay, O-15 labeled oxygen gas is inhaled for cerebral oxygen metabolism test, and then PET imaging is performed for 3 minutes. Again, wait for 15-20 minutes for radioactive decay, administer O-15 labeled water gas for blood flow examination, then PET imaging for 2 minutes. Therefore, the inspection time takes 40 to 50 minutes as a whole.

  In the conventional examination of the in vivo behavior of oxygen molecules using 0-15 labeled oxygen, the above-mentioned cerebral oxygen metabolism is examined on the basis of short-term administration of each of three kinds of labeled compounds containing 0-15 labeled oxygen. Latency between multiple independent PET imaging is necessary to attenuate the labeled compound. Since the PET imaging is performed while waiting for the attenuation of the drug administered for the previous PET imaging, the examination time increases from 30 minutes to 1 hour, but the head of the subject needs to be fixed over this long time There is. This fixing procedure is a heavy burden on the subject. Therefore, it is desirable to perform PET imaging in a shorter time (for example, within 10 minutes). Thereby, it becomes possible to examine the local cerebral blood flow, the local cerebral oxygen uptake rate, and the local oxygen metabolism in a short time by the PET examination.

  An object of the present invention is to make it possible to test the behavior of oxygen molecules in the body using 0-15 labeled oxygen in a shorter time.

The image quantification method using PET imaging according to the present invention is obtained by performing one continuous PET imaging while administering labeled oxygen and any one of labeled water and labeled carbon dioxide to a subject with a time difference. The data C _i (t) of the radiation density image reconstructed from the sinogram of the subject's tissue or the sinogram, and the radioactivity concentration A _o of the oxygen component in the blood of the subject obtained in parallel with this PET imaging Enter (t) and the radioactive concentration A _w (t) of the water component. And the following formula representing the sinogram or radiation concentration data C _i (t) in the tissue

（ここに、ｆは血流量、Eは酸素摂取率、Voは血管内の放射能濃度、ｐは水の分配定数、ｔは時間を示し、

(Where f is the blood flow rate, E is the oxygen uptake rate, Vo is the radioactive concentration in the blood vessel, p is the partition constant of water, and t is the time,

は重畳積分を示す）において、２つの重畳積分部分を、ｐを所定の一定値として、あるｆの範囲内の複数の離散的なｆの値に対して計算し、下記のＦ_１，Ｆ_２

Is a superposition integral), and two superposition integral parts are calculated with respect to a plurality of discrete f values within a range of f, where p is a predetermined constant value, and the following F ₁ and F ₂ are calculated.

とｆのテーブルとして記憶しておく。次に、前記のテーブルを用いて、前記の離散的なｆの値に対して

And f are stored as a table. Next, for the discrete values of f using the table,

におけるEとVoに対する解を最小自乗法により求める。次に、

Find the solution to E and Vo at next,

を最小とするｆ，Ｅ、Voを求める。

Find f, E, and Vo that minimize.

An image quantification device according to the present invention is
Radiation reconstructed from the sinogram or sinogram of the tissue of the subject obtained by performing one continuous PET imaging while administering the labeled oxygen and either labeled water or labeled carbon dioxide to the subject with a time difference Concentration data C _i (t) and the radioactivity concentration A _o (t) of the oxygen component of the blood of the subject obtained in parallel with this PET imaging and the radioactivity concentration A _w (t) of the water component Data input means for inputting;
The following formula representing the sinogram or radiation concentration data C _i (t) in the tissue

（ここに、ｆは血流量、Eは酸素摂取率、Voは血管内の放射能濃度、ｐは水の分配定数、ｔは時間を示し、

(Where f is the blood flow rate, E is the oxygen uptake rate, Vo is the radioactive concentration in the blood vessel, p is the partition constant of water, and t is the time,

は重畳積分を示す）において、２つの重畳積分部分を、ｐを所定の一定値として、あるｆの範囲内の複数の離散的なｆの値に対して計算し、下記のＦ_１，Ｆ_２

Is a superposition integral), and two superposition integral parts are calculated with respect to a plurality of discrete f values within a range of f, where p is a predetermined constant value, and the following F ₁ and F ₂ are calculated.

とｆのテーブルとして記憶しておくテーブル作成手段と、
前記のテーブルを用いて、前記の離散的なｆの値に対して

And a table creation means for storing as a table of f,
Using the table, for the discrete f value

におけるEとVoに対する解を最小自乗法により求め、次に、

Find the solution to E and Vo at, using the least squares method, then

を最小とするｆ，Ｅ，Voを求める未知数決定手段とからなる。

And an unknown quantity determining means for obtaining f, E, and Vo that minimizes.

An image quantification program by PET imaging executed by a computer according to the present invention is:
Radiation reconstructed from the sinogram or sinogram of the tissue of the subject obtained by performing one continuous PET imaging while administering the labeled oxygen and either labeled water or labeled carbon dioxide to the subject with a time difference A step of inputting density image data C _i (t);
The following formula representing the sinogram or radiation concentration data C _i (t) in the tissue

（ここに、ｆは血流量、Eは酸素摂取率、Voは血管内の放射能濃度、ｐは水の分配定数、ｔは時間を示し、

(Where f is the blood flow rate, E is the oxygen uptake rate, Vo is the radioactive concentration in the blood vessel, p is the partition constant of water, and t is the time,

は重畳積分を示す）において、２つの重畳積分部分を、ｐを所定の一定値として、あるｆの範囲内の複数の離散的なｆの値に対して計算し、下記のＦ_１，Ｆ_２

Is a superposition integral), and two superposition integral parts are calculated with respect to a plurality of discrete f values within a range of f, where p is a predetermined constant value, and the following F ₁ and F ₂ are calculated.

とｆのテーブルとして記憶しておくステップと、
次に、前記のテーブルを用いて、前記の離散的なｆの値に対して

Storing as a table of and f;
Next, for the discrete values of f using the table,

におけるEとVoに対する解を最小自乗法により求めるステップと、
次に、

Finding a solution for E and Vo at, using the method of least squares;
next,

を最小とするｆ，Ｅ、Voを求めるステップとからなる。ここで、投与した２つの薬剤のうち、先に投与した薬剤の血夜中および脳組織中の残留放射は上記の数式により予測し、後に投与した薬剤の放射線濃度は、先に投与した薬剤による残留放射の予測値を差し引くことにより評価する。

F, E, and Vo for minimizing. Here, of the two administered drugs, the residual radiation in the blood night and brain tissue of the previously administered drug is predicted by the above formula, and the radiation concentration of the subsequently administered drug is the residual due to the previously administered drug. Evaluate by subtracting the predicted value of radiation.

The effect of the present invention is that the inspection time can be shortened while maintaining the measurement accuracy only by performing one PET imaging while continuously administering two kinds of drugs.

It is a figure which shows the time passage of the conventional PET inspection method. It is a figure which shows the time passage of the PET inspection method in one Embodiment of invention. 1 is a block diagram of a system for PET imaging. It is a block diagram which shows the structure of a computer. It is a flowchart of quantitative analysis. It is a figure which shows an example of the time passage of the radiation density detected by PET test | inspection. It is a figure of the measurement result using a cynomolgus monkey.

Embodiments of the present invention will be described below with reference to the accompanying drawings.
In the examination by PET imaging of the in vivo behavior of oxygen molecules using 0-15 labeled oxygen, PET imaging is conventionally performed by independently administering three types of labeled compounds, labeled carbon monoxide, labeled oxygen and labeled water. (See Figure 1). On the other hand, in the embodiment of the present invention, the PET inspection time is dramatically shortened by introducing the following three points.

  The first point is that the cerebral blood volume can be estimated by mathematical theory in the cerebral blood volume correction conventionally performed by the labeled carbon monoxide administration test. This eliminates the need for a labeled carbon monoxide test.

  Secondly, instead of the administration of O-15 labeled water and O-15 labeled oxygen gas, which were performed separately in the past, O-15 labeled water and O-15 labeled oxygen gas were separated at short intervals of, for example, 3 minutes. The test method of continuous administration was adopted. As a result, the oxygen metabolism and blood flow, which were conventionally calculated separately, can be calculated simultaneously. Thereby, it can test | inspect by one PET imaging.

  The third point is to use mathematical theory to calculate images of multiple functions such as local oxygen metabolism, local cerebral oxygen uptake rate, and local cerebral blood flow within a short time (roughly 2 minutes) from the data of one imaging. It is possible. Specifically, the calculation is performed as follows. First, in an existing equation describing oxygen dynamics in the brain, a non-linear part, that is, a part describing oxygen uptake into a tissue and a part describing water uptake are respectively represented by a variable f (blood Table of flow rate). Normally, it is sufficient to calculate the blood flow in brain tissue every 0.01 mL / g / min within the range of 0 to 2 mL / g / min, and the tabulated part is 0 to 2 mL / g with respect to f. Within the range of / min, there are 200 values discretely every 0.01 mL / g / min. By treating these two tabulated terms as variables, the equation describing the oxygen dynamics is linearized and the unknown can be solved as a least square method. Here, 200 combinations are obtained with respect to f, and the most suitable combination of oxygen kinetics is taken out of these, and the cerebral oxygen metabolism and blood flow are obtained.

More specific description will be given below. In one embodiment of the invention, as shown in FIG. 2, labeled oxygen ( ¹⁵ O ₂ gas) and labeled water (H ₂ ¹⁵ O) are continuously applied to a subject at a short time difference (eg, every 3 minutes). Administer. Thereby, it is possible to continuously measure two drugs without waiting for attenuation of the previously administered drug in one PET imaging. In addition, since a calculation method that does not require a test for cerebral blood volume correction based on labeled carbon monoxide inhalation (administration) has been developed, PET imaging by carbon monoxide administration can be omitted. Therefore, the imaging time which normally required about 1 hour can be shortened to about 10 minutes by imaging by the continuous administration method of labeled oxygen and labeled water and omission of imaging by carbon monoxide administration. This greatly reduces the burden on the subject receiving the PET imaging. Based on the measurement data thus obtained, quantitative image evaluation of cerebral blood flow, cerebral oxygen metabolism, and cerebral oxygen uptake rate is performed as described later.

  A system for PET imaging will be described. As shown in FIG. 3, a PET apparatus (that is, a positron tomographic imaging apparatus) 10 is used to measure the radiation concentration of a subject. On the bed 12, the head of a subject (not shown) is fixed in the visual field of the PET apparatus. On the other hand, O-15 is generated by the cyclotron 14, and the labeled drug synthesizer 16 synthesizes O-15 labeled oxygen and O-15 labeled water using the O-15. O-15 labeled oxygen is inhaled from the mouth of the subject by the labeled gas administration device 18 in a predetermined time sequence, and then O-15 labeled water is administered by the labeled water injection device 20 to, for example, a vein of the subject. To do. On the other hand, at the time of imaging, blood is continuously drawn from the subject's arm, for example, by the blood collection pump 22, and the blood input function monitor 24 (eg, GSO sensor (N. Kudomi, E. Choi, H Watabe, KM Kim, M. Shidahara, M. Ogawa, N. Teramoto, E. Sakamoto, H. Iida, (2003) Development of a GSO Detector Assembly for a Continuous Blood Sampling System, IEEE TNS 50: 70-73) And the radiation concentration in the blood is measured with a BGO detector manufactured by Aloka). Measurement data of the PET apparatus 10 and the blood input function monitor 24 is stored in the computer 26.

  The computer 26 is, for example, a normal personal computer. The configuration of the system is the same as the conventional one. FIG. 4 shows an internal configuration of the computer 26. A CPU 30 that controls the entire system includes a ROM 32 that stores programs, data, a RAM 34 that is a work area, an input device 36 such as a keyboard and a mouse, a display device 38, a PET device 10, and a blood input function monitor 24. An interface 40 for transmitting and receiving and a hard disk device 42 as a storage device are provided. The hard disk of the hard disk device 42 stores measurement data 44 such as image data and blood data, and a quantitative analysis program 46 for analyzing the measurement data.

  Next, analysis of PET imaging data will be described. In the analysis of PET imaging data obtained by continuous administration of labeled oxygen and labeled water, residual radiation in the blood night and brain tissue of the previously administered drug is predicted by mathematical theory. Further, the radiation concentration of the drug administered later is evaluated by subtracting the predicted value of the residual radiation due to the drug administered earlier. In addition, the correction of the cerebral blood volume is evaluated simultaneously by incorporating the effect of the cerebral blood volume into the mathematical formula theory, so that PET imaging by administration of labeled carbon monoxide becomes unnecessary.

  In more detail, O-15-labeled oxygen is a diagnostic probe that traces the in vivo behavior of oxygen molecules, but its brain dynamics contribute not only to tissue oxygen metabolism but also to blood flow and radioactivity concentration in blood vessels. To do. This oxygen dynamics can be described by the following equation (1) (see Mintun MA et al. (1984) J Nucl Med 25: 177-187).

式（１）において、C_i(t)はＰＥＴ装置１０により観測される組織中の画素ｉでの放射線濃度の時間ｔによる経過を示す。また、ｆは血流量、Eは酸素摂取率、Voは血管内の放射能濃度、A_o(t)およびA_w(t)はそれぞれ血液中の酸素成分および水成分の放射能濃度、ｐは水の分配定数を示し、

In the equation (1), C _i (t) represents the progress of the radiation concentration at the pixel i in the tissue observed by the PET apparatus 10 over time t. F is the blood flow rate, E is the oxygen uptake rate, Vo is the radioactive concentration in the blood vessel, A _o (t) and A _w (t) are the radioactive concentrations of the oxygen and water components in the blood, respectively, and p is The partition constant of water,

は重畳積分を示す。酸素代謝量は酸素摂取率Eと血流量ｆを乗ずることで得られる。放射線濃度C_i(t)は右辺に示される３つの寄与の和である。右辺第１項は、組織の酸素分子の挙動、すなわち酸素分子の取り込みとその代謝物である水分子の洗い出しを示し、酸素代謝量E・ｆに関連する。右辺第２項は、体内での代謝により生成された水分子の挙動を示し、血流量に関連する。右辺第３項は、血管内の放射能濃度を示し、血液量に関連する。血液中の酸素成分の放射能濃度A_o(t)および水成分の放射能濃度A_w(t)は、血液中の全放射線濃度を測定し、体内での代謝により生成された標識水分子の量を評価して酸素成分および水成分に分離することで得られる（Iida H, Jones T, Miura S (1993) Modeling approach to eliminate the need to separate arteral plasma in oxygen-15 inhalation positron emission tomography, J Nucl Med 34:1333-1340参照)。また、式（１）において脳の検査に対しては水の分配定数ｐ＝０．８mL/g/minとすることができる（Iida JCBFM (1989)参照）。したがって、式（１）において、酸素摂取率Ｅ、血流量ｆおよび血管内の放射能濃度Voが評価すべき未知量である。

Indicates a superposition integral. The oxygen metabolism is obtained by multiplying the oxygen uptake rate E and the blood flow f. The radiation concentration C _i (t) is the sum of three contributions shown on the right side. The first term on the right side shows the behavior of oxygen molecules in the tissue, that is, the uptake of oxygen molecules and the washing out of water molecules that are metabolites thereof, and is related to the oxygen metabolism E · f. The second term on the right side shows the behavior of water molecules generated by metabolism in the body and is related to blood flow. The third term on the right side indicates the radioactive concentration in the blood vessel and is related to the blood volume. The radioactivity concentration A _o (t) of the oxygen component in the blood and the radioactivity concentration A _w (t) of the water component measure the total radiation concentration in the blood, and the labeled water molecules produced by metabolism in the body. It is obtained by evaluating the amount and separating it into oxygen and water components (Iida H, Jones T, Miura S (1993) Modeling approach to eliminate the need to separate arteral plasma in oxygen-15 inhalation positron emission tomography, J Nucl Med 34: 1333-1340). In the formula (1), the water distribution constant p = 0.8 mL / g / min can be used for the brain examination (see Iida JCBFM (1989)). Therefore, in equation (1), the oxygen uptake rate E, the blood flow f, and the radioactive concentration Vo in the blood vessels are unknown amounts to be evaluated.

  Next, a method for deriving the oxygen uptake rate E, the blood flow f, and the radioactive concentration Vo in the blood vessel will be shown. In Equation (1), the first integral term describing oxygen uptake into the tissue on the right side and the second integral term describing water uptake are nonlinear. Therefore, these two terms are discretely tabulated for the blood flow f. Specifically, the curve at that time is defined as follows for each 0.01 mL / g / min within the practical range f (0 to 2 mL / g / min).

これにより、式（1）は酸素摂取率Eと血管内の放射能濃度V_oのみを未知数とする式（３）として次のように書ける。

As a result, the equation (1) can be written as the following equation (3) in which only the oxygen uptake rate E and the radioactive concentration V _o in the blood vessel are unknown.

式（３）はある特定の血流量ｆに対して線形方程式として最小自乗法を用いて解くことができる。ここで、所定範囲内（０〜２mL/g/min）の２００通りのｆについて酸素摂取率Eと放射能濃度Voに対する解をいったん求める。次に、最小自乗法の誤差

Equation (3) can be solved using a least square method as a linear equation for a specific blood flow f. Here, a solution for the oxygen uptake rate E and the radioactivity concentration Vo is obtained once for 200 types of f within a predetermined range (0 to 2 mL / g / min). Next, the least squares error

を最小とするｆ，Ｅ，Voの組み合わせを求め、血流量ｆ、酸素摂取率Ｅ、血管内の放射能濃度Voに対する解とする。これを用いて式（１）より被検体の画像を再構成できる。

The combination of f, E, and Vo that minimizes is obtained as a solution for the blood flow f, the oxygen uptake rate E, and the radioactive concentration Vo in the blood vessel. Using this, the image of the subject can be reconstructed from the equation (1).

  In addition, although the water distribution constant p is constant at 0.8 mL / g / min for the brain, the value is obtained for other organs and can be constant.

  Next, the inspection procedure will be described.

  First, a patient or an experimental animal is fixed in the visual field of the PET apparatus 10.

  The labeled drug synthesizer 16 synthesizes labeled oxygen and labeled water. Although it is necessary to synthesize two kinds of labeled compounds in a short time, it is not necessary to synthesize labeled carbon monoxide, so the work load on the synthesis surface is reduced.

  Blood collection from the artery is started approximately 30 seconds before the first drug administration, and is continued during the test. This gives a total radioactivity concentration curve in blood.

  Next, labeled oxygen is administered by the drug administration device 18, and after 3 minutes, labeled water (or labeled carbon dioxide by the drug administration device 18) is administered to the subject by the drug injection device 20. The order of administration of these drugs can be reversed. In the state of “3 minutes” after drug administration, the first administered drug has not yet decayed, but in this test method, the second drug is administered in that state.

  Simultaneously with the first drug administration, imaging by the PET apparatus 10 is started, and imaging is continued for 6 minutes in this example. Thereby, projection data of radiation distribution in the brain (primary data, called sinogram) is obtained. By reconstructing this sinogram for each time t, a time series curve Ci (t) of radiation concentration data is obtained for each radioactivity distribution in the brain. Quantitative image evaluation of cerebral blood flow, cerebral oxygen metabolism, and cerebral oxygen uptake rate is performed using the radiation concentration data Ci (t).

  Thus, in quantitative image evaluation of cerebral blood flow, cerebral oxygen metabolism, and cerebral oxygen uptake rate by PET examination, an examination method in which O-15 labeled gas and O-15 labeled water are administered at short intervals of 3 minutes. Therefore, the inspection time can be shortened to 10 minutes or less. Moreover, the labeled carbon monoxide administration test for cerebral blood volume correction is not required. As a result, the inspection time, which normally takes about 1 hour, can be reduced to about 10 minutes.

  FIG. 5 is a flowchart of the quantitative analysis program 46 for executing the above-described analysis procedure. The radiation density Ci (t) at pixel i, which is image data, is read from the PET apparatus 10 (S10). Further, the total radiation concentration curve data in the blood is read from the blood input function monitor 24 (S12) and separated into the radioactivity concentration Ao (t) of the oxygen component and the radioactivity concentration Aw (t) of the water component (S12). S14).

Next, the two nonlinear parts (superimposed integral parts) F ₁ and F ₂ of the formula (2) are tabulated for 200 different blood flow rates f for a plurality of discrete values within a predetermined range (0 to 2 mL / g / min). Is stored (S16).

Next, for each pixel i in the image, the oxygen uptake rate E and the radioactivity concentration Vo in the blood vessel are calculated by the least square method for the above-mentioned 200 types of f (S18). Next, to determine the blood flow f that minimizes the error s ² of the least squares method of Formula (4), oxygen uptake rate E, the radioactivity concentration Vo in the vessel (S20). Then, the obtained measurement data (functional image data) is stored, and an image is displayed on the display device 38 (S22).

  FIG. 6 shows an example of the time lapse of the radiation concentration detected by the PET examination. In this example, labeled oxygen is administered at time 0 minutes and labeled water is administered at time 3 minutes. In FIG. 5, the solid line 61 represents the measured value Ci (t) of the radiation concentration at the left side of the above equation, that is, the pixel i in PET, and the broken line 62 represents the first term on the right side of the equation (1) (the behavior of oxygen molecules in the tissue). The broken line 63 represents the second term on the right side of the equation (1) (behavior of water molecules obtained by metabolism in the body), and the dotted line 64 represents the third term on the right side of the equation (1) (radioactivity concentration in the blood vessel). The broken line 63 suddenly increases corresponding to the administration of labeled water at time 3 minutes.

  FIG. 7 shows cerebral blood flow, cerebral oxygen uptake rate, and cerebral oxygen metabolism obtained respectively by the above-described new test method using cynomolgus monkey as a subject and the conventional method based on short-term administration of three kinds of labeled compounds. Measurement data (image) is shown. With the new inspection method, since the inspection can be completed with only one PET inspection, the measurement time can be greatly shortened within 10 minutes, while a measurement result with the same measurement accuracy as the conventional method was obtained. This confirmed the correctness and validity of the inspection method.

  For the blood flow test, labeled carbon dioxide can be used instead of labeled water. The labeled carbon dioxide is administered by the labeled gas administration device 18. In this case, as in the case of using labeled water, labeled oxygen and labeled carbon dioxide are continuously administered to the subject with a time interval, and the radiation concentration is obtained by one PET imaging.

  Residual radiation in the blood night and brain tissue of the previously administered drug is predicted by mathematical theory, and the radiation concentration of the subsequently administered drug is evaluated by subtracting the predicted residual radiation from the previously administered drug, The order of administration of the two drugs, labeled oxygen and labeled water (or labeled carbon dioxide), may be reversed.

  In the above example, the sinogram (projection data), which is the primary data from the PET apparatus 10, is first reconstructed into the image data Ci (t) of the radiation concentration, and then the cerebral oxygen metabolism and the like are calculated for each region. Then, a quantified image such as cerebral oxygen metabolism was obtained. However, instead, the cerebral oxygen metabolism amount as projection data may be calculated in the same manner from the time curve of the projection data, and the quantified image may be reconstructed from the calculation result.

In the image quantification described above, the cerebral blood volume correction, which has been performed by the labeled carbon monoxide administration test in the past, can be estimated by mathematical theory, so that a test using labeled carbon monoxide is unnecessary. Become. In addition, since a test method in which O-15-labeled water and O-15-labeled oxygen gas have been continuously administered separately at a short interval of, for example, 3 minutes has been adopted, the test can be performed with a single PET imaging. . Furthermore, using mathematical theory, it is possible to calculate images of a plurality of functions such as oxygen metabolism, oxygen uptake rate, and blood flow within a short time (approximately 2 minutes) from the data of one imaging. Therefore, the inspection time can be shortened while maintaining the measurement accuracy only by performing one PET imaging while continuously administering two kinds of drugs.

Claims (16)

Reconstructed from the sinogram or sinogram of the tissue of the subject obtained by performing one continuous PET imaging while administering the labeled oxygen and any one of labeled water and labeled carbon dioxide to the subject with a time difference. The radiation concentration data C _i (t), the radioactivity concentration A _o (t) of the oxygen component of the blood of the subject obtained in parallel with the PET imaging, and the radioactivity concentration A _w (t) of the water component Data input means for inputting
The following equation representing the sinogram or radiation concentration data C _i (t) in the tissue:

(Where f is the blood flow rate, E is the oxygen uptake rate, Vo is the radioactive concentration in the blood vessel, p is the partition constant of water, and t is the time,
[Equation 2]

Is a superposition integral), and two superposition integral parts are calculated with respect to a plurality of discrete f values within a range of f, where p is a predetermined constant value, and the following F ₁ and F ₂ are calculated.
[Equation 3]

And a table creation means for storing as a table of f,
Using the table, for the discrete f value, [Equation 4]

Find the solution to E and Vo at, using the least squares method, then
[Equation 5]

An image quantification apparatus based on PET imaging, comprising unknown quantity determining means for obtaining f, E, and Vo that minimizes f. The data C _i (t) is radiation density image data, and further, using the obtained f, E, and Vo, a quantified image of local cerebral blood flow, cerebral oxygen metabolism intake rate, or cerebral oxygen metabolism amount The image quantification apparatus according to claim 1, further comprising image calculation means for calculating The data C _i (t) is sinogram data, and a quantified image of local cerebral blood flow, cerebral oxygen metabolism uptake rate or cerebral oxygen metabolism is reproduced using the obtained f, E, and Vo. The image quantification apparatus according to claim 1 , further comprising an image calculation unit configured. Radiation reconstructed from the sinogram or sinogram of the tissue of the subject obtained by performing one continuous PET imaging while administering the labeled oxygen and either labeled water or labeled carbon dioxide to the subject with a time difference Concentration image data C _i (t), radioactivity concentration A _o (t) of oxygen component in the blood of the subject obtained in parallel with this PET imaging, and radioactivity concentration A _w (t) of water component Enter
The following equation representing the sinogram or radiation concentration data C _i (t) in the tissue:

(Where f is the blood flow rate, E is the oxygen uptake rate, Vo is the radioactive concentration in the blood vessel, p is the partition constant of water, and t is the time,
[Equation 7]

Is a superposition integral), and two superposition integral parts are calculated with respect to a plurality of discrete f values within a range of f, where p is a predetermined constant value, and the following F ₁ and F ₂ are calculated.
[Equation 8]

And f as a table,
Next, using the table, for the discrete f value, [Equation 9]

Find the solution to E and Vo at
next,
[Equation 10]

An image quantification method by PET imaging that obtains f, E, and Vo that minimize the frequency. The data C _i (t) is radiation density image data. Further, using the obtained f, E, and Vo, a quantified image of local cerebral blood flow, cerebral oxygen metabolism intake rate, or cerebral oxygen metabolism is obtained. The image quantification method according to claim 4, wherein: The data C _i (t) is sinogram data, and a quantified image of local cerebral blood flow, cerebral oxygen metabolism intake rate, or cerebral oxygen metabolism is reproduced using the obtained f, E, and Vo. The image quantification method according to claim 4, which is configured. The data C _i (t) is radiation density image data, and a quantified image of local cerebral blood flow, cerebral oxygen metabolism intake rate or cerebral oxygen metabolism is calculated using the obtained f, E, and Vo. The image quantification method according to claim 4. The data C _i (t) is sinogram data, and a quantified image of local cerebral blood flow, cerebral oxygen metabolism intake rate, or cerebral oxygen metabolism is reconstructed using the obtained f, E, and Vo. The image quantification method according to claim 4. Of the above two administered drugs, the residual radiation in the blood night and brain tissue of the previously administered drug is predicted by the above formula, and then the radiation concentration of the subsequently administered drug is determined by the previously administered drug. The image quantification method according to claim 4, wherein the evaluation is performed by subtracting a predicted value of residual radiation according to claim 5. Furthermore, the blood concentration data of the subject obtained in parallel with the PET imaging is input, and from this data, the radioactivity concentration of the oxygen component in the blood and the radioactivity concentration of the water component are calculated. 5. The image quantification method according to claim 4, wherein the calculated radioactivity concentrations are the input data A _o (t) and A _w (t). Radiation reconstructed from the sinogram or sinogram of the tissue of the subject obtained by performing one continuous PET imaging while administering the labeled oxygen and either labeled water or labeled carbon dioxide to the subject with a time difference A step of inputting density image data C _i (t);
The following equation representing the sinogram or radiation concentration data C _i (t) in the tissue:

(Where f is the blood flow rate, E is the oxygen uptake rate, Vo is the radioactive concentration in the blood vessel, p is the partition constant of water, and t is the time,
[Equation 12]

Is a superposition integral), and two superposition integral parts are calculated with respect to a plurality of discrete f values within a range of f, where p is a predetermined constant value, and the following F ₁ and F ₂ are calculated.
[Equation 13]

Storing as a table of and f;
Next, using the table, for the discrete f value, [Equation 14]

Finding a solution for E and Vo at, using the method of least squares;
next,
[Equation 15]

An image quantification program based on PET imaging, which is executed by a computer. The data C _i (t) is radiation density image data, and a quantified image of local cerebral blood flow, cerebral oxygen metabolism intake rate or cerebral oxygen metabolism is calculated using the obtained f, E, and Vo. The image quantification program according to claim 11. The data C _i (t) is sinogram data, and a quantified image of local cerebral blood flow, cerebral oxygen metabolism intake rate, or cerebral oxygen metabolism is reconstructed using the obtained f, E, and Vo. The image quantification program according to claim 11. Of the above two administered drugs, the residual radiation in the blood night and brain tissue of the previously administered drug is predicted by the above formula, and then the radiation concentration of the subsequently administered drug is determined by the previously administered drug. The image quantification program according to claim 11, wherein the evaluation is performed by subtracting a predicted value of residual radiation according to. Further, a step of inputting blood concentration data of the subject obtained in parallel with the PET imaging, and calculating a radioactivity concentration of an oxygen component and a water component in the blood from this data The image quantification program according to claim 11, wherein the calculated radioactivity concentrations are the input data A _o (t) and A _w (t). A computer-readable recording medium on which the image quantification program according to any one of claims 11 to 15 is recorded.

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