JP5283415B2 - Imaging apparatus and exposure control method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To photograph chemiluminescent materials and fluorescent materials distributed in living bodies to achieve their images with sufficient exposure without blur. <P>SOLUTION: A respiration sensor 36 is embedded in a mask 35 to be mounted to a living body 3 administered with a fluorescent material for the suction of anesthesia gas. A pulsation sensor 37 is mounted to the living body 3. While an image sensor 21 maintains the state of photoelectric conversion and electric charge accumulation, a timing control part 33 turns on an upper light source 16 or a bottom light source 17 on the basis of each signal from the respiration sensor 36 and the pulsation sensor 37 each time both state of respiration and state of pulsation of the living body 3 turn into a specific state to irradiate the living body 3 with exciting light, generate fluorescence from the fluorescent material, and make the image sensor 21 receive the fluorescence. <P>COPYRIGHT: (C)2010,JPO&amp;INPIT

Description

  The present invention relates to an imaging device that receives light from a labeled target substance distributed in a living body to generate an image, and an exposure timing control method at that time.

  2. Description of the Related Art Conventionally, apparatuses that place a subject in a housing and shoot the subject by irradiating the subject with a light source provided in the housing have been used in various fields. In the fields of biochemistry and molecular biology, chemiluminescent substances and fluorescent substances are used as labeling substances, and by reading these luminescence and fluorescence, gene sequences, gene expression levels, protein separation, identification, or molecular weight There are known imaging apparatuses that perform characteristic evaluation and the like.

  In addition, a gene, protein, antibody, or pharmacological substance labeled with the above-described labeling substance is given to a living body such as a mouse or rat, and light from the labeling substance distributed in the body or body surface of the living body is photographed with a camera. 2. Description of the Related Art An imaging apparatus that performs so-called in vivo imaging for imaging gene expression, pharmacological action, and the like is known (for example, see Patent Document 1). In this photographing apparatus, for example, when labeling is performed with a fluorescent substance, the living body is irradiated with excitation light to excite the fluorescent substance, and the generated fluorescence is received by a camera to generate an image.

  When photographing a living body, the part of the living body moves or the lung contracts / expands due to the breathing motion of the living body, and blurring occurs in the image generated by the camera. Therefore, in order to solve such a problem, Patent Documents 2 and 3 disclose CT apparatuses that perform X-ray imaging at a timing synchronized with the breathing of a patient (person) to be imaged during X-ray imaging. It has been.

Special Table 2000-502844 Japanese Patent Laid-Open No. 5-212024 JP 2000-139892 A

  By the way, for example, in a CT apparatus or the like for "person", the respiration rate of "person" is small and the time required for X-ray imaging of each tomographic plane is short. Good shooting can be performed if only synchronized shooting is performed. However, since chemiluminescence and fluorescence of a labeling substance used in an imaging device that images a living body such as a mouse or a rat are very weak light, a long exposure time (for example, 10 seconds) even if a high-sensitivity camera is used. Degree). Small animals such as mice and rats have much more respiratory rate and pulsation than humans. For example, the respiratory rate is 180 times / minute and the pulsation rate is 600 times / minute. Therefore, there is a problem that an exposure amount sufficient to generate an image cannot be obtained even if shooting is performed in synchronization with breathing, and it is difficult to obtain an image free from blurring due to breathing or the like.

The present invention was made in view of the above problem, an imaging device, and dew Desei control method capable of obtaining an image without blur from weak chemiluminescence or fluorescence from the living body such as a mouse or a rat The purpose is to provide.

In order to achieve the above object, the imaging apparatus according to claim 1 detects a respiratory state of a living body and outputs a respiratory signal corresponding to the respiratory state, and detects a pulsating state of the living body. And at a predetermined exposure timing synchronized with both the respiratory motion and the pulsation of the living body based on the pulsation detection means for outputting the pulsation signal according to the pulsation state and the respiratory signal and the pulsation signal. And a timing control means for controlling the exposure by the image sensor so as to receive light from a living body and performing multiple exposure until a predetermined exposure time is reached .

  In the imaging device according to claim 2, the timing control means sets a timing at which the living body is in a specific breathing state and a specific pulsation state as an exposure timing, and a period in which each of breathing and pulsation maintains a specific state In the exposure control, the image sensor continuously receives light from the living body.

  According to a third aspect of the present invention, there is provided a shutter mechanism that is disposed between the living body and the image sensor and changes between an open state that allows light from the living body to enter the image sensor and a closed state that blocks the incidence. The timing control means is configured to change the shutter mechanism from the closed state to the open state at each exposure timing and receive light from the living body by the image sensor.

  According to a fourth aspect of the present invention, the imaging apparatus includes an excitation light source that irradiates the living body with excitation light, and the timing control unit is configured to cause the image sensor to receive light from the living body by turning on the excitation light source at each exposure timing. is there.

In claim 5 of the dew Desei your method of imaging target organism respiratory status and beating state respectively detected for each predetermined exposure timing that is synchronized to both the respiration and heartbeat of the living body, from the organism Exposure is controlled so that light is received by an image sensor, and multiple exposure is performed until a predetermined exposure time is reached in substantially the same respiratory state and pulsation state.

  According to the present invention, the respiratory state of the living body and the pulsating state of the living body are detected, and the light from the living body is received by the image sensor at each predetermined exposure timing synchronized with both the breathing and the pulsation. Since multiple exposure is performed, a blur-free image can be obtained even from weak chemiluminescence or fluorescence.

[First Embodiment]
FIG. 1 shows the appearance of a photographing system embodying the present invention. The imaging system 2 receives light from a labeling substance distributed on the body surface of a living body 3 (see FIG. 2) such as a mouse or a rat (see FIG. 2) or a labeling substance distributed in the body (hereinafter referred to as an image of the labeling substance distributed on the living body 3). (Distributed image) is taken (generated) and displayed. In this embodiment, a case where a fluorescent substance that emits fluorescence by irradiating excitation light as a labeling substance is administered to the living body 3 and a distribution image of the fluorescent substance distributed in the living body 3 is generated will be described. The same applies to the case of generating a distribution image of a tissue that emits, for example, a tumor tissue.

  The photographing system 2 generates a distribution image, performs various settings on the photographing device 5 and performs various image processing on the distribution image generated by the photographing device 5 and displays the distribution image on the monitor 6a. It is composed of a PC (Personal Computer) 6 that performs recording on a medium. The PC 6 realizes a setting function, an image processing function, and the like for the photographing apparatus 5 by installing predetermined software. In this example, an anesthesia apparatus 7 for supplying an anesthetic gas is further provided.

  The photographing apparatus 5 has a photographing room 12 provided inside a hollow case 11 having a substantially rectangular parallelepiped shape. In the photographing room 12, a camera unit 14 (see FIG. 2), a photographing stage 15, an upper light source 16, a bottom light source 17 (see FIG. 2) and the like are arranged. The housing 11 is provided with a lid 18. By opening the lid 18, the living body 3 can be accommodated in the photographing room 12 and the living body can be taken out from the photographing room 12. When the lid 18 is closed, the inside of the photographing room 12 is shielded, and light other than fluorescence emitted from the living body 3 during photographing is prevented from entering the camera unit 14.

  In FIG. 2, the camera unit 14 is fixed to the upper part of the imaging room 12 and generates a distribution image of the living body 3. The camera unit 14 includes an image sensor 21, a photographing lens 22, a camera side filter 23, a cooling unit 24, and the like. The image sensor 21 is the same as that used in a digital camera or the like, and a large number of light receiving elements are arranged in a matrix on the light receiving surface.

  In the case of generating a distribution image, as will be described later, the image sensor 21 is maintained in a state where photoelectric conversion is performed by a light receiving element and electric charges are accumulated, and in the meantime, both respiration and pulsation of the living body 3 are synchronized. Thus, multiple exposure is performed by receiving fluorescence from the fluorescent material and accumulating the light as electric charges.

  The taking lens 22 images the fluorescence from the living body 3 on the image sensor 21. The camera-side filter 23 is a filter that blocks excitation light from the upper light source 16 and the bottom light source 17 and transmits fluorescence from the fluorescent material distributed in the living body 3. As the camera-side filter 23, for example, a low-pass filter that cuts light having a shorter wavelength than the fluorescence from the fluorescent material is used, and only the fluorescence from the living body 3 is received by the image sensor 21. The cooling unit 24 reduces dark current by cooling the image sensor 21 and suppresses noise in the generated distribution image.

  As the image sensor 21, various types such as a CCD type and a CMOS type can be used. Further, an image sensor using an organic photoelectric conversion film may be used in addition to a semiconductor that performs photoelectric conversion. Further, not only a single color but also a received light may be separated into a plurality of colors and photographed.

  A shooting stage 15 is arranged directly under the camera unit 14. The photographing stage 15 has a box shape including a stage surface 27 on which the living body 3 is placed and a housing 28 below the stage surface 27. A bottom light source 17 is disposed in the hollow interior of the photographing stage 15. The stage surface 27 has a transparent plate shape so that the living body 3 placed thereon is irradiated with excitation light from the bottom light source 17. The housing 28 is opaque so as to block the excitation light from the bottom light source 17 so that the excitation light is not emitted from other than the stage surface 27.

  An upper light source 16 is disposed above the photographing stage 15. Both the upper light source 16 and the above-described bottom light source 17 serve as an excitation light source that irradiates the living body 3 with excitation light for exciting the fluorescent material distributed in the living body 3 to emit light. Various light sources such as a halogen lamp, a strobe discharge tube, a laser, and a light emitting diode can be used as the light sources 16 and 17, but the light sources 16 and 17 are turned on in synchronization with the breathing and pulsation of the living body 3. A light source with high responsiveness is preferably used to turn off. In this example, a white LED and a wavelength range of fluorescence from the fluorescent material and a high-pass filter that cuts light on the longer wavelength side are used.

  The upper light source 16 is a so-called epi-illumination type excitation light source, which emits excitation light from the upper side of the living body 3, and the bottom light source 17 irradiates excitation light from the lower side of the living body 3. The top light source 16 and the bottom light source 17 are driven by the corresponding top light source driver 31 and bottom light source driver 32, respectively, under the control of the timing control unit 33.

  The mask 35 in the imaging room 12 is connected to the anesthesia apparatus 7 via a tube or the like, and anesthesia gas is supplied from the anesthesia apparatus 7. The mask 35 is attached to the living body 3, for example, the nose of the mouse, and causes the living body 3 to suck the anesthetic gas. Thereby, the anesthesia state of the living body 3 is maintained so that the posture does not change.

  A respiration sensor 36 is incorporated in the mask 35. The respiration sensor 36 detects a respiration state based on, for example, humidity, and outputs a respiration signal corresponding to the respiration state. The respiration sensor 36 may be detected using a technique other than this, or may be attached to another part. For example, the respiratory state may be detected by a pressure sensor incorporated in the mask 35.

  The pulsation sensor 37 is for detecting the pulsation (heartbeat) state of the living body 3, and is attached to the tail of the living body 3, for example, and detects the pulsating state by pressure, for example. The pulsation sensor 37 outputs a pulsation signal corresponding to the pulsation state of the living body 3. As the pulsation sensor 37, other methods, for example, an electrocardiograph that electrically detects a pulsation state, a heart sound transducer, or the like may be used. Moreover, you may mount | wear with another site | part.

  The timing control unit 33 performs multiple exposure by multiple exposures so that the image sensor 21 receives light from the living body 3 at every predetermined exposure timing synchronized with both the breathing and pulsation of the living body 3. Let it be done. As a result, both the breathing state and the pulsation state of the living body 3 at the time of each exposure are set to substantially the same state, and a distribution image is taken with a sufficiently long exposure time while preventing blurring of the image generated by the image sensor 21. I can do it.

  In this embodiment, by controlling the on / off timing of the excitation light source, that is, when both the breathing state and the pulsation state of the living body 3 are substantially the same state, in this example, as will be described later. 3, when the timing signal shown in FIG. 3 is output, T1, T2, T3..., The living body 3 is irradiated with excitation light, and the fluorescence from the fluorescent material distributed in the living body 3 is received by the image sensor 21. I try to do it. Therefore, one exposure of multiple exposure is performed by turning on the excitation light source once.

  The timing control unit 33 determines the exposure timing at which both the breathing state and the pulsation state of the living body 3 are substantially the same based on the respiratory signal and the pulsation signal, and the timing signal for each exposure timing. Is output. This timing signal has a pulse width corresponding to a period during which the image sensor 21 should receive fluorescence from the living body 3, that is, a period during which exposure is performed.

  In the timing control unit 33, the total exposure time by multiple exposure, the setting of the excitation light source to be used, and the like are set by the operation of the PC 6. The timing signal is sent to the upper light source driver 31 or the bottom light source driver 32 corresponding to the excitation light source to be used. In addition, the timing control unit 33 has a counter that accumulates the pulse width of the timing signal. When the content of the counter reaches the set total exposure time, the timing control unit 33 stops sending the timing signal and performs multiplexing. Outputs exposure complete signal.

  The driver 38 operates the image sensor 21 in response to the input of the multiple exposure start signal input from the timing control unit 33 to start photoelectric conversion of received light and accumulation of electric charge obtained by the photoelectric conversion. . In response to the input of the multiple exposure completion signal from the timing control unit 33, the driver 38 stops the photoelectric conversion in the image sensor 21 and converts the charge accumulated so far into an image signal. By outputting, a distribution image obtained by multiple exposure is sent to the PC 6.

  The top light source driver 31 and the bottom light source driver 32 turn on the light source while the pulsed timing signal is input. Thereby, when both the respiration state and the pulsation state of the living body 3 are substantially the same state, the living body 3 is irradiated with excitation light from the excitation light source to generate fluorescence from the fluorescent material. The living body may be irradiated with excitation light based on the timing signal by opening and closing the shutter or the like while the light source is turned on (lit state).

  FIG. 3 shows an example of waveforms such as a respiratory signal, a pulsation signal, and a timing signal. In this example, the respiratory signal and the pulsation signal are adjusted by the timing control unit 33 so as to have predetermined amplitudes, respectively, and are then binarized with predetermined threshold values Th1 and Th2 to be a respiratory binarized signal. , Beat binary signal. Then, the timing control unit 33 performs an AND operation on the obtained respiratory binarization signal and pulsation binarization signal to generate a timing signal.

  Specifically, by setting the threshold Th1, a state (period from timing Ta1 to timing Ta2) between the expiration of the living body 3 (respiration signal rise) and inspiration (respiration signal fall) is determined as a specific breath. State. Further, depending on the setting of the threshold Th2, the state of the living body 3 before and after the heart is contracted or blood pressure is increased (the pulsation signal is increased) to heart expansion or blood pressure is decreased (the pulsation signal is decreased) (timing from the timing Tb1). The period of Tb2) is a specific pulsation state. A timing signal is output when T1, T2, T3... Are in a specific state.

  From the input of the multiple exposure start signal to the input of the multiple exposure completion signal to the driver 38 is a charge accumulation period in which the image sensor 21 accumulates charges in order to generate one distribution image. During this charge accumulation period, light from the fluorescent material distributed in the living body 3 is received by the image sensor 21 in response to the top light source 16 or the bottom light source 17 being turned on by a plurality of timing signals, resulting in multiple exposure. Is done.

  In order to prevent the distribution image from blurring, it is important to perform each exposure in the multiple exposure when the part of the living body 3, particularly the part to be imaged, is at substantially the same position. It is not limited to a specific respiratory state and a specific pulsatile state. For example, in breathing, before and after the change from inspiration to expiration, a certain interval during inspiration or expiration may be set as a specific breathing state. It is also a useful aspect to perform multiple exposures in synchronization with only one of breathing and pulsation.

  Next, the operation of the above configuration will be described. First, the lid 18 is opened, and the living body 3 to which a fluorescent substance has been administered is placed on the imaging stage 15. At this time, the living body 3 is in a state in which pre-anesthesia is performed. Subsequently, the cover 18 is closed after the mask 35 and the pulsation sensor 37 are mounted on the living body 3. Then, supply of anesthetic gas from the anesthesia apparatus 7 is started.

  Next, the PC 6 is operated to set which of the top light source 16 and the bottom light source 17 is used, and after setting the total exposure time, the start of photographing is instructed. When the start of imaging is instructed, the timing control unit 33 outputs a respiration binarization signal and a pulsation binarization signal obtained by binarizing the respiration signal from the respiration sensor 36 and the pulsation signal from the pulsation sensor 37. After confirming that the multiple exposure has been performed, a multiple exposure start signal is sent to the driver 38.

  When the driver 38 receives the multiple exposure start signal, the image sensor 21 starts operating, and light received by each light receiving element is photoelectrically converted into electric charge and accumulated. On the other hand, the timing control unit 33 starts a process of generating a timing signal by performing an AND operation on the respiration binarization signal and the pulsation binarization signal. Each timing signal generated in this process is sequentially sent to the driver of the light source set to be used. For example, when the light source set to be used is the bottom light source 17, each timing signal is sequentially sent to the bottom light source driver 32.

  When the timing signal is input to the bottom light source driver 32, the bottom light source 17 is turned on, and the excitation light is irradiated through the stage surface 27 onto the living body 3 placed on the stage surface 27. The irradiated excitation light is diffused in the living body 3 to excite the fluorescent substance distributed in the body or body surface of the living body 3 to generate fluorescence. Thus, the fluorescence emitted from the fluorescent material distributed in the living body 3 is received by the image sensor 21 through the camera-side filter 23 and the photographing lens 22.

  Similarly, every time the timing signal is input to the bottom light source driver 32, the bottom light source 17 is turned on, and the fluorescence generated each time the light is turned on is received by the image sensor 21, and the charge due to the light reception is gradually accumulated. The

  When the upper light source 16 is set as the light source to be used, a timing signal is sent to the upper light source driver 31, and the upper light source 16 is turned on every time the timing signal is input, and excitation light is directed toward the living body 3. Is irradiated. Then, the fluorescence emitted from the fluorescent material by the irradiation is received by the image sensor 21 through the camera-side filter 23 and the photographing lens 22.

  As described above, while the multiple exposure is performed by turning on and off the light source, the timing control unit 33 performs the integration of the pulse width of the timing signal, that is, the integration of the exposure time. When the accumulated exposure time reaches the total exposure time set by the PC 6, the timing control unit 33 stops sending the timing signal and then sends a multiple exposure completion signal to the driver 38 to complete the multiple exposure. Is done.

  When the multiple exposure is completed as described above, the charge accumulated in the image sensor 21 is read by the drive signal from the driver 38, and the image signal of the distribution image obtained by the multiple exposure is the PC6. Sent to. In the PC 6, after performing various image processing, an image obtained by multiple exposure is displayed on the monitor 6a or recorded on a recording medium.

  The distribution image obtained as described above has a sufficient exposure time because multiple exposure is performed, and when both the breathing and pulsation of the living body 3 are in a specific state, that is, the part of the living body 3 is Since the images are generated by receiving fluorescence generated by irradiating excitation light when they are substantially at the same position, they are excellent without blurring.

[Second Embodiment]
In the second embodiment, an image sensor receives light from a living body at every predetermined exposure timing synchronized with both respiration and pulsation of the living body using a shutter device. In addition, except being demonstrated below, it is the same as that of 1st Embodiment, The same code | symbol is attached | subjected to the substantially same structural member, and the detailed description is abbreviate | omitted.

  In this example, as shown in FIG. 4, a shutter device 41 is provided between the image sensor 21 and the photographing lens 22. The shutter device 41 changes between an open state in which the fluorescence from the living body 3 is allowed to enter the image sensor 21 and a closed state in which the incidence is blocked. The shutter driver 42 opens the shutter device 41 only while the timing signal from the timing control unit 33 is input. The top light source 16 or the bottom light source 17 is always turned on during multiple exposure, but may be controlled so as to be turned on only when the shutter device 41 is in the open state.

  As the shutter device 41, various devices such as a mechanical shutter device that opens and closes an opening by operating shutter blades, an electro-optical shutter, and an image intensifier capable of gate operation can be used. A thing with high property is preferable. The shutter device 41 may be at any position between the living body 3 and the image sensor 21.

  According to this, since the top light source 16 or the bottom light source 17 is turned on, fluorescence is continuously emitted from the fluorescent material distributed in the living body 3, but the living body 3 is opened and closed by opening and closing of the shutter device 41 by the timing signal. Only the fluorescence when both the respiration and pulsation are in a specific state is received by the image sensor 21. Thereby, as in the first embodiment, it is possible to obtain a good distribution image with sufficient exposure time and without blurring.

  In addition, when the shutter device 41 is used in this way, it can also be used when photographing a distribution image of a chemiluminescent substance as a labeling substance. When taking a distribution image of a chemiluminescent substance, it is not necessary to irradiate excitation light with an excitation light source, and the camera-side filter 23 can be omitted.

[Third Embodiment]
In the third embodiment, a plurality of living bodies are photographed simultaneously. Other than that described below, the second embodiment is the same as the first embodiment. FIG. 5 shows only the main part of the photographing apparatus.

  As shown in FIG. 5, the imaging apparatus is provided with a first unit 50a and a second unit 50b. The first unit 50a includes an imaging stage 51a, a respiration sensor 52a, a pulsation sensor 53a, a bottom light source 54a provided in the imaging stage 51a, a light source driver 55a, and a timing control unit 56a.

  The respiration sensor 52a and the pulsation sensor 53a are attached to the living body 3 placed on the imaging stage 51a, and the timing control unit 56a generates a timing signal based on the respiration signal and the pulsation signal from them. The bottom light source driver 55a turns on the bottom light source 54a only while the timing signal from the timing controller 56a is input.

  The second unit 50b is the same as the first unit 50a, and includes a photographing stage 51b, a respiration sensor 52b, a pulsation sensor 53b, a bottom light source 54b provided in the photographing stage 51b, a light source driver 55b, and a timing control unit 56b. Is done. The respiration sensor 52b and the pulsation sensor 53b are attached to the living body 3 placed on the imaging stage 51b. The bottom light source driver 55b turns on the bottom light source 54b only while the timing signal generated by the timing control unit 56b is input based on the respiratory signal and the pulsation signal from the respiratory sensor 52b and the pulsation sensor 53b. To do.

  A partition plate 58 is disposed between the units 50a and 50b so that excitation light from the imaging stage on one unit side is not irradiated on the living body 3 of the other unit. The height of the partition plate 58 is adjusted so that vignetting does not occur.

  The time control unit 59 ends the charge accumulation period of the image sensor 21 when both the units 50a and 50b reach the set total exposure time, and the total exposure time for each unit 50a and 50b. The timing controllers 56a and 56b are controlled so that the transmission of the timing signal is stopped to the unit that has reached.

  According to the above configuration, the living body 3 on the first unit 50a side emits fluorescence by being irradiated with excitation light by the bottom light source 54a when both respiration and pulsation of the living body 3 are in a specific state. The fluorescence is received by the image sensor 21. The living body 3 on the second unit 50 side emits fluorescence when irradiated with excitation light from the bottom light source 54b when both breathing and pulsation of the living body 3 are in a specific state, and the fluorescence is emitted from the image sensor. 21 receives light. Thereby, a blur-free distribution image can be obtained simultaneously for any living body 3.

  In this embodiment, the example using the bottom light source has been described, but an epi-illumination type excitation light source may be used. In this case, an epi-illumination type excitation light source may be provided for each unit so that the excitation light of one unit is not irradiated to the living body of another unit. Alternatively, a shutter device may be provided directly above each living body, and the shutter device corresponding to each living body may be opened and closed. In this way, it can also be used when the labeling substance is a chemiluminescent substance. In the above, two units are used, but three or more units may be used.

[Fourth Embodiment]
The fourth embodiment uses a contact image sensor. In addition, except being demonstrated below, it is the same as that of 1st Embodiment, The same code | symbol is attached | subjected to the structural member which is substantially the same function, and the description is abbreviate | omitted.

  As shown in FIG. 6, an imaging stage 61 and an epi-illumination type excitation light source 62 are arranged inside the housing of the imaging device 5. The light source driver 63 turns on the excitation light source 62 while the timing signal generated by the timing control unit 33 is input.

  The upper surface of the imaging stage 61 is the light receiving surface 65 a of the image sensor 65. The image sensor 65 is driven by a driver 66 to generate a distribution image by receiving fluorescence from a fluorescent substance distributed in the living body 3 placed directly on the light receiving surface 65a. A cooling unit 67 for cooling the image sensor 65 is attached to the surface of the image sensor 65 opposite to the light receiving surface 65a. The cooling unit 67 is configured to release heat generated during cooling to the outside of the imaging device 5.

  FIG. 7 shows an example of the structure of the image sensor 65. The image sensor 65 is a so-called contact-type two-dimensional image sensor and uses an organic photoelectric conversion film. However, a contact-type two-dimensional image sensor using a semiconductor element may be used.

  The image sensor 65 includes a silicon substrate 71 on which a CMOS structure is formed, a photoelectric conversion unit 72, a filter 73, and a lens array 74 that are sequentially stacked on the silicon substrate 71. The lens array 65c is for imaging light from the living body 3 on the photoelectric conversion unit 72, and uses, for example, a SELFOC lens array (registered trademark). The filter 73 corresponds to the camera-side filter 23 in the first embodiment, and transmits only the fluorescence from the fluorescent material.

  The photoelectric conversion unit 72 is formed by laminating a transparent electrode film 72a, a photosensitive photoelectric conversion film 72b, an electrode film 72c, and an insulating film 72d in order from the upper side (the light receiving surface 65a side), and when light enters the photoelectric conversion film 72b. Electric charges corresponding to the amount of light are generated. The photoelectric conversion film 72b is an organic photoelectric conversion film, and the electric charges generated by the photoelectric conversion film 72b are formed in a columnar shape formed so as to penetrate the electrode film 72c and the insulating film 72d by applying a voltage to the electrode films 72a and 72c. The charge is accumulated in the charge accumulation region 76 provided in the silicon substrate 71 through the via 75.

  When the contact-type image sensor is used as described above, every predetermined exposure timing synchronized with both the breathing motion and pulsation of the living body 3, that is, the breathing and pulsation of the living body 3 are both in a specific state. The excitation light source 62 is turned on and the living body 3 is irradiated with excitation light. Then, the fluorescence from the fluorescent material distributed in the living body 3 is received by the image sensor 65 mounted on the light receiving surface 65a, thereby generating a distribution image.

  When a chemiluminescent substance is used as the labeling substance, multiple exposure is performed by providing a thin shutter device between the image sensor 65 and the living body 3 or on the living body side of the photoelectric conversion unit 72 of the image sensor 65. May be.

  In each of the above embodiments, the result of each exposure in multiple exposure is synthesized on the image sensor by continuing to accumulate the charge of the image sensor while performing multiple exposure. Alternatively, for each predetermined number of exposures, an image signal based on the accumulated charge may be output, and a distribution image may be generated by combining the images for each output by image processing such as a PC.

  In addition, the body immediately before the start of multiple exposure and immediately after the end of multiple exposure is normally photographed by irradiating white light, etc., and the movement of the posture during the multiple exposure of the living body is detected based on the images obtained by each photographing. Then, control such as adding the information or image to the distribution image or performing re-photographing (multiple exposure) when the allowable amount is exceeded may be performed. It is also possible to temporarily prevent the incidence of light on the image sensor used for multiple exposure with a shutter device so that normal shooting is performed in the middle of multiple exposure and the movement of the posture in the middle of multiple exposure can be detected. To perform normal shooting, it is convenient to provide a separate camera. However, for example, normal shooting immediately before and after the start of multiple exposure is performed using the camera unit that retracts the camera-side filter and captures the distribution image. May be.

It is a perspective view which shows the structure of the imaging | photography system which implemented this invention. It is a block diagram which shows the structure of an imaging device. It is a timing chart which shows the relationship between a respiration signal, a pulsation signal, and a timing signal. It is a block diagram which shows the structure of the imaging device of 2nd Embodiment which performs multiple exposure using a shutter apparatus. It is a block diagram which shows the structure of the imaging device of 3rd Embodiment which image | photographs several biological body. It is a block diagram which shows the structure of the imaging device of 4th Embodiment using a contact | adherence type image sensor. It is sectional drawing which shows an example of the structure of the image sensor of 4th Embodiment.

Explanation of symbols

DESCRIPTION OF SYMBOLS 5 Image pick-up device 14 Camera part 21,65 Image sensor 16, 17, 54a, 54b, 62 Light source 33, 56a, 56b Timing control part 36, 52a, 52b Respiration sensor 37, 53a, 53b Beat sensor 41 Shutter apparatus

Claims (5)

In a photographing apparatus equipped with an image sensor that receives light from a living body and generates an image,
Respiration detection means for detecting a respiration state of the living body and outputting a respiration signal corresponding to the respiration state;
Pulsation detecting means for detecting a pulsating state of a living body and outputting a pulsating signal corresponding to the pulsating state;
Based on the respiratory signal and the pulsation signal, the exposure at the image sensor is controlled so as to receive light from the living body at every predetermined exposure timing synchronized with both the respiratory movement and the pulsation of the living body. An imaging apparatus comprising timing control means for performing multiple exposure until a predetermined exposure time is reached .   The timing control means uses the timing at which the living body is in a specific breathing state and a specific pulsation state as an exposure timing, and the image continues during the period in which each of the breathing and pulsation maintains a specific state. 2. The photographing apparatus according to claim 1, wherein exposure is controlled so that light from a living body is received by a sensor. A shutter mechanism that is arranged between a living body and the image sensor, and changes between an open state that allows light from the living body to enter the image sensor and a closed state that blocks the incidence;
3. The photographing apparatus according to claim 1, wherein the timing control unit changes the shutter mechanism from a closed state to an open state at each exposure timing and causes the image sensor to receive light from a living body.   An excitation light source for irradiating a living body with excitation light is provided, and the timing control unit turns on the excitation light source at each exposure timing to cause the image sensor to receive light from the living body. The photographing apparatus according to 1 or 2. Detects the breathing state and pulsation state of the living body to be imaged, and controls exposure so that light from the living body is received by the image sensor at each predetermined exposure timing synchronized with both the breathing and pulsation of the living body. , dew Desei control method characterized by multiple exposure to substantially the same respiratory state and beating state reaches a predetermined exposure time.

Images