Patent Publication Number: US-2022230334-A1

Title: Pen-type medical fluorescent imaging device and system for aligning multiple fluorescent images using the same

Description:
RELATED APPLICATIONS 
     This application is a Divisional Application to U.S. application Ser. No. 15/749,871, filed Feb. 2, 2018, which claims priority to and the benefit of a 371 application of PCT/IB2016/055318, filed Sep. 6, 2016, which is hereby incorporated herein by reference in its entirety. 
    
    
     BACKGROUND 
     1. Field of the Invention 
     The present invention relates to a medical fluorescent imaging device and a system for aligning multiple fluorescent images using the same. 
     2. Discussion of Related Art 
     In general, various types of video equipment are being used to obtain biomedical imaging information at biological and medical sites. In such video equipment, in comparison to other imaging techniques, a biomedical imaging method employing light is widely being used due to its convenience of providing real-time information to an observer or a surgeon. 
     In addition, the rapid development of molecular imaging technology lately has made it possible to diagnose diseases and detect lesions. In particular, nuclear medicine imaging and magnetic resonance imaging (MRI) technology is attracting attention as examination systems that are very useful for diagnosing diseases. MRI technology is a method of obtaining anatomical, physiological, and biochemical information images of a body by using a phenomenon in which the spinning of hydrogen atoms is relaxed. MRI technology is an excellent diagnostic imaging technology that is not invasive towards body organs of a person or an animal and makes it possible to capture images thereof in real time. 
     However, in the diagnosis of a malignant glioma that is highly infiltrative, there are problems with such MRI in that it is difficult to determine the boundary between a malignant glioma and normal tissue. 
     During surgical operation on a tumor, it is necessary to check the positions and connections of cerebral blood vessels as well as the tumor for the safety of the patient. In particular, to increase the survival rate of patients and prevent recurrences of diseases, it is very important to completely remove a malignant tumor or a tumor and minimize damage to normal tissue by minimizing the removed parts. 
     Relevant to this, 5-aminolevulinic acid (5-ALA), which is a fluorescent luminescent material for marking tumors and blood vessels, is injected into the human body and then fluoresces due to generation of protoporphyrin IX (PpIX) derived from a material transformation process caused by metabolism in the body. With such a reaction process, 5-ALA serves as a target fluorescence marker targeting only cancer cells. 
     Also, indocyanine green (ICG), which is a fluorescent luminescent material for marking blood vessels, marks blood vessels and lymph nodes while circulating through the blood vessels and the lymph nodes. 
     In other words, 5-ALA is used to cause cancer cells to fluoresce, and ICG is used to cause blood vessels to fluoresce. 
     However, current surgical fluorescent imaging equipment for surgical microscopes may display only one type of fluorescent image due to one the presence of type of fluorescent luminescent material, and thus displays only ICG fluorescent images. Also, since fluorescent imaging equipment is very large, there is an inconvenience in terms of using fluorescent imaging equipment only for surgery. 
     Consequently, an apparatus for accurately detecting and showing the position of a glioma and the positions of blood vessels at the same time is required for a patient&#39;s safety and ease of surgery. 
     SUMMARY OF THE INVENTION 
     The present invention is directed to a fluorescent imaging device capable of detecting and showing the positions of blood vessels and the position of a glioma at the same time for a patient&#39;s safety and ease of surgery. 
     The present invention is also directed to a system for aligning multiple fluorescent images which makes it possible for an operator to accurately and easily check the positions and connections of a tumor and blood vessels by acquiring multiple fluorescent images in which the positions of the blood vessels and the boundary of a glioma are marked to luminesce due to multiple fluorescent materials, and by aligning and displaying the acquired multiple fluorescent images in real time. 
     According to an aspect of the present invention, a pen-type medical fluorescent imaging device is provided including: a probe configured to extend in a longitudinal direction and include an image capturing section at one end; a plurality of light sources configured to be arranged to surround the image capturing section; and a controller configured to control the light sources. The light sources include a first light source configured to emit light of a first wavelength range so that blood vessels are marked by a first fluorescent material, and a second light source configured to emit light of a second wavelength range so that a glioma is marked by a second fluorescent material. The first and second light sources are selectively controlled by the controller. 
     According to another aspect of the present invention, a system for aligning multiple fluorescent images is provided, the system including: the pen-type medical fluorescent imaging device; a fluorescent multi-image acquirer configured to acquire an actual image of a target part, a fluorescent vascular image in which blood vessels are marked by the first fluorescent material, and a fluorescent glioma image in which a glioma is marked by the second fluorescent material; a blood vessel extractor configured to extract a vascular shape from the acquired fluorescent vascular image; a glioma image processor configured to process the acquired fluorescent glioma image so that a boundary of the glioma becomes distinct; a fluorescent multi-image aligner configured to align the extracted fluorescent vascular image and fluorescent glioma image in real time; and a fluorescent image display configured to display a fluorescent multi-image in which the fluorescent vascular image and the fluorescent glioma image are aligned. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The above description and other objects; features and advantages of the present invention will become more apparent to those of ordinary skill in the art by describing in detail exemplary embodiments thereof with reference to the accompanying drawings, in which: 
         FIG. 1  is a perspective view of a pen-type medical fluorescent imaging device according to the present invention; 
         FIG. 2  is a front view of the pen-type medical fluorescent imaging device according to the present invention; 
         FIG. 3  is a conceptual diagram for facilitating understanding of the overall operation of a system for aligning multiple fluorescent images according to the present invention; and 
         FIG. 4  is a block diagram of the system for aligning multiple fluorescent images according to the present invention. 
     
    
    
     DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS 
     The present invention relates to a pen-type medical fluorescent imaging device capable of detecting and showing the position of a glioma and the positions of blood vessels at the same time for a patient&#39;s safety and ease of surgery. 
     Here, a pen type denotes a small pen shape that may be conveniently and freely used with a hand like a pen, which is a writing instrument. According to the present invention, a probe  110  may be formed in a pen shape. 
     The pen-type medical fluorescent imaging device according to the present invention includes: a probe that extends in a longitudinal direction and includes an image capturing section at one end; a plurality of light sources that are arranged to surround the image capturing section; and a controller that controls the light sources. The light sources include a first light source that emits light of a first wavelength range so that blood vessels are marked by a first fluorescent material, and a second light source that emits light of a second wavelength range so that a glioma is marked by a second fluorescent material. The first and second light sources are selectively controlled by the controller. 
     Meanwhile, the light sources may include filters. The first light source may include a first filter, and the second light source may include a second filter. 
     Here, the first fluorescent material may include indocyanine green (ICG), and the second fluorescent material may include one of 5-aminolevulinic acid (5-ALA) and protoporphyrin IX (PpIX) converted from 5-ALA. The light sources may include a third light source that emits white light. 
     Also, the first wavelength range may be 750 nm to 800 nm, and the second wavelength range may be 350 nm to 450 nm. The probe is formed of a flexible material. 
     In addition, the present invention relates to a system for aligning multiple fluorescent images. The system includes: the pen-type medical fluorescent imaging device; a fluorescent multi-image acquirer that acquires an actual image of a target part, a fluorescent vascular image in which blood vessels are marked by the first fluorescent material, and a fluorescent glioma image in which a glioma is marked by the second fluorescent material; a blood vessel extractor that extracts a vascular shape from the acquired fluorescent vascular image; a glioma image processor that processes the acquired fluorescent glioma image so that the boundary of the glioma becomes distinct; a fluorescent multi-image aligner that aligns the extracted fluorescent vascular image and the fluorescent glioma image in real time; and a fluorescent image display that displays a fluorescent multi-image in which the fluorescent vascular image and the fluorescent glioma image are aligned. 
     Here, the fluorescent multi-image acquirer includes a fluorescent vascular shape image acquirer that acquires the fluorescent vascular image in which the positions of the blood vessels are marked by the first fluorescent material, and a fluorescent glioma image acquirer that acquires the fluorescent glioma image in which the position of the glioma is marked by the second fluorescent material. 
     In addition, the fluorescent multi-image acquirer may acquire transformation parameters corresponding to the highest similarity by measuring pixel value-based similarities of a moving image with respect to the actual image, and match the moving image to the actual image by performing two-dimensional (2D) centered similarity registration based on the acquired transformation parameters so that coordinate errors between the actual image and the moving image are minimized, and the moving image may be one of the fluorescent vascular image and the fluorescent glioma image. 
     The fluorescent image display may display at least one of the actual image, the fluorescent vascular image, the fluorescent glioma image, and the fluorescent multi-image according to a selection of an operator or a user. The fluorescent image display may set individual opacity values of the actual image, the fluorescent vascular image, the fluorescent glioma image, and the fluorescent multi-image to simultaneously display a plurality of images overlapping with each other, and may adjust the opacity values of the individual images to display only a specific image as necessary. 
     The pen-type medical fluorescent imaging device may include a transmitter capable of transmitting the actual image, the fluorescent vascular image, and the fluorescent glioma image captured by the image capturing section to the fluorescent multi-image acquirer through wireless communication. 
     Hereinafter, exemplary embodiments of the present invention will be described in detail with reference to the accompanying drawings. Terms and words used in the present specification and claims are not to be construed to have general or dictionary meanings, but are to be construed to be meanings and concepts meeting the technical spirit of the present invention based on a principle that the present inventors may appropriately define the concepts of terms to describe their inventions in the best modes. 
     Therefore, exemplary embodiments described in this specification and configurations illustrated in the drawings are merely most preferable embodiments, but do not represent all of the technical spirit of the present invention. Consequently, the present invention should be construed as including all changes, equivalents, and substitutions of the embodiments at the time of the filing of this application. 
       FIG. 1  is a perspective view of a pen-type medical fluorescent imaging device according to the present invention,  FIG. 2  is a front view of the pen-type medical fluorescent imaging device according to the present invention,  FIG. 3  is a conceptual diagram for facilitating understanding of overall operation of a system for aligning multiple fluorescent images according to the present invention, and  FIG. 4  is a block diagram of the system for aligning multiple fluorescent images according to the present invention. A pen-type medical fluorescent imaging device and a system for aligning multiple fluorescent images according to the present invention will be described below with reference to  FIGS. 1 to 4  and exemplary embodiments. 
     The present invention provides a pen-type medical fluorescent imaging device  100  capable of detecting and showing the positions of blood vessels and the position of a glioma at the same time for a patient&#39;s safety and ease of surgery. 
     As shown in  FIGS. 1 and 2 , the medical fluorescent imaging device  100  of the present invention is formed as a pen type, and includes the probe  110  extending in a longitudinal direction and an image capturing section  120  and light sources  130  at one end of the probe  110 . 
     Here, a pen type denotes a small pen shape that may be conveniently and freely used with a hand like a pen, which is a writing instrument. According to the present invention, the probe  110  may be formed in a pen shape. 
     The probe  110  may include the image capturing section  120  and the light sources  130  at the end, and the light sources  130  may be plural in number to surround the image capturing section  120 . Here, the light sources  130  may include a first light source  131  and a second light source  132 . The first light source  131  may emit light of a first wavelength range so that blood vessels are marked by a first fluorescent material, and the second light source  132  may emit light of a second wavelength range so that a glioma is marked by a second fluorescent material. For reference, the light sources  130  may be light-emitting diode (LED) lamps, and may preferably be near-infrared LED lamps. The number of LED lamps that emit light may be adjusted according to the size and shape of a target part. 
     The image capturing section  120  of the present invention captures an image of a target part, and may be a general camera for capturing an actual image of a target part, a fluorescent vascular image in which blood vessels are marked by the first fluorescent material, and a fluorescent glioma image in which a glioma is marked by the second fluorescent material. 
     In particular, a digital camera or a near infrared ray camera capable of capturing and outputting or storing an image in real time may be used as the image capturing section  120 . For example, a charge coupled device (CCD) or complementary metal-oxide semiconductor (CMOS) camera may be used, and a CCD or CMOS camera having a resolution of megapixel level or greater may preferably be used. Such a camera with megapixel level resolution or greater may be used to acquire a vascular and/or glioma image at high resolution and to observe blood vessels in real time (it is possible to acquire images of 30 frames or more per second). Therefore, convenience for doctors and patients is improved, and it is possible to rapidly and easily observe blood vessels and/or a glioma during a medical examination and surgery of a patient. 
     In particular, according to the present invention, the light sources  130  and the image capturing section  120  are installed at a front end of the probe  110  such that loss of light and image quality may be reduced. 
     In addition, the fluorescent imaging device  100  of the present invention may include a controller  140  that controls the light sources  130 . The first light source  131  and the second light source  132  may be selectively controlled by the controller  140  to emit light. The controller  140  may be a conventional switch, and may be supplied with current from a power supply and may turn on or off the light sources  130 . Meanwhile, the controller  140  that controls the first light source  131  and the second light source  132  may be a first switch  141  and a second switch  142 . 
     In the present invention, ICG, 5-ALA, and the like, which are near-infrared fluorescent materials, may be used as fluorescent materials. The first fluorescent material may be ICG, and the second fluorescent material may be 5-ALA. 
     In particular, ICC, which is efficient in terms of detecting the positions of a patient&#39;s blood vessels and lymph nodes, is a fluorescent material that has been used since 1957 and has few side effects. When injected into a patient, ICG is combined with plasma protein, and when light in a range of 750 nm to 800 nm is transmitted, ICG radiates fluorescent light having a fluorescence peak value of 845 nm. 
     5-ALA, which is efficient in terms of detecting the position of a glioma, has a fluorescence peak value of 635 nm and radiates fluorescent light when light of about 400 nm transmitted to PpIX converted in cells (it is also possible to use radiated light of about 405 nm). Using this property, it is possible to distinguish between normal tissue and a malignant glioma. The use of 5-ALA increases a success rate of complete removal of a malignant glioma about 1.4 times, and reduces a malignant glioma which is not removed to 1/16 of its size, and is thus effective in terms of preventing recurrence of the malignant glioma. 
     Meanwhile, the medical fluorescent imaging device  100  of the present invention may emit light of various wavelengths through the light sources  130 , and a laser, an LED, and the like may be used as light sources. The light sources  130  may include a filter  150 , which filters an excitation wavelength band at which multiple fluorescent materials distributed in a target body such as a human body are excited and filters a light-emitting wavelength band at which light is emitted from the excited multiple fluorescent materials. The filter  150  may be provided to filter an excitation wavelength band and a light-emitting wavelength band that are different from each other. 
     More specifically, the first light source  131  may include a first filter, and the second light source  132  may include a second filter. 
     In particular, after ICG is intravenously injected into a patient and 5-ALA is ingested by the patient, light in a range of 750 nm to 800 nm may be transmitted to a treatment area of the patient through the first light source of the medical fluorescent imaging device  100  of the present invention. Then, ICG combined with plasma protein in the target body may radiate fluorescent light having a peak value of 845 nm. 
     Also, when the second light source  132  transmits light of 400 nm to the treatment area including PpIX converted from 5-ALA through metabolism in cells, fluorescent light having a peak value of 635 nm may be radiated by PpIX distributed to a glioma. 
     In other words, the first wavelength range may be 750 nm to 800 nm, and the second wavelength range may be 350 nm to 450 nm. 
     In addition, the medical fluorescent imaging device  100  of the present invention may include a third light source  133  that may radiate white light. The controller  140  for controlling the third light source  133  may be a third switch  143 . 
     More specifically, the third light source  133  may be used in diagnosis of a patient by a doctor, and medical personnel may use the third light source  133  as a substitute for a medical pen light. 
     Here, a pen light is used by a doctor to diagnose a patient. As a light formed in a pen shape, a pen light enables a user to conveniently carry it around or turn it on in the dark to identify objects. 
     The medical fluorescent imaging device  100  of the present invention may include a battery for power supply that is installed so as to be replaceable in the probe  110 . In addition, a clip (not shown) for fixing the medical fluorescent imaging device  100  to a doctor&#39;s gown may be included. 
     The medical fluorescent imaging device  100  having such a configuration including the third light source  133  may be used in a doctor&#39;s office, a ward, etc. to emit light on dim areas of a patient&#39;s body such as the mouth, nose, ears, etc., that natural light, general lighting, etc. cannot reach and to examine an affected area or used to emit light to an eye and check a pupillary reflex. 
     Meanwhile, the probe  110  of the present invention may be formed of a flexible material. In this case, a user may change the position of a total cross section irradiated by the light sources  130  as necessary, and may easily emit light to a part to be examined and capture an image of the part, such that the convenience and accuracy of work are improved. The probe  110  may be formed of a metal or a synthetic resin such as polypropylene (PP), polyethylene (PE), nylon, or the like, and a bellow pipe may be formed as a particular aspect. 
     Here, any flexible material fulfilling such a purpose may be used for the probe  110 . 
     The present invention relates to a system for aligning multiple fluorescent images which makes it possible for an operator to accurately and easily check the positions and connections of a tumor and blood vessels by acquiring multiple fluorescent images in which the positions of the blood vessels and the boundary of a glioma are marked to luminesce due to multiple fluorescent materials, and by aligning and displaying the acquired multiple fluorescent images in real time. 
     More specifically, referring to  FIGS. 3 and 4 , the system for aligning multiple fluorescent images according to the present invention includes the pen-type medical fluorescent imaging device  100 , a fluorescent multi-image acquirer  200  that acquires an actual image of a target part, a fluorescent vascular image  310  in which blood vessels are marked by the first fluorescent material, and a fluorescent glioma image  410  in which a glioma is marked by the second fluorescent material, a blood vessel extractor  500  that extracts vascular shapes from the acquired fluorescent vascular image  310 , a glioma image processor  600  that processes the acquired fluorescent glioma image  410  so that the boundary of the glioma becomes distinct, a fluorescent multi-image aligner  700  that aligns an extracted vascular image  510  of the blood vessel extractor  500  and a processed glioma image  610  in real time, and a fluorescent image display  800  that displays a fluorescent multi-image in which the extracted vascular image  510  and the processed glioma image  610  are aligned. 
     Here, the fluorescent multi-image acquirer  200  includes a fluorescent vascular image acquirer  300  that acquires the fluorescent vascular image  310  in which the positions of blood vessels are marked by the first fluorescent material, and a fluorescent glioma image acquirer  400  that acquires the fluorescent glioma image  410  in which the position of a glioma is marked by the second fluorescent material. 
     Meanwhile, the medical fluorescent imaging device  100  additionally includes a transmitter capable of transmitting the actual image, the vascular image, and the glioma image captured by the image capturing section  120  from the medical fluorescent imaging device  100  to the fluorescent multi-image acquirer  200  through wireless communication. 
     The transmitter may transmit images captured by the image capturing section  120  as well as the fluorescent multi-image acquirer  200  to devices capable of monitoring the images such as a computer, a smart phone, and the like. Doctors may check images captured in real time as required by using their smart phones. In this case, images may be transmitted through wireless Internet, Bluetooth, or the like. 
     The fluorescent multi-image aligner  700  acquires transformation parameters corresponding to the highest similarity by measuring pixel value-based similarities of moving images with respect to a fixed image to perform 2D centered similarity registration, and matches moving images to the fixed image by using normalized cross-correlation (NCC). 
     A fixed image denotes the actual image, and moving images denote the acquired fluorescent vascular image  310  and the acquired fluorescent glioma image  410 . 
     Meanwhile, the present invention may display one or more of the actual image, the fluorescent vascular image  310 , and the fluorescent glioma image  410  captured by the image capturing section  120  and a fluorescent multi-image  810  according to a selection of an operator or a user. The display  800  may simultaneously display a plurality of images to overlap with each other by separately setting the opacity of the actual image, the fluorescent vascular mage  310 , the fluorescent glioma image  410 , and the fluorescent multi-image  810 , and may display only specific images as necessary by adjusting an opacity value of each image. 
     A method of aligning multiple fluorescent images by using the system for aligning multiple fluorescent images including the pen-type medical fluorescent imaging device  100  according to the present invention will be described in detail below with reference to accompanying drawings. 
     First, ICG is intravenously injected into a patient, and 5-ALA is ingested by the patient. After 5-ALA is ingested, the time for a sufficient amount of PpIX to accumulate in tumor tissue is preferably necessary before excited light is emitted to excite PpIX, Specifically, it may take four to eight hours. 
     Subsequently, when light in a range of 750 nm to 800 nm is transmitted to a treatment area of the patient through the first light source  131  of the medical fluorescent imaging device  100 , ICG combined with plasma protein in the target body may radiate fluorescent light having a peak value of 845 nm. The fluorescent vascular image acquirer  300  may acquire the fluorescent vascular image  310  in which blood vessels radiate fluorescent light of 845 nm due to ICG combined with plasma protein. 
     Also, when the second light source  132  transmits light of about 400 nm to the treatment area including PpIX converted from 5-ALA through metabolism in cells, it is possible to acquire the fluorescent glioma image  410  in which a glioma radiates fluorescent light having a peak value of 635 nm due to PpIX distributed to the glioma. 
     Then, vascular positions are marked with fluorescence due to ICG as shown in the fluorescent vascular image  310  of  FIG. 3 , and also the position of the glioma is marked with fluorescence due to PpIX converted from 5-ALA as shown in the fluorescent glioma image  410 . 
     Here, the blood vessel extractor  500  may extract vascular shapes from the fluorescent vascular image  310 , and the vascular shapes may be extracted from the ICG fluorescent vascular image  310  by using histogram equalization and Otsu thresholding, which is an automatic binarization technique using a histogram. 
     The glioma image processor  600  may process the fluorescent glioma image  410  so that the position and the boundary of the glioma become more distinct. 
     For reference, the extracted vascular image  510 , excluding the blood vessels marked with fluorescence, may be converted into a grey color and then used for image alignment based on feature points (edges, line parts, or the like). Also, the processed glioma image  610 , excluding the glioma, may be converted into a grey color and then used for image alignment. 
     The fluorescent multi-image aligner  700  may perform image matching on even a fluorescent image that shows morphology slightly different from the color values of the actual image, and may align and match, as a functional image, two or three such images to each other to show different characteristics based on wavelength range. Therefore, it is possible for the operator to see a fluorescent image in which the positions of a glioma and blood vessels are distinct. 
     The fluorescent multi-image aligner  700  performs 2D centered similarity registration to minimize coordinate errors between the actual image and an infrared (IR) image (the extracted vascular image  510  or the processed glioma image  610 ). As shown in  FIG. 3 , the fluorescent multi-image aligner  700  acquires transformation parameters corresponding to the highest similarity by measuring a pixel value-based similarity of a moving image (the vascular shape image or the fluorescent glioma image) with respect to a fixed image (the actual image) to perform 2D centered similarity registration, and matches the moving image to the fixed image by using NCC. 
     The fluorescent multi-image aligner  700  measures a pixel value-based similarity of the fluorescent vascular image  310  with respect to the actual image and continuously changes the fluorescent vascular image  310  until a preset condition is satisfied. When the preset condition is not satisfied within the maximum number of interpolations, transformation parameters corresponding to a highest similarity are acquired. 
     A total of six parameters may be acquired through similarity registration: a scale factor, a radian-based angle, x and y values of a center position (x, y) of a moving image after transformation, and translated x and y values (x′, y′). 
     The six transformation parameters acquired through similarity registration are used to transform a vascular image to coincide with the actual image using Equation 1. In other words, similarity conversion parameters for rotation, translation, and uniform scaling of an ICG image (the fluorescent vascular image  310 ) are calculated with respect to the actual image that is a color image, and the calculated parameters are applied to the ICG image for resampling. Then, an image matching section matches the ICG image to the actual image. 
     
       
         
           
             
               
                 
                   
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     In Equation 2, R(x, y) denotes a calculated similarity value, T denotes a target image, and I denotes an original image. 
     The fluorescent vascular image  310  and the fluorescent glioma image  410  are aligned by the fluorescent multi-image aligner  700  so that different sets of data are transformed into one coordinate system. 
     The fluorescent image display  800  displays, to the operator, an image in which both the positions of blood vessels and the boundary of the glioma aligned by the fluorescent multi-image aligner  700  are distinctly marked. The fluorescent image display  800  displays at least one of the actual image of the treatment area, the fluorescent vascular image  310  in which blood vessels are marked to fluoresce due to ICG, the fluorescent glioma image  410  in which the boundary of a glioma is marked to fluoresce based on 5-ALA, and a fluorescent multi-image in which the fluorescent vascular image  310  and the fluorescent glioma image  410  are aligned according to a selection of the operator or a user. 
     Also, the fluorescent image display  800  may set an opacity value of each image and simultaneously display a plurality of images overlapping with each other, or may adjust the opacity value of each image and display only a specific image as necessary. 
     Due to such operations, it is possible to align, as one image, the fluorescent vascular image  310  in which the positions of blood vessels are marked due to ICG and the fluorescent glioma image  410  in which the boundary of the glioma is marked based on 5-ALA, and it is possible to provide the operator with an image in which both the positions of blood vessels and the boundary of the glioma are distinctly marked. 
     Since the pen-type medical fluorescent imaging device of the present invention includes both a first light source and a second light source for showing the positions of both a glioma and blood vessels, it is possible to selectively know the positions of the blood vessels and the glioma. 
     Since the pen-type medical fluorescent imaging device of the present invention is miniaturized in the form of a probe, it can be easily held by an operator and carried around. Also, it is possible to reduce loss of light and image quality by installing light sources and an image capturing section at a front end. 
     The system for aligning multiple fluorescent images of the present invention makes it possible for an operator to accurately and easily check the positions and connections of a tumor and blood vessels by acquiring multiple fluorescent images in which the positions of the blood vessels and the boundary of a glioma are marked to luminesce due to multiple fluorescent materials having different properties in a target part, and by aligning and displaying the acquired multiple fluorescent images in real time. 
     It will be apparent to those skilled in the art that various modifications can be made to the above-described exemplary embodiments of the present invention without departing from the spirit or scope of the invention. Thus, it is intended that the present invention covers all such modifications provided they fall within the scope of the appended claims and their equivalents. 
     DESCRIPTION OF REFERENCE NUMERALS 
     
         
         
           
               100 : FLUORESCENT IMAGING DEVICE 
               120 : IMAGE CAPTURING SECTION 
               130 : LIGHT SOURCES 
               131 : FIRST LIGHT SOURCE 
               132 : SECOND LIGHT SOURCE 
               133 : THIRD LIGHT SOURCE 
               140 : CONTROLLER 
               150 : FILTER 
               300 : FLUORESCENT VASCULAR IMAGE ACQUIRER 
               400 : FLUORESCENT GLIOMA IMAGE ACQUIRER 
               500 : BLOOD VESSEL EXTRACTOR 
               600 : GLIOMA IMAGE PROCESSOR 
               700 : FLUORESCENT MULTI-IMAGE ALIGNER 
               800 : FLUORESCENT IMAGE DISPLAY