Lens, imaging system for producing images of an eye and method for operation

Abstract

Objective for a confocal microscopy device (2) for generating images of an eye or a part of the eye, wherein a scanning beam is movable along a first spatial direction by at least one scanner device of the microscopy device (2), wherein the objective (3) comprises at least one optical element for beam guidance and / or shaping, wherein the objective (3) comprises at least one means for changing a focal point position at least along an optical axis of the objective (3), characterized in that the objective (3) has at least one signal interface (17) for signal and / or data communication with the confocal microscopy device (2), wherein information about at least one parameter of a movement of the scanning beam along the first spatial direction can be transmitted from the microscopy device (2) to the objective (3).

Description

The invention relates to a lens for a confocal microscopy device, an imaging system and a method for operating a lens and the imaging system. For a number of applications, it is desirable to generate images of a specimen. In the field of ophthalmology, confocal microscopy devices, such as the Heidelberg Retina Tomograph (HRT), are used to generate images of specific areas of the retina. In conjunction with an attachment module, such as the Rostock Cornea Module, images of the cornea, in particular, can be produced. A diagnosis can then be made based on these images. The document “Guthoff et al., In vivo confocal microscopy, an inner vision of the cornea - a major review, Clinical and Experimental Ophthalmology 2009; 37: 100-117 doi: 10.1111 / j.1442-9071.2009.02016.x” describes a Heidelberg Retina Tomograph and a so-called Rostock Cornea Module and their application. The publication “B. Bermaoui, “Confocal In-Vivo Investigations of the Human Eyelids and the Meibomian Glands”, Inaugural Dissertation, Rostock, University, 2012” describes confocal laser microscopy with a Heidelberg Retina Tomograph and a so-called Rostock Cornea Module. The Rostock Cornea Module refers to a module that enables the Heidelberg Retina Tomograph to be used for examinations of the anterior segment of the eye. However, a problem with using the Heidelberg Retina Tomograph with a Rostock Cornea Module is that while areas of interest, especially the cornea, can be imaged in real time in the frontal plane, a depth scan along a sagittal spatial direction is not possible in real time. To generate images in different transverse or sagittal planes, particularly of different corneal depths, it is necessary to change the cornea's position relative to the stationary Rostock Cornea Module. This can be achieved by moving a contact cap on the Rostock Cornea Module to shift the cornea. This shifts the cornea relative to the stationary microscopy device. A disadvantage of this method is that the pressure exerted by the contact cap can degrade image quality. Furthermore, the movement of the contact cap must be performed in such a way as to ensure constant corneal applanation. This is complex and time-consuming. To generate images in a sagittal or transverse plane, it may then be necessary to reconstruct the desired cross-sectional images with depth information from these generated images using image processing methods. However, this is time-consuming and computationally intensive. Thus, the spatial area of ​​an examination object that can be imaged in real time by the Heidelberg Retina Tomograph with the Rostock Cornea Module is limited to the frontal plane. US Patent 6,142,630 A discloses an arrangement with a variable focusing lens for use in confocal microscopy of the eye. DE 101 59 239 A1 discloses a microscope objective with an objective housing and several lenses, wherein at least one lens is arranged to be displaceable. The technical problem is to create a lens for a confocal microscopy device, an imaging system, and a method for operating the lens and the imaging system that magnify a spatial region of an object under investigation, particularly an eye, which can be imaged quickly, especially in real time, or that enable the rapid imaging, especially in real time, of an alternative spatial region of the object under investigation. In particular, the disadvantages described above should be avoided, and it should be ensured that at least one image axis of the image can be oriented at least partially along a sagittal direction. The solution to the technical problem is achieved by the objects having the features of claims 1, 10, 14 and 15. Further advantageous embodiments of the invention are set forth in the dependent claims. A lens for a confocal microscopy device is proposed for generating an image of a subject under investigation. The subject can be, in particular, an eye or a part thereof. However, the proposed lens is also suitable for generating images of other subjects, especially living and / or moving subjects, particularly a moving eye, as it enables rapid image generation and thus reduces motion artifacts. The confocal microscopy device can, in particular, be a confocal laser scanning microscope. Specifically, the confocal microscopy device can be configured as a so-called point scanner or a so-called line scanner. In a point scanner, a scanning beam generated by the microscopy device, in particular a focused laser beam, can be directed onto or into different spatial regions of an object under investigation, the scanning beam being moved along at least one, preferably along two different, spatial directions (scanning). Light reflected and / or scattered from the spatial regions of the object under investigation can then be directed onto a detector of the microscopy device. The scanning beam can be generated continuously, particularly by a CW laser device. Alternatively, the scanning beam can also be generated in pulses. The confocal microscopy device can comprise at least one device for generating a scanning beam and at least one detector device. Furthermore, the microscopy device can include optical elements such as a lens and / or a mirror. The microscopy device can also include a scanner device. The confocal microscopy device enables the generation of an image, in particular a two-dimensional image. The image can be generated specifically based on output signals from the detector device. In this process, a scanned area of ​​the object under investigation, defined by the direction of the scanning beam and the focus of the microscopy device, can be mapped onto a pixel in the image. Different pixels can thus be generated by different positions or directions of the scanning beam. In particular, the confocal microscopy device allows the scanning beam to be moved along a first spatial direction. Preferably, the scanning beam can also be moved along a second spatial direction, which differs from the first. In particular, the first spatial direction can be oriented perpendicular to the second spatial direction. Movement along the first and second spatial directions can be enabled by at least one scanner unit of the microscopy device. The scanner unit thus allows the direction of the scanning beam to be set. In particular, the confocal microscopy device can be a Heidelberg Retina Tomograph. The first and second spatial directions can differ from the spatial direction of an optical axis of the confocal microscopy device, and in particular can each be oriented perpendicular to the optical axis. The optical axis can, in particular, be an axis on which the focal point of the microscopy device, with an objective lens optionally mounted on the microscopy device, is located. For example, if an image of a portion of the human eye is generated using confocal microscopy, the first spatial direction, or a principal component thereof, can be oriented parallel to a transverse direction. Furthermore, the second spatial direction, or a principal component thereof, can be oriented along a longitudinal spatial direction. The terms transverse, longitudinal, and sagittal here refer to spatial directions within a body-related coordinate system known to those skilled in the art. For example, body planes in this body coordinate system can be a transverse plane oriented perpendicular to the longitudinal spatial direction. Another body plane can be a frontal plane oriented perpendicular to the sagittal spatial direction. A further body plane can be a sagittal plane oriented perpendicular to the transverse spatial direction. A principal direction component refers to the largest component of a vector in a predetermined coordinate system, in particular in the coordinate system defined by the transverse, longitudinal and sagittal spatial directions. Furthermore, the objective lens comprises at least one optical element for guiding and / or shaping the beam. This optical element can, in particular, be designed as a lens. An optical element can change the direction and / or shape of a beam projected through the objective lens. Naturally, the lens can comprise multiple optical elements. Furthermore, the objective lens can have or incorporate at least one mounting means or a mounting section for mechanically attaching the objective lens to the confocal microscopy device. This allows for repeatable attachment of the objective lens to the confocal microscopy device. Thus, the objective lens can also be referred to as an attachment module. Furthermore, the objective lens comprises at least one means for changing the focal point position at least or exclusively along an optical axis of the objective lens. The focal point can be a focal point of the object. If the objective lens is arranged on the microscopy apparatus, the focal point can be a focal point of the imaging system consisting of the microscopy apparatus and the objective lens. Furthermore, the lens may include at least one control device for controlling the change of the focal point position, in particular a control device for controlling the means for changing the focal point position. If the lens is used to examine the eye, the optical axis or a principal directional component of the optical axis may be oriented parallel to the sagittal spatial direction. The focal point position can be changed within a global reference coordinate system. The lens, or at least one optical element of the lens, can be movable relative to this global reference coordinate system. In particular, the reference coordinate system can be the previously described body coordinate system. It is also possible that the objective lens comprises at least one portion fixed in position relative to the global reference coordinate system and at least one portion movable relative to the global reference coordinate system. Furthermore, the confocal microscopy device, in particular the device for generating the scanning beam and / or the detector, can be fixed in position relative to the reference coordinate system. Thus, it is possible for the focal length of the lens or an optical element of the lens to be fixed or constant, whereby the lens or a movable part of the lens or the position of an optical element of the lens is changed to change the focal point position. This advantageously results in a lens that allows for a change in the focal point position along the optical axis during examinations of the eye, particularly without moving the object under investigation or any part thereof. Previously, different depth planes of the eye were achieved by moving the eye or a portion of the eye relative to the stationary lens. Changing the focal point position advantageously enables the rapid generation of image points with the described microscopy setup along a spatial direction whose principal component can be parallel to an optical axis of the microscopy setup or the objective lens. This optical axis, in turn, can be oriented parallel to the sagittal direction. In other words, a so-called depth scan can be performed quickly. Due to confocal microscopy, cellular or even subcellular resolution of the image, generated at least partially along the sagittal plane, can be achieved. In particular, cell layers, especially those of the epithelium, stroma, and endothelium, can be imaged quickly and with high image quality, thus enabling improved diagnosis. In particular, the focal point position can be varied such that a two-dimensional image can be generated, with different lines of the two-dimensional image being generated at different focal point positions along the optical axis of the lens. Image points of a line can be generated with a constant focal point position. Alternatively, image points of a line can be generated with an approximately constant focal point position. An approximately constant focal point position can mean that the focal point position changes by no more than 5 µm or less than 5 µm during the generation of an image line. In this case, however, image points of a line can be generated at different focal point positions. In particular, the lens enables the creation of an image of a plane within the object under investigation without changing its position, wherein the normal vector of the imaged plane forms a non-zero angle with the optical axis, preferably greater than or equal to 10°, and more preferably greater than or equal to 30°. In particular, the normal vector is not oriented parallel to the optical axis. If the object under investigation is an eye, the lens enables the creation of an image of a plane within the eye without changing the eye's position. The normal vector of the imaged plane forms a non-zero angle with the sagittal axis, preferably greater than or equal to 10°, and more preferably greater than or equal to 30°. The normal vector can, in particular, include a non-zero component oriented parallel to the longitudinal direction in space. Alternatively or cumulatively, the normal vector can include a non-zero component oriented parallel to the transverse direction in space. Furthermore, the normal vector can also include a component oriented parallel to the sagittal direction in space. In particular, the normal vector can be oriented parallel to the longitudinal spatial direction or parallel to the transverse spatial direction. However, the normal vector is not oriented parallel to the sagittal spatial direction. Thus, at least one image axis of the image, or a principal component thereof, can be oriented parallel to the sagittal direction. The other image axis, or a principal component thereof, can be oriented either parallel to the transverse or the longitudinal spatial direction. Compared to a conventional slit-lamp examination of the eye, the proposed lens, when used in an imaging technique, allows the maximum magnification to be increased from 30x to 800x, thus enabling the imaging of cellular structures. The correlations between conventional slit-lamp findings and ophthalmic pathology, accumulated over decades, can therefore be elevated to a completely new level of microscopic precision. Furthermore, the lens allows the images to be evaluated online or offline, e.g., by examining tissue volume and reconstructing sections, as in the well-known slit lamp examination. The proposed lens can also be used for histological examinations of specimens. Currently, specimens are cut into thin slices for microscopic examination. This process produces artifacts that are avoided with the proposed method. Naturally, the proposed lens can also be used for other applications, such as materials analysis. In a further embodiment, the lens has or forms at least one contact section for mechanically contacting an eye or a mounting section for a means of mechanically contacting the eye. Contact with the object under investigation can be established via the contact section or the means of mechanical contacting. Additionally, particularly for examinations of the eye, a contact material, especially tear gel, can be used, with contact occurring via the contact section or the means of mechanical contacting and the contact material. The contact section or the means of mechanical contacting can, in particular, be designed as a contact cap. In another embodiment, the focal point position can be changed continuously or stepwise. It is thus possible to continuously change the focal point position for or during the generation of a two-dimensional image, particularly also for or during the generation of different image lines. In this case, different pixels of a line of the image can be generated with different focal point positions. Alternatively, it is possible to change the focal point position stepwise for or during the generation of a two-dimensional image, particularly also for or during the generation of different image lines. In this case, each line can be generated with a constant focal point position. In a further embodiment, the objective lens has at least one means for changing the position of at least one optical element of the objective lens along an axis parallel to the optical axis of the objective lens. For example, the optical element can be a lens or a microscope objective whose position, particularly in the reference coordinate system, is changeable. In this case, a movable part of the objective lens can comprise the at least one optical element. A stationary part of the objective lens can comprise a housing of the objective lens, with the optical element arranged in the housing. The means for changing the position may include means for a mechanical connection between the optical element and a device for generating a driving force / torque for changing the position. This advantageously results in a change to the focal point position that is easy to implement. In a further embodiment, the lens has at least one means for changing the position of all optical elements of the lens along an axis parallel to the optical axis of the lens. It is possible for the positions of different optical elements to be changed independently of one another. However, it is also possible for the means for changing the position to change the position of all optical elements of the lens assembly in the same way. The entirety of optical elements can refer to all optical elements of the objective through which a scanning beam generated by the confocal microscopy device shines and / or through which a beam reflected and / or scattered by the object under investigation shines towards the microscopy device. In particular, all optical elements of the lens can be mounted on a common support structure, wherein the position of the support structure parallel to the optical axis can be changed by means of a position-changing device. In this case, a movable part of the lens can encompass all of the lens's optical elements. This advantageously results in a simple and easily implemented change of the focal point position. In a preferred embodiment, the lens comprises a housing, wherein the at least one optical element is arranged in the housing. Furthermore, the lens has at least one means for changing the position of the housing along an axis parallel to the optical axis of the lens. In this case, the movable part of the lens can thus comprise the housing with the at least one optical element. It is possible that the housing forms the previously described support structure for the assembly of optical elements. In particular, the housing can comprise all the optical elements of the lens. In particular, a movable part of the lens in this case can include a Rostock cornea module. In other words, the means of changing the position can alter the position of the Rostock cornea module along an axis parallel to the optical axis of the Rostock cornea module. This advantageously results in a particularly simple implementation of changing the focal point position. In a further preferred embodiment, the means for changing the position comprises at least one piezoelectric actuator. This advantageously results in a highly dynamic, i.e., rapid, changeability of the position, thereby enabling a highly dynamic, i.e., rapid, change of the focal point position. Alternatively, the means for changing the position can comprise at least one electromechanical or electromagnetic actuator, for example, a solenoid. Alternatively, the means for changing the position can comprise at least one ultrasonic motor. Alternatively, the means for changing the position can comprise at least one piezoelectric actuator. Such actuators also advantageously enable a highly dynamic, yet precise, change in the focal point position. Of course, other actuators can also be used to change the position. In a further embodiment, the focal point position can be changed, particularly quickly, such that a two-dimensional image with a predetermined line frequency and a predetermined vertical frequency can be generated, wherein different lines of the two-dimensional image are generated at different focal point positions along the optical axis of the lens. Image points of a line are thus generated with or for a constant or nearly constant focal point position. Thus, the change in focal position can depend on the desired, predetermined vertical frequency. In particular, the focal positioning speed, i.e., the change in focal position, depends on the desired vertical frequency as well as the desired travel distance. Furthermore, the vertical frequency can be lower than the horizontal frequency. The vertical frequency can, in particular, denote a frequency that indicates how often all lines of the two-dimensional image are sampled per second. The vertical frequency can thus also be referred to as the refresh rate. In particular, the vertical frequency can be in a frequency range of 1 Hz to 1 MHz. Preferably, the vertical frequency is 30 Hz, more preferably 60 Hz, and even more preferably 120 Hz. The horizontal frequency (or line frequency) can preferably be in a range of 1 kHz to 10 MHz. The preferred horizontal frequency can, in particular, be determined as a function of a desired resolution and the vertical frequency. For example, if it is assumed that the vertical frequency is in one of the aforementioned ranges and the resolution is 1000 pixels, then the horizontal frequency can be 30 kHz, more preferably 60 kHz, and even more preferably 120 kHz. The two-dimensional image can be generated in particular by the confocal microscopy device if the objective lens is attached to the confocal microscopy device to generate a two-dimensional image. In this case, lines of the image of a plane can be generated in the object under investigation, where the normal vector of the imaged plane, as explained above, includes an angle with the optical axis or with the sagittal axis, which has a value from the previously explained range of values. In particular, it is also possible that a line of the image represents a spatial area that is oriented parallel to the longitudinal spatial direction or to the transverse spatial direction. This advantageously results in an optimal adaptation of the dynamic properties of the lens, in particular the change in the focal point position, to the dynamic properties of the image generation of the confocal microscopy device. In particular, the focal point position can be changed such that a scanning beam reflected and / or scattered by the object under investigation is used at different focal point positions to generate different lines of the image or to generate different pixels within a line. A line can thus be focal point-specific. In other words, a line of the image, or the signals for generating this line, can be produced with a constant or nearly constant focal point position. If the confocal microscopy device includes a scanner that allows movement of the scanning beam in two spatial directions, then the change in the focal point position can be synchronized with the change in the position of the scanning beam along one of these spatial directions. For example, if different pixels of a row of the image are generated by moving the scanning beam along the first spatial direction, and different rows of the image can be generated by moving along the second spatial direction, then the change in the focal point position can be synchronized with the movement along the second spatial direction. In this way, a scanner device can be controlled accordingly. Specifically, it is possible to deactivate the movement of the scanning beam along the second spatial direction, i.e., to prevent it from occurring, while still moving or changing the focal point position using the movement parameters of the deactivated movement. The control of the focal point position can be based on control signals that are used to move the scanning beam along the second spatial direction by the scanner device. In other words, the existing control signals can be used even though the movement along the second spatial direction is deactivated. Such control signals can be generated, for example, by a higher-level system. Furthermore, such control signals can be dependent on or encode a vertical frequency.Alternatively, it is possible to generate control signals for the movement of the focal point position that are independent of the control signals for controlling the movement along the second spatial direction. In another embodiment, the lens is designed as an attachment. In particular, the lens can be designed as an attachment for the confocal microscopy device, and more specifically as an lens for a Heidelberg Retina Tomograph. This advantageously results in a simple, subsequent extension of a confocal microscopy device such that depth scans can be generated quickly. A further imaging system is proposed, comprising a confocal microscopy device and an objective according to one of the embodiments disclosed in this disclosure. The microscopy device and its possible configuration have already been explained above. The objective lens can be attached to the confocal microscopy device. In particular, the objective lens can be attached to the microscopy device in such a way that a scanning beam generated by the microscopy device can be directed through the objective lens to a specimen under investigation, and a beam scattered and / or reflected by the specimen under investigation can be directed through the objective lens to a detector of the confocal microscopy device. Because the lens allows for the changing of the focal point position, and thus also the position of the focal point of the imaging system, along the lens's optical axis, depth scans of the imaging system can be generated quickly. The proposed imaging system advantageously enables the generation of cross-sectional images by the eye in a plane that can be parallel to a sagittal plane or parallel to a transverse plane, or whose normal vector forms an angle with the optical axis or the sagittal axis that has a value from the previously explained range. According to the invention, the objective lens has at least one signal interface for signal and / or data communication with the confocal microscopy device. In particular, information about at least one parameter of the movement of the scanning beam along the first spatial direction and / or the second spatial direction described above is transmitted from the microscopy device to the objective lens. The parameter can, for example, be information about the speed or acceleration of the movement. The parameter can also encode the horizontal frequency or the vertical frequency described above. Naturally, several of these parameters can also be transmitted to the objective lens. The lens can also include a control and evaluation unit, whereby the change in the focal point position can be controlled by means of the evaluation unit depending on the information about at least one movement parameter of the microscopy device. In particular, as explained above, the control device can change the focal point position such that different lines with different focal point positions are generated. Specifically, a scanning beam can be directed into different spatial regions or points of an object under investigation with a constant or nearly constant focal point position, and the scanning beams reflected and / or scattered from these regions / points are used to generate image points of a line in the image. In other words, the spatial regions / points illuminated with a constant or nearly constant focal point position are mapped onto a line in the image. If lines of the image are generated as explained with a predetermined line frequency of the microscopy device, the change in the focal point position can depend on the vertical frequency of the microscopy device. Furthermore, it is advantageous that the imaging system can generate the aforementioned images without any movement of the eye or any part thereof. The use of a piezoelectric actuator also advantageously achieves sub-nanometer positioning accuracy for the focal point. In a further embodiment, a scanning beam generated by the microscopy device is movable along a first spatial direction, in particular by a scanner device of the microscopy device. Furthermore, the first spatial direction differs from the spatial direction of the optical axis of the objective. This can mean that the orientations of the spatial directions in the reference coordinate system are different from each other. The spatial direction of the optical axis can be a spatial direction parallel to the optical axis. In particular, the spatial direction of the optical axis can be oriented perpendicular to the first spatial direction. In particular, the scanning beam generated by the microscopy device is movable along the first spatial direction and the focal point position is variable such that a two-dimensional image can be generated by the microscopy device. Specifically, such a two-dimensional image can be generated with the previously described desired line frequency and vertical frequency. In this process, the generated scanning beam can be moved along the first spatial direction in such a way that the two-dimensional image can be generated with the predetermined line frequency. Furthermore, the focal point position can be changed in such a way that the two-dimensional image can be generated with the desired vertical frequency. This advantageously allows cross-sectional images of the eye to be generated in planes with the orientation described above without the need for additional image processing, whereby an existing confocal microscopy device can be used to generate these two-dimensional images. In a further embodiment, a scanning beam generated by the microscopy device is additionally movable along a second spatial direction, wherein the second spatial direction differs from the first spatial direction and from the spatial direction of the optical axis of the objective. In particular, the second spatial direction can be oriented perpendicular to the first spatial direction. Furthermore, the second spatial direction can be oriented perpendicular to the spatial direction of the optical axis. In other words, the scanning beam can be moved along two different spatial directions, and the focal point position can also be changed. This advantageously results in a simplified generation of images of a plane with a desired orientation, in particular images where one image direction is arranged in the frontal plane or a plane parallel thereto, and the other image direction has a non-zero component oriented parallel to the sagittal direction. However, it is possible that the movement of the scanning beam along the second spatial direction is deactivated and therefore not feasible if the objective lens is attached to the confocal microscopy device or if the objective lens is used for image generation by means of the microscopy device. Thus, the imaging system can also be operated in such a way that a scanning beam moving along a predetermined path in the first spatial direction is used to generate a line of the image, whereby the focal point position is not changed or is changed by no more than a predetermined amount during this movement. After the movement along the path is completed, the focal point position can be changed by more than the predetermined amount, in particular more than 0.1 µm, and the scanning beam can again be moved along the predetermined path in the first spatial direction, whereby the scanning beam is then used to generate another line of the image. Thus, the focal point position can also be moved along a predetermined path, with a row of the image being generated for each focal point position. As explained previously, the movement of the focal point position along the predetermined path can be a continuous movement or a movement divided into several steps. If the scanning beam can also be moved along a second spatial direction, then, once the focal point has completed its movement along the predetermined path, the scanning beam can be moved along this second spatial direction. At a new position along this second spatial direction, the focal point can then be moved again along the predetermined path, generating a line of the image for each focal point position. This advantageously results in an imaging system that enables a so-called volume scan, particularly since spatial regions along three spatial directions can be imaged by the confocal microscopy device. If movement along one of the spatial directions, especially along the second spatial direction, is deactivated, a two-dimensional image with depth information can be generated. According to the invention, the imaging system, in particular the microscopy device, and further in particular the scanner device of the microscopy device, comprises at least one acousto-optic modulator for moving the scanning beam along the first and / or along the second spatial direction. Alternatively or cumulatively, the imaging system, in particular the microscopy apparatus, and further in particular the scanner apparatus of the microscopy apparatus, comprises at least one electro-optical modulator for moving the scanning beam along the first and / or the second spatial direction. A modulator is therefore used to align the scanning beam. In particular, the imaging system can include an acousto-optic or electro-optic modulator for moving the scanning beam along the first or second spatial direction. Furthermore, the imaging system can include a galvanic mirror for moving the scanning beam along the remaining spatial direction. Alternatively, the imaging system can include an acousto-optic or electro-optic modulator for moving the scanning beam along the first or second spatial direction. Furthermore, the imaging system can include an acousto-optic or electro-optic modulator for moving the scanning beam along the remaining spatial direction. Exemplary acousto-optic and electro-optic modulators are described in the document "Handbook of Optical and Laser Scanning, ed. by GF Marshall, Marcel Dekker Inc., 2004". Acousto-optic modulators generate a density grating in an optically transparent medium by exciting it with an ultrasound signal. A laser beam, particularly the scanning beam, can be diffracted by this grating. By changing the excitation frequency, the grating period, and thus the deflection angle of the laser beam, can be altered. This change can be made very quickly because no mechanical components are required. In this way, a modulator can move a laser beam very rapidly in one direction over or through an object under investigation. Electro-optic modulators are based on changing the refractive index of a crystal as a function of an applied electric field. A laser beam, in particular the scanning beam, is deflected differently within the crystal due to the varying refractive indices. By changing the electric field, the deflection angle of the laser beam can be altered. This change can occur even faster than with acousto-optic modulators. For example, such modulators can replace the electroplating mirror used in a scanner device, which also serves to move the scanning beam. For example, the at least one modulator can be designed and / or arranged in such a way that images with a desired, in particular high, line frequency and / or with a desired, in particular high, vertical frequency can be generated. Typically, purely mechanical scanners cannot achieve line frequencies in the MHz range. However, acousto-optic or electro-optic modulators make line frequencies in the MHz range possible. This advantageously minimizes the time required to generate a single image, thereby reducing the influence of motion artifacts, such as those caused by eye movement. In particular, it should be possible to generate images with a refresh rate of at least 30 Hz or 60 Hz. However, it is also possible to generate images with a refresh rate significantly higher than 60 Hz, especially with the acousto-optic or electro-optic modulators described above.This allows for a particularly short exposure time per image, which in turn significantly reduces motion artifacts caused by rapid eye movements (microsaccades) during image production. If images are generated with a refresh rate higher than the desired refresh rate, e.g., higher than 30 Hz or 60 Hz, individual images can be selected from the set of generated images. Only the selected images are output or further processed, for example, stored in a storage device and / or transferred to an evaluation and / or display device. In particular, the selection of images can be carried out in such a way that images with the desired refresh rate are stored and / or transferred. The desired refresh rate could, for example, be one that allows for a sufficiently good display on a display device, such as a screen. In another embodiment, the scanning beam is generated in pulses. Here, the duty cycle of the generation is determined as the quotient of the time required to generate at least one image and the inverse of a desired frame rate. The duty cycle is defined as the ratio between the duration of the scanning beam activation and the time from the start of one activation to the start of the immediately following activation. The inverse of the desired refresh rate can be greater than the time required to generate at least one image. In particular, the desired refresh rate can be in the range of 30 Hz to 60 Hz, e.g., 30 Hz. The imaging system, in particular the microscopy unit, and further specifically the scanner unit of the microscopy unit, can enable the generation of images with a maximum frame rate that is higher than the desired frame rate. However, it may not be necessary to actually generate all images that can be produced at the maximum frame rate. In this case, the scanner can be operated in a mode where images are generated at the maximum frame rate, but the scanning beam is pulsed. Specifically, the scanning beam can be activated only for the duration necessary to generate an image. Afterwards, the scanning beam can be deactivated for a predetermined period, during which at least one, but preferably several, image(s) could be generated. Following this deactivation, the scanning beam can be reactivated. Furthermore, only the images generated when the scanning beam is activated can be output or processed further, for example stored in a storage device and / or transferred to an evaluation and / or display device. Preferably, the pulsed generation of the scanning beam is synchronized with the operation of the scanner device, in particular such that the scanning beam is activated at or before the time at which the generation of an image by the scanner device begins, and the scanning beam is deactivated at or after the time at which the generation of the image by the scanner device is terminated. This advantageously reduces the energy input into the object under investigation, such as the eye, during image generation. However, it is possible that the scanning beam in pulsed operation is generated with a higher instantaneous power compared to a continuously generated scanning beam. Overall, this advantageously allows a single image to be generated in a comparatively short time, which in turn reduces the previously described influence of motion artifacts. For example, if the desired frame rate is 30 Hz, the image generation time can be much shorter than 1 / 30 of a second. A further proposed method for operating a lens according to one of the embodiments described in this disclosure involves changing the focal point position of the lens. In particular, the focal point position of the lens can be changed such that a two-dimensional image of an object under investigation, especially a partial area of ​​the object under investigation, is generated. The two-dimensional image can be generated, in particular, such that different lines of the image are produced with different focal point positions, wherein one line of the image is produced with a constant focal point position. This and corresponding advantages have already been explained above. A further proposed method for operating an imaging system according to one of the embodiments described in this disclosure involves changing the focal point position of the lens. In particular, the focal point position of the lens can be changed such that a two-dimensional image is generated by the imaging system. The two-dimensional image can be generated, in particular, such that different lines of the image are produced with different focal point positions, with one line of the image being produced with a constant focal point position. This and corresponding advantages have already been explained above. In a further embodiment, a scanning beam generated by the microscopy device is additionally moved along a first spatial direction, wherein the first spatial direction differs from the spatial direction of the optical axis of the objective. This and corresponding advantages have already been explained above. In another embodiment, the wavelength of the scanning beam is changed. In particular, an object under investigation or a sub-area thereof can be imaged with different wavelengths. Specifically, images of the same sub-area with different wavelengths can be generated. The images can be generated sequentially. In particular, wavelengths can be set in a range preferably from 350 nm to 1800 nm. A wavelength from this range is preferably selected for examining an eye. Generally, however, the choice of wavelength depends on the application. Furthermore, it can be taken into account that the resolution increases with decreasing wavelength. This advantageously allows for the reliable detection of intercellular barrier disruptions in the generated images. For this purpose, it can be beneficial to first introduce a suitable dye, particularly fluorescein, into the object under investigation, especially the eye, and furthermore, particularly into the cornea. Furthermore, as explained above, it is possible to generate the scanning beam in pulsed mode. The invention is explained in more detail with reference to an exemplary embodiment. The figures show: Fig. 1 a schematic block diagram of an imaging system with a lens in a first embodiment, Fig. 2 a schematic block diagram of an imaging system according to the invention with a lens according to the invention according to a further embodiment, Fig. 3 a schematic block diagram of an imaging system according to the invention with a lens according to the invention in a further embodiment, Fig. 4 a schematic flowchart of a method according to the invention for operating an imaging system, and Fig. 5 a schematic block diagram of an imaging system according to the invention with a lens according to the invention in a further embodiment. In the following, identical reference symbols denote elements with the same or similar technical characteristics. Figure 1 shows a schematic block diagram of an imaging system 1. The imaging system 1 comprises a confocal microscopy device 2 and an objective 3. The confocal microscopy device 2 can be a laser scanning microscope, in particular a Heidelberg Retina Tomograph. The microscopy device 1 includes a device 4 for generating a scanning beam, in particular a diode laser device. The scanning beam can be generated continuously or in pulses. The microscopy device 2 further comprises a beam splitter 5 or a semi-transparent mirror, an objective system 6, and a scanner device 7. The objective system 6 of the confocal microscopy device can include at least one optical element, such as a lens. The microscopy device 2 further comprises a detector 8 and apertures 9. The apertures 9 are to be arranged at the focal point.However, it is not absolutely necessary to provide the apertures shown (9). For example, it is also possible to provide a single aperture located at an intermediate focus position, for example within the lens system (6). Using the scanner device 7, a scanning beam from the microscopy device can be moved along a first spatial direction x (not shown) and a second spatial direction y. The first spatial direction x can be oriented perpendicular to the second spatial direction y and into the plane of the drawing. A third spatial direction z is also shown, which can be oriented perpendicular to both the first and second spatial directions y. The scanner device 7 can include one or more electrochromic mirrors for moving the scanning beam. Alternatively or cumulatively, the scanner device 7 can include one or more acousto-optic or electro-optic modulators for moving the scanning beam. Imaging system 1 can, in particular, generate an image of the cornea 10 of an eye of the body, with the eye forming the object of investigation. If a part of the body forms the object of investigation, the first spatial direction can, in particular, correspond to a transverse spatial direction in a body coordinate system. The second spatial direction y can be oriented parallel to a longitudinal spatial direction in the body coordinate system. The third spatial direction z can be oriented parallel to a sagittal spatial direction in the body coordinate system. Thus, a reference coordinate system can be formed by the body coordinate system. The objective lens 3, which is arranged on the microscopy device 2, is further shown, in particular arranged such that an image of the cornea 10 can be generated by the imaging system 1. Thus, the objective lens 3 is attached to the microscopy device 2 in such a way that a scanning beam from the microscopy device 2 can be directed through the objective lens 3, in particular through its optical elements 11, into a specimen, in this case a cornea 10, and a light beam scattered or reflected by the cornea 10 can be directed through the objective lens 3 into the microscopy device 2 to the detector 8. The objective 3 comprises a first optical element 11a and a second optical element 11b. Both optical elements 11a and 11b can be configured as lenses. It is also possible for the first optical element 11a to be configured as a microscope objective. The second optical element 11b can be used to expand or align beams. The first optical element 11a can be used to focus beams. Furthermore, the objective includes a means, configured as a piezoelectric actuator 12, for changing the spatial position of the first optical element 11a along an optical axis of the objective 3. In particular, the spatial position can be changed within a reference coordinate system, whereby, for example, the microscopy apparatus 2 can be fixed in position within the reference coordinate system. Instead of the piezoelectric actuator 12, an electromagnetic actuator, an ultrasonic motor, or a capacitive actuator can also be used. The optical axis of lens 3 is oriented parallel to the third spatial direction z, which can also be referred to as the depth direction. Thus, the spatial direction of the optical axis can be oriented parallel to the sagittal direction in the body coordinate system. The second optical element 11b of the lens 3 is fixed in position relative to the reference coordinate system described above. The first optical element 11a can be moved along the optical axis to change the focal point position of the lens 3 along the optical axis. The imaging system 1, in particular the lens 3, further comprises a contact cap 13. This contact cap 13 can be attached to the lens 3 or be part of the lens 3. A contact material 14, for example a tear gel, can be arranged between the lens 3, in particular the contact cap 13, and the object under investigation, in this case the cornea 10. It is further shown that the lens 3 comprises a housing 15, in which the optical elements 11a, 11b and the piezoelectric actuator 12 are arranged. Thus, the lens 3 comprises a movable part 19, wherein the movable part 19 comprises the first optical element 11a. A stationary part 20 of the lens 3 comprises the second optical element 11b and the housing 15. A signal interface 16 of the microscopy device 2 and a signal interface 17 of the objective 3 are also shown. A signal and / or data connection between the microscopy device 2 and the objective 3 can be established via the signal interfaces 16 and 17. The objective 3 further comprises a control and evaluation unit 18, which controls the movement of the movable part 19 along the spatial direction parallel to the optical axis of the objective 3. The control and evaluation unit 18 is connected via signal and / or data to the signal interface 17 of the objective 3 and the piezo actuator 12. Information on the movement of the scanning beam along the first spatial direction and, if applicable, along the second spatial direction y can be transmitted to the lens 3 via the signal interfaces 16 and 17. Based on this information, the control and evaluation unit 18 can then change the position of the moving part 19 along the spatial direction parallel to the optical axis. Figure 2 shows a further embodiment of an imaging system with a lens 3. The embodiment shown in Figure 2 is essentially the same as the embodiment shown in Figure 1. In contrast to the embodiment shown in Fig. 1, the optical elements 11a, 11b are arranged in the housing 15 in a fixed position relative to the housing 15. Furthermore, the housing 15 can be displaced parallel to the optical axis of the lens 3 by means of the piezo actuator 12. Thus, the position of the focal point of the lens 3 along the optical axis can also be changed by means of the piezo actuator 12. In this case, the movable part 19 of the lens 3 therefore comprises the housing 15 with the optical elements 11a, 11b arranged therein. Furthermore, the contact cap 13 is fixedly arranged relative to the microscopy device 2. In particular, the contact cap 13 can be attached to the microscopy device 2, especially to a housing of the microscopy device 2, or be part of the microscopy device 2. Attachment can be effected, in particular, via a linkage. Of course, other types of attachment are also possible. Figure 3 shows a further embodiment of the imaging system 1. The embodiment shown in Figure 3 is essentially the same as the embodiment shown in Figure 1. In contrast to the embodiments shown in Fig. 1 and Fig. 2, the lens 3 comprises a third optical element 11c, which is arranged between the first optical element 11a and the second optical element 11b. The third optical element 11c can be configured as a lens. Furthermore, the objective includes a means, configured as a piezoelectric actuator 12, for changing the spatial position of the third optical element 11c along an optical axis of the objective 3. Thus, a movable part 19 of the objective 3 includes the third optical element 11c. The first and second optical elements 11a, 11b of the lens 3 are fixed in position relative to the reference coordinate system described above. The third optical element 11c can be moved along the optical axis to change the focal point position of the lens 3 along the optical axis. Furthermore, the contact cap 13 can be arranged in a fixed position relative to the microscopy device 2. In particular, the contact cap 13 can be attached to the microscopy device 2, especially to a housing of the microscopy device 2, or be part of the microscopy device 2. The contact cap 13 can also be attached to the fixed part 20 of the objective 3. Attachment can be effected, in particular, via a linkage. Of course, other types of attachment are also possible. Fig. 4 shows a schematic flowchart of a method according to the invention for operating an imaging system 1 (see Fig. 1 ). In a first step S1, the process is started. In a line scan step ZSS, a scanning beam is moved along a first spatial direction by the confocal microscopy device 2 until a line of a two-dimensional image to be generated is produced. For this purpose, the scanning beam can be moved along a predetermined path along the first spatial direction. The movement along the first spatial direction can be controlled by the scanner device 7 of the microscopy device 2, shown in Fig. 1. During this movement, the set focal point position is constant or approximately constant. In a test step PS, it is checked whether the desired maximum number of lines of the two-dimensional image to be generated has been reached. If this is not the case, in a focal point position change step BPVS, the position of the focal point of the lens 3 (see e.g. Fig. 1) along or parallel to the optical axis of the lens 3 is changed by more than a predetermined amount, or a new line of the image is generated. Following this, another line scan step ZSS is performed, again traversing the previously described path along the first spatial direction. Thus, during a line scan step ZSS, the focal point position along the optical axis remains constant or nearly constant. Once the desired maximum number of lines is reached, the process terminates in a further step S2. The generated image can then be output. A new image can then be created by starting the process again with the first step S1. Figure 5 shows a further embodiment of the imaging system 1. The embodiment shown in Figure 5 is essentially the same as the embodiment shown in Figure 1. In contrast to the embodiment shown in Figure 1, the imaging system 1, in particular the lens 3, does not include a contact cap 13 (see Figure 1). Therefore, no contact material 14 is necessary, which would otherwise have to be arranged between the contact cap 13 and the cornea 10. Reference symbol list 1 Imaging system 2 Confocal microscopy device 3 Objective 4 Beam generation device 5 Beam splitter 6 Objective system 7 Scanner device 8 Detector 9 Aperture 10 Cornea 11 Optical element 11a First optical element 11b Second optical element 11c Second optical element 12 Piezo actuator 13 Contact cap 14 Contact material 15 Housing 16 Microscopy device interface 17 Objective interface 18 Control and evaluation unit 19 Moving part 20 Fixed part x First spatial direction y Second spatial direction z Third spatial direction S1 Start step S2 End step ZSS Line scan step BPVS Focal point position change step PS Check step

Claims

Objective for a confocal microscopy device (2) for generating images of an eye or a part of the eye, wherein a scanning beam is movable along a first spatial direction by at least one scanner device of the microscopy device (2), wherein the objective (3) comprises at least one optical element for beam guidance and / or shaping, wherein the objective (3) comprises at least one means for changing a focal point position at least along an optical axis of the objective (3), characterized in that the objective (3) has at least one signal interface (17) for signal and / or data communication with the confocal microscopy device (2), wherein information about at least one parameter of a movement of the scanning beam along the first spatial direction can be transmitted from the microscopy device (2) to the objective (3). Lens according to claim 1, characterized in that the lens (3) has or forms at least one contact section for mechanical contacting an eye or a fastening section for a means for mechanical contacting the eye. Lens according to claim 1 or 2, characterized in that the focal point position can be changed continuously or stepwise. Lens according to one of the preceding claims, characterized in that the lens (3) has at least one means for changing the position of at least one optical element parallel to the optical axis of the lens (3). Lens according to claim 4, characterized in that the lens (3) has at least one means for changing the position of the entirety of optical elements of the lens parallel to the optical axis of the lens (3). Lens according to one of the preceding claims, characterized in that the lens (3) comprises a housing (15) wherein the at least one optical element is arranged in the housing (15), wherein the lens (3) has at least one means for changing a position of the housing (15) parallel to the optical axis of the lens (3). Lens according to one of claims 4 to 6, characterized in that the means for changing the position comprises at least one piezo actuator (12), one electromagnetic actuator, one electromechanical actuator, one capacitive actuator or one ultrasonic motor. A lens according to one of the preceding claims, characterized in that the focal point position can be changed in such a way that a two-dimensional image with a predetermined line frequency and a predetermined vertical frequency can be generated, wherein different lines of the two-dimensional image are generated at different focal point positions. Lens according to one of the preceding claims, characterized in that the lens (3) is designed as an attachment. Imaging system, wherein the imaging system (1) comprises a confocal microscopy device (2) and an objective (3) according to any one of claims 1 to 9, characterized in that the imaging system (1) comprises at least one acousto-optic modulator for moving the scanning beam along the first and / or the second spatial direction and / or at least one electro-optic modulator for moving the scanning beam along the first and / or the second spatial direction. Imaging system according to claim 10, characterized in that a scanning beam generated by the microscopy device (2) is movable along a first spatial direction, wherein the first spatial direction is different from the spatial direction of the optical axis of the objective (3). Imaging system according to claim 11, characterized in that a scanning beam generated by the microscopy device (2) is movable along a second spatial direction (y), wherein the second spatial direction (y) differs from the first spatial direction and from the spatial direction of the optical axis of the objective (3). Imaging system according to one of claims 10 to 12, characterized in that the scanning beam can be generated in a pulsed manner. Method for operating a lens (3) according to one of claims 1 to 9, characterized in that a focal point position of the lens (3) is changed. Method for operating an imaging system (1) according to one of claims 10 to 13, characterized in that a focal point position of the lens (3) is changed. Method according to claim 15, characterized in that a scanning beam generated by the microscopy device (2) is additionally moved along a first spatial direction, wherein the first spatial direction is different from the spatial direction of the optical axis of the object (3). Method according to one of claims 15 or 16, characterized in that a wavelength of the scanning beam is changed.

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