Fluorescence detecting apparatus

Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation

Reexamination Certificate

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C250S458100

Reexamination Certificate

active

06571119

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a fluorescence detecting apparatus suitable for use in a fluorescence diagnosing system; wherein a diagnosis of a tumor is carried out by irradiating excitation light to a region of interest in a living body, to which a photosensitive substance, that has a strong affinity for the tumor and is capable of producing fluorescence when it is excited with the excitation light, has been administered, and by detecting the intensity of fluorescence, which is produced by the photosensitive substance and an intrinsic dye in the living body when the region of interest in the living body is exposed to the excitation light; or wherein a diagnosis of a tumor is carried out by irradiating excitation light to a region of interest in a living body, to which no photosensitive substance has been administered, and by detecting the intensity of intrinsic fluorescence, which is produced by an intrinsic dye in the living body when the region of interest in the living body is exposed to the excitation light.
2. Description of the Related Art
Extensive research has heretofore been conducted on the so-called photodynamic diagnosis (PDD) technique. With the PDD technique, a photosensitive substance (such as ATX-S10, 5-ALA, NPe6, HAT-DO1 or Photofrin-2), which has an affinity for a tumor and is capable of producing fluorescence when it is excited with light, is employed as a fluorescent diagnosis drug. The photosensitive substance is administered to a living body and is absorbed by a tumor part, such as a cancer, of the living body. Excitation light, which has wavelengths falling within the excitation wavelength range for the photosensitive substance, is then irradiated to the region containing the tumor part, and fluorescence is thereby produced from the fluorescent diagnosis drug having been accumulated at the tumor part. By the detection of the fluorescence, the location and infiltration range of the diseased part is displayed as an image, and the displayed image is used in conducting a diagnosis of the tumor part.
Fluorescence diagnosing systems for carrying out the PDD technique have been disclosed in, for example, U.S. Pat. No. 4,556,057, and Japanese Unexamined Patent Publication Nos. 1(1989)-136630 and 7(1995)-59783. Basically, each of the disclosed fluorescence diagnosing systems comprises: an excitation light irradiating means for irradiating excitation light, which has wavelengths falling within the excitation wavelength range for a photosensitive substance, to a living body; an imaging means for detecting the fluorescence produced by the photosensitive substance and forming a fluorescence image of the living body, and an image displaying means for receiving the output from the imaging means and displaying the fluorescence image. In many cases, the fluorescence diagnosing systems take on the forms built in endoscopes to be inserted into the body cavities, operating microscopes, or the like.
Techniques for making a diagnosis of a tumor part without a photosensitive substance being administered to the living body have also been proposed. With the proposed techniques, excitation light, which has wavelengths falling within the excitation wavelength range for an intrinsic dye in the living body, is irradiated to a region of interest in the living body (i.e., the region which is to be used in making a diagnosis). The intrinsic dye in the living body is thus excited by the excitation light and produces fluorescence. By the detection of the fluorescence, the location and infiltration range of the diseased part is displayed as an image, and the displayed image is used in conducting a diagnosis of the tumor part.
Further, a different fluorescence diagnosing system has been proposed in, for example, Japanese Patent Application No. 7(1995)-252295. With the proposed fluorescence diagnosing system, instead of obtaining the two-dimensional image as described above, the intensity of fluorescence produced from each specific point in a region of a living body is detected. A judgment is then made as to whether each point in the region of the living body belongs or does not belong to a tumor part.
However, the above fluorescence diagnosing systems have the problems described below. Specifically, since a region in a living body has protrusions and recesses, the distance between the light source of the excitation light irradiating means and the region of interest in the living body is not uniform. Therefore, the irradiance of the excitation light at each part of the living body, which is exposed to the excitation light, is usually non-uniform. In general, the intensity of fluorescence is approximately in proportion to the irradiance of the excitation light, and the irradiance of the excitation light at a part of the living body exposed to the excitation light is in inverse proportion to the square of the distance between the light source of the excitation light irradiating means and that part of the living body exposed to the excitation light. Accordingly, the problems occur in that a normal part, which is located close to the light source, may produce the fluorescence having a higher intensity than the intensity of the fluorescence produced by a diseased part, which is located remote from the light source. The problems also occur in that the intensity of the fluorescence from a diseased part, which is located at a position inclined with respect to the incident direction of the excitation light, may become markedly low. Thus, if the irradiance of the excitation light is non-uniform, the intensity of the fluorescence will vary in accordance with the level of the irradiance of the excitation light, and therefore an error will often be made in diagnosis of a tumor part.
Therefore, fluorescence diagnosing systems, which are designed such that a change in the intensity of fluorescence due to the non-uniformity of the distance with respect to the region of interest in the living body may be compensated for, have been proposed in, for example, U.S. Pat. No. 4,768,513 and Japanese Patent Publication No.3 (1991)-58729. With the fluorescence diagnosing system proposed in Japanese Patent Publication No. 3(1991)-58729, excitation light is irradiated to a region of a living body, to which a photosensitive substance having a strong affinity for a diseased part has been administered, and the fluorescence produced by the photosensitive substance is detected. Also, the excitation light reflected from that region of the living body is detected. An image operation is then carried out including a division operation between the fluorescence component and the reflected excitation light component by each other. By the division operation, the term due to the distance with respect to the region of interest in the living body is cancelled. However, in the results of the division operation between the fluorescence component and the reflected excitation light component by each other, the term concerning the reflectivity of the portion exposed to the excitation light remains uncancelled. Consequently, the problems remain uneliminated in that a fluorescence image accurately reflecting the distribution of the fluorescent diagnosis drug cannot be obtained.
A different fluorescence imaging technique is proposed in, for example, “Fluorescence Imaging of Early Lung Cancer,” Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vol. 12, No. 3, 1990. With the proposed technique, intrinsic fluorescence, which is produced by an intrinsic dye in an region of interest in a living body when the region of interest is exposed to excitation light, is separated into a fluorescence component corresponding to a green wavelength range (hereinbelow referred to as the “green wavelength component G”) and a fluorescence component corresponding to a red wavelength range (hereinbelow referred to as the “red wavelength component R”). An image operation is then carried out including a division operation between the red wavelength component R and the green wa

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