JPH06258448A - Method for indentifying position of labeled substance in image of tissue sample of organism - Google Patents

Abstract

PURPOSE:To enhance accuracy in identification by a method for fixing the distribution of a radioactive labeled substance in a tissue sample based on a superposed image of tissue sample and inner and outer shapes thereof. CONSTITUTION:Upon irradiation with laser light 5, an accumulative phosphor sheet 1 emits light which impinges on preliminary reading optical guide 10 and received by an optical detector 11. The detector 11 detects only stimulated light which is delivered through an amplifier 12 to a control circuit 13. The sheet 1 is then transferred to a main reading section 3. Upon irradiation with laser light 15, the sheet 1 also emits light which impinges on a main reading optical guide 22 and received by an optical detector 23. The detector 23 detects only stimulated light which is delivered through an amplifier 24 and an A/D converter 25 to a signal processing circuit 26. The circuit 26 stores image signals read out from the sheet 1 in a memory and then displays the image signals on a screen. Previously recorded inner and outer shapes of tissue sample are also displayed on the screen while being superposed.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel method for identifying the position of a labeling substance in an image of a tissue sample of an organism. The present invention relates to an identification method which can be particularly advantageously used for identification of an autoradiographic image for obtaining positional information of a radiolabeled substance labeled with a radioisotope distributed in a tissue sample of an organism.

[0002]

2. Description of the Related Art After a substance labeled with a radioisotope is administered to an organism, the organism or a part of the tissue of the organism is used as a sample, and the sample and radiation such as high-sensitivity X-ray film are used. Autoradiography (radioauto), which consists of exposing the film to light (or exposure) by overlapping it with the film for a certain period of time, and obtaining the positional information (distribution, etc.) of the radiolabeled substance in the sample from the exposed area. Also called graf),
That is, the autoradiogram measuring method has been conventionally known. This autoradiography, for example,
It is used to study the metabolism, absorption, and excretion pathways and states of administered substances in organisms in detail.

Conventionally, the above-mentioned autoradiography has been carried out using a radiation film (photosensitive silver salt film), but there are some cases where the autoradiography using the photosensitive silver salt film is actually used. I have a problem. That is, in order to obtain an autoradiogram of a sample containing a radiolabeled substance, the sample and a radiation film such as a high-sensitivity X-ray film are overlapped for a certain period of time, and the film is exposed (exposed). This exposure operation requires a long time (tens of hours to several days). This is because the sample to be measured by autoradiography generally does not have high radioactivity. Then, this exposure operation is usually performed at a low temperature (for example, 0
C. to -80.degree. C.). The reason is that at a relatively high temperature such as room temperature, the latent image in the silver salt on the film formed by exposure to radiation or fluorescence tends to regress and become an image that cannot be developed. This is because chemical fogging is likely to occur due to migration of harmful components. When such a fog occurs in an image obtained by autoradiography, the accuracy of the positional information on the radiolabeled substance is significantly reduced. Further, in order to prevent deterioration of image quality due to chemical fog or the like, it is necessary to expose a sample containing a radiolabeled substance in a dried state by superimposing it on a radiation film. Therefore, the sample is usually dried or packed with a synthetic resin film or the like.

Incidentally, the silver salt as a photosensitive component of the radiation film has a drawback that it is susceptible to not only chemical stimuli but also physical stimuli associated with work such as movement and installation of the film.
This also makes the operation of autoradiography difficult and causes a decrease in its accuracy. That is, the radiation film tends to cause a physical fog phenomenon due to physical pressure caused by contact with the sample. Then, in order to avoid the occurrence of such physical fogging of the radiation film, a high level of skill and attention are required in the handling work, resulting in further complicating the operation of autoradiography.

Further, in conventional autoradiography, since the exposure operation is carried out for a long time as described above, the natural radioactivity contained in the sample other than the radio-labeled substance also contributes to the exposure of the radiation film and the resulting radioactivity is obtained. There is a problem that the accuracy of the position information of the labeling substance is reduced. In order to remove the interference due to such natural radioactivity, for example, parallel experiments using a control sample and optimization of the exposure time have been attempted. There is a drawback that the entire operation becomes complicated due to the necessity of preliminary experiments for determining the exposure time.

In order to solve the problems associated with conventional autoradiography using a photosensitive silver salt film photosensitive material as described above, a storage having a phosphor layer containing a stimulable phosphor as a photosensitive material. An invention using a luminescent phosphor sheet (radiation image conversion panel) has already been proposed (JP-A-59-83057).

[0007]

A conventional radiation film is used for autoradiography using a stimulable phosphor sheet (radiation image conversion panel) having a phosphor layer containing a stimulable phosphor as a light-sensitive material. Compared with autoradiography, there are many advantages such as the fact that autoradiography can be obtained with a small radiation dose and that autoradiography can be performed at room temperature in a short time. However, on the other hand, since a radiographic image is obtained by autoradiography for a short time with a small radiation dose, there is a problem that the radiographic image in the boundary region such as a region with a small amount of radioactive material is likely to be unclear. In such a case, it may be difficult to associate the tissue sample of the organism with the radiation image (determine which part of the tissue sample of the organism corresponds to which part of the radiation image). .

In the above description, the problems relating to the identification operation of the autoradiographic image using the radiation image conversion method using the stimulable phosphor sheet are described, but the difficulty in the image identification is the conventional X-ray film. There is also a problem in autoradiography using (silver salt photographic film). Further, not only autoradiography using a radioactive labeling substance as a labeling substance but also autofluorography using a fluorescent substance as a labeling substance has the same problem. Furthermore, PET images (positron emission tomography images), CT images (computer tomography images), SPECT images (single photon emission CT images), which are used for analysis of tissue samples of organisms such as humans and other animals. In MRI images (magnetic resonance tomography images) and the like, similar difficulties occur when identifying the position of the labeling substance in the obtained image in the actual tissue sample.

[0009]

The present invention resides in an identification method comprising the following steps for obtaining positional information of labeling substances distributed in an image of a tissue sample of an organism: 1) In the tissue sample A step of obtaining an image signal showing the positional information of the labeling substance; 2) a step of simultaneously displaying an image of the tissue sample based on the image signal and a figure showing the external and / or internal shape of the tissue sample on a display screen; 3) On the display screen, the position of the image of the tissue sample and the position of the figure showing the external and / or internal shape of the tissue sample are relatively moved so that the image of the former tissue sample corresponds to the latter shape diagram. Adjusting to overlap;
And 4) a step of identifying the distribution of the radiolabeled substance in the tissue sample from the image of the superimposed tissue sample and the figure showing the external and / or internal shape of the tissue sample.

The invention also lies in particular in a method of identifying an autoradiographic image which comprises the following steps for obtaining positional information of a radiolabeled substance labeled with a radioisotope distributed in a tissue sample of an organism: 1 ) By accumulating the tissue sample on a stimulable phosphor sheet containing a stimulable phosphor layer for a certain period of time, radiation energy emitted from a radiolabeled substance is absorbed in the stimulable phosphor layer to record the accumulation. 2) Exciting the stimulable phosphor layer of the stimulable phosphor sheet with an electromagnetic wave to release the radiation energy stored and recorded in the stimulable phosphor layer as stimulable light. A step of obtaining an image signal showing the positional information of the radiolabeled substance by detecting the stimulated light; 3) an autoradiographic image based on the image signal and the outside of the tissue sample And / or displaying a figure showing the internal shape on the display screen at the same time; 4) Relatively, on the display screen, the position of the autoradiographic image and the position of the figure showing the external and / or internal shape of the tissue sample. And adjusting the former autoradiographic image so as to be superposed corresponding to the shape of the latter; and 5) the superposed autoradiographic image and the external and / or internal shape of the tissue sample. The process of identifying the distribution of the radiolabeled substance in the tissue sample from the figure shown.

In the present invention, "positional information" of a radiolabeled substance distributed in a tissue sample of an organism means various information centered on the position of the radiolabeled substance or an aggregate thereof in the tissue sample, for example, a sample. It means various information obtained as one or any combination of information consisting of the position and shape of the aggregate of radioactive substances present therein, the concentration and distribution of the radioactive substance at that position.

Next, the present invention is applied to a radiation image conversion method using a stimulable phosphor sheet, which is a typical embodiment of the method for identifying the position of a labeling substance in an image of a tissue sample of an organism of the present invention. The identification operation of the autoradiography image based on this will be described in detail as an example.

The stimulable phosphor sheet used in the present invention is also called a radiation image conversion panel, an example of which is described in Japanese Patent Application Laid-Open No. 55-12145, and its general structure is already known. It is known. That is, the stimulable phosphor sheet is made of a stimulable phosphor, and the stimulable phosphor of the sheet absorbs the radiation energy transmitted through the subject or the radiation energy emitted from the subject. By exciting the sheet with an electromagnetic wave (excitation light) in the visible to infrared region, the radiation energy accumulated in the stimulable phosphor of the sheet can be emitted as fluorescence. . Therefore, the radiation image of the subject or the subject is photoelectrically read in to convert the fluorescence into an electric signal, and the obtained electric signal is reproduced as a visible image on a recording material such as a photographic film or a display device such as a CRT. Alternatively, it can be represented as digitized or symbolized position information.

The stimulable phosphor sheet has a basic structure of
It comprises a support and a phosphor layer provided on one surface thereof. However, when the phosphor layer itself is self-supporting, it is not always necessary to provide a support. In addition, a transparent protective film is generally provided on the surface of the phosphor layer (the surface on the side not facing the support when the support is provided on one surface of the phosphor layer). Protects the layer from chemical alteration or physical impact.

The phosphor layer is basically a layer composed of a binder which contains and supports a particulate stimulable phosphor in a dispersed state.

As described above, the stimulable phosphor is a phosphor that exhibits stimulated emission upon irradiation with radiation and then irradiation with excitation light. From a practical point of view, the wavelength is 400 to 900 n.
A phosphor that exhibits stimulated emission in the wavelength range of 300 to 500 nm by excitation light in the range of m is desirable.
Examples of the stimulable phosphor used in the stimulable phosphor sheet used in the present invention include the following.

SrS: Ce, Sm, SrS: Eu, Sm, ThO described in US Pat. No. 3,859,527.
₂ : Er, and La ₂ O ₂ S: Eu, Sm, JP-A-5-
ZnS: Cu, Pb, Ba described in Japanese Patent No. 5-12142
O.xAl ₂ O ₃ : Eu (however, 0.8 ≦ x ≦ 1
0) and M ^II O.xSiO ₂ : A (where M ^II is M
g, Ca, Sr, Zn, Cd or Ba, where A is C
e, Tb, Eu, Tm, Pb, Tl, Bi, or Mn
And x is 0.5 ≦ x ≦ 2.5),

(Ba _1-xy , Mg _x , Ca _y ) FX: aEu ²⁺ described in JP _-A- 55-12143 (where X is at least one of Cl and Br, and x and y is 0 <x + y ≦ 0.6 and xy ≠ 0, and a is 10 ⁻⁶ ≦ a ≦ 5 × 10 ⁻² ),

Ln described in JP-A-55-12144
OX: xA (where Ln is La, Y, Gd, and L
at least one of u, X is at least one of Cl and Br, A is at least one of Ce and Tb, and x is 0 <x <0.1),

(Ba _1-x , M ²⁺ _x ) FX: yA described in JP-A-55-12145 (where M ²⁺ is M
At least one of g, Ca, Sr, Zn, and Cd, X is at least one of Cl, Br, and I, A is Eu, Tb, Ce, Tm, Dy, Pr, Ho,
At least one of Nd, Yb, and Er, and x is 0 ≦ x ≦ 0.6, y is 0 ≦ y ≦ 0.2),

M ^II FX.xA: yLn described in JP-A-55-160078 [wherein M ^II is Ba, Ca,
At least one of Sr, Mg, Zn, and Cd, A is BeO, MgO, CaO, SrO, BaO, Z
nO, Al ₂ O ₃ , Y ₂ O ₃ , La ₂ O ₃ , In ₂ O
₃ , SiO ₂ , TiO ₂ , ZrO ₂ , GeO ₂ , SnO
₂ , at least one of Nb ₂ O ₅ , Ta ₂ O ₅ , and ThO ₂ , and Ln is Eu, Tb, Ce, Tm, D
y, Pr, Ho, Nd, Yb, Er, Sm, and Gd
At least one of X, Cl is at least one of Cl, Br, and I, and x and y are 5 respectively.
× 10 ⁻⁵ ≦ x ≦ 0.5 and 0 <y ≦ 0.2], the phosphor represented by the composition formula:

(Ba _1-x , M ^II _x ) F ₂ .aBaX ₂ : yEu, zA described in JP-A-56-116777.
[Wherein M ^II is at least one of beryllium, magnesium, calcium, strontium, zinc, and cadmium, X is at least one of chlorine, bromine, and iodine, and A is at least one of zirconium and scandium. , A, x, y, and z
Are 0.5 ≦ a ≦ 1.25, 0 ≦ x ≦ 1, 10 ^{−6, respectively.}
≦ y ≦ 2 × 10 ⁻¹ , and 0 <z ≦ 10 ⁻² ], the phosphor represented by the composition formula:

[B] described in JP-A-57-23673
a _1-x , M ^II _x ) F ₂ · aBaX ₂ : yEu, zB [where M ^II is beryllium, magnesium, calcium,
At least one of strontium, zinc and cadmium, X is at least one of chlorine, bromine, and iodine, and a, x, y, and z are 0.5 ≦ a ≦ 1.25 and 0 ≦, respectively. x ≦ 1, 10 ⁻⁶ ≦ y ≦ 2 ×
10 ⁻¹ , and 0 <z ≦ 2 × 10 ⁻¹ ], the phosphor represented by the composition formula:

[B] described in JP-A-57-23675
a _1-x , M ^II _x ) F ₂ · aBaX ₂ : yEu, zA [wherein M ^II is beryllium, magnesium, calcium,
At least one of strontium, zinc and cadmium, X is at least one of chlorine, bromine and iodine, A is at least one of arsenic and silicon, and a, x, y and z are each 0. 5 ≦ a
≦ 1.25, 0 ≦ x ≦ 1, 10 ⁻⁶ ≦ y ≦ 2 × 10 ⁻¹ , and 0 <z ≦ 5 × 10 ⁻¹ ],

M described in JP-A-58-69281
^III OX: xCe [M ^III is Pr, Nd, P
m, Sm, Eu, Tb, Dy, Ho, Er, Tm, Y
b, and at least one trivalent metal selected from the group consisting of Bi, X is one or both of Cl and Br, and x is 0 <x <0.1] A phosphor represented by the formula,

B described in JP-A-58-206678
a _1-x M _{x / 2} L _{x / 2} FX: yEu ²⁺ [where M is L
represents at least one alkali metal selected from the group consisting of i, Na, K, Rb and Cs; L represents Sc,
Y, La, Ce, Pr, Nd, Pm, Sm, Gd, T
b, Dy, Ho, Er, Tm, Yb, Lu, Al, G
represents at least one trivalent metal selected from the group consisting of a, In, and Tl; X represents at least one halogen selected from the group consisting of Cl, Br, and I; and x represents 10 ^-2. ≦ x ≦ 0.5, y is 0 <y
≦ 0.1], the phosphor represented by the composition formula:

B described in JP-A-59-27980
aFX · xA: yEu ²⁺ [wherein X is Cl, Br,
And at least one halogen selected from the group consisting of I and I; A is a calcined product of a tetrafluoroborate compound; and x is 10 ⁻⁶ ≦ x ≦ 0.1, y is 0 <y
≦ 0.1], the phosphor represented by the composition formula:

B described in JP-A-59-47289
aFX · xA: yEu ²⁺ [wherein X is Cl, Br,
And at least one halogen selected from the group consisting of I and I; A is selected from the group of hexafluoro compounds consisting of salts of monovalent or divalent metals of hexafluorosilicic acid, hexafluorotitanic acid and hexafluorozirconic acid. A baked product of at least one compound; and x is 10 ⁻⁶ ≦ x ≦ 0.1, y is 0 <y ≦
0.1], the phosphor represented by the composition formula:

B described in JP-A-59-56479
aFX · xNaX ′: aEu ²⁺ [however, X and X ′
Is at least one of Cl, Br, and I, respectively, and x and a are 0 <x ≦ 2 and 0 <a ≦ 0.2, respectively.],

M described in JP-A-59-56480
^II FX · xNaX ′: yEu ²⁺ : zA [where M ^II is
Is at least one alkaline earth metal selected from the group consisting of Ba, Sr, and Ca; X and X ′ are
Each is at least one halogen selected from the group consisting of Cl, Br, and I; A is V, Cr, M
at least one transition metal selected from n, Fe, Co, and Ni; and x is 0 <x ≦ 2 and y is 0.
<Y ≦ 0.2, and z is 0 <z ≦ 10 ⁻² ], the phosphor represented by the composition formula:

M ^II described in JP-A-59-75200
FX ・ aM ^I X '・ bM' ^II X " ₂・ cM ^III X"' ₃・
xA: yEu ²⁺ [where M ^II is Ba, Sr, and C]
at least one alkaline earth metal selected from the group consisting of a; M ^I is Li, Na, K, Rb, and C
is at least one alkali metal selected from the group consisting of s; M ^'II is at least one trivalent metal selected from the group consisting of Be and Mg; M ^III is Al,
X is at least one trivalent metal selected from the group consisting of Ga, In, and Tl; A is a metal oxide; X
Is at least one halogen selected from the group consisting of Cl, Br, and I; X ′, X ″ and X ″ ′ are
Is at least one halogen selected from the group consisting of F, Cl, Br, and I; and a is 0 ≦ a ≦
2, b is 0 ≦ b ≦ 10 ⁻² , c is 0 ≦ c ≦ 10 ⁻² , and a
+ B + c ≧ 10 ⁻⁶ ; x is 0 <x ≦ 0.5, y is 0
A phosphor represented by the composition formula of <y ≦ 0.2],

M ^II described in JP-A-60-84381
X ₂ · aM ^II X ′ ₂ : xEu ²⁺ [wherein M ^II is Ba,
At least one alkaline earth metal selected from the group consisting of Sr and Ca; X and X ′ are Cl, Br
And at least one halogen selected from the group consisting of and I and X ≠ X ′; and a is 0.1 ≦ a ≦
10.0, x is 0 <x ≦ 0.2], and a stimulable phosphor represented by the composition formula:

M described in JP-A-60-101173
^{II FX · aM I X ':} xEu 2+ [ However, M ^II is Ba,
At least one alkaline earth metal selected from the group consisting of Sr and Ca; M ^I is at least one alkali metal selected from the group consisting of Rb and Cs; X is from the group consisting of Cl, Br and I At least one halogen selected; X ′ is F, Cl, Br
And at least one halogen selected from the group consisting of I and; and a and x are each 0 ≦ a ≦
4.0 and 0 <x ≦ 0.2], a stimulable phosphor represented by the composition formula:

M described in JP-A-62-25189
^I X: xBi [However, M ^I is at least one alkali metal selected from the group consisting of Rb and Cs;
X is at least one halogen selected from the group consisting of Cl, Br and I; and x is 0 <x ≦ 0.2.
And a photostimulable phosphor represented by the composition formula:

L described in JP-A-2-229882
nOX: xCe (where Ln is at least one of La, Y, Gd, and Lu, X is Cl, Br, and I)
At least one of the two, x is 0 <x ≦ 0.2,
The atomic ratio of Ln to X is 0.500 <X / Ln ≦
A cerium-activated rare earth oxyhalide phosphor having a maximum wavelength λ of 0.998 and a stimulable excitation spectrum of 550 nm <λ <700 nm).

In the M ^II X ₂ · aM ^II X ′ ₂ : xEu ²⁺ stimulable phosphor described in JP-A-60-84381, the following additives are added to M ^II X. ₂・ aM
^II X 'may be included in the following proportions per ₂ mole.
BM ^I X described in JP 60-166379 discloses "
(However, M ^I is at least one alkali metal selected from the group consisting of Rb and Cs, and X ″ is F, C
at least one halogen selected from the group consisting of 1, Br and I, and b is 0 <b ≦ 10.0); bK described in JP-A-60-221483.
X "・ cMgX"' ₂・ dM ^III X "" ₃ (However, M ^III
Is at least one trivalent metal selected from the group consisting of Sc, Y, La, Gd and Lu, and X ″, X ″ ′ and X ″ ”are all selected from the group consisting of F, Cl, Br and I. At least one halogen, and b,
c and d are 0 ≦ b ≦ 2.0, 0 ≦ c ≦ 2.
0, 0 ≦ d ≦ 2.0, and 2 × 10 ⁻⁵ ≦ b + c
+ D); yB described in JP-A-60-228592 (where y is 2 × 10 ⁻⁴ ≦ y ≦ 2 × 10 ⁻¹ ); described in JP-A-60-228593. bA
(However, A is at least one oxide selected from the group consisting of SiO ₂ and P ₂ O ₅ , and b is 1
0 ^-4 ≤ b ≤ 2 x 10 ^-1 ); JP-A-61-1208
BSiO described in Japanese Patent Publication No. 83 (where b is 0 <b ≦ 3
× 10 ^-2 at a); bSnX described in JP 61-120885 discloses _"2 (wherein, X 'is at least one halogen selected from the group consisting of F, Cl, Br and I, and b Is 0 <b ≦ 10 ⁻³ ); bCsX ″ · cSn described in JP-A-61-235486.
X "' ₂ (where X" and X "' are F, Cl,
Is at least one halogen selected from the group consisting of Br and I, and b and c are each 0 <
b ≦ 10.0 and 10 ⁻⁶ ≦ c ≦ 2 × 10 ⁻² );
And bCsX ″ · yLn ³⁺ described in JP-A-61-235487 (where X ″ is F, Cl or B).
It is at least one halogen selected from the group consisting of r and I, and Ln is Sc, Y, Ce, Pr, Nd, S.
at least one rare earth element selected from the group consisting of m, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu, and b and y are each 0 <b ≦ 1.
0.0 and 10 ⁻⁶ ≦ y ≦ 1.8 × 10 ⁻¹ ).

Among the above-described stimulable phosphors, the divalent europium-activated alkaline earth metal halide-based phosphor and the cerium-activated rare earth oxyhalide phosphor are particularly preferable because they exhibit high-intensity stimulated emission. However, the stimulable phosphor used in the present invention is not limited to the above-mentioned phosphor, and may be any phosphor that exhibits stimulated emission when irradiated with excitation light after irradiation with radiation. It may be.

The stimulable phosphor layer of the stimulable phosphor sheet of the present invention is not only composed of a stimulable phosphor and a binder which contains and supports the stimulable phosphor in a dispersed state, but does not contain a binder. It is also possible to use a composition composed only of aggregates of stimulable phosphors, or a phosphor layer in which a gap between the aggregates of stimulable phosphors is impregnated with a polymer substance.

Next, the method for producing the stimulable phosphor sheet of the present invention will be described by taking as an example the case where the phosphor layer is composed of a stimulable phosphor and a binder which contains and supports the stimulable phosphor in a dispersed state.

The phosphor layer can be formed on the support by the following known method. First, a stimulable phosphor and a binder (eg, nitrocellulose, acrylic resin, thermoplastic elastomer) are added to a solvent, and this is mixed thoroughly to make the stimulable phosphor uniform in the binder solution. A dispersed coating solution is prepared. The mixing ratio of the binder and the stimulable phosphor in the coating liquid is the characteristics of the target stimulable phosphor sheet,
Generally, the mixing ratio of the binder and the phosphor is 1: 1 to 1: 100 (weight ratio), although it depends on the kind of the phosphor.
It is preferable to select from the range of, and especially from the range of 1: 8 to 1:40 (weight ratio).

The coating solution containing the phosphor and the binder prepared as described above is then uniformly applied to the surface of the support to form a coating film. This application operation is
It can be carried out by using a usual coating means, for example, a doctor blade, a roll coater, a knife coater or the like.

The support can be arbitrarily selected from materials known as a support for conventional stimulable phosphor sheets. In the known stimulable phosphor sheet, a phosphor layer is used to strengthen the bond between the support and the phosphor layer or to improve the sensitivity or image quality (sharpness, graininess) of the stimulable phosphor sheet. A polymer material such as gelatin is applied to the surface of the support on which it is provided to form an adhesion-imparting layer, or a light-reflecting layer made of a light-reflecting material such as titanium dioxide, or a light-absorbing material such as carbon black. It is known to provide a light absorbing layer and the like. The support used in the present invention can also be provided with these various layers, and their configuration can be arbitrarily selected according to the desired purpose and application of the stimulable phosphor sheet. Further, JP-A-58-20020
As described in Japanese Unexamined Patent Publication (Kokai) No. 0, the surface of the support on the side of the phosphor layer (adhesion-imparting layer, light reflection When a layer, a light absorption layer, or the like is provided, it means the surface thereof), and fine irregularities may be formed. After forming the coating film on the support as described above, the coating film is dried to complete the formation of the stimulable phosphor layer on the support.
The layer thickness of the phosphor layer varies depending on the characteristics of the target stimulable phosphor sheet, the type of phosphor, the mixing ratio of the binder and the phosphor, etc., but is usually 20 μm to 1 mm. However, this layer thickness is preferably 50 to 500 μm.

The transparent protective film is, for example, cellulose acetate,
Cellulose derivatives such as nitrocellulose; or transparent polymeric substances such as polymethylmethacrylate, polyvinyl butyral, polyvinyl formal, polycarbonate, polyvinyl acetate, vinyl chloride / vinyl acetate copolymer, and other transparent polymeric substances dissolved in a suitable solvent It can be formed by a method of applying the solution prepared in this way to the surface of the phosphor layer. Alternatively, polyethylene terephthalate, polyethylene naphthalate, polyethylene,
It is also formed by a method of separately forming a plastic sheet made of polyvinylidene chloride, polyamide, etc .; and a protective film forming sheet such as a transparent glass plate and adhering it to the surface of the phosphor layer with an appropriate adhesive. be able to. Alternatively, it may be formed by a coating film of an organic solvent-soluble fluororesin, or perfluoroolefin resin powder or silicone resin powder may be dispersed and contained in the protective film.

The film thickness of the transparent protective film of the stimulable phosphor sheet is suitably selected according to the type and content of the radioisotope contained in the sample, the intensity of the emitted radiation and the like. That is, in order to measure the distribution of a substance labeled with a radioactive label having a relatively high radiation energy in a sample, a stimulable phosphor sheet having a thick protective film is used, and a relatively low radiation energy is used. In order to measure the distribution of the substance labeled with the radioactive label in the sample, a stimulable phosphor sheet having a thin protective film or a stimulable phosphor sheet having no protective film is used.

Next, a method of identifying an autoradiographic image, which is a typical embodiment of the present invention, will be described. The autoradiographic operation in the method for identifying an autoradiographic image of the present invention uses the above-mentioned stimulable phosphor sheet instead of the conventional light-sensitive material comprising a radiation film, and the exposure operation is a radioactive labeling substance. By stacking the sample containing the and the stimulable phosphor sheet for a certain period of time, the sheet absorbs at least a part of the radiation emitted from the radiolabeled substance of the sample.

Samples to be recorded by autoradiography of the present invention include animal brain, digestive system tissue, circulatory system tissue,
It is a sample of tissue (all or part) of an organism such as the whole body of an animal, a part and the whole of a plant.

The radiolabeled substance contained in the above sample can be obtained by allowing a sample to be recorded or a specific substance in the sample to hold a radioisotope by a known method.
The radioactive isotope used in the present invention is radiation (α-ray,
Any nuclide may be used as long as it emits β-ray, γ-ray, neutron ray, X-ray, etc., but typical ones are ³ H, ¹²³ I, ¹³¹ I, ¹⁴ C described above. , ³⁵ S,
¹⁸ F, and ³² P can be mentioned.

In the exposure operation, the above-mentioned sample is superposed on the stimulable phosphor sheet as it is or after being subjected to any treatment such as a drying treatment and a fixing treatment of the separated development product, whereby an autoradiograph of the specimen is accumulated. Accumulated and recorded on the fluorescent sheet. The state in which the sample and the stimulable phosphor sheet are overlapped is usually realized by bringing the sample and the stimulable phosphor sheet into close contact with each other, but it is not always necessary to bring them in close contact, and they are placed in a state of being close to each other. It may have been done.

The exposure time depends on the type of radioisotope contained in the sample, its radiation intensity, the concentration and density of the radiolabeled substance, the sensitivity of the stimulable phosphor sheet, the positional relationship between the sample and the stimulable phosphor sheet, and the like. Although varying, the exposure operation requires a certain time, for example, several seconds or more. However,
When the stimulable phosphor sheet of the present invention is used, the exposure time is significantly shortened as compared with the exposure time required when using a conventional radiation film.

The temperature at which the exposure operation is carried out is not particularly limited, but autoradiography using the stimulable phosphor sheet of the present invention can be carried out at an ambient temperature such as 10 to 35 ° C. However, the low temperatures (eg, 5) used in conventional autoradiography
The exposure operation may be performed at a temperature of about 0 ° C. or lower.

The reading device (or reading device) shown in FIG. 1 for the method for reading the positional information of the radiolabeled substance shown in the autoradiographic image stored and recorded on the stimulable phosphor sheet in the present invention will be described below. It will be briefly described with reference to the example of. FIG. 1 shows a stimulable phosphor sheet (including a support and a stimulable phosphor layer.
In general, a protective layer is provided on the stimulable phosphor layer. In the following, it may be abbreviated as a sheet) 1) a pre-reading read-out unit 2 for temporarily reading the one-dimensional or two-dimensional position information of the radiolabeled substance accumulated and recorded in 1 and the position information of the radiolabeled substance. 1 is a schematic view of an example of a reading device including a main reading reading unit 3 having a function of reading an autoradiographic image stored and recorded on a sheet 1 for output.

In the read-ahead reading section 2, the following read-ahead operation is performed. The laser light 5 generated from the laser light source 4 passes through the filter 6 to be excited by the laser light 5 so that the stimulable phosphor sheet 1 can be excited.
The portion of the wavelength region corresponding to the wavelength region of stimulated emission generated from is cut. Next, the laser light is deflected by an optical deflector 7 such as a galvanometer mirror, and a plane reflecting mirror 8
After being reflected by, the sheet 1 is one-dimensionally deflected and incident on the sheet 1. The laser light source 4 used here is selected so that the wavelength region of the laser light 5 does not overlap with the main wavelength region of stimulated emission emitted from the sheet 1. The stimulable phosphor sheet 1 is transported in the direction of arrow 9 with the protective film side facing upward under the irradiation of the polarized laser light 5. Therefore, the deflected laser light is applied to the entire surface of the sheet 1. Regarding the output of the laser light source 4, the beam diameter of the laser light 5, the scanning speed of the laser light 5 and the transfer speed of the sheet 1, the energy of the laser light 5 in the pre-reading operation is smaller than the energy used in the main reading operation. Adjusted to. When the stimulable phosphor sheet 1 is irradiated with the above-mentioned laser light, the stimulable phosphor sheet 1 exhibits stimulated emission of a light amount proportional to the radiation energy accumulated in the stimulable phosphor layer. It is incident on 10. The light guide 10 is arranged in close proximity so that its incident surface is linear and faces the scanning line on the stimulable phosphor sheet 1, and its exit surface forms a ring, and is used as a photomultiplier or the like. The light receiving surface of the photodetector 11 is connected. The light guide 10 is made by processing a transparent thermoplastic resin sheet such as an acrylic synthetic resin, and the light incident from the incident surface is totally reflected inside and transmitted to the emission surface. Is configured. The stimulated emission from the stimulable phosphor sheet 1 is guided through the light guide 10 to reach the emission surface, emitted from the emission surface and received by the photodetector 11. Only the light in the wavelength region of stimulated emission is transmitted through the light receiving surface of the photodetector 11 and the excitation light (laser light)
A filter that cuts off light in the wavelength region is attached so that only stimulated emission can be detected. Photo detector 1
The stimulated emission detected by 1 is converted into an electric signal, further amplified by the amplifier 12, and output. Amplifier 12
The accumulated recording information output from the above is input to the control circuit 13 of the main reading reading unit 3. The control circuit 13 obtains an image having the most uniform density and contrast and excellent observation / interpretation performance according to the obtained accumulated record information.
The amplification factor setting value a, the recording scale factor b, and the reproduced image processing condition setting value c are output.

The stimulable phosphor sheet 1 for which the pre-reading operation is completed as described above is transferred to the main reading-out reading section 3. In the main reading reading section 3, the following main reading operation is performed. The laser light 15 emitted from the main reading laser light source 14 passes through a filter 16 having the same function as the filter 6 described above, and then the beam expander 17 strictly adjusts the beam diameter. Next, the laser light is deflected by an optical deflector 18 such as a galvanometer mirror, reflected by a flat reflecting mirror 19, and then one-dimensionally deflected and incident on the stimulable phosphor sheet 1. An fθ lens 20 is arranged between the optical deflector 18 and the plane reflecting mirror 19 so that a uniform beam velocity is always maintained when the deflected laser light scans the sheet 1. . The stimulable phosphor sheet 1 is transported in the direction of the arrow 21 with the protective film side facing up under the irradiation of the polarized laser light as in the case of the pre-reading operation. Therefore, as in the pre-reading operation, the entire surface of the sheet 1 is irradiated with the deflected laser light. When the stimulable phosphor sheet 1 is irradiated with the laser light as described above, the stimulable phosphor sheet 1 has the same structure as in the pre-reading operation.
The stimulated emission of light is emitted in an amount proportional to the accumulated radiation energy, and this light is incident on the main reading light guide 22. This book-reading light guide 22 is a pre-reading light guide 10.
It has the same material and structure as the
The photostimulated luminescence that is guided while repeating the total reflection inside 2 is emitted from the emission surface and is received by the photodetector 23. A filter that selectively transmits only the wavelength region of stimulated emission is attached to the light receiving surface of the photodetector 23.
3 detects only stimulated emission. The photostimulated luminescence detected by the photodetector 23 is converted into an electric signal, which is amplified to an appropriate level electric signal in the amplifier 24 whose sensitivity is set according to the amplification factor setting value a, and then the A / D converter 25. Entered in. A / D converter 25
Is converted into a digital signal with a scale factor suitable for the signal fluctuation width according to the recording scale factor setting value b, and is input to the signal processing circuit 26.

After performing the above-described read operation of the stimulable phosphor sheet, the signal processing circuit 26 first reads the position information (image signal) obtained from the stimulable phosphor sheet.
Is temporarily stored in a memory (that is, a non-volatile memory such as a buffer memory or a magnetic disk).

Regarding the method for reading out the radio-labeled substance in the sample accumulated and recorded in the stimulable phosphor sheet, the read-out operation consisting of the pre-reading operation and the main reading operation has been described above, but it is used in the present invention. The read operations that can be performed are not limited to the above examples. For example, if the content of the radioactive substance in the sample, its radiation intensity, and the exposure time of the stimulable phosphor sheet for the sample are known in advance, the prefetch operation can be omitted in the above example. Further, as a method for reading out the positional information of the radiolabeled substance in the sample accumulated and recorded in the stimulable phosphor sheet according to the present invention, it is naturally possible to use an appropriate method other than those exemplified above. .

In the method for identifying an autoradiographic image of the present invention, the above image signal is then retrieved from the memory and displayed as an autoradiographic image (radiation image) on the display screen. At the same time, a diagram showing the external and / or internal shape of the tissue sample for autoradiography that has been created in advance and recorded in a recording device such as a magnetic disk (even if it is not a figure of the shape itself, It may be something like a rough outline drawing, rough structure drawing, or stylized schematic drawing). In addition,
When displaying a diagram showing the external and / or internal shape of this tissue sample, it is desirable to display the information (name of tissue sample, site, etc.) related to the tissue sample shown in the diagram together. . Such information may be recorded and stored in a recording medium together with the above figures.

FIG. 2 attached herewith shows a schematic diagram 31 of an autoradiographic image of rat brain tissue, and FIG. 3 shows a schematic diagram showing the external shape of the rat brain tissue. FIG. 3 shows the external shape 32 of rat brain tissue and the shape of the skull 33 around it. The diagram showing the shape of the tissue sample of FIG. 3 may be created from an actual sample, or may be a schematic diagram showing the normal shape of the tissue targeted for autoradiography. Good. That is, for example, the shape of the brain tissue of a rat is almost the same for a large number of rats if the type of the rat is fixed and the sizes thereof are roughly aligned. Therefore, in such a case, if one type of brain tissue shape diagram is created,
This can be used repeatedly. Alternatively, in the case of autoradiography of a whole-body image of a rat, if a fixing method (posture) for the whole-body image is determined in advance and a shape schematic diagram according to the posture is created, one kind of The shape schematic can be used repeatedly.

Next, as shown in FIG. 4, the autoradiography image of FIG. 2 or the shape schematic diagram of FIG. 3 is appropriately moved on the display screen for alignment.
That is, for example, the position of the shape schematic diagram is fixed, and the autoradiography image is moved vertically and horizontally using a mouse or the like, as shown in FIG.
The image and the shape schematic diagram are made to coincide in position. In this way, by positioning the autoradiographic image and the shape schematic diagram in position, the correspondence between the tissue sample and the autoradiographic image is clarified, and therefore the respective positions of radioactive substances in the tissue sample are clarified. Moreover, the concentration of the radioactive substance at each position can be easily quantified. The position of the radioactive substance in the tissue sample and the quantification of the concentration of the radioactive substance at each position can be determined by a program on a computer, but may be visually determined by the operator if necessary.

That is, by the above method, the identification of the autoradiographic image of the tissue sample of the organism using the stimulable phosphor sheet can be easily carried out with high accuracy.

[0060]

The image of the tissue sample of the organism of the present invention (eg,
Autoradiography image, Autofluorography image, PET image, CT image, SPECT image, MR
I image, etc.) has the advantage that the position of the labeling substance in the image of the tissue sample of the organism can be identified with high accuracy and reliability even by an unskilled person. is there.

In particular, when the present invention is applied to a method for identifying an autoradiographic image, the above-mentioned problems associated with the conventional autoradiography using a photosensitive silver salt film are solved, and the storage property is improved. It solves the problem that it is difficult to determine the positional correspondence between the autoradiography image and the sample, which was a disadvantageous requirement in the identification operation of the autoradiography image of the tissue sample of the organism using the phosphor sheet. is there. Therefore, by utilizing the autoradiographic image identification method of the present invention,
There is an advantage that even an unskilled person can identify an autoradiographic image of a tissue sample of an organism with high accuracy and certainty.

[Brief description of drawings]

FIG. 1 shows an example of the configuration of a reading (reading) device for reading the position information of a radiolabeled substance in a sample stored and recorded in a stimulable phosphor sheet.

FIG. 2 shows an example of a schematic diagram of an autoradiographic image of rat brain tissue.

FIG. 3 shows an example of a schematic diagram showing the external shape of rat brain tissue.

FIG. 4 shows a process of moving the autoradiographic image of FIG. 2 on a display screen to align the autoradiographic image with the schematic pattern diagram of FIG.

5 shows a state where the autoradiography image and its shape schematic diagram match on the display as a result of the alignment in FIG.

[Explanation of symbols]

1 stimulable phosphor sheet 2 read-out section for pre-reading 3 read-out section for main reading 4 laser light source 5 laser light 6 filter 7 light deflector 8 plane reflecting mirror 9 transfer direction 10 pre-reading light guide 11 photodetector 12 amplifier 13 control circuit 14 Laser light source 15 Laser light 16 Filter 17 Beam expander 18 Optical deflector 19 Planar reflecting mirror 20 fθ lens 21 Transfer direction 22 Optical guide for reading 23 Photodetector 24 Amplifier 25 A / D converter 26 Signal processing circuit 31 Rat's Schematic diagram of autoradiographic image of brain tissue 32 Schematic diagram showing external shape of rat brain tissue 33 Schematic diagram showing shape of skull around rat brain tissue

Claims (4)

[Claims] 1. An identification method comprising the following steps for obtaining positional information of a labeling substance distributed in an image of a tissue sample of an organism: 1) An image signal indicating the positional information of the labeling substance in the tissue sample. 2) simultaneously displaying on the display screen an image of the tissue sample based on the image signal and a diagram showing the external and / or internal shape of the tissue sample; 3) the position of the image of the tissue sample on the display screen And the position of the figure showing the external and / or internal shape of the tissue sample, relative to each other, and adjusting so that the image of the former tissue sample overlaps corresponding to the latter shape diagram;
And 4) a step of identifying the distribution of the radiolabeled substance in the tissue sample from the image of the superimposed tissue sample and the figure showing the external and / or internal shape of the tissue sample. 2. An image of a tissue sample of an organism is an autoradiographic image of a tissue sample of the organism, and the labeling substance distributed in the tissue sample of the organism is a radioactive label labeled with a radioisotope. An identification method for obtaining positional information of a labeling substance which is a substance and which is distributed in an image of a tissue sample of an organism according to claim 1 including the following steps: 1) The tissue sample is a stimulable phosphor. A step of allowing the stimulable phosphor layer to absorb and store the radiation energy emitted from the radiolabeled substance by superimposing the layer on the stimulable phosphor sheet including the layer for a certain period of time; 2) the stimulable phosphor sheet Of the stimulable phosphor layer is excited by an electromagnetic wave to release the radiation energy accumulated and recorded in the stimulable phosphor layer as stimulable light, and the stimulable light is detected to obtain a radioactive label. Obtaining an image signal indicating quality position information; 3) Simultaneously displaying an autoradiographic image based on the image signal and a diagram showing the external and / or internal shape of the tissue sample on a display screen; 4) Display On the screen, the position of the autoradiographic image and the position of the figure showing the external and / or internal shape of the tissue sample are relatively moved, and the former autoradiographic image is superposed corresponding to the latter shape drawing. And 5) a step of identifying the distribution of the radiolabeled substance in the tissue sample from the superimposed autoradiographic image and the figure showing the external and / or internal shape of the tissue sample. 3. The method for identifying an autoradiographic image according to claim 2, for obtaining positional information of a radiolabeled substance labeled with a radioisotope distributed in a tissue sample of an organism. The method also comprises quantifying the concentration of the radiolabeled substance at the distribution position of. 4. The method for identifying an autoradiographic image according to claim 2, for obtaining positional information of a radiolabeled substance labeled with a radioisotope distributed in a tissue sample of the organism. A method wherein the tissue sample is a brain slice of an animal.