DE10257169A1 - Method and device for in vivo detection of the material properties of a target area of a human or animal body - Google Patents

Abstract

The invention relates to 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, comprising 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 detected response signal with regard to its properties, in particular its periodic properties and / or its vibration modes, and d) assignment of the properties of the analyzed Response signal and / or the excitation signal to predetermined property classes, each representing at least one material quality of the excited target area (2). This provides an improved method 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 a human or animal body according to the preamble of the claim 1 and one to carry out of the method according to the invention suitable device according to the preamble of Claim 42.

The in vivo detection of different Materials play a clinical role in diagnosis and therapy a big Role. Such material detection is used, for example, at a endoscopic stone crushing (Lithotripsy) used to target targeted destruction of body concretions, in particular of kidney stones or gallstones. The material detection is particularly important if the material processing or destruction of body concrements by means of high irradiated laser energy should be carried out, as damage to the surrounding tissue must be excluded by the laser pulse.

From the 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 calculus to be processed is used to control the material-processing laser.

From the 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 of detection of body concretions can for example, by the presence of bleeding in their detection performance limited his.

The one used in the recognition process Optical detection method must also be among the most practically occurring unfavorable Conditions such as a high proportion of scattered light and changing surface conditions the target surface, as well as with changing fiber positions, inclination angles and different intervals the optical fiber can be used in relation to the target material. Known methods are also suitable, inter alia. not for immediate clinical Use with regard to an existing target material with unknown Material components, because here before each analysis of the examined Material essential material-specific parameters always beforehand are to be determined, so that only the critical presetting the requirements for the Analysis can be done. A fundamental disadvantage of this and others known methods, which primarily the material for analysis purposes Properties for identification, classification or for material recognition by trying to label the ones in the target area Obtain substances based on certain spectroscopic features is that in the case of the practically existing target material with a Many different substances, each with unknown and different Compositions and concentrations as well as with inhomogeneous spatial Distribution as is well known to those skilled in the art is an extremely complex one Spectral behavior with hardly visible variabilities to lead can. This results in for the known methods of this type the fundamental disadvantage that a clear and quick detection of certain significant spectral Features practically impossible is, which makes the use of spectral information to obtain material-specific Features as well as a classification and recognition among the occurring practical conditions is excluded in most cases. Especially mainly used in most laser applications visible spectral range or near infrared range show e.g. different tissue types no tissue-specific marked characteristic and significant and usable for labeling Absorption bands. As well as those skilled in the art is known to occur in a spectroscopic analysis of blood flow Fabric only for Blood specific spectral characteristics in the form of the characteristic hemoglobin gangs significant in appearance, what with the known methods, which the optical spectral parameters for determining the presence of tissue or stone material, leads to the disadvantage that it is in the case of bleeding, which during clinical use e.g. of laser lithotripsy can occur with a corresponding frequency, depending according to the type of analysis used and based on spectroscopic methods lead to inevitable errors can. It is particularly disadvantageous, for example, when laserithotripsy procedures of this type, which in certain circumstances without additional Visual check and thus sudden bleeding so it cannot be determined that in this case, due to incorrect detection of stone material instead of tissue material, a tissue-damaging emission of high laser energy can be done. It is also conceivable that it already is in the presence of well-perfused areas of tissue such as Parenchymgeweben to accidental damage opposite this other less perfused tissue types to be particularly absorbent and above also leads to particularly radiation-sensitive tissues.

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

The task is accomplished through a process solved with 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 in such a way that first the target area a non-destructive Experiences excitation by means of at least one optical excitation signal. The at least one acoustic emitted from the excited target area and / or mechanical response signal is then detected and then one Analysis to determine its properties, especially its periodic properties and / or its vibration modes. The properties of the detected response signal determined from the analysis then become property classes, each with at least one material quality represent the excited target area, assigned. By assigning the properties of the detected Response signal to a property class can be in this way Statement about the homogeneous or heterogeneous material properties of the excited Hit target area.

The method according to the invention uses the photoacoustic Effect out. The photoacoustic effect manifests itself in such a way that that into a specimen radiated optical radiation energy is absorbed by this and inside the specimen is converted into mechanical vibrations. These mechanical vibrations can then on the surface of the specimen or in its vicinity as mechanical vibrations and / or as acoustic signal can be detected.

So it is advantageous that for detection the known optical detection methods are not used, because this system-related when the unfavorable mentioned occur Conditions are not sufficiently stable and reliable determination of the Material properties due to the optical parameters by the backscattered into the optical fiber Allow light.

To effect a specific Excitation of the target area and to differentiate between the detected acoustic and / or mechanical response signal from artifacts the at least one optical excitation signal of at least one regarding specific parameters, in particular the excitation wavelength, the Excitation energy, phase, temporal expansion and / or the pulse train controllable light source generated. As a light source here in particular a laser is advantageously provided, since with a on the one hand, the necessary excitation energies are provided can be and on the other hand the parameters of the laser are reproducible and in one wide range can be varied. The different parameters of the light source and in particular of the laser can be inside of an excitation signal also run through a sequence. To this Way, a specific excitation sequence of the excitation signal, which, for example, depends on the specific properties of the expected Material is matched, are generated. The following The analysis can evaluate the detected response signal, among other things can also be based on the specific excitation signal.

The detection of the mechanical and / or acoustic Depending on the application and practicality, the response signal can be at least one inside and / or outside of the body arranged detector can be made. When using multiple On the one hand, detectors can improve the signal quality by adding them up and on the other hand, this allows the spreading characteristics the mechanical and / or acoustic waves. The application of at least two different detectors on different ones Detection locations enabled further, from the relationship of the resulting at least two response signals to each other the spatial direction of propagation and / or to determine the speed of propagation of the response signal as well as locate the target area.

To analyze the response signal efficient with a high proportion of information and a low one Perform noise component to be able can in particular the detected response signal before the analysis by reinforcing, Filter, transform, and other ways to improve of the signal / noise ratio and / or processed by averaging become. For the exact determination of the one initiated by the excitation signal Response signal can Excitation signal and response signal are correlated with one another, to determine the relationships of the two signals from the correlation data to be able to determine each other and unnecessary signal components, for example to suppress echoes. These can be derived from the correlation data of several response signals based on the determined temporal and / or phase correlation data synchronize with each other and / or in another desired time and / or desired Set phase relationship to each other. By synchronizing the response signals let yourself the signal / noise ratio continue to improve. The response signal prepared in this way is now ready for the following analysis ready.

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. To get a clear picture of that To obtain material of the excited target area, the oscillation properties, in particular the photoacoustic oscillation 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 become. The cavitation periods determined can also be used Conclusions on pull the material of the excited target area.

From those determined in the analysis Inferences can be drawn from the properties of the detected response signal pull the material properties of the target area. For easy Handling and for direct evaluation of the properties of an excited The target area is the properties obtained in the analysis of the analyzed response signal 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 determined in particular on the basis of the Correlation properties of the periodic properties, the vibration properties and / or the cavitation properties. The predestination of Summary of certain properties to property classes and the material properties belonging to the property classes can be analytical and / or empirical. In an analytical way the respective materials are based on their respective vibration properties theoretically / analytically examined. Empirically a sufficient number of test measurements on the materials of interest carried out and summarized their findings into significant properties. Those obtained analytically and / or empirically Findings are then summarized into property classes, each for one Material have significant properties.

A simple distinction between a body stone and leaves this surrounding tissue for example, that if there are periodic components in the analyzed response signal of a solid state of the target area, i.e. the presence of a body concrement becomes. The knowledge that the photoacoustic Effect in solids already occurs at lower energies than with predominantly liquid ones Materials. From specific periodic components of the analyzed Response signal of the target area, in particular the recognized photoacoustic Vibration modes, lets yourself in a finer executed Classify the specific material of a solid.

In the assignment of the respective properties of the detected response signal for the respective property classes can also include parameters of the excitation signal. In particular, it is too note that specific periodic properties of a specific Material only occur under equally specific excitation conditions. The analyzed vibration properties of the excited Target area can also in connection with the excitation conditions, in particular with the excitation energy, the excitation wavelength and the excitation pulse shape be connected in order to infer the respective material.

In a further variant of the invention become those that occur with a variation of the excitation conditions Variations of the detected response signal in the assessment of the Material quality included. In particular, a variation of the excitation wavelength and / or the excitation intensity a specific behavior of the respective stimulated target area, so that from the resulting properties of the detected response signal in turn specific material properties can be concluded.

Also from the properties of the cavitation events in the target area, taking into account the respective Excitation conditions include specific material properties. at A variation of the excitation conditions can also be found here resulting variation of the cavitation conditions specific Derive material properties.

Furthermore, the direction of propagation also leaves and / or the rate of propagation of that emitted from the target area acoustic and / or mechanical response signal an assignment of the target area to at least one property class. in this connection Among other things, the knowledge is used that both in the solid state Transversal as well as longitudinal waves can be transmitted, whereas in a liquid Phase such as soft tissue material only transports longitudinal waves can be.

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 optical 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 introduced an optical fiber endoscopically into a body cavity for stone destruction, can do so on the basis of the resulting tone character Simply determine whether the end of the optical fiber is in the area of the body's concrement or whether the optical fiber points in the direction of the surrounding tissue. 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.

For an optical representation of the response signal and / or the excitation signal can also display a graphic representation on a Screen can be used. The excitation signals and the response signals are advantageously parameterized in a coordinate system. For example, the excitation signal on the abscissa is advantageous and the response signal on the ordinate of a coordinate system displayed. This is when the target area is excited and then detected of the response signal on the screen forming graphs, patterns and trajectories can be characteristic of a certain material quality assign.

In a further variant of the invention the respective properties of the response signal are combined with the excitation conditions in multidimensional feature vectors summarized, which is also shown on a screen can be. The representations resulting in the respective feature space are also specific to a certain material.

To an operator at work reliable to support, the steps to identify the material properties of the Repeat target area continuously or periodically. This will the target area is constantly checked.

The assignment of the target area to A material quality can also be used for automatic control the material processing of the target area, especially for lithotripsy be used. With such an embodiment of the method according to the invention the material-processing laser pulse is automatically released by the process. The operating surgeon only has to deal with the endoscopic guidance of the take care of the respective optical fiber, the trigger of the respective stone destroying The impulse then takes place automatically. In another embodiment of the method according to the invention will trigger a material-processing impulse, for example by a Operator, only released when in the excited target area a certain material quality, in particular a body concretions is detected has been. That way you can damage of the surrounding tissue or accidental triggering of the material processing Laser pulse can be avoided, thereby reducing the operational safety of the Procedure increased becomes.

In an extension of the process will be additional to the detected mechanical and / or acoustic response signals of the excited target area also at least one ultrasound signal the target area detected by ultrasound echoscopy. different Methods of ultrasound echoscopy are well known and are used in the clinical area widely used.

This is advantageous with the ultrasound echoscopy method generated and received ultrasound signal with at least one optical excitation signal and / or at least one photoacoustic Response signal correlated. about The correlation data obtained can be the ultrasonic signal with at least one excitation signal and / or with at least one Synchronize response signal and / or in another predetermined temporal relationship and / or a predetermined phase relationship to each other put. That way you can at the same time an ultrasound image and information about the Material quality of the target area of interest obtained become.

Because also the ultrasonic signal through the mechanical vibrations of the optically excited target area is modulated, can also be obtained from the received ultrasound signals by determining periodic properties and / or determination the photoacoustic vibration modes of the ultrasonic signal properties of the target area.

A clear representation of the Leaves the target area reach themselves if that with the ultrasound echoscopy method obtained ultrasound image with those determined using the method according to the invention Material properties of the respective target area is provided. Can in the ultrasound image so different material properties specified and marked are displayed clearly which supports the work of an operator. It is advantageous to generate a representation of a Ultrasound image and / or the representation of an ultra sound image provide controllable at least one response signal.

The task continues through a device for performing of the described method with the features of claim 42 solved.

Accordingly, the device for execution the method at least one light source for optical excitation 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 analytical means for analyzing the properties of the detected response signals and at least one display means for Representation of 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 is related to its parameters, in particular its wavelength, its intensity and its Pulse sequence can be controlled relatively easily.

The light source can either be on be attached to the endoscope itself or it will be an optical fiber provided for guiding the light emitted by the light source. This optical fiber can be simply arrange on an endoscope.

An inexpensive and reliable detector for Mechanical and / or acoustic vibrations are detected by Piezo elements executed.

In summary it can be stated that the present invention on a method and apparatus for irradiation of body tissues, body fluids or solid body concrements with With the help of specifically identified radiation energy. The target area exposed to the radiation energy (target material) shows different types due to the introduced photonic energies photo-induced reactions, which are both diagnostic but also for different therapeutic purposes or for material processing can be used. A selective therapeutic application and / or Material processing takes place under feedback-controlled conditions, if appropriate information is derived from the diagnostic procedure and the material properties that were found serve the specifications for a specified and appropriately controlled setting of the Radiation parameters and emission of radiation energy for each therapeutic application or material processing to be carried out to enable.

The effects of radiation energies can on the target material on the one hand consist of certain photo-induced entropic or elastic reversible states are excited in the present target material and on the other hand at certain, higher ones Radiation energies also include specific desired irreversible structural changes such as for example photoablation and / or photothermoplasty on tissues or a smash or fragmentation of body concretions (Gallstones, kidney stones, bladder stones, saliva stones, etc.) be achieved. Those with a targeted exposure accordingly specified radiation energy associated different Interactions with different radiation parameters the respective target material be used in such a way that with the help of appropriately specified optical excitation and suitable detection and analysis methods destructive in vivo analysis to determine the material properties of the irradiated Target area enabled becomes. Based on these analysis results, immediate Follow a selective and controlled therapeutic application or material processing of the same target area and target material can be achieved, with appropriate feedback for process automation Procedures can be implemented.

The present invention provides Method and an apparatus with which in a first step a non-destructive in vivo analysis of the respective target material 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 possible is. In a subsequent step, a targeted and selective application of the same target area and the same Radiation energy introduced into target material to various types therapeutic purposes and for processing the target material according to the requirements of the previous in vivo analysis results. This is done the therapy process or material processing process through current in each case specified and controllable different settings radiation energy as well as other relevant radiation parameters in the course of the diagnostic process or by appropriately suitable ones Feedback process routines.

In case of applying the procedures and device in the field of laser lithotripsy Invention the possibility that only if the stone material to be processed is available for plasma release and stone crushing required high laser energy is applied selectively. This ensures that the high laser energy used for lithotripsy at no time meets the tissue to be protected. This eliminates any unwanted colla terale damage of the tissue surrounding the stone with certainty excluded. It is still a reliable one and safe selective material processing even without visual inspection possible, even in the case of a blind process, the selective stone fragmentation without damage of the surrounding tissue is achieved by what is appropriate Appropriate automated feedback process control can be achieved can. Here, before each processing step and at each previous analysis step each determined analysis data used for feedback control of the selective laser machining process.

To determine the in the target area each material properties are used for analysis purposes different photo-induced interactions with the target material used individually or in combination to make them reliable, clear and significant target-specific characteristics for discrimination, Get classification, material and structure recognition, whereby the method according to the invention derived therefrom has the advantage of for the Application of sufficient selectivity has and a suitable in a simple and immediate manner Analysis result is achieved.

This also leads to the determination of mate Radial energy applied to the target area under no circumstances leads to optical plasma emission or denaturation, damage, destruction or perforation of the biological tissue to be analyzed.

Only low radiation energies are therefore advantageous used to excite the target area, which indeed corresponds to a specified optical required within the meaning of the analysis process Lead excitation of the target material, however an injury completely exclude.

The detection process can be both with different laser types at different wavelengths as also with pulsed lasers with different laser pulse durations as well also for CW lasers or modulated CW lasers can be used.

The use of non-optical detection systems has the advantage that to determine the material properties the different structural dynamics of the by optical excitation of the target material photoacoustic, photothermal or photoelastic effects is exploited. The main advantage of this type of detection is to see in this that the detected signal exclusively from actually in the target material absorbed radiant energy depends, causing no interference with the Measurement by the strong one that usually occurs with such materials Scattered radiation can occur and thus the related ones Disadvantages of the known optical detection methods are eliminated. Another advantage is that effective stimulation of the target material for analysis purposes, practically unlimited possibilities usable radiation energies are available, with whole different radiation sources and radiation conditions can be worked. Thus, the photonic used for excitation Emission in principle with largely any spectral distribution and also over one extremely broadband wavelength range take place, which gives the advantage of a largely free choice of Depending on the application, the wavelengths or wavelength ranges used and the radiation source used. The opposite of the known methods particularly advantageous high detection sensitivity of the detection method in connection with that achievable with this solution high specificity and selectivity The analysis procedure is based on the essential difference that the tissue materials to be examined are fundamentally not clear and sufficiently precise with regard to their purely material Characteristics can be differentiated, since most fabrics differ in terms of their material Do not significantly differentiate content and composition. The corresponding tissue types differ significantly with regard to their morphological structures, which in turn are based on immediate way with the functional physiological properties connected are. The analysis of these structural characteristics thus brings the advantage with it that the application is structurally dynamic and rheological analysis methods to determine and exact Differentiation of tissue properties and for functional characterization are suitable.

Therefore, the use is more appropriate acoustic or mechanical vibration detectors or others known methods advantageous, with which the target area thermal, acoustic or elastic waves can be detected.

The detection of this thermal, acoustic or elastic waves has the further advantage that this is about size Distances in the body tissue spread yourself linearly and get to the surface of the body, where they are also without the body sensors to be introduced and without further effort by means of Body surface attached Sensors can be easily detected. This solution points the additional advantage of adding additional Sensors at different positions on the body surface spatial and temporal assignment of the acoustic waves emitted by the target area possible is. Simultaneous registration with multiple detectors at different Detector positions and / or the use of appropriately arranged and operationally coupled sensors e.g. for focused Detection on certain selected That is why target points or target areas are particularly important advantageous because with this solution in addition to a spatial Positioning the acoustic source also other additional significant target-specific features regarding the different acoustic radiation characteristics in connection with the others due to the photoacoustic structural-dynamic interactions obtained by photothermal or photoelastic interactions Features for analysis purposes and also for assessing the with every therapeutic radiation exposure achieved therapy success or to evaluate the laser energy Processing status and the effectiveness of the processing can be used can.

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 only in soft body tissue longitudinal wave propagation takes place. These different properties of acoustic wave propagation known to the person skilled in the art are advantageous for the analysis purposes according to the invention as well as to achieve a reliable discrimination performance, material classification or material detection.

So it is particularly advantageous if this, e.g. in the case of laser lithotripsy, the application without visual inspection (blind process) and with this solution the the degree of fragmentation of the stone concrement reached was easily determined and can be displayed accordingly. There is an additional benefit also from the fact that when used in the blind process with the solution according to the invention also a navigation and positioning aid easy to implement is what to achieve one for the effective stone destruction optimal fiber position or an optimal stone contact exploited can be. This solution has the advantage that navigation and sounding too larger target areas even in the cases exists if there is an endoscopic visual inspection due to the lack Access for the endoscope is impossible is, but due to the significantly smaller fiber diameter Laser fiber has access to this fiber in certain cavitations lower lumen such as Bile ducts is still possible. With this solution the safe clinical application area will be expanded considerably.

The recognition process to determine the Material properties can also be changed without any prior knowledge the type and composition of the material components immediately and Clinically used everywhere without corresponding preliminary examinations become. There will be the beneficial relationship between the different structural, structural dynamic and functional rheological Properties of body materials exploited. This solution founds be aware that between the morphological properties of biological Tissue structures and their corresponding specific ones physiological functionality there is a reciprocal relationship. As from the Structure theory, structural biology and biophysics of tissues is known the tissue morphological structure formation processes are constituted with correspondingly proven adaptive plasticity and the associated with it functional physiological or pathophysiological functionality mutually in a highly specific and complementary way. The detection according to the invention and determination of certain extremely significant tissue elastic present in the target area Properties (tissue rheology) and their related standing highly specific structural or structural dynamic Features will be advantageous for sensitive and secure detection, selective distinction, classification and detection of biological Concrete materials and / or solid bodies 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, it is also different Novel in vivo analysis tools for biomedical research purposes for clarification diverse biological energy and structural transformation processes or more structural Vibration modes and their dynamics are possible, e.g. with different types cellular Organizational processes or in morphogenetic development phases and growth processes, which are characterized by specific conformational changes and / or activation states distinguished. Here certain tissue mechanical functionalities play, such as Plasticity, entropic elasticity or viscoelasticity an important role. Also the possibility for in vivo investigation various mechanisms of mechanotransduction or certain photoelastic and thermoelastic transduction processes, and much more open thus far-reaching application prospects for future biotechnological, biomedical in vivo analysis methods and clinical diagnostic methods. Conceivable are also also various uses for selective and feedback-controlled biomedical intervention e.g. for selective photoelastic, structural integration induced photothermally or photoacoustically or disintegration in selected regional tissue compartments, cellular structures or for targeted Generation and servo control of specific anisotropies and gradient fields, viscoelastic and tissue rheological conditions, as well as certain local ones Mikroakzellerationen. Further conceivable applications arise in accordance with the principles of the method according to the invention with the targeted application of selected biological micro and Nanostructures with specifically controllable radiation energy with the help suitable optical applicators and the achievable photo-induced selective local sonic excitation or sono-stimulation, to achieve various types of controllable, highly specific physiological effects, e.g. the specific influence 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 microcirculatory hemodynamic Parameter. As part of a selective and controlled laser-induced shock wave application the possibility according to the invention results both to use the method for various conservative physiotherapeutic or orthopedic Shock wave treatments as well as their invasive application.

A particular principle advantage of the solution according to the invention lies in the fact that the structural-dynamic order states generated in the target material by means of optical excitation and detectable and correspondingly analyzable 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, which results in a largely unrestricted selection of the radiation systems that can be used for this purpose. There is the possibility of using the method for excitation over an extremely broad wavelength range, for example from the microwave, IR, VIS or UV range up to X-ray or gamma radiation.

Furthermore, one will be appropriate appropriate operationalization of the non-destructive in vivo detection method and material detection system with correspondingly selected corresponding ones Applicator systems brought about. These applicator systems, which are used for the selective application of the Target material present in each case are suitable and which with selected accordingly and for the achievement of the respective material processing task or therapeutic Task suitable radiation type work and what, on the Basis of the material properties found, one accordingly Controlled delivery of radiation energies with precisely defined ones Irradiation parameters is reached. This operationalization if necessary, under online condition under implementation certain application-specific process routines performed.

Such a e.g. semi-automatic Process routine can include are that after the material property with the help of the recognition system, on the basis of correspondingly more suitable ones specific characteristics, each was automatically determined, the Users based on this data according to their own requirements, to achieve its specific and selective Radiation application caused, processing or therapeutic Intervention continues until the processing target is due after each processing step using the detection system found desired Progress is achieved. So that the progress achieved in each case processing and achieving the processing goal for the user Appropriate means are easily recognizable at any time provided which is based on a suitable visual and / or acoustic representation and display the current analysis data, a quick and easy Assessment of effectiveness or the success of the processing. This can be advantageous Different known parametric in the sense of the method and / or symbolic representation techniques for the appropriate online presentation of the acute analysis result are used, which the user also additional probing and / or Navigation and / or positioning aids for optimal application the radiation energies such as for targeted leadership and selective positioning an optical fiber introduced into the corresponding cavitation.

Appropriate aids can also be advantageous be provided, which is easy to use and quick Allow setting of the required radiation parameters. This process routine used in the sense of the invention serves on the one hand of control for a targeted, effective and selective material processing and on the other hand also as a security system, which is undesirable in any case damaging Application of the radiation energy to the material to be protected or surrounding tissue with certainty. In addition to a semi-automatic Operationalization of the method according to the invention are also automatic process routines conceivable, with the help of which a direct Feedback control possible is. You can do this Appropriate control parameters from the analysis process data obtained are derived in real time, which are then used for control and regulation of the various radiation parameters can be used. Advantageous It is when these process routines also have appropriate control logic contain, which with the help of implemented security criteria the various risks of incorrect operation and mishandling as well as tissue damage excludes.

The invention is described below Reference to the drawings of the figures using three exemplary embodiments explained in more detail. It demonstrate:

1 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 schematic representation of the inventive method and the inventive device in a second embodiment with automatic or semi-automatic material processing, and

3 schematic representation of the method and the device of the 2 with additional ultrasound echoscopy method.

In 1 the process of material detection and the necessary device is shown schematically. An optical fiber 1 is carried out by the surgeon in the target area concerned 2 the body of the patient to be treated, for example, with the help of an endoscope. Through the optical fiber 1 can about a laser 7 (laser sources) an optical excitation signal in the target area 2 be directed. The individual parameters of the laser 7 are about a control facility 6 (laser paramter control) controlled manually or automatically. About the control device 6 For example, the laser wavelength or the laser wavelengths, the intensity of the laser, the irradiation duration or the pulse sequence and their respective variation can be set.

The target area 2 can so over the optical fiber 1 with the laser 7 with one in its parame tern specified optical excitation signal. About the control device 6 different parameter profiles for the laser 7 retrieve or run through sequences of different parameter profiles 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, 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 corresponding spatial irradiation positions on the specimen.

Outside or inside the patient's body is a detector 8th attached with which acoustic and / or mechanical response signals can be recorded. Through the detector 8th are those of the excited target area 2 emitted acoustic and / or mechanical response signals, which are emitted in response to the optical excitation signal. This from the detector 8th Answer signals recorded are first in a processing stage 8a (detector signal processing) processed. 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. That in the preparation stage 8a processed signal is now in an analysis stage 11 (analyzing procedures) analyzed.

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 due to the photoacoustic effect with optical excitation of the target area 2 be stimulated. 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 allocation unit 12a (classification and recognition) the determined properties of the response signal are now assigned to property classes that each represent 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 classification of properties of the response signal can be done in different ways. In a particularly simple variant of the invention, the response signal only examined whether in the target area after the optical Any suggestion at all a specific photoacoustic event is taking place. by virtue of knowledge of the material properties under different excitation conditions is it possible to decide whether the optical excitation of a solid or of the surrounding tissue. In the case of the solid state specific vibration modes in the response signal at a particular Excitation energy recognizable, whereby in the case of excitation of the surrounding With this excitation energy, no vibration modes can then be detected are.

In a second assignment procedure is taken into account the fact that different homogeneous or heterogeneous materials different photoacoustic vibration modes exhibit. Will be at higher Excitation energies also excited vibrational modes in the area of the tissue, so they have a completely different spectrum than, for example that of a stone. The analysis of the excited target area can here, for example, also take place in such a way that the analyzed ones Signals represented as two- or multi-dimensional vectors and are applied, for example, on a screen. The resulting trajectory or trajectory are specific for the stimulated material of the target area. Continue to change the trajectory specifically under different excitation conditions, in particular at different excitation wavelengths and different Excitation energies. This also by changing the excitation conditions initiated changes of the response signal submit a specific signature of the material.

A further simple possibility of distinguishing between tissue and body calculus 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 sonification. In a simple case, the processed or analyzed signal is applied, for example, to a voltage-controlled oscillator (VCO) and is 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 can be used for further signal processing for the purpose of auditing and / or sonification and / or other known means for generating different, parametrically appropriately controlled and / or modulated electro-acoustic sound effects, triggered by the respective response signal. The surgeon can easily distinguish between the surrounding tissue and a body concrement, in particular a gall or kidney stone due to the received pitch, the received sound and / or the received tonal pattern. The surgeon can thus determine the correct time and the correct position of the optical fiber to destroy the respective concretions of the body.

Another way to analyze and classify of the detected response signal is the determination of the cavitation properties of the excited target area. Here again are different Methods applicable. For one, it is possible through cavitation in the target area excited vibration modes of the respective material in the Measure the target area and treat it as before described above. From the vibration modes of the target area, the different materials due to the significant differences determined in the spectrum of the vibration modes of the respective materials become.

Another option is through the determination of the cavitation periods themselves. Thereby the knowledge exploited that the cavitation periods depend on the one hand on the radiated energy and the radiated wavelength, on the other hand, a clear dependency of excited material. Based on the knowledge of the excitation signal can thus from the determined cavitation period on the material getting closed.

In a parameterized dynamic The method is the cavitation period for different excitation energies certainly. The course of the cavitation periods when the Excitation energy is also significant for different materials. This parameterized dynamic method can also be used with different excitation wavelengths and excitation dynamics.

From the analysis of the cavitation properties or the vibration modes excited in the target area can continue with knowledge of the excitation conditions can be recognized whether in the target area bleeding occurs. Because hemoglobin is characteristic shows spectral absorption properties, the excited vibration modes change or the cavitation periods in the target area during bleeding, because the excitation of the target area due to the hemoglobin is characteristic is modified. The identification of bleeding can also be carried out in the analysis of the vibration modes, since the excitation conditions of the target area significantly based on the characteristic Change bands of hemoglobin.

Another analysis option is when at least two detectors 8th 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. The knowledge is exploited 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 dependency of the sound fields emitted by the optically excited target material is also used, advantageously suitable detection systems in a suitable number or with a suitable spatial arrangement in Reference to the acoustic target source can be used. 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 on the body surface can also be used 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 dispensed with entirely, 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, the specific temporal correlations between the Lase can also be used excitation and the respectively detected photoacoustic signals or the ultrasound echo signals reflected on the target material advantageously use further features for the purpose of stone / tissue recognition as well as for artifact-free signal detection and for improving 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 stone-surrounding tissue.

The whole process 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 parametric controlled optical excitation of the target area intrinsic photoelastic, photoacoustic and photothermal properties of the excited Target area determined by analyzing periodic properties can be and can be assigned to a specific material type. With The characteristic stimulus makes certain achievable intrinsic sample-specific nonlinear effects, e.g. photoelastic, photoacoustic or photothermal transduction processes a characteristic signature of the complex properties of the specimen receive. These take place in the specimen nonlinear intrinsic transduction processes hang up characteristic way, among other things, both of the structure-elastic, plastoelastic, thermodynamic and optical properties as well as the material composition of the sample material as also depend on the nature of its surface and are related with those chosen accordingly Characterizing excitation conditions for the type, material property and composition of the specimen. The method aims at being multiple and with each other interacting complex but also highly significant dispersive photonically induced interactions as it were a kind of complex Signature (fingerprint) of the specimen under operative in vivo To get conditions.

The process discriminates, recognizes and interprets it using multiple parametric radiation excitation of the specimen triggered complex modal vibration events and their modal radiation and is able to close the recognized specimen locate and display.

For an automated or semi-automated classification of the response signals can different types of decision algorithms, such as B. threshold discriminators, spectral window discriminators, fuzzy discriminators, neuronal Networks and more are used. One more way the analysis or classification of the response signal lies in certain properties obtained in the analysis of the response signal of the detected response signal together with the excitation conditions in an n-dimensional Store feature space. Each measurement is therefore with its excitation parameters and with their significant analysis parameters to a point in the N-dimensional feature space mapped. Based on already known Feature vectors can be decided so which material certain feature vector is to be assigned.

In 2 Another embodiment of the invention is shown. In turn, one or more optical fibers 1 (beam delivery) by the surgeon to the target area of the body of the patient to be treated 2 introduced. 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 determined by the laser sources selected for this purpose 7 (laser sources) and the laser parameters that can be set with them 6 (laser parameter control) predefined and combined into corresponding predefined groups of excitation sequences, which can be in the form of correspondingly stored data records. Because of the parameter profiles contained in the different excitation sequences 4 (parameter setting), which come from the corresponding stored data records, are by means of a corresponding control unit 5 (parametric drive), the laser parameters using a corresponding process routine 6 (laser parametric control) automatically controlled in such a way that the laser sources 7 (laser sources) emit the specified radiation.

For this purpose, different and different types of radiation sources, conditions and parameters can be used for suitable stimulation or stimulation of the present target material in the target area 2 used individually or in combination with one another in order to obtain certain target-specific features with the aid of the structure-dynamic analysis with the aid of the formation of thermal, elastic or acoustic wave fields that is dependent on the structure of the target material in a sensitive and selective manner. 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 the respective desired applications, such as the selective and specifically controllable processing of the target material for the purpose of ablation, plastic deformation (thermoplastic, angioplasty, etc.) .), Laser section of tissue material, laser coagulation or for fragmentation (fractionation) of solid body concretions. It is also conceivable here to simultaneously process tissue materials for the purpose of biostimulation or photodynamic therapy or conservative photo-induced physiotherapeutic ultrasound treatment or shock wave therapy.

Different conceivable shapes dynamically dispersive and / or spectrally dispersive laser excitation can are used, e.g. a transient excitation with an or a series of short laser pulses or by an appropriately selected periodic and / or with randomized and / or parametric laser excitation Using a modulated CW laser source with a specifically identified Amplitude modulation and / or frequency modulation and / or pulse code modulation, as well as due to different spectral parameters specified laser excitation at different wavelengths, which all individually or in combination, each in a specific way Defined dynamic input function for the examined excitation and detection system and what in connection with the respectively detected dynamic Output function that characterizes the target material in a significant way System transfer property can be determined.

In a special embodiment was used as a laser source 7 a Freddy laser is used. The parameter profile that can be used here has two different laser wavelengths at 532 nm and 1064 nm with a gradable laser energy in the range from 20 mJ to 124 mJ 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 multiple pulse excitation and the possibility of pulse frequency variation, the laser system also provides the prerequisite for time-dispersive laser excitation.

With the help of a number of appropriately trained extracorporeal and / or intracorporeal detector systems 8th (n-detectors), which are attached to appropriately selected different positions of the patient's body, are those of the excited target area 1 receive outgoing response signals and further signal processing 8a (detector signal processing). In this case, 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 / noise ratio and others, in order to ensure optimal conditions for the subsequent analysis step 11 (analyzing procedures). As detector systems, two or three piezoelectric transducers can be attached to the patient's body surface in a suitable manner so 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 using suitable known correlation methods 9 (signal correlation) the temporal or phase correlations 10 (phasing and timing) with regard to the temporal relationships between the laser excitation taking place 6 and the detected response signals 9 determined. Furthermore, it is possible to correspondingly synchronize the respective response signals with one another or to modify them accordingly with regard to a desired temporal relationship to be achieved, such as, for example, according to 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 respective laser excitation and the different signal responses of one or more detectors 8th can be used at different spatial positions 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 excited with low laser energy (for example 20 mJ) can thereby be generated 2 are still sufficiently demonstrated. 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 is used on the one hand to locate the target area and on the other hand to hide reflected acoustic signal components. With the help of an appropriately set time window, only the direct and unreflected response signals can be recorded.

In connection with the parametrically specified excitation profile 4 Laser irradiation, including its temporal determination, becomes the response signals of one or more signal channels of a subsequent analysis that correlate with it and are prepared accordingly 11 (analyzing procedures).

In the analysis, a certain one Number of properties of the respective response signal determined. The properties to be determined can be determined empirically or analytically gained knowledge can be selected. Various are used for analysis Analysis strategies used individually or in combination. Hardness Differentiate body concrements themselves from soft tissue material among other things with regard to their triggered by the specified laser excitation and different types of modal vibrations and their material-specific different spectral absorption behavior, which is based on corresponding combined dynamic Features of the respective response signal in connection with corresponding energy-dependent Detect threshold characteristics as well as certain wavelength-dependent characteristics leaves.

In a simple form of the procedure are those obtained from the dynamics of the excited vibration modes Features which e.g. obtained by means of a corresponding dynamic analysis with the respective specific characteristic threshold energies combined at different laser wavelengths. In this In this case, the assignment to the property classes can be limited to determine whether at a certain laser energy and laser wavelength at all Vibration modes are present in the excited target area.

Another, also with little Effort to be implemented arises from the application of the knowledge that the optical excited vibration modes as well as the spread of the related acoustic wave fronts in the surrounding body tissue for firm Stone material or soft tissue material in a significant way differ. The stone material or the fabric material act here as the corresponding characteristic sound sources. For analysis, the synchronized response signals from two or several detectors at different detector positions the body surface of the Patients used and these in the form of two or multi-dimensional Signal vectors shown. The generated trajectories of the signal vectors therefore describe characteristic trajectories, which one clear assignment to property classes and thus a stone / tissue classification enable and detection.

An evaluation of the significant Trajektorienverläufe with repetitive or periodic excitation and / or with multiple pulse excitation and / or under different energies and / or excitation wavelengths use for more extensive analysis purposes. The Course of the respective trajectories for assignment to property classes used.

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. The response signals for each channel are processed in such a way that the response signal, which is filtered with a corresponding bandpass and synchronized with the laser pulses, controls a voltage-controlled oscillator (VCO) in a fixed manner, so that the detected dynamic waveforms in the form of a characteristic Way is represented in the pitch dynamically changed acoustic sound signal. The surgeon can then use the respective characteristic change in pitch to determine whether the optical fiber is 1 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 in turn be obtained from this frequency-modulated response signal.

Another way to perform the procedure is formed by the laser excitation with certain laser energies Formation of cavitations in the target area. As is known cavitation bubbles expand under the effect of the introduced Laser energy out and collapse with characteristic cavitation dynamics or periodic. From the with the help of a specified laser excitation generated and synchronized with this and detected response signals then the characteristic and material-specific cavitation periods determined on the basis of the different vibration modes generated. Can be advantageous the time differences between the occurrence of the first and second cavitation signal (T2 - T1) = TK can be determined. These characteristic values for the cavitation period TK, as well as its significant dependency from the laser parameters, such as B. from the laser energy E and / or the laser wavelength λ are made from the connection with the stimulation profile running through determined.

The cavitation periods can be determined at selected laser energies and selected laser wavelengths, with one or the other parameter being kept constant. 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) at a fixed wavelength λ and variable energies E fundamentally have a significantly different course 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 being largely in line with the laser energy E have a linearly increasing profile. 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 800 ms with a radiated power of 120 mJ. This allows stones and the surrounding tissue to be clearly distinguished from one another.

This procedure can continue through the measurement is more wavelength-dispersive Properties are improved. The cavitation period characteristics are used for this in terms of of energy and wavelength determined at certain energies and certain wavelengths, from which on the one hand additional information about the Type of sample material can be obtained and on the other hand also the selectivity the stone / tissue recognition additionally is improved.

In another embodiment the invention is additional the possibility bleeding in the target area during a lithotripsy treatment to recognize. This is particularly advantageous in cases where the Use of the claimed process in the blind process should and at the same time clinically relevant information about the existence or about the Measure more 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 highly perfused tissue compartments or vascularizations for the further treatment is crucial. The embodiment is the Underlying knowledge that the absorption properties of hemoglobin have very characteristic bands, so that with the help of a according to specified wavelength dispersive and energy dispersive Excitation of the sample material a reliable detection of bleeding or blood-rich tissue types possible is. The data can also be used to measure the degree of blood flow to tissues be derived.

The properties obtained from the analysis of the detected response signal are together with the corresponding Data of the excitation parameters converted into feature data sets and then to multidimensional feature vectors summarized accordingly classified and used for the detection of stone or tissue material.

Various suitable ones can be used here Criteria can be used individually or in context. Depending on the embodiment come here e.g. which are distinguishable when stone or fabric material is present dynamic and / or spatial Signal parameters for use, which result from the respective material-specific determined dynamic system transmission properties. As is known, can be deduced from the system-theoretical context between the accordingly chosen Dynamic input function in the form of the optical excitation function Laser radiation and those emanating from the target material and detected accordingly Dynamic output function due to the interactions in the target material as well as through the transmission medium specified dynamic system transmission properties determine.

Only after the detection of stone material are the appropriate control signals 13 (control signal derivation) via a feedback control loop 14 (feedback control), 15 (cControl signal processing) thereupon the laser powers, pulse sequences and pulse frequencies or wavelengths required for selective stone processing, for example laser lithotripsy, are set such that 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 using control units 17 (user platform).

Appropriate control signals are generated after the detection of stone material 13 , which takes the form of a corresponding automated feedback control 14 and a subsequent further appropriately suitable signal processing 15 is subjected. The laser parameters are then set to the previously determined and appropriately selected stone processing mode, by means of the optical fiber 1 a correspondingly high laser power, sufficient to destroy the stone, is only applied to the stone material found. 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 method without visual inspection, or on the basis of a requirement of the operator, 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 used by the user with the aid of the correspondingly selected analysis routine with the aid of an appropriate interface for process control 16 and an appropriately trained user interface 17 established.

In addition to certain input media 17a (input actuators) are available to the user or the operator with the interface 16 and the user interface 17 also various appropriately trained output media 17b (output representations) are available. The output media 17b enable different means of representation and types of representation, such as. B. to 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 certain parts of the process flow or this as a whole semi-automatic or automatic control, the automated Stone / tissue recognition also parallel to a corresponding one subjective evaluation, classification and recognition by the user can be done.

The control and regulation of the various Processing processes and / or their feedback control according to the requirements of material properties determined during each analysis cycle based on correspondingly specified control parameters, which with regard to the particular embodiment and application used beforehand be determined.

In 3 is the process of 2 supplemented by an additional ultrasound analysis option.

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

In image generation 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 course of time of a corresponding scanning algorithm in a suitable manner both with the radiation excitation and with the photoacoustic detection 8th and / or with the detection of thermal waves 19 (thermal wave detector) and / or other conceivable intracorporeal and / or extracorpural detection methods used 20 (other detection schemes) synchronized and correlated with each other accordingly 21a (phasing and timing procedures). On the basis of 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, these can be coordinated with one another in a predetermined manner by appropriately trained means.

Corresponding correlations are also used for targeted coordination 10 obtained suitable correlation data of the photoacoustic method used. Certain image scans, which are time-correlated both with the excitation and with one another, are obtained from the specimen, such as adaptive 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), which, among other things, can be used to mark certain desired or highlighted image areas 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 help of imaging and correspondingly processed, adapted and temporally correlated is processed using various process routines 22 (adapted frame procedures) for display 23 (correlated adapted images). The process information is then in the form of an appropriately selectable representation 17b shown accordingly, which allows the user various alternatives with regard to the correspondingly significant visualization forms 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 terms of their different relevance and significance are then extracted by means of a parameter and feature extraction 24 (parameter and feature extraction) is extracted accordingly, whereby, for example, certain texture parameters or certain texture features are obtained from the structural properties. Likewise, from the correlated relationships between the excitation and the complementarily determined relationships and the pro derived body fronts derived certain properties of the sound radiation characteristic and the sound propagation conditions, from which the relevant parameters or significant features are then determined.

The additional information obtained about the properties of the target area is based on the corresponding parameters or feature extraction 24 evaluated for their spatiotemporal correlation 25 (spatiotemporal image correlations) and these additional results are fed to the downstream and correspondingly expanded analysis method.

The same also applies to the echoscopic echoscopy used in parallel and correlated with one another in a complementary manner 18 , photoacoustic 8th , photothermal or radiometric 19 and / or other suitable intracorporeal and / or extracorporeally applied detection methods 20 , These response signals, which are registered synchronously with one another by means of corresponding detectors, are processed further in parallel in corresponding signal channels 8a , with the dynamic signal correlation on the one hand from the respective time signals 9 are determined with respect to their respective phase position and / or time relationship and, on the other hand, from the imaging methods used in parallel 18 . 19 likewise the spatiotemporal implications 25 with regard to their correlations or functional relationships obtained in the image information in a corresponding manner. In addition, the different 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 (complemetary correlatinos). These corresponding correlations then become that in the embodiment 2 described analysis methods supplied and processed accordingly.

The selective lithotripsy procedure with selective stone / tissue detection underlying technical Features are therefore characterized in that on the one hand a suitable laser beam (treatment beam) with high energy and correspondingly excellent radiation parameters for the purpose the stone destruction used being connected in the target area to dielectric breakdown with a plasma release and thus to the intended fragmentation of the stone concrement comes. On the other hand, for the purpose of determining which is present in the target area Material properties and especially for in vivo stone / tissue detection the same or another suitable laser beam with as much as possible low energy and with correspondingly excellent radiation parameters used in such a way that in the course of stone / tissue recognition an undesirable dielectric breakdown or plasma formation with certainty is excluded so that no damaging laser effect on the surrounding tissue or embedding the stone. In the method according to the invention become the different in laser excitation of the target area Known reversible photothermal, achievable below the plasma threshold, photoelastic or photoacoustic effects exploited to thereby non-destructive stone / tissue discrimination to achieve which is specific to the detection and analysis of the target material excitable material-specific and easily distinguishable structural elastic dynamic modes. This solution is based on the knowledge that with the help of an appropriately suitable dynamic application the laser radiation in pulsed or modulated operation optically stimulated target material in the target area a material-specific Determined source of thermal and / or elastic and / or acoustic wave fields which is detected by means of suitable detectors and can be evaluated accordingly in the sense of the invention.

This also works with the laser These conditions optically excited target material in the target area for one ultrasound beam aimed at this area as a material specific Determined ultrasound reflector, the reflection behavior under the dynamically controlled laser excitation in a significant way changed. The echo signals received by means of an ultrasound receiver from the opto-acoustically excited target surface due to the contained therein Material-specific features in the sense of the invention accordingly be evaluated. Can be advantageous for sending and receiving of ultrasound signals also the known ultrasound echoscopy methods with corresponding additional control circuit use for the purpose of the invention.

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 for analysis purposes or for therapy purposes in each case by appropriate means to the different conditions required for this, a suitable non-destructive excitation of the Target materials with correspondingly low laser energies (below the plasma threshold), but also for destructive material processing with correspondingly high laser energies, can currently be set. 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 a suitable feedback process control routine. This process can take place until a predetermined degree of fragmentation of the stone is reached be repeated speaking.

In another embodiment the laser beam is used for analysis by means of an additional, separate laser source independently generated by the laser source used for material processing, so that both laser beams together in one fiber be optically coupled, which then on the target material present is directed. However, the use of separate ones is also conceivable Fiber systems for this. This execution in the form of a two-beam arrangement is particularly advantageous in the case if under circumstances more versatile excitation conditions are desirable. That's how it is Basically no suggestion more on the use of the same wavelength or on the use short laser pulses as in the therapy laser system, but limited leaves one largely free choice of for Optimally matched laser wavelengths used for analysis purposes as well the most suitable pulse or modulation parameters to. For the case that e.g. a modulated CW analysis laser in conjunction with one necessarily pulsed therapy laser used in a two-beam arrangement there is the advantage that the CW analysis laser for continuous Analysis or to examine larger target areas or for the purpose of navigation and positioning aid in the case a blind process can be used. There is also the possibility to achieve different types and each usable Modulation types (e.g. AM, FM, PCM etc.) and modulation parameters (e.g. modulation frequencies, degrees of modulation, FM hub, frequency sweeps and much more).

In addition to applying the invention for selective feedback-controlled laser lithotripsy with implemented non-destructive In vivo stone / tissue detection are expanded as examples below applications shown. The claimed methods and Devices in the field of clinical endoscopy for the purpose of a Use laser-stimulated functional endoscopy (LFE). This Solution points the benefit of that in addition to the well-known phenomenological morphological diagnosis by inspection of the endoscopic image also an objective non-destructive in vivo functional diagnostic analysis simultaneously with the current inspected tissue area can take place.

A related one, not shown here embodiment has an optical system for this purpose, which is exemplary can consist of appropriately trained optical fibers, both introduced into the endoscopy channel as well as into the working channel become. Various types of laser sources can be used to generate the excitation light with appropriately trained laser generators and drivers as well Laser controllers are used. The analysis system consists of the operative connection of the correspondingly trained procedures and devices for the optical excitation of the tissue material, in functional relationship with certain appropriate procedures and Devices for the detection of photo-induced specific tissue reactions, such as. with the help of appropriately trained photoacoustic detection systems and / or by means of appropriately trained ultrasound echoscopy methods.

Basis of all these applications are the specific ones with appropriate photonic excitation dynamic entropic-elastic and / or thermoelastic and / or rheological changes in state of the Tissue. Thus the functional morphology can be numerous and different types of physiologically or pathophysioplogically modified Tissue types with the help of the claimed system analytical processes and device non-destructively and be examined objectively under in vivo conditions. Next the advantage of a specifically localizable application of photonic Energies on certain tissue areas there is also the possibility the radiation parameters used for the respective application largely free to choose and this in the course of the process either according to the specified control parameters or according to the analysis data determined measures to control in a recursive manner (feedback control). The invention and accordingly specified endoscopic radiation application can also be advantageous for the purposes of selective biostimulation under feedback control with regard to the stimulation effects to be achieved in each case become. For example, through a targeted endoscopic Laser stimulation in different tissue types and at different Tissue layers or tissue compartments a variety of different types known effects on the in vivo biochemical, biophysical subcellular, cellular or intercellular Achieve processes for appropriate therapeutic purposes.

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 rheological features of the tissue can therefore be used for tissue diagnosis based on the reversible entropic-elastic state changes acutely induced by means of a suitable laser excitation and on 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 diagnosis is over all advantageous where a tissue sample should be or must be avoided, for example by means of a biopsy and with subsequent histological in vitro laboratory examination. A major disadvantage of conventionally known histological examinations of biopsy material that has been removed is that, due to the method, this only permits a correspondingly delayed and sample-like in vitro diagnosis. Another fundamental disadvantage of all known in vitro examination methods is that the taking of the tissue samples and the associated isolation of the tissue from its morphological and functional context, and also as a result of the use of appropriate histological preparation techniques, means only extensive examinations unphysiological conditions are possible. These fundamental disadvantages are avoided by using the claimed in vivo method. Furthermore, in contrast to the known histological methods, the application 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 special advantage over the known methods in which tissue removal is required is that the tissue examinations after the method according to the invention always repeated on the intact tissue and on the same substrate at any time can be what the additional Benefit shows that this results in both kinetic and course diagnostic Have investigations carried out. In addition, the different physiological or pathophysiological functionalities the preservation of the intact tissue morphology is always reproducible and also objectively quantifiable. This results in all first the possibility with the help of the claimed method to an objective and therapy accompanying Assessment of the effects of certain therapeutic interventions to come, which also gives the possibility of a feedback-controlled selective and effective based on the immediate success of therapy Treatment results. Likewise, those with taking tissue samples associated risks and side effects are excluded. Further applications The invention can also be seen in the fact that this in the sense of a advanced clinical tissue diagnostics and / or to elucidate diverse structural dynamics cellular or tissue rheological processes such as at different Tissue compartments or vascular sections can be used advantageously. It is conceivable, for example, that by means of a correspondingly specified laser excitation on certain sections of the vessel in connection with a detection method suitable in the sense of the invention, these also as tracer methods for different circulatory parameters (e.g. flow, pulse transit time, compliance etc.) for determination various clinically relevant hemodynamic or vaso-elastic or vaso-motor parameters can be used.

Other advantageous applications the invention also arise everywhere where there are certain volume changes or other diverse specific tissue mechanical activities and reactivities may occur, which then result in different forms of movements, local accellerations, 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 3 , This complementary photoacoustic-echoscopic analysis method can be used in conjunction with the various imaging ultrasound methods used in connection with it. By using the image modes that can be displayed with the known ultrasound methods (e.g. A, -B, TM mode) in conjunction with the structural-dynamic tissue conditions caused by laser excitation, novel function-specific image representations are possible by means of temporally correlated photoacoustic and echoscopic image generation ( e.g. occurence imaging, strain imaging, phased imaging etc.). In this case, the ultrasound images of certain photoacoustically excited tissue compartments are evaluated and displayed in their correlating correlation with one another in synchronism with the laser excitation. 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).

Other conceivable applications of the method according to the invention can also be found therein, for example exist 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 for in vivo diagnostics of tissue also in connection with the previously described embodiments can be used. Here, the tissue-specific so-called heat dissipation deliver functions, the thermal diffusion lengths, thermal conductivities, heat transfers as well corresponding thermoregulatory parameters etc. appropriate clinically relevant features e.g. about tissue blood flow, metabolic activity, diffusion processes and much more (Clinical use e.g. for arthroscopic or laprascopic Method).

In addition, the inventive method over the clinical diagnostic applications also for quantitative and objective dosimetry of various physical therapy methods such as. with conservative laser therapy or conservative Use extracorporeal shock wave therapy.

Claims (55)

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 of the excited target area ( 2 ) emitted acoustic, thermal and / or mechanical response signal, 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) assignment of the properties of the at least one analyzed response signal and / or at least one excitation signal to predetermined property classes, each of which has at least one material quality of the excited target area ( 2 ) represent. Method according to Claim 1, characterized in that the at least one excitation signal from at least one light source 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 ( 7 ), in particular a laser. A method according to claim 1 or 2, characterized in that that the excitation signal at least one predeterminable sequence of different Parameter passes through. Method according to one of the preceding claims, characterized in that the response signal with at least one detector arranged inside and / or outside the body ( 8th ) is detected. A method according to claim 4, characterized in that at least two detectors arranged at different detection locations ( 8th ) are provided for the detection of at least two response signals. A 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 each other, the spatial Direction of propagation, location, source and / or speed of propagation of the response signal is determined. Method according to one of the preceding claims, characterized characterized in that the detected response signal before analysis especially by reinforcing, Filtering, transforming, improving the signal-to-noise ratio and / or Averaging is prepared. Method according to one of the preceding claims, characterized characterized in that the detected response signal with the excitation signal to determine the temporal and / or phase correlation data is correlated. A method according to claim 8, characterized in that the detected response signals based on the temporal and / or Phase correlation data are synchronized with one another and / or into a desired one temporal or phase relationship to each other. Method according to one of the preceding claims, characterized characterized in that the analysis of the detected response signal the periodic properties of the detected response signal are determined become. A method according to claim 10, characterized in that the vibration properties, especially the photoacoustic Vibration properties of the detected response signal can be determined. A method according to claim 10 or 11, characterized in that the vibration modes, in particular, from the detected response signal the photoacoustic vibration modes of the excited target area are determined by means of dynamic analysis. A method according to claim 10, characterized in that the cavitation period of those occurring in the excited target area Cavitation events is determined. Method according to one of the preceding claims, characterized characterized that the assignment of the properties of the analyzed Response signal to property classes based on the determined correlation properties, periodic properties, vibration properties and / or cavitation properties carried out becomes. A method according to claim 14, characterized in that if there are periodic components of the analyzed response signal, especially in the presence of vibration modes, the target area the solid state is assigned to a property class represents. A method according to claim 15, characterized in that specific periodic components of the analyzed response signal, in particular the vibration modes assigned to property classes be the specific solid represent. Method according to one of the preceding claims, characterized characterized that in the assignment of the properties of the analyzed Response signal to the property classes the excitation conditions, especially the parameters of the excitation signal. A method according to claim 17, characterized in that the target area ( 2 ) in the presence of periodic components of the analyzed response signal at a predetermined excitation intensity and / or a predetermined excitation wavelength, solid-state properties. Method according to claim 17 or 18, characterized in that that a variation of the excitation conditions, in particular the excitation wavelength and / or the excitation intensity, is made and from the variation of the properties of the detected Response signal the assignment of the target area to the material quality representing Property class is made. Method according to one of the preceding claims, characterized characterized that from the excitation conditions of the excitation signal and the determined cavitation period an assignment of the target area for at least one property class. A method according to claim 20, characterized in that from a variation of the excitation conditions, in particular a variation in wavelength and / or the intensity, resulting variation of the cavitation period to assign the target area is used for at least one property class. Method according to one of the preceding claims, characterized in that the direction of propagation and / or speed of propagation of the acoustic, thermal and / or mechanical response signal emitted by the excited target area for assigning the target area ( 2 ) is used for at least one property class. Method according to one of the preceding claims, characterized characterized in that the detected response signal, the conditioned Response signal and / or the analyzed response signal acoustically and / or is represented optically. A method according to claim 23, characterized in that the excitation conditions, in particular the parameters of the excitation signal, go into the acoustic and / or visual representation. Method according to claim 23 or 24, characterized in that that the response signal and / or the excitation signal via a voltage controlled oscillator (VCO) and / or other means made audible becomes. Method according to one of claims 23 to 25, characterized in that that the response signal and / or the excitation signal is visible on a screen be made. A method according to claim 26, characterized in that the excitation signal and / or the response signal is parametric represented in the form of coordinates and is displayed. Method according to one of the preceding claims, characterized characterized that the steps to identify the material quality of the target area can be repeated continuously or periodically. Method according to one of the preceding claims, characterized in that the assignment of the target area to a property class representing a material quality for controlling material processing of the target area ( 2 ), especially for lithotripsy. A method according to claim 29, characterized in that 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. Method according to one of claims 29 or 30, characterized in that after a step of material processing in turn a detection of the material properties of the target area ( 2 ) is made. 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. Method according to one of the preceding claims, characterized in that at least one ultrasound signal of the target area ( 2 ) is detected using ultrasound echoscopy. A method according to claim 33, characterized in that the ultrasonic signal by means of at least one ultrasonic transmitter ( 18 ) and transmitted by means of at least one ultrasound receiver ( 18 ) is detected. A method according to claim 33 or 34, characterized in that at least one ultrasound signal with at least one excitation signal and / or at least one response signal is correlated. A method according to claim 35, characterized in that the ultrasonic signal with at least one excitation signal and / or at least one response signal synchronized and / or in a predetermined temporal relationship and / or phase relationship is set to each other. Method according to one of claims 33 to 36, characterized in that from the excited target area ( 2 ) reflected ultrasonic signals properties of the target area are determined. A method according to claim 37, characterized in that the ultrasonic signals to determine their properties, especially their periodic properties. A method according to claim 38, characterized in that the properties of the ultrasound signal, especially under Inclusion of the excitation conditions, at least one property class are assigned, each of at least one material quality represents. Method according to one of claims 33 to 39, characterized in that that the detected ultrasound signal optically and / or acoustically is pictured. A method according to claim 40, characterized in that certain areas of the target area ( 2 ) are marked in an optical representation based on the properties determined from the response signal and / or the ultrasound signal. Method according to claim 40 or 41, characterized in that that the generation of a representation of an ultrasound image and / or the representation of an ultrasound image by at least one response signal is controllable. Device for carrying out the method according to at least one of the preceding claims with at least one light source ( 7 ) for optical excitation of a target area ( 2 ) in a human or animal body, at least one detector which can be arranged on or in the body ( 8th ) 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 ) to represent the response signal and / or the properties of the analyzed response signal. Device according to claim 43, characterized in that the light source is a laser ( 7 ) is. 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. Device according to one of the preceding claims 43 to 45, characterized in that an optical fiber ( 1 ) to direct the light source ( 7 ) emitted light is provided. Device according to claim 46, characterized in that the optical fiber ( 1 ) and / or the light source ( 1 ) are arranged on an endoscope. Device according to one of claims 43 to 47, characterized in that at least one detector ( 8th ) is designed as a piezo element. Device according to one of claims 43 to 48, characterized in that at least one allocation means ( 12a ) to assign the properties of the analyzed response signal to at least one property class. Device according to one of claims 43 to 49, characterized in that the display means ( 17b . 100 ) comprise an acoustic electroacoustic transducer, in particular a loudspeaker, controlled by a voltage-controlled oscillator and / or other means. Device according to one of claims 43 to 50, characterized in that the display means ( 17b . 100 ) include at least one screen. 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. Device according to one of the preceding claims 43 to 52, characterized by a device for taking ultrasound images ( 18 ). Device according to claim 53, characterized in that an ultrasound head ( 18 ) is provided with at least one ultrasound source and at least one ultrasound detector. Device according to claim 53 or 54, characterized in that that means for generating a representation of an ultrasound image and / or the representation of an ultrasound image are provided can be controlled by at least one response signal.