Surgery – Diagnostic testing – Detecting nuclear – electromagnetic – or ultrasonic radiation
Reexamination Certificate
1998-09-18
2001-04-03
Kamm, William E. (Department: 3737)
Surgery
Diagnostic testing
Detecting nuclear, electromagnetic, or ultrasonic radiation
Reexamination Certificate
active
06212425
ABSTRACT:
DESCRIPTION
1. Technical Field
The present invention relates to a device for “in vivo diagnosis” by means of an intrinsic or foreign photosensibilisator light-induced reaction in biological tissue.
2. State of the Art
The method of diagnosis performed with a device of this type is also referred to in medicine as photodynamic diagnosis (PDD) or as fluorescence diagnosis. Moreover, using photosensibilisators for photodynamic therapy (PDT) is also known. With regard to this see WO 93/20810 to which, moreover, reference is explicitly made for the explanation of all terms and process steps not explained more closely herein.
Furthermore, it has been proposed to perform endoscopic photodynamic diagnosis and therapy using a device which utilizes a Krypton ion laser with a wavelength of approximately 410 nm and power of more than 200 mWatt as the light source. The light of this laser is guided via a quartz light conductor having a small numerical aperture through an endoscope to the to-be-irradiated sites of the human body.
In order to trigger a light-induced reaction in biological systems, the patient is given a photosensibilisator, which either has a hematoporphyrin basic structure such as the substance photofrin and photosan-3, or delta amino levulinic acid (ALA), recently in use in urology and dermatology, in a concentration of few mg/kg body weight. The hematoporphyrin derivatives are dispensed intravenously, whereas delta amino levulinic acid can be applied locally, i.e. it is injected as a solution, by way of illustration, into the urinary bladder. These substances accumulate in tumor tissues in double to ten-fold concentrations. This selective accumulation in tumor tissue represents a decisive basis for photodynamic diagnosis and photodynamic therapy.
For diagnosis, the to-be-examined tissue is irradiated endoscopically with violet light, in known devices practically solely laser light, approximately 2-12 hours following dispensing the photosensibilisator (ALA). The porphyrin derivatives, high concentrations of which are present in the tumor tissue, are excited by this light and subsequently have a typical red fluorescence, by means of which the tumor can be localized.
In addition to fluorescence, due to the accumulation of the photosensibilisator in the tissue, so-called autofluorescence of the tissue may be triggered due to so-called fluorophorene, i.e. intrinsic fluorescence substances.
In photodynamic therapy, irradiation is conducted with red light, because this light with a wavelength of more than 630 nm penetrates the tissue to a depth of about 5 mm contrary to light with shorter wavelengths, which penetrates strikingly less deep. Despite the use of this optimum wavelength, the indication for use of photodynamic therapy is presently limited to flat, surface carcinoma.
It can be assumed the biological course of the light-induced reaction is as follows:
The photosensiblisator stored in the tissue is excited by the absorption of a light quantum with a defined energy content emitted by the respective light source. If violet light is irradiated within the scope of the photodynamic diagnosis, fluorescence radiation is emitted upon returning to the initial state.
If photodynamic therapy occurs in conjunction with radiation using red laser light of higher power density, there is a transition from the excited state to a metastabilized intermediate state, from which the energy which is released by the return to the initial state is transmitted to the molecular oxygen, which absorbs this energy forming excited singulet oxygen. This aggressive singulet oxygen destroys the cell structures in the concerned tissue by means of photooxidation. This cellular damage in conjunction with the simultaneous collapse of the tumor vessel system leads to complete destruction of the tumor (phototoxic effect).
However, this procedure has certain problems depending on the photosensibilators employed. If photofrin and photosan-3 are used as photosensibilisators for photodynamic diagnosis, technologically very complicated devices have to be employed for fluorescence detection, because due to the interfering intrinsic-fluorescence, the fluorescence of the tumor tissue can only be suitably detected with the aid of very complicated, computer-supported image processing technology and highly sensitive cameras with low-light amplifiers.
If delta amino levulinic acid is utilized, the induced fluorescence is strong enough that it can be visibly recognized. However, the fluorescence obtained with the delta amino levulinic acid does not yield an optimum quality endoscopic image for recording for the diagnosis. The use of a quartz light conductor with a small numerical aperture, such as is employed for light transmission of a laser beam, permits only very poor illumination of the image.
Employing an additional light conductor, which could improve illumination, reduces the lumen available for the other channels in the endoscope to such an extent that it drastically decreases the possibility of utilizing other endoscopic instruments.
Above all, when using known devices, the additional light introduced into the endoscope may superimpose the, even with delta amino levulinic acid, relatively weak fluorescence image.
Moreover, the aforedescribed processes for the diagnosis and therapy require different light sources, and in particular laser sources, which, on the one hand, increases costs and, on the other hand, makes handling the endoscopic system more difficult.
Similar problems arise when conducting photodynamic diagnosis using a microscope and, in particular using a surgical microscopic.
SUMMARY OF THE INVENTION
The object of the present invention is to improve a device for diagnosis by means of an intrinsic or foreign photosensibilisator light-induced reaction or a reaction caused by intrinsic fluorescence in biological tissue in such a manner that the induced fluorescence can be detected with a strong contrast while at the same time there being sufficient illumination, preferably not using lasers, for observing the tissue area.
The solutions of the object of the present invention are based on the following fundamental concept:
The net transmittance in the light delivering part and in the image-generating part of the invented device are selected in such a manner that, on the one hand, practically no light with a wavelength of &lgr; from the range used for excitation, which by nature has relatively high intensity, “reaches” via the image-generating part of the device into the proximal image plane, whereas light with a wavelength of &lgr; from the range in which fluorescence occurs can only reach the proximal image plane if it comes from the illuminated area of tissue and not from the illumination system. On the other hand, the net transmittance of the light delivering part and of the image-generating part of the device ensures that the illuminated area of tissue is so strongly illuminated with light of a wavelength which lies neither in the range of the excitation spectrum nor in the range of the fluorescence spectrum, that the examining individual can perceive, due to this wavelength range of the directly reflected light, details of the illuminated area of tissue independent of the fluorescence radiation.
In other words, an element of the present invention is that the image of the tissue area illuminated with excited light is simultaneously generated by means of fluorescence light and reflected illumination light, with the two portions contributing to image generation are of such a nature with regard to wavelength and with regard to their intensity that they do not “interfere” with each other.
The invented device for diagnosis by means of a light-induced reaction in biological tissue by means of an intrinsic or foreign photosensibilisator respectively by means of intrinsic fluorescence is provided with an illumination system having at least one light source, a light delivering unit which directs the light of the illumination system at the to-be-diagnosed area of tissue and an imaging unit which images the light c
Baumgartner Reinhold
Ehrhardt Andre
Irion Klaus
Stepp Herbert
Strobl Karlheinz
Kamm William E.
Karl Storz GmbH & Co. KG
St. Onge Steward Johnston & Reens LLC
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