WO2015121147A1

WO2015121147A1 - Photonic device with smooth tip and improved light output

Info

Publication number: WO2015121147A1
Application number: PCT/EP2015/052419
Authority: WO
Inventors: Christian Reich; Gerhardus Wilhelmus Lucassen; Klaas Cornelis Jan Wijbrans; Torre Michelle BYDLON; Waltherus Cornelis Jozef Bierhoff; Bernardus Hendrikus Wilhelmus Hendriks; Stephan Voss; Axel Winkel; Marjolein Van Der Voort
Original assignee: Koninklijke Philips N.V.
Priority date: 2014-02-14
Filing date: 2015-02-05
Publication date: 2015-08-20

Abstract

In general, a biopsy device according to the invention comprises a shaft and an optical fiber accommodated within the shaft, wherein the distal surface of the shaft is slanted, i.e. forms a bevel surface, and wherein the distal end of the optical fiber is arranged inside the channel and adjacent to the bevel surface of the shaft. In particular, a plug is provided in front of the front surface of the optical fiber.

Description

Photonic device with smooth tip and improved light output

FIELD OF THE INVENTION

The invention generally relates to a device and a system including the same. Particularly, the invention relates to an interventional device with optical fibers. BACKGROUND OF THE INVENTION

In order to position a needle under image guidance more accurately in a suspicious tissue, tissue sensing at the tip of the device may be required. Current needles often do not have such tissue feedback possibilities. Recently, elongated interventional devices have been reported with optical fibers integrated into the device which provide feedback from the tissue at the tip of the device. Such devices allow for fine-guidance towards small volumes of suspicious tissue, in particular for tissue which does not show sufficient contrast in imaging. In order to allow tissue discrimination, these devices employ diffuse reflectance spectroscopy (DRS).

A photonic needle, i.e. a needle device including at least one optical fiber for emitting and receiving light, may determine tissue type by sending light with a broadband spectrum into the body, measuring the reflected spectrum and determining the type of tissue by the application of an algorithm on this spectrum. In the original concept of the photonic needle, a needle with straight cut fibers was used. Though the shape of the light beam is advantageous, it has the severe disadvantage of having pockets in which tissue stays behind thus polluting the measurement.

Slanted fiber ends along the sharp bevel angle of the cannula would ensure smooth, unobstructed puncturing of the needle, however, coupling the light output with straight cut fibers is found to be more efficient compared to the light coupling with slanted fiber ends. The use of a beveled fiber changes the direction of the light out of the needle reducing the light output significantly due to internal reflection, with even no output (total internal reflection).

WO 2013/035076 describes a needle device with an optical fiber integrated in an insert being movably arranged in a hollow shaft. The insert is movable between a first condition with a distal end portion of the optical fiber being located inside the hollow shaft, and a second condition with the distal end portion of the optical fiber being located outside the hollow shaft so as to be in close contact to tissue in front of the hollow shaft.

US 5,280,788 describes systems including a needle employed in the use of spectroscopy in the diagnosis of tissue. The needle comprises an optically transparent tip and an optical fiber bundle, with a proximal surface of the tip being optically coupled to the distal surface of the fiber bundle.

WO 2013/001394 describes a needle including a hollow shaft and a multilumen insert, wherein a front surface of the shaft is inclined with a different angle relative to central axis than the front surface of the insert.

SUMMARY OF THE INVENTION

The general problem is how to integrate optical fibers into the elongated tube of the interventional device in a way which optimizes the coupling of light into tissue for illumination and detection. Furthermore, the solution should be cost effective since comparable commercial needles without tissue sensing are low cost disposable devices.

More specific, the problem may be that the slanted edge of the fiber acts as a prism. This means that the light is deflected downwards, according to the refractive index of the different materials. Because the light output of the fiber is a cone at a certain moment part of the light will be reflected internally, and if the angle gets sharp enough all light will be reflected internally. In the case of the photonic needle when inserted to the body, the refractive index in the body is approximately 1.33 (refractive index of water). The refractive index of the core of a silica/silica fiber is approximately 1.52. At a bevel angle of 15°, it then follows that all light is reflected internally. Into air, the situation is even worse because the refractory index of air is approximately 1. So, also with a bevel angle of 30° in air almost no light exists from the needle, thus making calibration of the needle before the procedure difficult.

To solve the problem, embodiments in accordance with the invention propose designs to ensure a smooth needle insertion where the optical fiber ends are adapted to the needle tip design, with the requirement that the light loss is minimized to an acceptable level. The following advantages are achieved by the inventive concepts of a biopsy device with optical sensing:

(i) Sticking of tissue to the needle is prevented.

(ii) Sufficient light output and collection is ensured.

(iii) It is ensured that the needle is sharp enough for easy insertion into tissue. The proposed embodiments focus on optimizing the light coupling into tissue. Accordingly, the light output from the slanted fiber ends is enhanced by utilizing a plug in front of the tip of the optical fiber, with the plug having a refractive index similar to that of water. Thereby, the probability for light being reflected downwards at the slanted interface due to a mismatch in refractive index is reduced by the presence of an interface as defined in accordance with the invention.

In general, an interventional device according to the invention comprises a shaft, an optical fiber accommodated within the shaft, wherein the distal surface of the shaft is slanted, i.e. forms a bevel surface, and wherein the optical fiber is made of a first material having a first refractive index. In particular, a plug is provided in front of the optical fiber, wherein the plug is made of a second material having a second refractive index. The plug serves as a kind of a lense which reduces the internal reflection and thus improves the emitting of light out of the distal surface of the device.

In the following, geometrical aspects will be defined for a better understanding. First of all, the device includes a longitudinal main axis, usually the center axis of a rotationally symmetrical shaft. Further, the tip portion of the device is cut at an angle to the main axis forming the bevel. The pointed tip of the bevel is directed to the 'front' of the needle. As a result, looking from the 'side', i.e. 'laterally', it is possible to recognize the angle between the bevel and the main axis.

A 'bevel' is a geometrical structure allowing for introducing the device, for example a needle into tissue. Usually, a shaft of the device includes a circular cross section. The distal end of the shaft is cut such that an oval surface is formed, which is inclined relative to the longitudinal axis of the shaft. The bevel forms a pointed tip at the most distal end of the biopsy device. It should be noted that the bevel might form an acute angle with the shaft, such that the biopsy device includes a pointed tip. The acute angle might be between 20° and 40°, preferably 32°.

It should be noted that the end surface of an optical fiber at the opening in the bevel may have a circular shape or a more or less oval shape in case of a substantially circular cross section of the fiber. Depending on the angle at which the fiber ends at the bevel surface, the shape of the end surface of the fiber will be effected and therefore also the direction of the emitted or received light.

Due to the slanted bevel surface, the distance between the fiber ends may be greater than the diameter of the shaft. For example, the distance may be more than 1.1 times greater than the diameter. Particularly, the distance may be more than 1.25 times greater than the diameter. Preferably, the distance may be more than 1.5 times greater than the diameter. In other words, the distance between the fiber ends should be as great as possible. Such distances are measured from the central axis of one of the fibers to the central axis of the other one of the fibers.

According to an embodiment, a device may comprise an elongated shaft including a bevel surface, wherein a plane is defined by the bevel surface. The shaft further includes a channel extending through the shaft parallel to the longitudinal axis, the channel forming an opening in the bevel surface. The device further comprises an optical fiber with a front surface, wherein the optical fiber is arranged within the channel of the shaft so that the front surface is located adjacent the bevel surface. Further, a plug with a first surface and a second surface is provided, wherein the plug is arranged in the channel so that the first surface of the plug is in contact with the front surface of the optical fiber for transmitting light from the optical fiber through the plug, and the second surface lies in the plane defined by the bevel surface thus forming a smooth distal surface at the distal end of the device. The optical fiber may be made of a first material having a first refractive index and the plug may be made of a second material having a second refractive index, wherein the second refractive index differs from the first refractive index. According to an embodiment, the material of the plug may have a refractive index similar to that of water.

The second surface of the plug may have the size and shape of the opening formed in the bevel surface, so that a smooth distal surface without any gaps is formed at the distal end by the bevel surface and the second surface when the optical fiber together with the plug are accommodated within the channel.

According to an embodiment may the front surface of the optical fiber be arranged with an angle relative to the longitudinal axis in the range of 60° to 90°, preferably in the range of 60° to 80°.

According to an embodiment, the second material may be adapted for a wideband optical transmission and low attenuation. For example, the second material may comprise Teflon.

According to an embodiment, the elongated shaft comprises more than one channel, wherein a first opening formed in the bevel surface by a first channel is located more proximally than the a second opening formed in the bevel surface by a second channel, and wherein the needle comprises more than one fiber-plug combinations each arranged within one of the channels. According to an embodiment, the elongated shaft may comprise three channels each forming an opening in the bevel surface, wherein a first opening is located proximally, a second opening is located in the proximity of the first opening, and a third opening is located distally, and wherein the needle comprises at least one combination of an optical fiber with a plug, the combination being arranged in at least one of the channels of the elongated shaft, respectively.

According to a further embodiment, a reflective coating may be provided at a channel wall of the channel. It is noted that the coating may be provided in all channels, but also in only one or two of the channels. Furthermore, it may be advantageous to provide the coating only in a section of a channel.

According to another embodiment, a system may be provided including the above described device as well as a console including a light source, a light detector and a processing unit for processing the signals provided by the light detector, wherein one of the light source and the light detector may provide wavelength selectivity. The light source may be one of a laser, a light-emitting diode or a filtered light source, and the console may further comprise one of a fiber switch, a beam splitter or a dichroic beam combiner. Furthermore, the device may be adapted to perform at least one out of the group consisting of diffuse reflectance spectroscopy, diffuse optical tomography, differential path length spectroscopy, and Raman spectroscopy.

According to another embodiment, the device may further comprise a channel for injecting or extracting a fluid. Such a channel may be an additional channel formed in the shaft or in an insert, and extending through that insert in a longitudinal direction, but may also be formed in the wall of the shaft or between the insert and the shaft or between the shaft and an additional outer tubular member.

According to a further embodiment, the device may further comprise a tissue retraction channel, wherein a suction device may apply vacuum to the channel for retracting a sample of tissue. For example, the channel in which an insert is accommodated within the hollow shaft, may be used for retracting a sample, after removing the insert. Alternatively, the channel may be formed in the shaft or an insert between optical fibers which are preferably arranged as much as possible at opposite sides of the shaft or insert.

According to another aspect, a method for producing a device as described is provided, the method comprising the steps of providing a shaft with a channel formed parallel to a longitudinal axis of the shaft, and with a bevel surface formed with an acute angle relative to the longitudinal axis, providing an optical fiber with a front surface, the fiber being formed from a first material, positioning the optical fiber in the channel so that the front surface of the optical fiber is arranged adjacent to the bevel surface.

It is noted that 'adjacent' means within a few millimeters, i.e. less than the diameter of the shaft, in other words less than 1 mm up to 5 mm.

Finally a plug is provided, so that a first surface of the plug is in contact with the front surface of the optical fiber and wherein a second surface of the plug is arranged in a plane defined by the bevel surface, so that the second surface of the plug together with the bevel surface of the shaft form a smooth distal surface of the needle.

The aspects defined above and further aspects, features and advantages of the present invention may also be derived from the examples of embodiments to be described hereinafter and are explained with reference to examples of embodiments. The invention will be described in more detail hereinafter with reference to examples of embodiments but to which the invention is not limited. BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is an illustration of light reflection within an optical fiber.

Figure 2 illustrates a device according to an embodiment.

Figure 3 shows an embodiment of a device with rough fiber ends.

Figure 4 shows embodiments with different fiber arrangements.

Figure 5 shows a system including a biopsy device and a console.

Figure 6 shows a log plot of absorption coefficient of blood, water and fat.

Figure 7 shows fluorescence curves for collagen, elastin, NADH and FAD.

Figure 8 is a flow chart illustrating steps of a method according to an embodiment.

The illustration in the drawings is schematically only and not to scale. It is noted that similar elements are provided with the same reference signs in different figures, if appropriate.

DETAILED DESCRIPTION OF EMBODIMENTS

Figure 1 is a sectional view of a distal end portion of an optical fiber 40. The fiber includes a core 20, a cladding 22 and a buffer 24. As indicated by the arrows in figure 1, light is internally reflected for rays with an angle Θ < 90-9c where 9c is the critical angle at which the rays still undergo total internal reflection at the core cladding interface. Light coupling in or out from the fiber occurs for rays with angles Θ < 9max. Internal reflection at a slanted fiber interface towards cladding and buffer causes reduced light output coupling for illumination and in coupling for detection since the angle Θ for these rays will be θ > 90-Θ c and do not undergo total reflection but is transmitted to the buffer and can be absorbed and scattered by the buffer material.

A needle tip can be shaped in a way so that it does not contain any undesired ridges, has a smooth shape to minimize pockets by adjusting the optical insert with a slanted angle matching to that of the needle bevel angle. This can be achieved by polishing/grinding the entire needle tip including the optical fibers.

As depicted in figure 1 , due to the typical refractive index mismatch between the optical fiber ends (n=~l .52) and the tissue (n=~l .33), the reflection at the slanted front surface 45 of the fiber 40 may redirect a significant part of the light into the cladding 22 and buffer material of the fibers where it may be lost due to absorption.

For example by applying a reflective coating to the sides of the lumen, the light hitting the sides of the lumen may be re-directed outwards and upwards.

In figure 2, a possibility for an improvement of the light output out of a fiber end is shown.

In front of the optical fiber 40 a plug 50 may be provided, the plug having a first surface 55 being in contact with the front surface of the optical fiber, wherein the plug may be made from a plastic material with wide-band optical transmission and low attenuation like a Teflon based plastic, for example CYTOP that is used in Gigabit optical fibers. The plastic material of the plug may be different to the material of the optical fiber 40, so that light refraction occurs at the contact surface. Exemplary beams of light are indicated in figure

2 by the arrow chains.

According to an embodiment, the contact surface may be straight-cut being perpendicular to the longitudinal axis of the shaft. The loss of light from the straight-cut fiber into a CYTOP plug as a distal tip portion is minimal, with a refractive index of the material of the plug nl of 1.34 and a refractive index of the material of the optical fiber n2 of 1.52, only 0.6% of the light is lost through reflection.

At a slanted second surface 56 between the CYTOP plug 50 and a watery environment of a body, the deflection of the light is determined by nl of 1.33 and n2 of 1.34, resulting in a change in direction of only 1.7 degrees. As a result, there is negligible loss of light at the tip of the fiber compared to fibers with slanted edges. By applying a reflective coating to the sides of the lumen, i.e. the wall of the channel, also the light hitting the sides of the lumen will be re-directed outwards and upwards. In the embodiment shown in figure 2, the first surface 55 between the fiber 40 and the plug 50 is slanted. This may additionally be used to direct the light in a specific direction.

By adjusting the slanting angle β of the fiber towards the plug, the direction of the beam can be steered upwards or downwards (or even sideways if that proves advantages). By using a different slant on the top and bottom fiber, the area where the cones of the two fibers cross can be adjusted.

As a further improvement, it is possible to give the plug 50 a cone shape. The cone shape allows for better emission of the light into the tissue. In addition, the exact position of the straight-cut fiber end becomes less critical and especially if a manufacturing process is used where first the fiber is inserted into the shaft 10 or an insert 35 and then the distal tip portions in form of plugs are molded into the resulting cavities. It is noted that the plug can compensate for tolerances in the exact end position of the fibers.

In figure 3, another effect is visualized, namely that an undesired internal reflection at a slanted front surface of an optical fiber may be reduced by roughening the surface 45. The effective light output at the slanted interface is enhanced for roughly polished fibers (average surface roughness of 30μιη) as compared to fine-polished fibers (roughness 1 μιη). The signal is particularly enhanced in the wavelength range from 400nm to 500nm.

For treating the front surface of the optical fiber, a rough tool may be utilized with an appropriate fineness of grind. According to an embodiment, the roughness may be suitable for polishing, thus having a roughness between 1 μιη and 5 μιη. If it is desired to have a rougher surface, the roughness of the tool may be between 20 μιη and 60 μιη or between 25 μιη and 40 μιη. It will be understood that the front surface of the optical fiber will be provided with a corresponding roughness, when treated with such a tool. For example, a treatment of the front surface of the optical fiber with a tool having a roughness of 10 μιη will result in a roughness of the front surface of approximately 10 μιη.

The roughening can be done in a variety of ways. To ensure a uniformly roughened needle tip surface including a front surface of an optical fiber, without any structure, such as rifts with a preferred direction. It is noted that the polishing can be applied by moving the foil continuously in an ,,8-shape" above the needle tip surface, or by moving the foil in a linear, oval or circular direction.

Alternatively, the needle tip surface could be also fine polished to achieve a very smooth surface (without any macroscopic gaps), and then roughened up again by sandblasting using grains with a size corresponding to the desired end surface roughness. It will be understood that the achieved roughness on a surface depends on the size of the used sand grain.

In figure 4, embodiments are shown, which differ with respect to the arrangement of the front surfaces of the fibers 40 in the bevel surface 30 of the shaft 10, wherein the respective bevel surface 30 of these embodiments is formed by a combination of a bevel surface of an insert 30 and a co-planar bevel surface of an outer tubular shaft 10. This can be seen in particular on the right side in the figure, showing front views of the embodiments. It is noted that each of the fibers 40 may also be a combination of a fiber with a plug as described with respect to figure 2.

According to the embodiment "CI 2", the shaft 10 comprises three channels each forming an opening in the bevel surface 30, wherein a first opening is located proximally, a second opening is located in the proximity of the first opening, i.e. beside the first opening, and a third opening is located distally, and wherein the needle comprises at least one optical fibers 40 arranged in the channels of the elongated shaft, respectively.

Preferably, the optical fiber which ends distally is used as a source fiber, i.e. for emitting light out of the biopsy device and into tissue.

The arrangement of the optical fibers 40 at the needle tip can affect the light output efficiency. For instance, for two embodiments, such as "CIO" and "CI 2" in Figure 4, where the fibers 40 has a different orientation, the signal output may differ in case the insert 35 and/or the inner surface of the shaft 30 reflect light differently (e.g. due to different surface roughness, etc.). Due to the manufacturing, the inner surface of the shaft may be more smooth (and may have better light reflection) than the insert at the tip. This becomes relevant for the fraction of light which is reflected from the slanted fiber tip back into the cladding/buffer, and then hits the metal which is holding the fiber. The more reflective the metal surface is, the higher the probability that part of this light is being back-reflected out of the optical fiber.

Although the tip angle a and the distance between the fiber tips is the same for both designs, the light intensity output is different due to the positioning of the fiber tip ends next to either the inner surface of the shaft or the insert.

As shown in figure 5, the fibers 40 of the interventional device are connected to an optical console 60. The optical fibers can be understood as light guides or optical waveguides. In an embodiment, the console 60 comprises a light source 64 in the form of a halogen broadband light source with an embedded shutter, and an optical detector 66. The optical detector 66 can resolve light with a wavelength substantially in the visible and infrared regions of the wavelength spectrum, such as from 400 nm to 1700 nm. The combination of light source 64 and detector 66 allows for diffuse reflectance measurements. For a detailed discussion on diffuse reflectance measurements see R. Nachabe, B.H.W. Hendriks, A.E. Desjardins, M. van der Voort, M.B. van der Mark, and H.J.C.M. Sterenborg, "Estimation of lipid and water concentrations in scattering media with diffuse optical spectroscopy from 900 to 1600nm", J. Biomed. Opt. 15, 037015 (2010).

Optionally it is also possible that the console is couple to an imaging modality capable of imaging the interior of the body, for instance when the biopsy is taken under image guidance. In this case it is also possible to store the image of the interior when the biopsy is taken to a container of the biopsy. In this case the in- vivo information of the optical biopsy needle, the information of the pathology of the biopsy as well as the location where the biopsy was taken may be brought together for advanced pathology.

On the other hand, also other optical methods can be envisioned like diffuse optical tomography by employing a plurality of optical fibers, differential path length spectroscopy, fluorescence and Raman spectroscopy to extract tissue properties.

Further shown in figure 5 are a suction device 70, a device 80 for obtaining ex- vivo pathology information, and a storage container 90. The suction device may be connected to a proximal end of the biopsy device, such that underpressure or a vacuum can be applied through the biopsy device to the distal end of the same.

The device 80 may be connected to the console 60 by means of a wire or wireless, for interchanging information like control commands or data representing pathological aspects of an inspected tissue sample. The device 80 may be a digital pathology systems consisting of an optical scanner and an image management system to enable digitizing, storage, retrieval, and processing of tissue staining images, reading the

information stored in the storage box container, and integrating this information with the digitized staining data set, to be presented to the pathologist. In addition to this, the data set from the photonic biopsy device may be either presented next to the histopathology image or the two data sets may be fused in the image, characterized and recognizable by a certain coloring pattern of the image. For instance the oxygenation level measured in-vivo could be added as a red color, where deep red means low oxygenation and bright red would mean high oxygenation level. Additionally, molecular spatial distributions from FTIR or Raman could be added as a color coded mapping to the pathology slide of specific molecules. The tissue sample, which may firstly be subjected to an in- vivo tissue inspection, i.e. an inspection within a living body, and which may secondly subjected to an ex-vivo tissue inspection by means of the device 80, may be situated in the container 90. Molecular diagnostics can also be performed on the tissue biopsy (e.g. sequencing or PCR), or part of the biopsy

A processor transforms the measured spectrum into physiological parameters that are indicative for the tissue state and a monitor 68 may be used to visualize the results.

A computer program executable on the processor may be provided on a suitable medium such as an optical storage medium or a solid-state medium supplied together with or as part of the processor, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems.

For fluorescence measurements the console must be capable of providing excitation light to at least one source fiber while detecting tissue-generated fluorescence through one or more detection fibers. The excitation light source may be a laser (e.g. a semiconductor laser), a light-emitting diode (LED) or a filtered light source, such as a filtered mercury lamp. In general, the wavelengths emitted by the excitation light source are shorter than the range of wavelengths of the fluorescence that is to be detected. It is preferable to filter out the excitation light using a detection filter in order to avoid possible overload of the detector by the excitation light. A wavelength-selective detector, e.g. a spectrometer, is required when multiple fluorescent entities are present that need to be distinguished from each other.

In case fluorescence measurements are to be combined with diffuse reflectance measurements, the excitation light for measuring fluorescence may be provided to the same source fiber as the light for diffuse reflectance. This may be accomplished by, e.g., using a fiber switch, or a beam splitter or dichroic beam combiner with focusing optics.

Alternatively, separate fibers may be used for providing fluorescence excitation light and light for diffuse reflectance measurements.

To perform spectroscopy, the acquired spectra may be fitted using a custom made Matlab 7.9.0 (Mathworks, Natick, MA) algorithm. In this algorithm, a widely accepted analytical model was implemented, namely the model introduced by the reference T. J.Farrel, M.S.Patterson and B.C.Wilson, "A diffusion theory model of spatially resolved, steady-state diffuse reflectance for the non-invasive determination of tissue optical properties", Med.Phys. 19 (1992) p.879-888, which is hereby incorporated by reference in entirety. The input arguments for the model of this reference are the absorption coefficient μ₃(λ), the reduced scattering coefficient μ₅' (λ) and the center-to-center distance between the emitting and collecting fibers at the tip of the probe.

In the following part, the model will be explained briefly. The used formulas are mainly based on work of Nachabe et al., and reference is thus made to R.Nachabe, B.H.W. Hendriks, M. van der Voort, A.E., and H.J.C.M. Sterenborg "Estimation of biological chromophores using diffuse optical spectroscopy: benefit of extending the UV-VIS wavelength range to include 1000 to 1600 nm", Optics Express, vol. 18, 2010, pp. 1432-

1442, which is hereby incorporated by reference in entirety, and furthermore reference is made to R. Nachabe, B.H.W. Hendriks, A.E. Desjardins, M. van der Voort, M.B. van der Mark, and H.J.C.M. Sterenborg, "Estimation of lipid and water concentrations in scattering media with diffuse optical spectroscopy from 900 to 1600nm", J. Biomed. Opt. 15, 037015

(2010), which is also hereby incorporated by reference in entirety.

A double power law function can be used to describe the wavelength dependence of the reduced scattering, where the wavelength λ is expressed in nm and is normalized to a wavelength value of ο =800 nm. The parameter a corresponds to the reduced scattering amplitude at this specific wavelength. μ₅(1) = a (p_MR ( ) + (1 - p_MR) ( ) ) [cm-¹ ] (Eq. 1)

In this equation the reduced scattering coefficient is expressed as the sum of Mie and Rayleigh scattering where p_MR is the Mie-to-total reduced scattering fraction. The reduced scattering slope of the Mie scattering is denoted b and is related to the particle size. For a homogeneous distribution of absorbers, the total light absorption coefficient μ_α(λ) can be computed as products of the extinction coefficients and volume fraction of the absorbers (see Figure 7)

μ1^0ία1 = μ + h l + h& + - (Eq. 2)

Instead of modeling the absorption coefficient μ_α (λ) as the sum of absorption coefficients weighted by the respective concentrations of the four chromophores of interest, it was decided to express the tissue absorption coefficient as

μ^η CU)v_Bioodr^od (A) + v_WLrf ^L (1) [cm-¹] (Eq. 3)

where μ ^ΐ00ά (A) corresponds to the absorption by blood and μ™¹ (1) corresponds to absorption by water and lipid together in the probed volume. The volume fraction of water and lipid is v_WL = [Lipid] + [H₂0], whereas v_Blood represents the blood volume fraction for a concentration of hemoglobin in whole blood of 150 mg/ml. The factor C is a wavelength dependent correction factor that accounts for the effect of pigment packaging and alters for the shape of the absorption spectrum. This effect can be explained by the fact that blood in tissue is confined to a very small fraction of the overall volume, namely blood vessels. Red blood cells near the center of the vessel therefore absorb less light than those at the periphery. Effectively, when distributed homogeneously within the tissue, fewer red blood cells would produce the same absorption as the actual number of red blood cells distributed in discrete vessels. The correction factor can be describ

where R denotes the average vessel radius expressed in cm. The absorption coefficient related to blood is given by

μ^Β _α ^100ά (1) =

(1) + (1 - ctM* (1) [cm^"1] (Eq. 5)

where ί^°°² (λ) and ^° ( ) represent the basic extinction coefficient spectra of oxygenated hemoglobin Hb0₂ and deoxygenated hemoglobin Hb, respectively. The oxygenated hemoglobin fraction in the total amount of hemoglobin is noted

aBL ⁼ [Hb0₂]/ ([Hb0₂] + [Hb]) and is commonly known as the blood oxygen saturation. The absorption due to the presence of water and lipid in the measured tissue is defined as (1) =

[cm^"1] (Eq. 6)

In this case the concentration of lipid related to the total concentration of lipid and water together can be written as a_WF = [Lipid]/ ([Lipid] + [H₂0]), where [Lipid] and [H₂0] correspond to the concentration of lipid (density of 0.86g/ml) and water, respectively.

This way of relating the water and lipid parameters in the expression of the absorption coefficient defined in Eq.6, rather than estimating separately the water and lipid volume fraction corresponds to a minimization of the co variance of the basic functions for fitting resulting in a more stable fit cf. the reference R.Nachabe, B.H.W. Hendriks, M. van der Voort, A.E., and H.J.C.M. Sterenborg "Estimation of biological chromophores using diffuse optical spectroscopy: benefit of extending the UV-VIS wavelength range to include 1000 to 1600 nm", Optics Express, vol. 18, 2010, pp. 1432-1442. For further explanation and validation of this theorem reference is made to the reference R. Nachabe, B.H.W. Hendriks, A.E. Desjardins, M. van der Voort, M.B. van der Mark, and H.J.C.M. Sterenborg,

"Estimation of lipid and water concentrations in scattering media with diffuse optical spectroscopy from 900 to 1600nm", J. Biomed. Opt. 15, 037015 (2010). For example by means of the described algorithm optical tissue properties may be derived such as the scattering coefficient and absorption coefficient of different tissue chromophores: e.g. hemoglobin, oxygenated haemoglobin, water, fat etc. These properties are different between normal healthy tissue and diseased (cancerous) tissue.

The main absorbing constituents in normal tissue dominating the absorption in the visible and near-infrared range are blood (i.e. hemoglobin), water and fat. In figure 7 the absorption coefficient of these chromophores as a function of the wavelength are presented. Note that blood dominates the absorption in the visible range, while water and fat dominate in the near infrared range.

The total absorption coefficient is a linear combination of the absorption coefficients of for instance blood, water and fat (hence for each component the value of that shown in figure 6 multiplied by its volume fraction). By fitting the model to the measurement while using the power law for scattering, the volume fractions of the blood, water and fat as well as the scattering coefficient may be determined.

Another way to discriminate differences in spectra is by making use of a principal components analysis. This method allows classification of differences in spectra and thus allows discrimination between tissues. Apart from diffuse reflectance also fluorescence may be measured. Then for instance parameters like collagen, elastin, NADH and FAD could be measured too (see figure 7). Especially, the ratio NADH/FAD, which is called the optical redox parameter, is of interest because it is an indicator for the metabolic state of the tissue, as described in Zhang Q., et al. "Turbidity-free fluorescence spectroscopy of biological tissue", Opt. Lett., 2000 25(19), p. 1451-1453, which is changed in cancer cells and assumed to change upon effective treatment of cancer cells.

It is also possible to detect the response of the body to exogenous fluorophores that can be detected by the optical biopsy device. Furthermore, these could also be linked to measurements of the exogenous fluorophores by imaging modalities like optical

mammography based on diffuse optical imaging.

The flow-chart in figure 8 illustrates the principle of the steps performed in accordance with an embodiment described herein. It will be understood that the steps described, are major steps, wherein these major steps might be differentiated or divided into several sub-steps. Furthermore, there might be also sub-steps between these major steps.

In step SI, a shaft 10 is provided with a channel formed parallel to a longitudinal axis of the shaft, and with a bevel surface 30 formed with an acute angle relative to the longitudinal axis. In step S2, an optical fiber is provided with a front surface. The front surface may be slanted relative to the longitudinal axis of the shaft.

In step S3, the optical fiber is positioned in the channel so that the front surface of the optical fiber is arranged adjacent the bevel surface of the shaft. Preferably, the front surface is arranged in the channel of the shaft, without any portion of the optical fiber protruding out of the bevel surface.

In step S4, a plug is provided in front of the optical fiber, the plug filling a cavity formed between the plane defined by the bevel surface of the shaft and the front surface of the optical fiber. One surface of the plug together with the bevel surface of the shaft form a smooth distal surface of the needle.

In step S5, which is an optional step, the distal surface of the device, i.e. the front surface of the optical fiber together with the bevel surface, may be polished to provide a uniform roughness at the distal surface of the device.

While the invention has been illustrated and described in detail in the drawings and foregoing description, such illustration and description are to be considered illustrative or exemplary and not restrictive; the invention is not limited to the disclosed embodiments. Other variations to the disclosed embodiments may be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims.

In the claims, the word "comprising" does not exclude other elements or^' steps, and the indefinite article "a" or "an" does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measured cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.

LIST OF REFERENCE SIGNS:

10 shaft

20 core

22 cladding

24 buffer

30 bevel surface

35 insert

40 optical fiber

45 front surface

50 plug

55 first surface

56 second surface

60 console

64 light source

66 light detector

68 monitor

70 suction device

80 device for ex- vivo tissue inspection

90 storage container

Claims

CLAIMS:

1. A device for tissue inspection, the device comprising a distal end and a longitudinal axis, the device further comprising:

an elongated shaft (10) including a bevel surface (30) formed at the distal end with an acute angle to the longitudinal axis, wherein a plane is defined by the bevel surface, the shaft further includes a channel extending through the shaft parallel to the longitudinal axis, the channel forming an opening in the bevel surface,

an optical fiber (40) having a front surface (45), wherein the optical fiber is made of a first material having a first refractive index and is arranged within the channel of the shaft so that the front surface is located inside the channel and adjacent to the bevel surface, and

a plug (50) with a first surface (55) and a second surface (56), wherein the plug is arranged in the channel so that the first surface of the plug is in contact with the front surface (45) of the optical fiber for transmitting light from the optical fiber through the plug, and the second surface lies in the plane defined by the bevel surface (30) for forming a smooth distal surface at the distal end of the device, wherein the plug is made of a second material having a second refractive index, wherein the second refractive index differs from the first refractive index.

2. The device of claim 1, wherein the front surface of the optical fiber is arranged with an angle relative to the longitudinal axis in the range of 60° to 90°, preferably in the range of 60° to 80°.

3. The device of claim 1 or 2, wherein the second material is adapted for a wideband optical transmission and low attenuation, the second material comprising Teflon.

4. The device of any one of claims 1 to 3, wherein the elongated shaft (10) comprises more than one channel, wherein a first opening formed in the bevel surface by a first channel is located more proximally than the a second opening formed in the bevel surface by a second channel, and wherein the needle comprises more than one combination of an optical fiber (40) and a plug, each combination being arranged within one of the channels.

5. The device of any one of claims 1 to 4, wherein the elongated shaft (10) comprises three channels each forming an opening in the bevel surface (30), wherein a first opening is located proximally, a second opening is located in the proximity of the first opening, and a third opening is located distally, and wherein the needle comprises at last one combination of an optical fiber (40) and a plug, the combination being arranged in one of the channels of the elongated shaft.

6. The device of any one of claims 1 to 5, wherein a reflective coating is provided at a channel wall of the channel.

7. The device of any one of claims 1 to 6, wherein the second surface of the plug has a predetermined roughness.

8. A system comprising:

a device according to any one of claims 1 to 7, and

a console (60) including a light source (64), a light detector (66) and a processing unit for processing the signals provided by the light detector.

9. The system of claim 8, further comprising a display device (68).

10. The system of claim 8 or 9, wherein the system is adapted to perform at least one out of the group consisting of diffuse reflectance spectroscopy, diffuse optical tomography, differential path length spectroscopy, and Raman spectroscopy.

11. A method for producing a device according to claim 1 , the method comprising the steps of:

- providing a shaft (10) with a channel formed parallel to a longitudinal axis of the shaft, and with a bevel surface (30) formed with an acute first angle relative to the longitudinal axis,

providing an optical fiber (40) with a front surface (45) formed with a blunt second angle relative to the longitudinal axis, positioning the optical fiber in the channel so that the front surface of the optical fiber is arranged adjacent to the bevel surface, and

providing a plug with a first surface being in contact with the front surface of the optical fiber and a second surface being arranged in a plane defined by the bevel surface.

12. The method of claim 11, wherein a cavity is formed between the front surface of the optical fiber and the plane defined by the bevel surface, and wherein the plug is molded into the cavity.

13. The method of claim 11 or 12, wherein the second surface of the plug is treated so as to have a predetermined roughness.