WO2004049928A1

WO2004049928A1 - Method and device for conducting in vivo identification of the material composition of a target area of a human or animal body

Info

Publication number: WO2004049928A1
Application number: PCT/DE2003/003999
Authority: WO
Inventors: Horst Prehn; Rainer Sus
Original assignee: W.O.M. World Of Medicine Ag
Priority date: 2002-12-03
Filing date: 2003-12-02
Publication date: 2004-06-17
Also published as: DE10257169A1

Abstract

The invention relates to a method for conducting in vivo identification of the material composition of a target area of a human or animal body, particularly for differentiating body stones from surrounding tissue in the target area. The inventive method comprises the following steps: a) carrying out the essentially nondestructive stimulation of the target area (2) by at least one optical stimulation signal; b) detecting at least one acoustic, thermal and/or mechanical response signal emitted by the stimulated target area (2); c) analyzing the detected response signal with regard to its properties, particularly with regard to its periodic properties and/or its oscillation modes, and; d) assigning properties of the analyzed response signal and/or of the stimulation signal to predetermined property classes that each represent at least one material composition of the stimulated target area (2). This results in the provision of an improved method for conducting in vivo identification of the material composition of a target area of a human or animal body.

Description

Method and device for in vivo detection of the material properties of a target area of a human or animal body

description

The invention relates to a method for in vivo detection of the material properties of a target area of a human or animal body according to the preamble of claim 1 and a device suitable for carrying out the inventive method according to the preamble of claim 42.

The in vivo detection of different materials plays a major role in clinical diagnosis and therapy

Role. Such material detection is used for example in endoscopic stone disintegration (lithotripsy) to enable targeted destruction of body concrements, especially kidney stones or gallstones. The material detection is particularly important if the material processing or destruction of body concrements is to be carried out by means of high irradiated laser energies, since damage to the surrounding tissue by the laser pulse must be excluded.

From EP 0 312 650 A1, a method and a device for material processing with the aid of a laser is known, in which light reflected back from a body concrement to be processed is used to control the material-processing laser.

From US 4,939,336 a method and a device for material processing with a laser is known, in which the light scattered back from a stone to be processed is used via a detector arrangement to control the material-processing laser.

The known methods for recognizing body concrements can be limited, for example, by the presence of bleeding in their detection performance.

The optical detection method used in the detection process must also be usable under the unfavorable conditions that occur in practice, such as a high proportion of scattered light, changing surface conditions of the target surface, as well as with changing fiber positions, inclination angles and different distances of the optical fiber in relation to the target material. Known methods are also unsuitable, inter alia, for immediate clinical use with regard to a target material with unknown material constituents, since this involves essential material-specific parameters before each analysis of the material to be examined must always be determined beforehand, so that the critical presetting of the parameters for the analysis can only take place. A fundamental disadvantage of this and other known methods, which primarily use the substance properties for identification, classification and / or material recognition for analysis purposes, in that they try to obtain an identification of the substances present in the target area on the basis of certain spectroscopic features that the In the case of the practically available target material with a large number of different substances, each with unknown and different compositions and concentrations, and with an inhomogeneous spatial distribution, as is well known to the person skilled in the art, this can lead to extremely complex spectral behavior with variabilities that are difficult to overlook. This results in the fundamental disadvantage for the known methods of this type that a clear and quick determination of certain significant spectral features is practically hardly possible, as a result of which the use of spectral information for obtaining material-specific features as well as a classification and recognition under the occurring practical conditions in most Cases is excluded. Especially in the visible spectral range or near infrared range, which is mainly used in most laser applications, various tissue types, for example, do not show tissue-specific, characteristic and significant absorption bands that can be used for identification. As is also well known to the person skilled in the art in this field, only the spectral features specific to blood in the form of the characteristic hemoglobin bands appear significantly in a spectroscopic analysis of perfused tissue, which is the case with the known methods which determine the optical spectral parameters exploiting the presence of tissue or stone material leads to the disadvantage that in the case of bleeding, which in clinical use, for example, laser lithotripsy with the corresponding Frequency can occur, depending on the type of analysis method used and based on spectroscopic methods, can lead to inevitable errors. It is particularly disadvantageous, for example, if laserithotripsy procedures of this type, which are carried out under certain circumstances without additional visual inspection and thus sudden bleeding cannot be determined, that in this case, due to an incorrect determination of stone material instead of tissue material, a tissue harmful delivery of the high laser energy can take place. It is also conceivable that even in the presence of well-perfused tissue areas such as, for example, parenchyma tissue, unintentional damage to this tissue compared to other less perfused tissue types leads to particularly highly absorbent and, moreover, particularly radiation-sensitive tissues.

The object of the present invention is to provide an improved method and an improved device for in vivo detection of the material properties of a target area of a human or animal body.

The object is achieved by a method having the features of claim 1.

Accordingly, the method according to the invention for in vivo detection of the material properties of a target area of a human or animal body is carried out in such a way that the target area first experiences non-destructive excitation by means of at least one optical excitation signal. The at least one acoustic and / or mechanical response signal emitted by the excited target area is then detected and then subjected to an analysis to determine its properties, in particular its periodic properties and / or its vibration modes. The properties of the detected The response signals are then assigned to property classes, each of which represents at least one material quality of the excited target area. By assigning the properties of the detected response signal to a property class, it is possible in this way to make a statement about the homogeneous or heterogeneous material properties of the excited target area.

The method according to the invention takes advantage of the photoacoustic effect. The photoacoustic effect manifests itself in such a way that the optical radiation energy radiated into a sample body is absorbed by the latter and converted into mechanical vibrations within the sample body. These mechanical vibrations can then be detected on the surface of the specimen or in the vicinity thereof as mechanical vibrations and / or as an acoustic signal.

It is therefore advantageous that the known optical detection methods are not used for detection, since, due to the system, these do not permit a sufficiently stable and reliable determination of the material properties due to the optical parameters due to the light scattered back into the optical fiber when the aforementioned unfavorable conditions occur.

In order to effect a specific stimulation of the target area and discriminating the detected acoustic and / or mechanical response signal from ^■ artifacts is the at least one excitation optical signal from at least one loading züglich specific parameters, in particular the excitation wavelength of the excitation energy, the phase of the time expansion, and / or the pulse sequence controllable light source generated. In particular, a laser is advantageously provided as the light source, since on the one hand the necessary excitation energies can be provided and on the other hand the parameters of the laser are reproducible and can be varied within a wide range. The different parameters of the light source and in particular the laser can also run through a sequence within an excitation signal. In this way, a specific excitation sequence of the excitation signal, which is matched, for example, to the specific properties of the expected material, can be generated. In the subsequent evaluation of the detected response signal, the analysis can also be based on the specific excitation signal, among other things.

Depending on the application and practicality, the detection of the mechanical and / or acoustic response signal can be carried out with at least one detector arranged inside and / or outside the body. When using several detectors, on the one hand the signal quality can be improved by summation and, on the other hand, the propagation characteristics of the mechanical and / or acoustic waves can be determined in this way. The use of at least two different detectors at different detection locations further enables the spatial propagation direction and / or the propagation speed of the response signal to be determined from the relationship of the resulting at least two response signals to one another, and the target area to be localized.

In order to be able to carry out the analysis of the response signal efficiently with a high information component and a low noise component, the detected response signal can be processed before the analysis in particular by amplifying, filtering, transforming and other possibilities for improving the signal-to-noise ratio and / or by averaging. For precise determination of the response signal initiated by the excitation signal, the excitation signal and the response signal can be correlated with one another in order to determine the relationships of the two signals to one another from the correlation data to be able to determine and suppress unnecessary signal components, such as echoes. From the correlation data, a plurality of response signals can be synchronized with one another on the basis of the temporal and / or phase correlation data determined and / or can be set in another desired temporal and / or desired phase relationship to one another. The signal / noise ratio can be further improved by synchronizing the response signals. The response signal prepared in this way is now ready for the following analysis.

When analyzing the detected response signal or the processed and / or correlated response signal, the periodic properties contained in the response signal are determined, among other things. In order to obtain precise information about the material of the excited target area, the vibration properties, in particular the photoacoustic vibration modes of the detected response signal, can also be determined during the analysis from the periodic properties. This determination of the photoacoustic vibration modes of the excited target area is advantageously obtained using the known method of dynamic analysis.

Furthermore, the periodic properties of cavitation events occurring in the target area can be determined. Conclusions about the material of the excited target area can also be drawn from the determined cavitation periods.

Conclusions regarding the material properties of the target area can be drawn from the properties of the detected response signal determined in the analysis. The properties of the analyzed response signal obtained in the analysis are used for simple handling and for direct evaluation of the properties of an excited target area assigned to predetermined property classes, which in turn represent certain material properties. The assignment of the properties of the analyzed response signal of the excited target area is carried out in particular on the basis of the determined correlation properties of the periodic properties, the oscillation properties and / or the cavitation properties. The predetermination of the combination of certain properties into property classes and the material properties belonging to the property classes can be carried out analytically and / or empirically. The respective materials are theoretically / analytically examined for their respective vibration properties in an analytical way. A sufficient number of test measurements are carried out empirically on the materials of interest and their findings summarized in significant properties. The insights gained analytically and / or empirically are then combined into property classes, each of which has significant properties for a material.

A simple distinction between a body concrement and the tissue surrounding it can be carried out, for example, in such a way that if there are periodic components in the analyzed response signal, it is assumed that the target area has a solid structure, that is to say the presence of a body concrete. Here, the knowledge is used that the photoacoustic effect in solids already occurs at lower energies than with predominantly liquid materials. From specific periodic components of the analyzed response signal of the target area, in particular the detected photoacoustic oscillation modes, the specific material of a solid body can be concluded in a more detailed classification. Parameters of the excitation signal can also be included in the assignment of the respective properties of the detected response signal to the respective property classes. It should be noted in particular that specific periodic properties of a specific material only occur under equally specific excitation conditions. The respectively analyzed vibration properties of the excited target area can also be related in connection with the excitation conditions, in particular with the excitation energy, the excitation wavelength and the excitation pulse shape, in order to infer the respective material.

In a further variant of the invention, the variations in the detected response signal that occur when the excitation conditions are varied are included in the assessment of the material properties. In particular, a specific behavior of the respective excited target area is initiated by varying the excitation wavelength and / or the excitation intensity, so that specific material properties can in turn be inferred from the resulting properties of the detected response signal.

Specific material properties can also be inferred from the properties of the cavitation events in the target area, taking into account the respective excitation conditions. If the excitation conditions are varied, specific material properties can also be derived from the resulting variation in the cavitation conditions.

Furthermore, the direction of propagation and / or the speed of propagation of the acoustic and / or mechanical response signal emitted by the target area also allows the target area to be assigned to at least one property class. Here, among other things, the knowledge is used that both transverse and longitudinal waves can be transmitted in the solid, whereas only longitudinal waves can be transported in a liquid phase such as soft tissue material.

For simple classification of the detected response signal, for example by an operator, it can be represented acoustically and / or optically. The excitation conditions, in particular the parameters of the excitation signal, can also be included in the acoustic and / or visual representation. A voltage-controlled oscillator (VCO) can be used for the acoustic representation of the response signal and / or the excitation signal. The surgeon using the method according to the invention, who, for example, has inserted an optical fiber endoscopically into a body cavity for stone destruction, can easily determine on the basis of the resulting tone characteristics whether the end of the optical fiber is in the area of the body's concrement or whether the optical fiber is in the direction of the surrounding tissue indicates. If the end of the optical fiber is in the area of the stone to be broken, the operator can trigger a laser pulse suitable for material processing.

A graphic representation, for example on a screen, can also be used for an optical representation of the response signal and / or the excitation signal. The excitation signals and the response signals are advantageously displayed in a coordinate system. For example, the excitation signal is advantageously depicted on the abscissa and the response signal on the ordinate of a coordinate system. The graphs, patterns and trajectories that form on the screen when the target area is excited and the response signal is subsequently detected can be characteristically assigned to a specific material quality. In a further variant of the invention, the respective properties of the response signal together with the excitation conditions are combined in multidimensional feature vectors, which can also be displayed on a screen. The representations resulting in the respective feature space are also again specific to a certain material quality.

In order to reliably support an operator in his work, the steps for recognizing the material properties of the target area are repeated continuously or periodically. This means that the target area is constantly checked.

The assignment of the target area to a material quality can also be used for the automatic control of the material processing of the target area, in particular for lithotripsy. In such an embodiment of the method according to the invention, the material-processing laser pulse is automatically released by the method. The operating surgeon thus only has to take care of the endoscopic guidance of the respective optical fiber, the triggering of the respective stone-destroying impulse then takes place automatically. In another embodiment of the method according to the invention, the triggering of a material-processing impulse, for example by an operator, is only released when a certain material quality, in particular a body concrete, has been detected in the excited target area. In this way, damage to the surrounding tissue or accidental triggering of the material-processing laser pulse can be avoided, which increases the operational reliability of the method.

In an extension of the method, in addition to the detected mechanical and / or acoustic response signal As well as the excited target area, at least one ultrasound signal of the target area is also detected by means of ultrasound echoscopy. Different methods of ultrasound echoscopy are widely known and are widely used in the clinical field.

The ultrasound signal generated and received with the ultrasound echoscopy method is advantageously correlated with at least one optical excitation signal and / or at least one photoacoustic response signal. Using the correlation data obtained, the ultrasound signal can be synchronized with at least one excitation signal and / or with at least one response signal and / or can be set in another predetermined temporal relationship and / or a predetermined phase relationship to one another. In this way, an ultrasound image and information about the material properties of the target area of interest can be obtained simultaneously.

Since the ultrasonic signal is also modulated by the mechanical vibrations of the optically excited target area, properties of the target area can also be learned from the received ultrasonic signals by determining periodic properties and / or determining the photoacoustic oscillation modes of the ultrasonic signal.

A clear representation of the target area can be achieved if the ultrasound image obtained with the ultrasound echoscopy method is provided with the material properties of the respective target area determined with the method according to the invention. In this way, different material properties can be indicated and marked in the ultrasound image and displayed clearly, which supports the work of an operator. It is advantageous to generate an ultrasound image and / or an ultrasound image. Provide sound image controllable by at least one response signal.

The object is further achieved by a device for performing the described method with the features of claim 42.

Accordingly, the device for carrying out the method has at least one light source for the optical excitation of a target area in a human or animal body, at least one detector arranged on or in the body for the detection of mechanical and / or acoustic response signals, at least one analysis means for analysis the properties of the detected response signals and at least one display means for displaying the response signal and / or the properties of the analyzed response signal.

In order to have a sufficiently energetic and modular light source available, it is advisable to use a laser as the light source. The laser can be controlled relatively easily with regard to its parameters, in particular its wavelength, its intensity and its pulse sequence.

The light source can either be attached to the endoscope itself or an optical fiber is provided for guiding the light emitted by the light source. This optical fiber can be easily arranged on an endoscope.

An inexpensive and reliable detector for the detection of mechanical and / or acoustic vibrations is implemented by piezoelectric ducks.

In summary, it can be stated that the present invention is based on a method and apparatus for radiation of body tissues, body fluids or solid body concrements with the help of specifically designated radiation energy. The target area exposed to the radiation energy (target material) shows various photo-induced reactions due to the introduced photonic energies, which can be used for diagnostic purposes as well as for different therapeutic purposes or for material processing. A selective therapeutic application and / or material processing can also take place under feedback-controlled conditions if appropriate information is derived from the diagnostic method and the material properties determined thereby serve to specify the requirements for a specified and appropriately controlled setting of the radiation parameters and To enable delivery of the radiation energy for the respective therapeutic application or material processing.

The effects of the radiation energies on the target material can consist on the one hand in that certain photo-induced entropic or elastic reversible states are excited in the present target material and on the other hand at specific, higher radiation energies also specific desired irreversible structural changes such as photoablation and / or photothermoplasty on tissues or crushing or fragmentation of body concretes (gallstones, kidney stones, bladder stones, saliva stones, etc.) can also be achieved. The different interactions with different radiation parameters associated with the respective target material associated with a specific exposure to correspondingly specified radiation energy can be used in such a way that with the aid of correspondingly specified optical excitation and suitable detection and analysis methods, a non-destructive in vivo analysis for Determination of the material properties of the irradiated target area is made possible. On On the basis of these analysis results, a selective and controlled therapeutic application or material processing of the same target area and target material can be achieved in immediate succession, with suitable feedback processes being implemented for process automation.

The present invention specifies a method and a device with which, in a first step, a non-destructive in vivo analysis of the respective target material is achieved, with which a determination and classification or recognition of the material or certain material properties due to its different material - Compositions and / or structural properties and / or its structural dynamic or rheological behavior is possible. In a subsequent step, a targeted and selective application of the radiation energy applied to the same target area and the same target material can then take place for different therapeutic purposes and for processing the target material according to the requirements of the previous in vivo analysis results. Thereby, the therapy process or material processing process takes place through currently specified and controllable different settings of the radiation energy as well as through other relevant radiation parameters in the course of the diagnostic process or through correspondingly suitable feedback process routines.

In the case of application of the method and device in the field of laser lithotripsy, the invention offers the possibility that the high laser energy required for plasma release and stone fragmentation is selectively applied only if the stone material to be processed is present. This ensures that the high laser energy used for lithotripsy never hits the tissue to be protected. Any unwanted colla- teral damage to the tissue surrounding the stone is excluded with certainty. Reliable and safe selective material processing is also possible without visual inspection, whereby even in the case of a blind process, selective stone fragmentation is achieved without damage to the surrounding tissue, which can be achieved by means of an appropriately suitable automated feedback process control. Here, the analysis data determined before each processing step and in each preceding analysis step are used for feedback control of the selective laser processing method.

To determine the material properties present in the target area, various photo-induced interactions with the target material are used individually or in combination for analysis purposes in order to obtain reliable, unambiguous and significant target-specific features for discrimination, classification, material and structure recognition, the inventions derived therefrom method has the advantage of sufficient selectivity for the application and a suitable analysis result is achieved in a simple and immediate manner.

Likewise, the radiation energy applied to the target area to determine material properties in no case leads to optical plasma emission or denaturation, damage, destruction or perforation of the biological tissue to be analyzed.

Advantageously, therefore, only low radiation energies are used to excite the target area, which indeed lead to a correspondingly specified optical excitation of the target material that is necessary in the sense of the analysis method, but completely exclude damage. The detection method can be used with different laser types at different wavelengths as well as with pulsed lasers with different laser pulse durations as well as for CW lasers or modulated CW lasers.

The use of non-optical detection systems has the advantage that the different structural dynamics of the photoacoustic, photo-thermal or photo-elastic effects triggered by optical excitation of the target material are used to determine the material properties. The principle advantage of this type of detection is that the detected signal depends exclusively on the radiation energy actually absorbed in the target material, which means that no disturbances in the measurement can occur due to the strong scattered radiation that usually occurs with such materials and thus the disadvantages of the known optical detection methods in this regard omitted. Another advantage can be seen in the fact that there are practically unlimited possibilities of usable radiation energies available for the effective excitation of the target material for analysis purposes, it being possible to work with very different radiation sources and radiation conditions. Thus, the photonic emission used for excitation can basically take place with a largely arbitrary spectral distribution and also over an extremely broadband wavelength range, which results in the advantage of a largely free choice of the wavelengths or wavelength ranges used depending on the application and the radiation source used. The particularly advantageous high detection sensitivity of the detection method compared to the known methods in connection with the high specificity and selectivity of the analysis method that can be achieved with this solution is due to the essential difference that the tissue materials to be examined are fundamentally not clear and sufficiently precise with regard to their purely material characteristics because most fabrics do not differ significantly in terms of their material content and composition. However, the corresponding tissue types differ significantly in terms of their morphological structures, which in turn are directly linked to the functional physiological properties. The analysis of these structural characteristics therefore has the advantage that the use of structural dynamic and rheological analysis methods are suitable for determining and precisely differentiating tissue properties and for functional characterization.

It is therefore advantageous to use appropriate acoustic or mechanical vibration detectors or other known methods with which the thermal, acoustic or elastic waves emanating from the target area with optical excitation can be detected.

The detection of these thermal, acoustic or elastic waves has the further advantage that they spread linearly over large distances in the body tissue themselves and reach the surface of the body, where they are applied without additional sensors and without further effort sensors attached to the body surface can be easily detected. This solution has the further advantage that a spatial and temporal assignment of the acoustic waves emitted by the target area is possible by attaching additional sensors at different positions on the body surface. The simultaneous registration with several detectors at different detector positions and / or the use of correspondingly arranged and operatively coupled sensors, e.g. for focused detection on certain selected target points or target areas, is particularly advantageous because with this solution, in addition to a spatial position determination of the acoustic source also further additional significant target-specific features with regard to the different acoustic radiation characteristics in connection with the other structural dynamic features obtained on the basis of the photoacoustic, photothermal or photoelastic interactions taking place in the target material itself for analysis purposes and also also for assessing the therapeutic success achieved with each therapeutic radiation exposure or else can be used to evaluate the processing state brought about by the laser energy and the effectiveness of the processing.

For example, solid materials such as stone concrements differ from soft tissue material not only in terms of their structural diversity, but also significantly in terms of their different sound propagation properties, with solid-state concrements having both transverse and longitudinal wave propagation, but in contrast in the soft body - tissue only longitudinal wave propagation takes place. These different properties of acoustic wave propagation known to the person skilled in the art are advantageously used for the analysis purposes according to the invention and for achieving a reliable discrimination performance, material classification or material detection.

It is particularly advantageous if, as in the case of laser lithotripsy, for example, the application is carried out without visual inspection (blind procedure) and with this solution, the degree of fragmentation of the stone concrement achieved can be easily determined and displayed accordingly. An additional benefit also results from the fact that when used in the blind process, the solution according to the invention can also be used to easily implement a navigation and positioning aid, which is necessary to achieve an optimal fiber position for the effective stone destruction or an optimal stone contact can be exploited. This solution has the advantage that even larger target areas can still be navigated and probed even if an endoscopic visual inspection is impossible due to the lack of access for the endoscope, but due to the considerably smaller fiber diameter of the laser fiber, access to it is impossible Fiber in certain cavitations with a lower lumen such as bile ducts is nevertheless possible. This solution significantly extends the safe clinical application area.

The detection method for determining the material properties can be used clinically immediately and without any prior knowledge of the type and composition of the material constituents, even without any prior knowledge. The advantageous relationship between the different structural, structural dynamic and functional rheological properties of body materials is used. This solution is based on the knowledge that there is a reciprocal relationship between the morphological properties of biological tissue structures and their corresponding specific physiological functionality. As is known from structure theory, structural biology and biophysics of tissues, the tissue morphological structure formation processes with correspondingly proven adaptive plasticity and the associated functional physiological and pathophysiological functionality mutually constitute each other in a highly specific and complementary way. The detection and determination according to the invention of certain extremely significant tissue elastic properties (tissue rheology) present in the target area and their associated highly specific structural or structural dynamics features is advantageous for the sensitive and reliable detection, selective differentiation, classification and detection of biological materials and / or solid body concrete used. Further advantageous applications of the invention are to be seen in the fact that with the help of the solution according to the invention, different novel in vivo analysis tools for biomedical research purposes for the elucidation of diverse biological energy and structure conversion processes or structural vibration modes and their dynamics are also possible, such as with different types of cellular organizational processes or in morphogenetic development phases and growth processes, which are characterized by specific conformational changes and / or activation states. Certain tissue mechanical functionalities, such as plasticity, entropic elasticity or viscoelasticity, play an important role here. The possibility of in vivo investigation of various mechanisms of mechanotransduction or certain photoelastic and thermoelastic transduction processes, etc., opens up far-reaching application perspectives for future biotechnological, biomedical in vivo analysis methods and clinical diagnostic methods. Various uses are also conceivable for selective and feedback-controlled biomedical intervention, for example for selective photoelastic, photothermal or photoacoustic-induced structural integration or disintegration in selected regional tissue compartments, cellular structures or for the targeted generation and servo control of specific anisotropies and gradient fields, viscoelastic and tissue rheological conditions, as well as certain local microaccellations. Further conceivable applications arise according to the principles of the method according to the invention in connection with the targeted application of selected biological micro- and nanostructures with specifically controllable radiation energy with the help of suitable optical applicators and through the photo-induced selective local sonic excitation or sono-stimulation which can be achieved thereby. to achieve various controllable, highly specific physiological effects, such as For example, the specific influencing of certain specific local cellular motility, surface and volume changes or of transport and regulation processes or the servo control or modulation of physiologically relevant fluid-dynamic pump mechanisms or targeted influencing of microcirculatory hemodynamic parameters. In the context of a selective and controlled laser-induced shock wave application, the possibility according to the invention arises both for the use of the method for various conservative physiotherapeutic or orthopedic shock wave treatments and for their invasive application.

A particular principal advantage of the solution according to the invention lies in the fact that the structural-dynamic order states that are generated in the target material by means of optical excitation and can be detected and analyzed with the aid of the designated detection method are largely independent of the properties of the spectral emission of the stimulating radiation energy used in each case results in a largely unrestricted selection of the radiation systems that can be used for this purpose. This enables the method to be used over an extremely wide wavelength range, e.g. from the microwave, IR, VIS, or UN range to X-ray or gamma radiation for excitation.

A correspondingly suitable operationalization of the non-destructive in vivo detection method and material detection system with correspondingly selected corresponding applicator systems is also brought about. These applicator systems, which are suitable for the selective application of the target material in each case and which work with radiation types which have been selected appropriately and are suitable for achieving the respective material processing task or therapeutic task, and so on on the basis of the determined material properties, a correspondingly controlled delivery of the radiation energies is achieved with precisely defined radiation parameters. This operationalization is possibly carried out under online conditions with the implementation of certain application-specific process routines.

Such a semi-automatic process routine, for example, can consist in that, after the material property has been automatically determined with the aid of the recognition system, based on suitable specific characteristics, the user can use this data according to his own specifications to achieve his specific and with the help the selective radiation application, processing or therapeutic intervention continues until the processing target is reached on the basis of the desired progress ascertained after each processing step by means of the recognition system. In order that the progress of the processing and the achievement of the processing target can be easily recognized by the user at any time, appropriate means are provided which, based on a suitable visual and / or acoustic representation and display of the current analysis data, enable quick and easy assessment allow the effectiveness or success of the processing. For this purpose, different known parametric and / or symbolic representation techniques can be advantageously used for the appropriate online representation of the acute analysis result, which also provide the user with additional probing and / or navigation and / or positioning aids for optimal application of the radiation energies such as for example for the targeted guidance and selective positioning of an optical fiber introduced into the corresponding cavitation. Corresponding aids can also advantageously be provided, which allow easy operation and quick adjustment of the required radiation parameters. This process routine used in the sense of the invention serves on the one hand the control for a targeted, effective and selective material processing and on the other hand also serves as a safety system which in any case excludes with certainty an undesired and damaging application of the radiation energy to the material to be protected or the surrounding tissue. In addition to a semi-automatic operationalization of the method according to the invention, automatic process routines are also conceivable, with the aid of which direct feedback control is possible. For this purpose, suitable control parameters can be derived in real time from the analysis process data obtained, which are then used to control and regulate the various radiation parameters. It is advantageous if these process routines also contain a corresponding control logic, which, with the aid of appropriately implemented security criteria, excludes the various risks of incorrect operation and incorrect handling as well as tissue damage.

The invention is explained in more detail below with reference to the drawings of the figures using three exemplary embodiments. Show it:

1 shows a schematic representation of the method according to the invention and the device according to the invention for in vivo detection of the material properties of a target area of a human or animal body,

2 shows a schematic representation of the method according to the invention and the device according to the invention in a second embodiment with automatic or semi-automatic material processing, and Fig. 3 is a schematic representation of the method and the device of Figure 2 with additional ultrasound echoscopy.

In Figure 1, the process of material detection and the necessary device is shown schematically. The surgeon guides an optical fiber 1 into the relevant target area 2 of the body of the patient to be treated, for example with the aid of an endoscope. An optical excitation signal can be directed into the target area 2 through the optical fiber 1 via a laser 7 (laser sources). The individual parameters of the laser 7 are controlled manually or automatically via a control device 6 (laser parameter control). The control device 6 can thus be used, for example, to set the laser wavelength or laser wavelengths, the intensity of the laser, the radiation duration or the pulse sequence and their respective variation.

The target area 2 can thus be acted upon by the optical fiber 1 with the laser 7 with an optical excitation signal specified in its parameters. Different parameter profiles for the laser 7 can also be called up via the control device 6 or sequences of different parameter profiles can be run as sequences. Such a parameter profile is specified, among other things, by several values for the corresponding sequences of excitation sequences to be run through, such as the radiation energies and radiation powers applied here, the dynamic parameters, the types of modulation (e.g. AM, FM, PM, PRBSC) and the modulation parameters (e.g. modulation frequency , Degree of modulation), the spectroradiometric parameters (eg wavelengths, spectral composition) as well as the radiation field parameters and the speaking spatial irradiation positions on the specimen.

A detector 8 is attached outside or inside the body of the patient to be treated, by means of which acoustic and / or mechanical response signals can be recorded. The acoustic and / or mechanical response signals emitted by the excited target area 2, which are emitted in response to the optical excitation signal, are recorded by the detector 8. These response signals picked up by the detector 8 are first processed in a processing stage 8a (detector signal processing). The processing of the response signals includes, for example, amplifying the signal, filtering, in particular using a bandpass filter, transforming the response signal, averaging or other methods for improving the signal / noise ratio. The signal processed in processing stage 8a is now analyzed in an analysis stage 11 (analyzing procedures).

To analyze the response signal, for example, the periodic properties of the detected response signal are determined. This is done, for example, using known methods such as Fast Fourier Transformation (FFT), Wavelet or others. Using the known method of dynamic analysis, the vibration modes of the excited target area can also be determined from the response signal, which are excited by the photoacoustic effect with optical excitation of the target area 2. Furthermore, the cavitation period of cavitation events taking place in the excited target area can also be determined. Cavitation occurs in the target area due to the vaporization of the liquid phase and the subsequent adiabatic cooling.

In an assignment unit 12a (classification and recognition) the determined properties of the response signals assigned to property classes, each representing material properties. This classification of the properties of the response signal can also take place with the aid of the excitation parameters of the optical excitation signal.

The properties of the response signal can be classified in different ways. In a particularly simple variant of the invention, the response signal is only examined to determine whether a specific photoacoustic event takes place in the target area after the optical excitation. Based on the knowledge of the material properties under different excitation conditions, it is possible to decide whether the optical excitation has affected a solid or the tissue surrounding it. In the case of the solid body, specific oscillation modes can be identified in the response signal at a specific excitation energy, and in the case of excitation of the surrounding tissue, no oscillation modes can then be detected with this excitation energy.

In a second assignment process, the fact is taken into account that different homogeneous or heterogeneous materials have different photoacoustic vibration modes. If vibrational modes in the area of the tissue are also excited at higher excitation energies, these have a completely different spectrum than, for example, that of a stone. The analysis of the excited target area can also be carried out here, for example, in such a way that the analyzed signals are represented as two- or multi-dimensional vectors and are, for example, plotted on a screen. The resulting path curves or trajectories are each specific to the excited material of the target area. Furthermore, the trajectory curves change specifically under different excitation conditions, especially with different excitation wavelengths. and different excitation energies. These changes in the response signal initiated by changing the excitation conditions can also give a specific signature of the material.

A further simple possibility of distinguishing between tissue and body concrement in the excited target area can be carried out in such a way that the processed response signal or the analyzed response signal is made audible. This can be achieved by using known methods and means for auditing and / or bonuses. In a simple case, the processed or analyzed signal is applied, for example, to a voltage-controlled oscillator (VCO) and thus made audible in the hearing range of the human ear. In this case, certain filter methods, mathematical transformations, methods for slowing down or accelerating the signal responses, various types of modulation methods, encoding methods, signal synthesis methods and / or other known means for generating different ones by the respective can be used for further signal processing for the purpose of auditing and / or bonusing Response signal triggered, parametrically controlled and / or modulated electroacoustic sound effects are used. The surgeon can thus easily distinguish between the surrounding tissue and a body concrete, in particular a gall or kidney stone due to the received pitch, the received sound and / or the received tonal pattern. The operator can thus determine the right time and the correct position of the optical fiber to destroy the respective body concrement.

Another possibility for analyzing and classifying the detected response signal is to determine the cavitation properties of the excited target area. Different methods can be used here. For one thing it is possible to measure the vibration modes of the respective material excited by the cavitation in the target area and to treat them as already described above. The different materials can be determined from the vibration modes of the target area on the basis of the significant differences in the spectrum of the vibration modes of the respective materials.

A further possibility is offered by the determination of the cavitation periods themselves. The knowledge is exploited that the cavitation periods depend on the one hand on the irradiated energy and the irradiated wavelength, and on the other hand show a clear dependence on the excited material. Based on the knowledge of the excitation signal, the material can be concluded from the determined cavitation period.

In a parameterized dynamic method, the cavitation period is determined for different excitation energies. The course of the cavitation periods with variation of the excitation energy is also significant for different materials. This para etrized dynamic method can also be carried out with different excitation wavelengths and excitation dynamics.

From the analysis of the cavitation properties or the vibration modes excited in the target area, knowledge of the excitation conditions can also be used to determine whether bleeding is occurring in the target area. Since hemoglobin shows characteristic spectral absorption properties, the excited oscillation modes or the cavitation periods in the target area change during bleeding, since the excitation of the target area is modified characteristically due to the hemoglobin. Bleeding can also be identified when analyzing the vibration modes, since the excitation conditions of the Change target area significantly due to the characteristic hemoglobin bands.

A further analysis option is available if at least two detectors 8 are used, the signal shape of which is compared or correlated with respect to their phase, their intensity and / or their transit time, so that a direction of propagation of the emitted response signal can be determined. This exploits the knowledge that both transverse waves and longitudinal waves can propagate in the solid, whereas only longitudinal waves are propagated in the liquid phase and in soft tissue. On the basis of this knowledge, it is again easy to differentiate between a body concrement and the surrounding tissue.

Furthermore, the different radiation characteristics associated with the laws of sound propagation in acoustic wave propagation between soft tissue material and hard stone material can also be used in the sense of the invention to determine and discriminate the optically excited target material. It is generally known that only in the presence of solid bodies (stone material), in addition to the longitudinal waves also occurring in the soft tissue material, do additional transverse waves occur. This difference is used according to the invention in such a way that an analysis of the corresponding sound wave propagation times and the spatial directional dependence of the sound fields emitted by the optically excited target material is also used, advantageously suitable detection systems in a corresponding number or with a correspondingly suitable spatial one Arrangement can be used in relation to the acoustic target source. In addition to the acoustic detection methods, which are introduced intracorporeally in the vicinity of the target area , it is also particularly advantageous that different types of extracorporeal detection systems can also be used on the body surface for the purpose according to the invention. This method offers the advantage that further additional electrical signal lines or appropriately designed optical fibers can be completely dispensed with, which serve for the purpose of electrical transmission of the sensor signals and the voltage supply of the detector elements or for the optical or acoustic transmission of the sound signals. Instead, the free and linear propagation of sound waves through the body tissue without additional carrier material down to the body surface can be advantageously exploited, whereby a simple and flexible choice of the suitable detection locations and detector arrangements can be made, which also allows a quick exchange of the detector systems used , Based on the knowledge of the invention, it is also possible to use the specific temporal correlations between the laser excitation and the respectively detected photoacoustic signals or the ultrasound echo signals reflected on the target material for the purpose of stone / tissue recognition as well as for artifact-free signal detection and Advantageously use improvement of the signal / noise ratio in the sense of the invention. The improvement in the S / N ratio achieved with this method has the advantage that under these conditions a further reduction in the laser power required for excitation is possible, which leads to optimal protection of the tissue surrounding the stone.

The entire method for in vivo detection of the material properties of a target area of a human or animal body is based on the knowledge that by means of a parametrically controlled optical excitation of the target area, intrinsic photoelastic, photoacoustic see and photothermal properties of the excited target area can be determined by analysis of periodic properties and can be assigned to a specific material type. With the characteristic excitation, certain intrinsic sample-specific nonlinear effects, such as photoelastic, photoacoustic or photothermal transduction processes, which can be achieved thereby, are used in order to obtain a characteristic signature of the complex properties of the sample body. These nonlinear intrinsic transduction processes taking place in the specimen depend in a characteristic way on the structure-elastic, plasto-elastic, thermodynamic and optical properties as well as on the material composition of the sample material as well as on the quality of its surface characterizing selected excitation conditions, for the type, material properties and composition of the specimen. The method aims to obtain a kind of complex signature (fingerprint) from the specimen under operational in vivo conditions due to these multiple and interacting complex but also highly significant dispersive photonically induced interactions.

The method discriminates, recognizes and interprets the complex modal oscillation events triggered by means of multiple parametric radiation excitation of the specimen and their modal radiation and is able to locate and display the recognized specimen.

For an automated or semi-automated classification of the response signals, different types of decision algorithms, such as. For example, threshold discriminators, spectral window discriminators, fuzzy discriminators, neural networks and others are used. Another possibility The analysis or classification of the response signal lies in storing certain properties of the detected response signal obtained in the analysis of the response signal together with the excitation conditions in an n-dimensional feature space. Each measurement is thus mapped with its excitation parameters and with its significant analysis parameters to a point in the n-dimensional feature space. Based on already known feature vectors, it can thus be decided which material a certain feature vector should be assigned to.

A further embodiment of the invention is shown in FIG. One or more optical fibers 1 (beam delivery) are in turn guided by the surgeon to the target area of the body of the patient 2 to be treated. The target area 2 is then optically excited with a correspondingly specified pulse sequence or one or more defined sequences according to modulated laser radiation. The conditions of the radiation applied in each case are selected accordingly for this

Laser sources 7 (laser sources), as well as previously defined by the laser parameters 6 (laser parameter control) that can be set with them and combined into corresponding predefined groups of excitation sequences, which can be in the form of correspondingly stored data records. On the basis of the parameter profiles 4 (parameter setting) contained in the different excitation sequences, which originate from the corresponding stored data records, the laser parameters are automatically checked by means of a corresponding control unit 5 (parametric drive) in such a way that a corresponding process routine 6 (laser parametric control) the laser sources 7 (laser sources) emit the correspondingly specified radiation.

Different and different types of radiation sources, conditions and parameters can be Excitation or stimulation of the present target material in target area 2 can be used individually or in combination with one another in order to determine specific target-specific features with the aid of the formation of thermal, elastic or acoustic wave fields that is dependent on the structure of the target material and is sensitive and selective a structural dynamic analysis. This results in a variety of different embodiments of the analysis method or the processing or therapy method in connection with the process routines required for this in each case for the desired applications, such as, for example, the selective and specifically controllable processing of the target material for the purpose of ablation, plastic deformation (thermoplastic, Angioplasty etc.), laser sectioning of tissue material, laser coagulation or for breaking up (fractionation) of solid body concrements. It is also conceivable to simultaneously process tissue materials for the purpose of biostimulation or photodynamic therapy or conservative photo-induced physiotherapy ultrasound treatment or shock wave therapy.

Different conceivable forms of dynamically dispersive and / or spectrally dispersive laser excitation can be used, such as, for example, a transient excitation with one or a series of short laser pulses or by means of an appropriately selected periodic and / or randomized and / or parametric laser excitation with the aid a modulated CW laser source with specifically identified amplitude modulation and / or frequency modulation and / or pulse code modulation, as well as through a laser excitation at different wavelengths specified on the basis of different spectral parameters, all of which individually or in combination each have a specifically defined dynamic input function represents for the examined excitation and detection system and, in connection with the respectively detected dynamic output function, which the target material system transfer characteristic that can be determined in a significant manner.

In a special embodiment, a Freddy laser was used as the laser source 7. The parameter profile that can be used here has two different laser wavelengths at 532 nm and 1064 nm with a graduable laser energy in the range from 20 mJ to 124 J and the possibility of optional single pulse, double pulse or triple pulse excitation with a variable pulse frequency up to 15 Hz , This laser system provides the necessary prerequisites for frequency-dispersive excitation at two different wavelengths, the green component at 532 nm constantly having an energy of approx. 18 mJ, whereas the infrared component at 1064 nm can be varied in the entire specified laser energy range. Furthermore, due to the selectable multi-pulse excitation and the possibility of pulse frequency variation, the laser system also provides the prerequisites for time-dispersive laser excitation.

With the aid of a number of appropriately trained extracorporeal and / or intracorporeally used detector systems 8 (n-detectors), which are attached to appropriately selected different positions of the patient's body, the response signals originating from the excited target area 1 are received and further signal processing 8a (detector signal processing). Here, the detected response signals can be subjected to known and available analog and / or digital methods such as, for example, certain mathematical signal transformations, filtering techniques, correlation techniques or techniques for improving the signal-to-noise ratio, and others, in order in this way to optimal conditions for the subsequent analysis step 11 (analyzing procedures). Two or three piezoelectric sensors on the patient's body surface can be used as detector systems in a suitable manner. They are attached in such a way that the acoustic signals imitated by the target area are received at different body positions and then processed accordingly in separate channels. Artifacts such as body noises are also sufficiently suppressed by means of a corresponding bandpass filter.

The next step is to use suitable known correlation methods 9 (signal correlation) to determine the temporal or phase correlations 10 (phasing and timing) with regard to the temporal relationships between the laser excitation 6 taking place and the detected response signals 9. Furthermore, it is possible to synchronize the respective response signals with one another accordingly or with regard to a desired temporal relationship to be achieved, e.g. Modify accordingly in accordance with the different signal propagation times and with regard to the time differences that occur, so that the information determined therefrom about the temporal relationships between the laser excitation taking place and the different ones

Signal responses from one or more detectors 8 at different spatial positions can be used in the subsequent analysis. The temporal synchronization of the respective response signals takes place with respect to the point in time at which the excitation signals are emitted with the aid of appropriate trigger circuits, as a result of which a certain number of response signals can be added up coherently over time, which improves the signal / noise ratio. Correspondingly weak response signals of a target area 2 excited with low laser energy (for example 20 mJ) can thus still be adequately detected. This increases the detection sensitivity of the detection. Furthermore, the temporal synchronization of the response signals with one another and with the laser pulses also ensures a determination of the sound propagation times or the sound propagation speeds, which on the one hand Location of the target area and on the other hand is also used to hide reflected acoustic signal components over time. With the help of an appropriately set time window, only the direct and unreflected response signals can be measured.

In connection with the parametrically specified excitation profile 4 of the laser radiation, including its temporal determination, the response signals of one or more signal channels which are correlated and prepared accordingly are subjected to a subsequent analysis 11 (analyzing procedures).

During the analysis, a certain number of properties of the respective response signal are determined. The properties to be determined can be selected on the basis of empirically or analytically gained knowledge. Different analysis strategies are used individually or in combination for the analysis. Hard body stones differ from soft tissue material, among other things, in terms of their different and modal vibration states triggered by the laser excitation specified and in terms of their material-specific different spectral absorption behavior, which can be determined on the basis of corresponding combined dynamic characteristics of the respective response signal in conjunction with corresponding energy-dependent threshold characteristics and certain wavelength-dependent ones Features can be reliably demonstrated.

In a simple form of the procedure, the

Dynamics of the excited vibration modes, which are obtained, for example, by means of a corresponding dynamic analysis, are combined with the respectively specific characteristic threshold energies at different laser wavelengths. In this case, the assignment to the property classes can be limited to determining whether vibration modes exist at all in the excited target area at a certain laser energy and laser wavelength.

Another solution, which can also be implemented with little effort, results from the application of the knowledge that the optically excited vibration modes and the spread of the relevant acoustic wave fronts in the surrounding body tissue differ significantly for solid stone material or soft tissue material. The stone material or the fabric material act as the corresponding characteristic sound sources. For the analysis, the synchronized response signals from two or more detectors at different detector positions on the patient's body surface are used and these are represented in the form of two- or multi-dimensional signal vectors. The generated trajectories of the signal vectors therefore describe characteristic tractors, which enable clear assignment to property classes and thus stone / tissue classification and recognition.

An evaluation of the significant trajectory curves with repetitive or periodic excitation and / or with multiple pulse excitation and / or under different energies and / or excitation wavelengths can be used for further analysis purposes. The course of the respective trajectories is used to assign property classes.

In a further simple embodiment of the invention, the assignment to property classes is based on making the appropriately prepared and analyzed response signals audible. Here, the response signals for each channel are processed in such a way that the respective one filtered with a corresponding bandpass and with the laser Pulse-synchronized response signal controls a voltage-controlled oscillator (VCO) in a defined manner, so that the detected dynamic waveforms are represented in the form of an acoustic tone signal that is dynamically changed in pitch. The surgeon can then use the respective characteristic change in pitch to determine whether the optical fiber 1 is in the target area in the area of a stone or in the area of the tissue surrounding the stone. Suitable characteristics for automatic stone recognition can be obtained from this frequency-modulated response signal.

Another possibility for executing the method is formed by the formation of cavitations in the target area that occur with laser excitation with certain laser energies. As is known, cavitation bubbles expand under the effect of the laser energy introduced and collapse with a characteristic cavitation dynamic or periodic. The characteristic and material-specific cavitation periods are then determined from the response signals generated with the aid of a specified laser excitation and synchronized and detected with this, on the basis of the different vibration modes generated in the process. The time differences between the occurrence of the first and second cavitation signals (T2 - Tl) = TK can advantageously be determined. These characteristic values for the cavitation period TK, as well as their significant dependence on the laser parameters, such as. B. of the laser energy E and / or the laser wavelength λ are determined from the context of the excitation profile that is passed through in each case.

The cavitation periods can be determined at selected laser energies and selected laser wavelengths, with one or the other parameter being constant in each case is held. From the data obtained in this way, significant information can in turn be obtained with regard to the properties to be determined of the respective sample material in the target area. This embodiment is based on the knowledge that the characteristics of the cavitation period TK (E) with a fixed wavelength λ and variable energies E generally have a significantly different profile for different materials. For example, the cavitation periods for gallstones in the laser system used with an energy range from E = 30 to 120 mJ are in the range from TK = 400 to 800 ms, the TK (E) characteristic curves having a curve that increases largely linearly with the laser energy E. , In contrast, cavitation in tissues only occurs at significantly higher energy thresholds, for example in the case of a gallbladder at energies greater than 60 mJ, and also shows much lower values of the cavitation period TK than gallstones over the entire range of characteristic curves. For example, the cavitation period for gallbladder tissue is 500 ms with an irradiated energy of 120 mJ, the cavitation period for gallstones being 800 ms with an irradiated power of 120 mJ. This allows stones and the surrounding tissue to be clearly distinguished from one another.

This method can be further improved by measuring wavelength-dispersive properties. For this purpose, the cavitation period characteristics with respect to the energy and the wavelength at certain energies and certain wavelengths are determined, from which, on the one hand, additional information about the type of sample material can be obtained and, on the other hand, the selectivity of the stone / tissue recognition is additionally improved.

In a further embodiment of the invention, the possibility is additionally given of bleeding in the target area in the To recognize the course of a lithotripsy treatment. This is particularly advantageous in cases when the claimed method is to be used in the blind method and clinically relevant information about the presence or the extent of acute bleeding is important or if there is reliable information about the presence of particularly blood-rich tissue material , such as B. parenchyma tissue or from heavily perfused tissue compartments or vascularizations is crucial for further treatment. The embodiment is based on the knowledge that the absorption properties of the hemoglobin have very characteristic bands, so that with the aid of a correspondingly specified wavelength-dispersive and energy-dispersive excitation of the sample material, reliable detection of bleeding or blood-rich tissue types is possible. A measure of the degree of blood flow to tissues can also be derived from the data.

The properties of the detected response signal obtained from the analysis are combined with the corresponding ones

Data of the excitation parameters are converted into feature data sets and then combined into multidimensional feature vectors, classified accordingly and used for the detection of stone or tissue material.

Various suitable criteria can be used individually or in context. Depending on the embodiment, there are, for example, the presence of stone or. Tissue material distinguishable dynamic and / or spatial signal parameters for use, which result from the material-specific determined dynamic system transmission properties. As is known, the system-theoretical relationship between the correspondingly chosen dynamic input function in the form of the optical excitation function of the laser irradiation and that emanating from the target material can be used accordingly detected dynamic output function determine the dynamic system transmission properties specified by the interactions in the target material and by the transmission medium.

It is only after stone material has been determined that the corresponding control signals 13 (control signal derivation) via a feedback control loop 14 (feedback control), 15 (control signal processing) then trigger the laser powers required for selective stone processing, for example laser lithotripsy, pulse sequences and pulse frequencies or wavelengths set in such a way that a stone fragmentation is achieved by means of the treatment beam. The change between the material detection mode and the processing mode is carried out automatically by appropriately implemented process routines 16 (procedural control) or semi-automatically by the user by means of control units 17 (user platform).

After the discovery of stone material will be appropriate

Control signals are generated 13, which is subjected in the form of a corresponding automated feedback control 14 and a subsequent further, correspondingly suitable signal processing 15. The laser parameters are then set to the previously determined and correspondingly selected stone processing mode, as a result of which a correspondingly high laser power which is sufficient for stone destruction is applied exclusively to the determined stone material by means of the optical fiber 1. After repeated or periodic use of the processing, the intended fragmentation of the stone material occurs, with the tissue surrounding the stone being protected.

The stone processing is carried out either under automatic feedback control, for example when using the claimed process without visual inspection, or on the basis of a requirement of 0- perateurs, e.g. B. after inspection of the degree of fragmentation, until the treatment goal has been achieved. If tissue material is found, the diagnostic mode is continued either automatically or by appropriate measures by the user or surgeon. For this purpose, the radiation parameters specified for this excitation mode are determined by the user with the aid of the correspondingly selected analysis routine with the aid of a corresponding interface for process control 16 and a correspondingly designed user interface 17.

In addition to certain input media 17a (input actuators), the user or the operator with the interface 16 and the user interface 17 also have various appropriately designed output media 17b (output representations) available. The output media 17b enable different display means and display types, such as. B. Represent graphic displays with corresponding forms of mathematical, logical, numerical, graphic or symbolic representations or corresponding color-graphic encodings of system-related or process-related parameters and their functional, logical and semantic relationships. Advantageous real-time process visualization can also be achieved by displaying functional relationships, graphs or transfer properties, state variables, state spaces, feature spaces, vector spaces, trajectory plots, Lorenz plots, Poincare plots and various mapping methods.

There is still the possibility of certain parts of the

Process flow or to control this in its entirety semi-automatically or automatically, whereby the automated stone / tissue recognition can also be carried out in parallel with a corresponding subjective evaluation, classification and recognition by the user. The control and regulation of the various processing processes and / or their feedback control according to the requirements of the material properties determined during each analysis cycle is carried out on the basis of correspondingly specified control parameters which are determined beforehand with regard to the embodiment and application used in each case.

In Figure 3, the method of Figure 2 is supplemented by an additional ultrasound analysis option.

Corresponding ultrasound echoscopy methods are used in parallel with the acoustic detection of the sound wave front emanating from the target area, the transducer 18 used here (US echoscopy scanner) being aligned with the same target area 2, which is stimulated by radiation accordingly. The corresponding ultrasound images are thus in one or more of the known scan modes, such as A-mode, B-mode, TM-mode, 4D-mode and others each won from the same target area 2.

In the imaging and image processing 21 (US imaging procedures) of the ultrasound images, the temporal relationships of the imaging for each ultrasound beam in the respective scan channel or in the time profile of a corresponding scanning algorithm are appropriately determined both with the radiation excitation and with the photoacoustic detection 8 and / or with the detection of thermal waves 19 (thermal wave detector) and / or other conceivable intracorporeal and / or extracorpural detection methods 20 (other detection schemes) used accordingly synchronized and correlated 21a (phasing and timing procedures). Here, due to the temporal relationships currently occurring in the process, such as, for example, with regard to the sound wave propagation times and / or with regard to the dynamic conditions or kinetics, appropriately trained means are coordinated with one another in a predetermined manner.

Corresponding suitable correlation data of the photoacoustic method obtained from the correlation 10 are also used for the targeted coordination. Certain image scans, time-corrected both with the excitation and with one another, are obtained from the specimen, e.g. a- daptive images, faced images, strain images, occurrence images and modular images. These images can be created on the basis of the ultrasound images or the image sequences and / or the thermographic images and / or the infrared images or of other types of images which are generated by using further corresponding suitable imaging methods.

Corresponding known means of image processing can also be used 21b (encoding and symbolization procedures), as a result of which, among other things, certain desired or excellent image areas can be marked accordingly. For this purpose, using known and correspondingly suitable methods, for. B. a targeted local time control of the image brightness or the image contrast and / or a targeted parametrically controlled selective spatial frequency filtering or staining for marking certain image areas and / or certain temporal relationships of the corresponding image sequences. The image information obtained with the aid of imaging and correspondingly processed, adapted and temporally correlated is displayed using various process routines 22 (adapted frame procedures) 23 (correlated adapted images). The process information is then displayed in the form of a correspondingly selectable representation 17b, which gives the user various alternatives with regard to the correspondingly significant video Forms of visualization allowed for better assessment of the properties of the target area.

The image parameters and image features contained in the adapted and time-correlated image information and differing in their different relevance and significance are then extracted accordingly by means of a parameter and feature extraction 24, with e.g. certain texture parameters or certain texture features are obtained from the structural properties. Likewise, certain properties of the sound radiation characteristic and the sound propagation conditions can be derived from the correlated relationships between the excitation and the wave fronts that are determined complementarily to one another and reflected on the specimen, from which corresponding relevant parameters or significant features are then determined.

The additional information obtained about the properties of the target area are evaluated 25 according to their parameters or feature extraction 24 with regard to their spatiotemporal correlation (spatiotemporal image corrections) and these additional results are fed to the downstream and correspondingly expanded analysis method.

The same applies correspondingly to the echoscopic 18, photoacoustic 8, photothermal or radiometric 19 and / or other suitable intracorporeal and / or extracorporeal detection methods 20 used in parallel and complementarily correlated with one another. These response signals registered synchronously with one another by means of corresponding detectors are correspondingly further processed 8a in parallel in corresponding signal channels, the dynamic signal correlation 9 with respect to their respective phase position on the one hand from the respective time signals and / or temporal relationship are determined and, on the other hand, the spatiotemporal implications 25 with respect to their correlations or functional relationships obtained in a corresponding manner in the image information are also determined from the imaging methods 18, 19 used in parallel. In addition, the various detection methods used in parallel and complementary to one another and the time and / or image signals transmitted in the correspondingly assigned channels are also correlated with one another 26 (complementary correlatinos). These corresponding correlations are then fed to the analysis method described in the embodiment according to FIG. 2 and processed accordingly.

The technical features on which the selective lithotripsy method with selective stone / tissue recognition is based are thus characterized in that on the one hand a suitable laser beam (treatment beam) with high energy and correspondingly excellent radiation parameters

Purpose of stone destruction is used, with dielectric breakdown in connection with a plasma release in the target area and thus the intended fragmentation of the stone concrement. On the other hand, for the purpose of determining the material properties present in the target area and in particular for in vivo stone / tissue recognition, the same or a further suitable laser beam with the lowest possible energy and with correspondingly excellent radiation parameters is used in such a way that an undesirable one occurs in the course of the stone / tissue recognition dielectric breakthrough or plasma formation is excluded with certainty so that there is no damaging laser effect on the surrounding tissue or the stone embedding tissue. In the method according to the invention, the various known known values that can be achieved with laser excitation of the target area below the plasma threshold are Versible photothermal, photoelastic or photoacoustic effects are used to achieve a non-destructive stone / tissue discrimination, which is based on the detection and analysis of the material-specific and easily distinguishable structure-elastic dynamic modes that can be specifically stimulated in the target material. This solution is based on the knowledge that, with the aid of a correspondingly suitable dynamic application of the laser radiation in pulsed or modulated operation, the optically excited target material in the target area represents a material-specific determined source of thermal and / or elastic and / or acoustic wave fields, which can be detected by means of suitable detectors and evaluated accordingly in the sense of the invention.

Likewise, the target material optically excited with the laser under these conditions acts in the target area for an ultrasound beam aimed at this area as a material-specific determined ultrasound reflector, the reflection behavior changing significantly under the dynamically controlled laser excitation. The echo signals received by means of an ultrasound receiver from the opto-acoustically excited target surface can be evaluated accordingly in the sense of the invention on the basis of the material-specific features contained therein. The known ultrasound echoscopy methods with a corresponding additional control circuit can advantageously also be used for the purpose according to the invention for transmitting and receiving ultrasound signals.

In one embodiment of the invention, the analysis laser beam is generated directly with the aid of the same laser source, which is also determined for the purpose of using lithotripsy, the radiation parameters used in each case for analysis purposes or for therapy purposes using appropriate means to suit the different conditions required for this, one suitable non-destructive excitation of the target material with correspondingly low laser energies (below the plasma threshold), but also for destructive material processing with correspondingly high laser energies. In the case of a positive stone detection that is clearly determined by the analysis system, the laser parameters required to carry out stone fragmentation are automatically set with the aid of an appropriately suitable feedback process control routine. This process can be repeated accordingly until a predetermined degree of fragmentation of the stone is reached.

In a further embodiment, the laser beam is generated for the purpose of analysis by means of an additional, separate laser source independently of the laser source used for material processing, so that both laser beams are optically coupled together in a common fiber, which is then directed at the target material present. However, the use of separate fiber systems is also conceivable for this. This design in the form of a two-beam arrangement is particularly advantageous in the case when more versatile excitation conditions are desirable. In principle, the excitation is no longer restricted to the use of the same wavelength or to the use of short laser pulses as in the therapy laser system, but allows a largely free choice of the optimally matched laser wavelengths that can be used for analysis purposes and the most suitable pulse or modulation parameters too. In the event that, for example, a modulated CW analysis laser is used in conjunction with a necessarily pulsed therapy laser in a two-beam arrangement, there is the advantage that the CW analysis laser is used for continuous analysis or for examination larger target areas or for the purpose of navigation and positioning aid in the case of a blind procedure can. In addition, there is the possibility of achieving various types of modulation (such as AM, FM, PCM etc.) and modulation parameters (such as modulation frequencies, degrees of modulation, FM hub, frequency sweeps, and much more).

In addition to the application of the invention for selective feedback-controlled laser lithotripsy with implemented non-destructive in vivo stone / tissue detection, the following are examples of extended possible uses. The claimed methods and devices can advantageously be used in the field of clinical endoscopy for the purpose of laser-stimulated functional endoscopy (LFE). This solution has the advantage that, in addition to the known phenomenological morphological findings through inspection of the endoscopic image, an objective, non-destructive in vivo functional diagnostic analysis can also be carried out simultaneously with the tissue area currently being inspected.

A related embodiment, not shown here, has an optical system for this purpose, which can consist, for example, of appropriately designed optical fibers which are introduced both into the endoscopy channel and into the working channel. Various types of laser sources with appropriately trained laser generators and drivers as well as laser controllers can be used to generate the excitation light. The analysis system consists of the operative connection of the appropriately trained methods and devices for the optical excitation of the tissue material, in the functional context with certain suitable methods and devices for the detection of the photo-induced specific tissue reactions, such as with the help of appropriately trained photoacoustic detection systems and / or by means of an appropriately trained ultrasound echoscopy method. All of these applications are based on the specific dynamic entropic-elastic and / or thermoelastic and / or rheological changes in the state of the tissue that occur under appropriate photonic excitation or stimulation. Thus, the functional morphology of numerous and different types of physiologically or pathophysiologically modified tissue types can be objectively examined with the aid of the claimed system-analytical methods and device and under in vivo conditions. In addition to the advantage of a specifically localizable application of photonic energies to certain tissue areas, there is also the possibility to largely freely select the radiation parameters used for the respective application and to use them recursively in the course of the process either according to the specified control parameters or according to the criteria determined from the analysis data Way to control (feedback control). The endoscopic radiation application according to the invention and correspondingly specified can also be used advantageously for the purposes of selective biostimulation under feedback control with regard to the stimulation effects to be achieved in each case. For example, a variety of known effects on the in vivo biochemical, biophysical, subcellular, cellular or intercellular processes for appropriate therapeutic purposes can be achieved by targeted endoscopic laser excitation in the different tissue types and on different tissue layers or tissue compartments.

When using the method according to the invention for in vivo tissue function diagnosis, for example on various types of connective tissue, the knowledge is exploited that such so-called bradytrophic tissue types each have a very specific, significant and physiologically relevant structural plasticity. Such tissue rheological features leave consequently make use of the diagnostic diagnosis of the tissue due to the reversible entropic-elastic state changes acutely induced by means of a suitable laser excitation as well as the associated analysis of the structural dynamic modes that occur. The use of the claimed method and the corresponding devices for non-destructive and functional in vivo tissue diagnostics is advantageous wherever a removal of tissue samples, for example by means of a biopsy and with subsequent histological in vitro laboratory examination, should or must be avoided. A major disadvantage of conventionally known histological examinations of biopsy material that has been removed is that, due to the method, this permits only a correspondingly delayed and sample-like in vitro determination. Another fundamental disadvantage of all known in vitro examination methods is the fact that by taking the tissue samples and isolating the tissue from its morphological and functional context and also by using appropriate histological preparation techniques, only examinations are possible under largely unphysiological conditions. These fundamental disadvantages are avoided by using the claimed in vivo method. Furthermore, in contrast to the known histological methods, the use of the invention is not limited to just a few samples, but accordingly also enables large-area tissue screening under the respectively prevailing physiological or pathophysiological conditions.

A particular advantage over the known methods in which a tissue sample is required, ^is' is that the tissue analysis by the inventive method always intact tissue and on the same substrate can be repeated at any time, whereby the additional benefit results that characterized both kinetic and also have historical diagnostic examinations carried out. In addition, the different physiological or pathophysiological functionalities determined here are always reproducible and also objectively quantifiable due to the maintenance of the intact tissue morphology. This is the only way to get an objective and therapy-accompanying evaluation of the effects of certain therapeutic interventions with the help of the claimed method, which also results in the possibility of a feedback-controlled selective treatment that is measured by the immediate success of the therapy. The risks and side effects associated with taking tissue samples are also excluded. Further applications of the invention are also to be seen in the fact that it can be used advantageously in the sense of expanded clinical tissue diagnostics and / or for the elucidation of diverse structural-dynamic cellular or tissue rheological processes, such as, for example, on different tissue compartments or vessel sections. It is conceivable, for example, that by means of a correspondingly specified laser excitation on certain vascular sections in connection with a detection method suitable in the sense of the invention, these also as tracer methods for different circulatory parameters (for example flow, pulse transit time, compliance etc.) for the determination various clinically relevant hemodynamic or vaso-elastic or vaso-motor parameters can be used.

Further advantageous applications of the invention also arise wherever certain volume changes or other diverse specific tissue-mechanical activities and reactivities can occur, which then result in different forms of movements, local cell ions, mass transfer processes and gradient formation or in structural, manifest rheological or viscoelastic phase transitions. Further advantageous applications of the invention result from the use of the special embodiment according to FIG. 3. This complementary photoacoustic-echoscopic analysis method can be used in connection with the various imaging ultrasound methods used in connection therewith. By using the image modes that can be represented with the known ultrasound methods (eg A, -B-, TM-mode) in connection with the structure-dynamic tissue conditions caused by the laser excitation, new types are created by means of a temporally correlated photoacoustic and echoscopic image generation Function-specific image representations possible (e.g. occurence imaging, strain imaging, phased imaging etc.). Here, in synchronism with the laser excitation, the ultrasound images of certain photoacoustically stimulated tissue compartments are correspondingly evaluated and displayed in their correlating phase relationship. The different contrasts that occur synchronously with one another under these conditions can advantageously be used for a morphological-functional tissue diagnosis. The designation thus opens up completely new complementary functional diagnostic findings of tissues in connection with the known ultrasound imaging methods with regard to a far-reaching analysis or diagnosis of different tissue-specific photothermal, thermochemical, thermodynamic, photochemical and biochemical transduction processes, regeneration processes or growth processes, all of which are directly connected with the specific entropic-elastic structural-dynamic changes in state are connected. The systematic application of the methods according to the invention enables the evaluation and quantification of specific tissue features (eg morphogenesis, diversification, differentiation, rigidity, plasticity, viscoelasticity, rheology and much more). Further conceivable applications of the method according to the invention can also consist, for example, in that, instead of an ultrasound imaging method, correspondingly suitable thermographic imaging methods (for example thermal imaging) can also be used advantageously.

Another conceivable embodiment would also be suitable for achieving additional photothermal contrasts which, in the sense of the invention, can also be used for the in vivo diagnosis of tissues in connection with the previously described embodiments. Here, the tissue-specific so-called heat dissipation functions, the thermal diffusion lengths, thermal conductivity numbers, heat transfers and corresponding thermoregulatory parameters, etc. suitable clinically relevant characteristics e.g. about tissue blood flow, metabolic activity, diffusion processes and much more (Clinical use e.g. in arthroscopic or laprascopic procedures).

In addition, the methods according to the invention can also be used for the quantitative and objective dosimetry of various physical therapy methods such as e.g. use in conservative laser therapy or conservative extracorporeal shock wave therapy.

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Claims

claims

1. A method for in vivo detection of the material properties of a target area of a human or animal body, in particular for distinguishing body concrements from the surrounding tissue in the target area, with the steps:

a) Essentially non-destructive excitation of the

Target area (2) by at least one optical excitation signal,

b) detection of at least one acoustic, thermal and / or mechanical response signal emitted by the excited target area (2),

c) analysis of the at least one detected response signal with regard to its properties, in particular its periodic properties and / or its vibration modes, and

d) assigning the properties of the at least one analyzed response signal and / or at least one excitation signal to predetermined property classes, each of which represents at least one material quality of the excited target area (2).

2. The method as claimed in claim 1, characterized in that the at least one excitation signal is generated by at least one light source (7), in particular a laser, which can be controlled with respect to parameters, in particular the excitation wavelength, the excitation energy, the phase, the temporal extent and / or the pulse sequence ,

3. The method according to claim 1 or 2, characterized in that the excitation signal passes through at least one predeterminable sequence of different parameters.

4. The method according to any one of the preceding claims, characterized in that the response signal is detected with at least one detector (8) arranged inside and / or outside the body.

5. The method according to claim 4, characterized in that at least two detectors (8) arranged at different detection locations are provided for the detection of at least two response signals.

6. The method according to claim 5, characterized in that from the relationship of the at least two response signals to one another, in particular from the temporal, the intensity and / or the phase relationship to one another, the spatial direction of propagation, the location, the source and / or the speed of propagation Response signal is determined.

7. The method according to any one of the preceding claims, characterized in that the detected response signal before the analysis, in particular by amplifying, filtering,

Transforming, improving the signal-to-noise ratio and / or averaging is prepared. Method according to one of the preceding claims, characterized in that the detected response signal is correlated with the excitation signal for determining the temporal and / or the phase correlation data.

9. The method according to claim 8, characterized in that the detected response signals are synchronized with one another on the basis of the temporal and / or phase correlation data and / or in a desired temporal or

Phase relationship to each other.

10. The method according to any one of the preceding claims, characterized in that the periodic properties of the detected response signal are determined in the analysis of the detected response signal.

11. The method according to claim 10, characterized in that the vibration properties, in particular the photoacoustic vibration properties of the detected response signal are determined.

12. The method according to claim 10 or 11, characterized in that the vibration modes, in particular the photoacoustic vibration modes, of the excited target area are determined by means of dynamic analysis from the detected response signal.

13. The method according to claim 10, characterized in that the cavitation period is determined from cavitation events occurring in the excited target area.

14. The method according to any one of the preceding claims, characterized in that the properties of the analyzed response signal are assigned to property classes on the basis of the determined correlation properties, periodic properties, vibration properties and / or cavitation properties.

15. The method according to claim 14, characterized in that in the presence of periodic components of the analyzed response signal, in particular when vibration modes are present, the target area is assigned to a property class which represents the solid state.

16. The method according to claim 15, characterized in that specific periodic components of the analyzed response signal, in particular the vibration modes, are assigned property classes which represent specific solids.

17. The method according to any one of the preceding claims, characterized in that the excitation conditions, in particular the parameters of the excitation signal, are included in the assignment of the properties of the analyzed response signal to the property classes.

18. The method according to claim 17, characterized in that the target area (2) in the presence of periodic components of the analyzed response signal with a predetermined excitation intensity and / or a predetermined Solid-state properties are attributed to the excitation wavelength.

19. The method according to claim 17 or 18, characterized in that a variation of the excitation conditions, in particular the excitation wavelength and / or the excitation intensity, is carried out and from the variation of the properties of the detected response signal, the assignment of the target area to a property class representing the material quality is carried out ,

20. The method according to any one of the preceding claims, characterized in that the excitation conditions of the excitation signal and the determined cavitation period are used to assign the target area to at least one property class.

21. The method according to claim 20, characterized in that the variation of the cavitation period resulting from a variation of the excitation conditions, in particular a variation of the wavelength and / or the intensity, is used to assign the target area to at least one property class.

22. The method according to any one of the preceding claims, characterized in that the direction and / or speed of propagation of the acoustic, thermal and / or mechanical response signal emitted by the excited target area is used to assign the target area (2) to at least one property class.

23. The method according to any one of the preceding claims, characterized in that the detected response signal, the processed response signal and / or the analyzed response signal is represented acoustically and / or optically.

24. The method according to claim 23, characterized in that the excitation conditions, in particular the parameters of the excitation signal, are included in the acoustic and / or optical representation.

25. The method according to claim 23 or 24, characterized in that the response signal and / or the excitation signal is made audible via a voltage-controlled oscillator (VCO) and / or other means.

26. The method according to any one of claims 23 to 25, characterized in that the response signal and / or the excitation signal are made visible on a screen.

27. The method according to claim 26, characterized in that the excitation signal and / or the response signal is represented and represented parametrically in the form of coordinates.

28. The method according to any one of the preceding claims, characterized in that the steps for recognizing the material properties of the target area are repeated continuously or periodically.

29. The method according to any one of the preceding claims, characterized in that the assignment of the target area to a property class representing a material quality is used to control material processing of the target area (2), in particular for lithotripsy.

30. The method according to claim 29, characterized in that a material processing of the target area with a high-energy optical signal is only possible if the properties of the target area (2) are assigned to at least one specific property class.

31. The method according to any one of claims 29 or 30, characterized in that after a step of material processing, the material quality of the target area (2) is in turn recognized.

32. The method according to claim 31, characterized in that the material processing takes place in a predetermined, in particular short or pulsed, time period and then a new determination of the material properties of the target area (2) is carried out.

33. The method according to any one of the preceding claims, characterized in that at least one ultrasound signal of the target area (2) is detected by means of ultrasound echoscopy.

34. The method according to claim 33, characterized in that the ultrasound signal is emitted by means of at least one ultrasound transmitter (18) and is detected by means of at least one ultrasound receiver (18).

35. The method according to claim 33 or 34, characterized in that at least one ultrasound signal is correlated with at least one excitation signal and / or at least one response signal.

36. The method according to claim 35, characterized in that the ultrasound signal is synchronized with at least one excitation signal and / or at least one response signal and / or is set in a predetermined temporal relationship and / or phase relationship to one another.

37. Method according to one of claims 33 to 36, characterized in that properties of the target area are determined from the ultrasound signals reflected by the excited target area (2).

38. The method according to claim 37, characterized in that the ultrasonic signals are analyzed to determine their properties, in particular their periodic properties.

39. The method according to claim 38, characterized in that the properties of the ultrasound signal, in particular taking into account the excitation conditions, are assigned to at least one property class, each of which represents at least one material quality.

40. The method according to any one of claims 33 to 39, characterized in that the detected ultrasound signal is displayed optically and / or acoustically.

41. The method according to claim 40, characterized in that certain areas of the target area (2) are marked in an optical representation on the basis of the properties determined from the response signal and / or the ultrasound signal.

42. The method according to claim 40 or 41, characterized in that the generation of a representation of an ultrasound image and / or the representation of an ultrasound image can be controlled by at least one response signal.

43. Device for carrying out the method according to at least one of the preceding claims, with at least one light source (7) for the optical excitation of a target area (2) in a human or animal body, at least one detector (8) which can be arranged on or in the body. for the detection of mechanical and / or acoustic response signals, at least one analysis means (11) for analyzing the properties of the detected response signals and at least one display means (17b, 100) for displaying the response signal and / or the properties of the analyzed response signal.

44. Device according to claim 43, characterized in that the light source is a laser (7).

45. Device according to claim 44, characterized in that the laser (7) can be modulated with regard to its parameters, in particular its wavelength, its intensity and its pulse sequence.

46. Device according to one of the preceding claims 43 to 45, characterized in that an optical fiber (1) is provided for guiding the light emitted by the light source (7).

47. Device according to claim 46, characterized in that the optical fiber (1) and / or the light source (1) are arranged on an endoscope.

48. Device according to one of claims 43 to 47, characterized in that at least one detector (8) is designed as a piezo element.

49. Device according to one of claims 43 to 48, characterized in that at least one assignment means (12a) for assigning the properties of the analyzed response signal to at least one property class.

50. Device according to one of claims 43 to 49, characterized in that the display means (17b, 100) comprise an acoustic electro-acoustic transducer, in particular a loudspeaker, controlled via a voltage-controlled oscillator and / or other means.

51. Device according to one of claims 43 to 50, characterized in that the display means (17b, 100) comprise at least one screen.

52. Device according to one of claims 43 to 51, characterized in that correlation means (9) are provided for correlating the excitation signal with the response signal.

53. Device according to one of the preceding claims 43 to 52, characterized by a device for recording ultrasound images (18).

54. Device according to claim 53, characterized in that an ultrasound head (18) with at least one ultrasound source and at least one ultrasound detector is provided.

55. Device according to claim 53 or 54, characterized in that means for generating a representation of an ultrasound image and / or the representation of an ultrasound image are provided which can be controlled by at least one response signal.

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