Patent Description:
Excitation and emission characteristics of IR700 are shown in <FIG>. As the graph shows, peak wavelengths of excitation sensitivity (maximum excitation sensitivity at λp,ex = <NUM>) and of emission of fluorescence light (λp,em = <NUM>) are very close to each other.

When it is intended to image a scene by fluorescence light from IR700 which is excited by excitation light, the excitation light should have a wavelength close to the emitted fluorescence light. However, such excitation light disturbs the imaging by the fluorescence light. A separation of these two lights such that the imaging system gets enough fluorescence signal without a lot of excitation light is difficult.

On the other hand, for therapeutic usage, a high specific energy accumulation such as <NUM> J/cm<NUM> at the peak excitation wavelength of IR700 (<NUM>) and a few nm around the peak excitation wavelength is required. Otherwise, it may take a long time to make therapeutic reaction.

The requirements for imaging and for therapeutic usage are in conflict with each other if imaging and therapy are to be performed by a single endoscope.

CIE <NUM> links between distributions of wavelengths in the electromagnetic visible spectrum and physiologically perceived colors in human color vision. <FIG> shows a gamut according to CIE1931 (x-y-plane, taken from people. The area in the middle (without color notations) denotes whitish light. The numbers at the border of the gamut indicate the wavelength (in nm) of the respective spectral clean light. White light has the coordinates x=<NUM>/<NUM>; y=<NUM>/<NUM>; and z=<NUM>/<NUM>.

<CIT> and its US family member <CIT> disclose a tumor treatment method for treating a tumor in a subject. The method comprises step I for administering to the subject a therapeutically effective amount of one or more antibody-molecules capable of specifically binding to a cell surface protein in the tumor; step II for inserting an optical probe into the subject; step III for emitting light having a wavelength of <NUM>-<NUM> from the optical probe to give at least <NUM> J/cm<NUM> energy to at least a part of the tumor; step IV for waiting for a period of time for eliciting an immune reaction in the tumor; step V for inserting an energy device into the subject; and step VI for extirpating the subject's tissue including the tumor using the energy device.

It is an object of the present invention to improve the prior art.

The present invention provides an improved illumination system allowing both imaging based on fluorescence from IR700 and therapeutic usage of IR700, e.g. for cancer therapy.

It is provided an illumination apparatus for outputting an output light, comprising a first light source configured to emit first light with a first peak wavelength in a first range of <NUM> to <NUM>; a second light source configured to emit second light with a second peak wavelength in a second range of <NUM> to <NUM>; wherein the second peak wavelength is larger than the first peak wavelength by at least <NUM>; the second light source is configured to be switched on and off independently from the first light source; the apparatus is configured to output the first light as the output light if the second light source is switched off and to output the first light and the second light as the output light if the second light source is switched on.

Further details, features, objects, and advantages are apparent from the following detailed description of the preferred embodiments of the present invention which is to be taken in conjunction with the appended drawings, wherein:.

Herein below, certain embodiments of the present invention are described in detail with reference to the accompanying drawings, wherein the features of the embodiments can be freely combined with each other unless otherwise described. However, it is to be expressly understood that the description of certain embodiments is given by way of example only, and that it is by no way intended to be understood as limiting the invention to the disclosed details.

According to a first embodiment, the illumination apparatus has at least two light sources:.

For fluorescent imaging of a scene, only light source <NUM> is typically used. Thus, the light at wavelengths of <NUM> and larger wavelengths coming from the scene mainly results from fluorescence by IR700.

In therapeutic usage, both "Light source <NUM>" & "Light source <NUM>" are typically turned on to boost therapeutic reaction of PIT. Thus, the procedure time is reduced compared to illumination with one of the light sources only to reduce the burden for patients and medical professionals.

The light sources <NUM> and <NUM> typically may be laser diodes or LEDs. Examples of light source <NUM> are laser diode L690-<NUM>-<NUM> (from USHIO OPTO SEMICONDUCTORS, INC); and MRL-III-<NUM> (see
http://www. com/red_laser690. An example of light source <NUM> is laser diode MLL-FN-<NUM> (see
http://www. com/Red-Laser-<NUM>.

In addition, the apparatus may comprise a light source <NUM> for another imaging mode, such as white light imaging. For white light imaging, the third light source <NUM> emits light such that the light is closer to the white point (x=y=z=<NUM>/<NUM>) of CIE <NUM> than the light from the first light source. The term "closer to the white point" means a shorter Euclidian distance in the x-y-plane of the gamut of CIE1931 from the white point x=y=<NUM>/<NUM> (the z-direction is ignored). The Euclidian distance of an illumination light with coordinates xi, yi in the x-y-plane from the white point is (xi-<NUM>/<NUM>)<NUM>+(yi-<NUM>/<NUM>)<NUM>.

White light imaging is just one example of another imaging mode. If appropriate, instead of (or in addition to) white light imaging, imaging with colored light or with UV light or with (far) infrared light (in general: spectrum imaging) may be performed.

The lights from the two or three light sources are combined by a combiner. For two light sources, a dichroic mirror may be used. For three light sources, two dichroic mirrors may be used. The two dichroic mirrors may be functionally combined in a crosscube comprising two dichroic interfaces.

<FIG> shows an embodiment of such an illumination apparatus. <FIG> shows the reflectivity of the dichroic interfaces of the crosscube used in the illumination apparatus of <FIG>. As can be seen from <FIG>, the light from the light source <NUM> and the light from the light source <NUM> are reflected at respective dichroic interfaces of the crosscube. The light from light source <NUM> passes through both dichroic interfaces. Accordingly, in this example, one of the dichroic interfaces reflects light around the peak wavelength λp1 of the first light source, and the other of the dichroic interfaces reflects white light, e.g. in a range of <NUM> to <NUM>, as shown in <FIG>. The reflection bands are typically separated from each other. The dichroic interfaces pass light of other wavelengths such as of the peak wavelength λp2 of the second light source and of wavelengths around λp2.

The combined light may be condensed by a condenser (such as a convex lens) on an optical connector which inputs the light into an optical fiber to illuminate a scene. For example, the emission end of the optical fiber may be arranged in a distal rigid tip portion of an endoscope to illuminate a scene which is imaged by an imaging device (objective lens) arranged in the rigid tip portion of the endoscope.

If the illumination apparatus is arranged close to the scene to be illuminated, e.g. if the illumination apparatus is arranged in the rigid tip portion of an endoscope, the condenser, optical connector, and optical fiber may be omitted. <FIG> provide respective examples. In this case. light source <NUM> and light source <NUM> are typically LEDs, e.g. based on AlGaInP material. Some embodiments comprise two different types of LEDs. In some embodiments, LED1 may be of the same type as LED2, but covered with a filter correspondingly to the filter described further below with respect to <FIG>.

As shown in <FIG>, the illumination apparatus provided in the rigid tip portion at the distal end of an endoscope comprises only LED1 and LED2 arranged on one or two circuit boards. In addition, the illumination apparatus may comprise further LEDs such as a blue LED and a violet LED, as shown in <FIG>. Still furthermore, the LEDs may be covered by a phosphor layer and/or a transparent cap, as shown in <FIG>. Preferably, the phosphor layer has an excitation spectrum such that fluorescence or luminescence is not excited by the light from LED1 or LED2. , for the light from LED1 and LED2, the phosphor layer is substantially transparent.

In some embodiments, the lights of even more light sources with different peak wavelengths may be combined through an appropriate number of dichroic reflective interfaces (n light sources → n-<NUM> dichroic reflective interfaces). Up to four dichroic interfaces may be arranged jointly in a respective crosscube (two dichroic interfaces to reflect lights from first and second light sources arranged in a first plane comprising the propagation direction of the output light, and two dichroic interfaces to reflect lights from third and fourth light sources arranged in a second plane comprising the propagation direction of the output light, wherein the first plane intersects the second plane; typically, the second plane is perpendicular to the first plane).

An example of such an illumination apparatus is shown in <FIG>. In <FIG>, each of the three crosscubes (in general: crossprisms) has two dichroic interfaces. The lights of three near infrared (NIR) light sources NIR1, NIR2, and NIR3 are combined by the first crosscube, and the second and third crosscubes combine RGB lights (red, green, blue) and UV light (ultraviolet) with the light output by the first crosscube. Through the RGB lights, white light imaging may be achieved. The UV light, potentially together with the green light, may be used for enhanced vascular imaging. In the example of <FIG>, the lights from the light sources are collimated by respective lenses before they enter the respective crosscube. The arrangement of the light sources may be changed if the dichroic reflective interfaces have appropriate reflection characteristics. For example, some or all of the RGB light sources may exchange their positions with the positions of the NIR light sources.

In general, each of the light sources of the illumination apparatus may be separately controllable. That is, each of them may be switched on and off independently from the other light sources. In addition, in some embodiments, the light intensity or the emitted color of at least one of the light sources may be controlled independently from the other light sources. Some embodiments include a controller to perform the controlling.

For example, if only the first light source is switched on, the illumination apparatus may illuminates a scene to be imaged on an imaging surface. For the imaging, an imaging device may be used. The imaging device typically comprises an objective lens for imaging the scene on the imaging surface.

However, the imaging device is not limited to a lens optic but it may comprise e.g. reflective components (catoptric system).

Furthermore, in some embodiments, the imaging device comprises a filter (excitation light cut filter) which may be a band filter. Namely, in the wavelength range between <NUM> and <NUM>, this filter passes fluorescence light from IR700 (i.e. a wavelength band in a range above <NUM> and below <NUM>) and blocks the excitation light in the range below <NUM>. Thus, the excitation light does not disturb (or hardly disturbs) the image of the fluorescence light. In general, the filter may block light below a preset wavelength which is in the range of <NUM> to <NUM> and passes light above the preset wavelength.

In addition, as shown in <FIG>, the filter may pass white light (wavelength below <NUM>) from the third light source such that the same imaging device may be used for fluorescence imaging through illumination by the first light source and white light imaging through illumination by the third light source.

The image on the imaging surface may be captured by an image sensor, such as a CMOS array or a CCD array. In some embodiments, the image on the imaging surface may be observed directly or via a relay optic.

In some embodiments, the beam may be divided by a further dichroic mirror. The further dichroic mirror may reflect the fluorescence light such that the fluorescence image may be observed by a first image sensor while other light is blocked from the first image sensor. The further dichroic mirror may pass other light such as white light (or one of the RGB lights) or UV light from one or more of the other light sources. Thus, the image due to the illumination with the other light may be observed by a second image sensor. The observations may be performed simultaneously on the first and second image sensors. In some embodiments, the further dichroic mirror may pass the fluorescence light and reflect the other light instead of the above described configuration.

In addition, the sensor configuration may comprise an excitation light cut filter (such as the one described hereinabove) to filter the excitation light, in particular if the further dichroic mirror does not include a corresponding filter function. Such a sensor configuration is shown in <FIG>. The objective lens and other optical components are omitted from <FIG> for the sake of clarity. In this case, the excitation light cut filter passes light having a wavelength of at least <NUM> below the preset wavelength. Preferably, the difference is even larger (e.g. <NUM> or even <NUM>) such that hardly any excitation light passes the excitation light cut filter, while white light (or any of RGB light) or UV light passes the excitation light cut filter.

Hereinafter, differences between the second embodiment and the first embodiment are described. If not otherwise stated or made clear from the context, the description of the first embodiment applies to the second embodiment, too.

In the second embodiment, as shown in <FIG>, the illumination apparatus comprises only one NIR light source (first light source) having a peak wavelength λp1 in the range <NUM> ≤ λp1 <<NUM> and an emission spectrum which extends beyond <NUM> with at least <NUM>% of the intensity at the peak wavelength.

In addition, an optical filter (e.g. a bandpass filter) is located on the light path between the light source and the output of the illumination apparatus (e.g. between the light source and the light connector). The bandpass filter is movable such that it may be in the light path or outside the light path. The bandpass filter passes the excitation light and blocks substantially light in the wavelength range of the fluorescence light emitted by IR700. For example, the bandpass filter may pass light of a wavelength less than a predefined wavelength and block light of a wavelength larger than the predefined wavelength, wherein the predefined wavelength is in a range between <NUM> and <NUM>.

In order to be effective as a filter, the light intensity of the first light source at the predefined wavelength is at least <NUM>% of the light intensity at the peak wavelength of the light from the first light source. Preferably, it is at least <NUM>%, or even at least <NUM>%.

The filter may be moved into and out of the light path by a moving device. The moving device may be e.g. a motor. The motor may be controlled by a controller. The moving device may be e.g. a handle or some other mechanism such that the filter may be moved manually. The movement may be e.g. a linear movement or a rotational movement. If the filter is moved out of the light path, the light output from the illumination apparatus comprises the light from the light source without having passed through any filter filtering out more than <NUM>% of the light intensity of any wavelength in the relevant wavelength range between <NUM> and <NUM>.

If the filter is in the light path, the one light source may be used for imaging because the light from the light source corresponding to the fluorescence light is substantially blocked. If the bandpass filter is not in the light path, the light source may be used for therapy with a high radiation power.

As shown in <FIG>, the illumination apparatus of the second embodiment may additionally (optionally) comprise a second light source (e.g. a white light source). The second light source corresponds to the third light source of the first embodiment and may be used e.g. for white light imaging. The lights from the first light source (having filtered by the movable filter, if it is inserted in the light path) and from the second light source may be combined by a dichroic reflective surface (e.g. dichroic mirror). <FIG> shows an example of the reflectivity of the dichroic reflective surface when the light from the first light source around the peak wavelength λp (shown schematically in <FIG>, too) should be reflected and the white light from the white light source should pass through the reflective dichroic surface. The reflection band in this case comprises also (at least a part of) the spectrum from the first light source which may be cut off by the movable filter.

<FIG> shows an example of a transmission spectrum of the movable filter. The filter transmits only light of the lower wavelength range from the first light source. In the example of <FIG>, it transmits substantially only light below the peak wavelength of the light from the first light source. However, this is not mandatory. The transmission band may be set such that sufficient light for exciting the fluorescence of IR700 passes and a sufficiently large portion of light of larger wavelength (corresponding to the fluorescence light) is blocked.

<FIG> shows an example of the light emitted by the first light source of the second embodiment (black squares) over the excitation spectrum and emission spectrum of IR700 shown in <FIG>. In this case, the spectrum of the light from the first light source corresponds substantially to the peak of the excitation spectrum of IR700. Thus, the light from the first light source efficiently excites fluorescence of IR700. A large energy dose may be deposited in the tissue.

In contrast, <FIG> shows the spectrum of the light from the first light source filtered by the movable filter (black squares) over the excitation spectrum and emission spectrum of IR700 shown in <FIG>. In this example, the part of the emitted light at larger wavelengths (above about <NUM>) is cut off. Thus, this light still excites fluorescence of IR700 but hardly interferes with the fluorescence light generated by IR700.

The imaging device of the second embodiment may be the same as that of the first embodiment. Also, the illumination apparatus of the second embodiment may comprise further light sources emitting different wavelengths than the first light source, such as one or more RGB light sources, a UV light source, or a (far) IR light source, similar to the illumination apparatus shown in <FIG>.

The illumination apparatus according to some embodiments of the invention may be arranged in an external box (light source box or processor system). The light from the external box may be guided from the proximal end of the endoscope to the distal tip of the endoscope through one or more optical fibers in order to illuminate an object space of an imaging device (e.g. objective lens) arranged at the distal tip of the endoscope. However, the illumination system may be arranged in a control body, an endoscope connector, or even in the distal tip of an endoscope instead.

In some embodiments, the optical fiber and optics (e.g. optical connector) to direct the light from the illumination apparatus into the optical fiber may be considered as belonging to the output portion of the illumination apparatus. In these embodiments, their influence on the light output from the crosscube may be taken into account when designing the light sources and the combiner(s) such as the dichroic reflective interface(s).

Some embodiments of the invention comprise a combination of a mother scope and a baby scope. Such a combination may be used to approach thin and peripheral area or organ like bronchus. In this case, mother scope behaves as a conventional endoscope. Baby scope is guided by mother scope through the working channel of the mother scope. , the baby scope is much thinner than the mother scope.

The light output from the external box (light source box) may be divided in appropriate proportions to mother scope and baby scope by a beam splitter such that both mother scope and baby scope illuminate the respective scene by a same light. The beam splitter may be a part of the optical connector from the light source box.

The endoscope comprising the illumination apparatus may be a capsule endoscope without a shaft (e.g. rigid or flexible tube) or an endoscope comprising a rigid tip portion at the distal end and a shaft (e.g. rigid or flexible tube). The rigid tip portion may be connected to the shaft directly or indirectly via an angulation segment. The endoscope may be suitable for being inserted into a lumen of a human body.

Claim 1:
Illumination apparatus for outputting an output light, comprising
a first light source configured to emit first light with a first peak wavelength in a first range of <NUM> to <NUM>;
wherein the illumination apparatus is characterized by further comprising
a second light source configured to emit second light with a second peak wavelength in a second range of <NUM> to <NUM>; wherein
the second peak wavelength is larger than the first peak wavelength by at least <NUM>;
the second light source is configured to be switched on and off independently from the first light source;
the apparatus is configured to output the first light as the output light if the second light source is switched off and to output the first light and the second light as the output light if the second light source is switched on.