Device and method for frequency-domain thermoacoustic sensing

Abstract

The invention relates to a device (100) and a corresponding method for thermoacoustic sensing, in particular thermoacoustic imaging, the device (100) comprising: a) an irradiation unit (10) configured to generate electromagnetic and/or particle energy exhibiting a first modulation, the first modulation comprising at least one frequency and to continuously emit the energy towards a target (1), whereby acoustic waves are continuously generated in the target, the acoustic waves exhibiting a second modulation, the second modulation comprising the at least one frequency and/or a harmonic frequency of the at least one frequency; b) a detection unit (20) configured to simultaneously detect the acoustic waves exhibiting the second modulation while the energy exhibiting the first modulation is being continuously emitted towards the target (1); and c) a processing unit (30) configured to determine at least one thermoacoustic value of an amplitude and/or a phase of the second modulation of the acoustic waves at the at least one frequency and/or at a harmonic frequency of the at least one frequency. The invention allows for fast and economic thermoacoustic sensing, in particular imaging of a region of interest of an object.

Claims

1. A device for thermoacoustic sensing, the device comprising: a) an irradiation unit comprising an electromagnetic radiation source or a particle beam source, the irradiation unit being configured to: generate electromagnetic or particle radiation, respectively, modulate an intensity or frequency of the electromagnetic or particle radiation, respectively, with a first modulation, the first modulation simultaneously comprising at least two modulation components, wherein each modulation component is a periodic modulation at a distinct frequency, wherein the at least two modulation components of the first modulation are concurrently emitted, and wherein the first modulation corresponds to a superposition of the at least two modulation components, and continuously emit the modulated electromagnetic or particle radiation, respectively, towards a target so that the at least two modulation components at the distinct frequencies impinge upon the target at the same time, whereby acoustic waves are continuously generated in the target, the acoustic waves exhibiting a second modulation, the second modulation simultaneously comprising acoustic wave components at the distinct frequencies of the at least two modulation components or at harmonic frequencies of the distinct frequencies of the at least two modulation components, b) a detection unit comprising one or more sensors, the detection unit configured to simultaneously detect the acoustic waves exhibiting the second modulation while the modulated electromagnetic or particle radiation, respectively, is being continuously emitted towards the target, and c) a processing device configured to determine thermoacoustic values of at least one of an amplitude and a phase of each of the acoustic wave components at the distinct frequencies of the at least two modulation components or at harmonic frequencies of the distinct frequencies of the at least two modulation components.

2. The device according to claim 1, the processing device being configured to derive at least one property of the target based on the determined thermoacoustic values of at least one of the amplitude and the phase.

3. The device according to claim 2, the at least one property of the target relating to an absorption of the continuously emitted electromagnetic or particle radiation by the target.

4. The device according to claim 2, the at least one property of the target relating to an image or a map of a spatial distribution of the at least one property of the target.

5. The device according to claim 1, wherein the second modulation corresponds to at least one of: a. a modulation of the intensity or the frequency of the continuously generated acoustic waves, and b. a modulation comprising a linear combination of two or more frequencies contained in the first modulation.

6. The device according to claim 1, the first modulation or the second modulation corresponding to a periodic modulation of the continuously emitted electromagnetic or particle radiation or the continuously generated acoustic waves, respectively.

7. The device according to claim 1, the first modulation or the second modulation exhibiting a rectangular, triangular or sawtooth shape.

8. The device according to claim 1, the modulation components corresponding to two or more sinusoids at the distinct frequencies.

9. The device according to claim 8, the first modulation corresponding to a sum of the two or more sinusoids at the distinct frequencies.

10. The device according to claim 2, wherein the distinct frequencies of the at least two modulation components of the first modulation or the distinct frequencies of the two or more acoustic wave components of the second modulation are in a frequency range according to at least one of the following conditions: if the distinct frequencies are below 15 MHz, then the at least one property shall be determined within a first maximum sensing depth within the target; if the distinct frequencies are in a frequency range between 15 MHz and 50 MHz, then the at least one property shall be determined within a second maximum sensing depth within the target, the second maximum sensing depth being smaller than the first maximum sensing depth; if the distinct frequencies are above 50 MHz, then the at least one property shall be determined within a third maximum sensing depth within the target, the third maximum sensing depth being smaller than the second maximum sensing depth; and the distinct frequencies are in a frequency range corresponding to a detection bandwidth of the detection unit.

11. The device according to claim 1, the irradiation unit being configured to emit the electromagnetic or particle radiation at two or more different wavelengths.

12. The device according to claim 11, the irradiation unit being configured to emit the electromagnetic or particle radiation consecutively or simultaneously at the two or more different wavelengths, the electromagnetic or particle radiation at each of the two or more different wavelengths exhibiting a first modulation consisting of two or more modulation components at distinct frequencies.

13. The device according to claim 1, the detection unit configured to detect the acoustic waves, which are generated in the target while the electromagnetic or particle radiation exhibiting the first modulation is being emitted towards the target, at two or more different positions around the target.

14. The device according to claim 13, the detection unit configured to detect the acoustic waves at two or more different positions located on at least one of a straight line, a circular line, and a cylindrically shaped area around the target.

15. A method for thermoacoustic sensing, the method comprising: a) continuously emitting electromagnetic or particle radiation, respectively, exhibiting a first modulation simultaneously comprising at least two modulation components, wherein each modulation component is a periodic modulation at a distinct frequency, towards a target so that the at least two modulation components at the distinct frequencies impinge upon the target at the same time, wherein the first modulation corresponds to a superposition of the at least two modulation components such that the at least two modulation components of the first modulation are concurrently emitted, whereby acoustic waves are continuously generated in the target, the acoustic waves exhibiting a second modulation, the second modulation simultaneously comprising acoustic wave components at the distinct frequencies of the at least two modulation components or at harmonic frequencies of the distinct frequencies of the at least two modulation components, b) simultaneously detecting the acoustic waves exhibiting the second modulation while the electromagnetic or particle radiation exhibiting the first modulation is continuously emitted towards the target, and c) determining thermoacoustic values of at least one of an amplitude and a phase of each of the acoustic wave components at the distinct frequencies of the at least two modulation components or at the harmonic frequencies of the distinct frequencies of the at least two modulation components.

16. A device for thermoacoustic sensing, the device comprising: a) an irradiation unit comprising an electromagnetic radiation source or a particle beam source, the irradiation unit being configured to: generate electromagnetic or particle radiation, respectively, modulate an intensity or frequency of the electromagnetic or particle radiation, respectively, with a first modulation, the first modulation simultaneously comprising at least two modulation components at distinct frequencies, and continuously emit the modulated electromagnetic or particle radiation, respectively, towards a target so that the at least two modulation components at the distinct frequencies impinge upon the target at the same time, wherein each modulation component is a periodic modulation at a distinct frequency, wherein the at least two modulation components of the first modulation are concurrently emitted and the first modulation corresponds to a superimposition of the at least two modulation components, whereby acoustic waves are continuously generated in the target, the acoustic waves exhibiting a second modulation, the second modulation simultaneously comprising acoustic wave components at the distinct frequencies of the at least two modulation components or at harmonic frequencies of the distinct frequencies of the at least two modulation components, b) a detection unit comprising one or more sensors, the detection unit configured to simultaneously detect the acoustic waves exhibiting the second modulation while the modulated electromagnetic or particle radiation, respectively, is being continuously emitted towards the target, whereby the acoustic wave components at the distinct frequencies of the at least two modulation components or at harmonic frequencies of the distinct frequencies of the at least two modulation components are detected at the same time, and c) a processing device configured to determine at least one thermoacoustic value of at least one of an amplitude and a phase of each of the acoustic wave components at each of the distinct frequencies of the at least two modulation components or at each of the harmonic frequencies of the distinct frequencies of the at least two modulation components.

Description

(1) The above and other elements, features, characteristics and advantages of the present invention will become more apparent from the following detailed description of preferred embodiments with reference to the attached figures showing:

(2) FIG. 1 an example of a device for thermoacoustic sensing or imaging;

(3) FIG. 2 an example of a device which is particularly adapted for skin imaging;

(4) FIG. 3 an example of an integrated handheld device;

(5) FIG. 4 an example of a device which is particularly adapted for endoscopic imaging, the insert showing embodiments of a fiber tip;

(6) FIG. 5 a diagram of detected acoustic waves in the Fourier domain; and

(7) FIG. 6 a schematic representation of an example of a device configured to implement imaging based on the geometrical characteristics of the energy emitted (left part) and a schematic representation of the illumination signal (right part).

(8) FIG. 1 shows a schematic representation of an example of a device 100 for thermoacoustic sensing comprising a source device 10 configured to emit transient electromagnetic radiation and/or particle radiation and a detector device 20 configured to detect acoustic waves generated in a sample 1 upon irradiation with the emitted electromagnetic radiation and/or particle radiation.

(9) The device 100 further comprises a data acquisition and processing device 30 configured to process thermoacoustic signals corresponding to the detected acoustic waves and to derive at least one property of the sample 1 based on the processed thermoacoustic signals.

(10) Moreover, the device 10 comprises a control/modulation device 40, a sample holder 50 configured to receive and/or hold the sample 1, and a motion device 60 configured to generate a rotational and/or translational motion of the sample 1, on the one hand, and the source device 10 and/or detector device 20, on the other hand, relative to each other.

(11) The source device 10 comprises at least one source 11 emitting transient energy. Preferably, the source 11 comprises a light source, such as a laser source or a light emitting diode (LED). The light source provides the ability to emit intensity modulated illumination patterns at predefined frequencies consecutively or simultaneously by superimposing driving signals at multiple discrete frequencies. Dependent on the desired application, the source 11 can also be a radiofrequency (RF) or microwave source.

(12) Transient energies in the form of light, RF waves or microwaves, respectively, are coupled to the sample 1 preferably by means of waveguides 12, comprising an optical fiber, a RF waveguide or cable, an antenna, or mirrors, respectively. To achieve homogeneous illumination, the sample 1 is illuminated from multiple angles using energy couplers 13.

(13) For example, as the source 11 a laser array is provided which is configured to emit light at three wavelengths at 680 nm, 780 nm and 860 nm. Further, as the detector device 20 an acoustic wave detector with a central frequency of 7.5 MHz and a cut-off frequency of 11 MHz is provided.

(14) Frequency domain multispectral optoacoustic tomography (FD-MSOT) is performed, for example, by using three groups of modulation frequencies with five frequencies per group, i.e. group .sub.1 at 680 nm:

(15) f.sub.680=5.1 MHz, 6.1 MHz, 7.1 MHz, 8.1 MHz, 9.1 MHz, 10.1 MHz, group .sub.2 at 780 nm:

(16) f.sub.780=5.3 MHz, 6.3 MHz, 7.3 MHz, 8.3 MHz, 9.3 MHz, 10.3 MHz, and group .sub.3 at 860 nm:

(17) f.sub.860=5.5 MHz, 6.5 MHz, 7.5 MHz, 8.5 MHz, 9.5 MHz, 10.5 MHz.

(18) It has to be noted that the frequency shift in each modulation group is not limited to 1 MHz but can also be lower than 1 MHz or higher than 1 MHz.

(19) Furthermore, the frequency deviation from one group to the other (in the above given example: f.sub.680_780=0.2 MHz) can also be lower (f.sub.680_780<0.2 MHz) or higher (f.sub.680_780>0.2 MHz) on the condition that the spectral component of the stimulation frequency of wavelength .sub.x can be resolved from the stimulation frequency of wavelength .sub.y. Moreover, the number of frequencies per group is not limited to five but can also be lower or higher.

(20) Thus, the FD-MSOT device 100 is configured to perform real time and simultaneous visualization of at least one, but preferably several biomarkers and/or EME absorbers in tissue at high resolution using backprojection and/or model based reconstruction methods combined with spectral unmixing algorithms.

(21) The detector device 20 is adapted to measure mechanical stress waves, in particular ultrasound signals, emanating from thermoacoustic sources, i.e. absorbers of transient energy, particularly electromagnetic energy. In the present example, the detector device 20 comprises a single element transducer 21 which can be rotated around the object 1 using the motion device 60. Alternatively or additionally, similar to ultrasound imaging, an array of acoustic sensors with multiple sensing elements (e.g. 64, 128, 256 elements or more) is preferably used to detect thermoacoustic signals. The ultrasound detector is advantageously based on PZT/PVdF technology or on CMUT (capacitive micromachined ultrasonic transducers) technology; alternatively or additionally, optical detection methods based on interferometry can also be employed to sense mechanical pressure waves.

(22) Preferably, the detection bandwidth of the detector device 20 is matched to the size of absorbers within the imaged ROI and also the modulation frequencies of the source device 10.

(23) The acquisition and processing device 30 is adapted to measure amplitude 33 and phase 34 components (or complex numbers) of the generated thermoacoustic signals. Preferably, homodyne/heterodyne detection by means of a lock-in amplifier 32 is employed where the detection unit is locked to the reference frequency provided by the control unit 40. Amplitude 33 and phase 34 components are decomposed by the lock-in detector and stored in a storage unit 35 before the image reconstruction device 36 generates a thermoacoustic image.

(24) Alternatively to the lock-in amplifier 32, a spectrum analyzer 32 can be utilized to resolve amplitude and phase components of the thermoacoustic signal. Furthermore, amplitude 33 and phase 34 components of the thermoacoustic signals can be retrieved by measuring signals over time. In this case, transformation in the Fourier domain yields the phase 34 and amplitude 33 of the signal. Further alternatively, an IQ demodulator can be used to measure the amplitude and phase of the optoacoustic signal.

(25) Optionally, thermoacoustic signals are pre-amplified using a low noise amplifier 31.

(26) The image reconstruction device 36 is adapted to generate images of absorption of transient energy within a region of interest. Preferably, the reconstruction device 36 is configured to model the illumination and detection geometry and to perform dedicated inversion algorithms to produce a quantitative tomographic image showing a representative map of energy absorbers. Modeling includes a photon propagation model, the size of detectors and acoustic heterogeneities within the ROI.

(27) Reconstructed images 4 of the ROI, i.e. absorbers 2 and 3 with different absorption characteristics can be displayed on an output device 37 such as a screen, a printer, a computer, or a data storage device.

(28) The control device 40 comprises a signal generator (for example a function generator or an arbitrary waveform generator) 41 configured to drive the source device 10 with predetermined modulation frequencies. In the case of optical excitation, the source device 10 can be based on a driver providing a modulated current which drives a laser diode, LED etc. Alternatively, the intensity of EME can be modulated by means of an acousto-optic modulator AOM. Preferably, the control device 40 is configured to provide signals at discrete and/or distinct modulation frequencies consecutively; as an example, the signal generator 41 drives the source device 11 with a sinusoidal signal at multiple frequencies, i.e. starting in discrete steps from f.sub.1=1 MHz reaching f.sub.5=5 MHz with f=MHz frequency steps. At each discrete frequency step, the acquisition and processing device 30 measures amplitude and phase components of the signal.

(29) Alternatively, the control device 40 is configured to generate signal patterns containing multiple frequency components simultaneously. This is achieved by signal combiners/adders or arbitrary waveform generators to yield a superimposed signal with multiple spectral (phase and amplitude) components.

(30) The sample 1 is fixed on a dedicated carrier unit 50 which enables immobilizing the sample during the experiment. The carrier unit 50 further enables exact positioning of the sample 1 in the imaging setup. Preferably, to acquire a tomographic data set, either the detection unit 20 is rotated with a rotation stage 62 around the object 1, or the object 1 is rotated. The motion stage 60 is controlled by a motion controller 61 and synchronized with the data acquisition unit 30.

(31) FIG. 2 shows an example of a device which is particularly adapted for skin imaging. The illumination devices 13 and the detector device 21 are arranged outside the object 1 which is illuminated with, preferably, two or more wavelengths to perform frequency domain multispectral imaging at several wavelengths including multiple modulation frequencies.

(32) The detector element 21 can be a single element transducer but, preferably, comprises an array of transducers to acquire acoustic signals simultaneously over multiple projection angles or positions across the object 1. The detector 21 and the illumination devices 13 are connected to a casing 38 of the FD-MSOT device where signals are optionally pre-amplified, acquired and stored for further processing and visualization. The FD-MSOT approach allows for illuminating the object 1 at several wavelengths at different groups of modulation frequencies to achieve real-time scanning of skin diseases.

(33) The object 1 can be scanned at multiple different angles around the object 1 (tomographic signal acquisition) or according to a raster scanning method where the sample 1 is imaged at different x-y positions (x-y-horizontal scanning). Furthermore, the detection can be performed by translating and/or rotating the illumination/sensing unit 13/21 (combination of raster scanning with signal detection at multiple projections) to extend the field of view.

(34) Preferably, the device can be adapted for imaging on multiple scales, i.e. on the macroscopic, mesoscopic and microscopic scale, simultaneously or independently.

(35) When used as a microscopic FD-MSOT device, the detection unit 21 comprises a high frequency ultrasound detector (single element or array) which is preferably based on PZT/PvdF/CMUT technology, but can also be a mechanical pressure sensor which is based on interferometry, e.g. a Fabry-Perot or a Fiber Bragg grating based ultrasound sensor. Illumination is provided by multiple (at least one) illumination units 13 each encoded with a specific group of modulation frequencies as described above.

(36) Advantageously, different imaging scales can also be combined. As an example, the EME/laser can be modulated at two different frequency groups in the low-MHz region for macroscopic imaging

(37) .sub.1,macroscopic:

(38) f.sub.1,macroscopic=5.1 MHz, 6.1 MHz, 7.1 MHz, 8.1 MHz, 9.1 MHz, 10.1 MHz,

(39) while simultaneously driving the laser with a higher frequency group

(40) .sub.2,macroscopic:

(41) f.sub.2,macroscopic=80 MHz, 81 MHz, 82 MHz, 83 MHz, 84 MHz, 85 MHz,

(42) for microscopic imaging in real time. In this case, two different detectors with a detection bandwidth matching the modulation frequencies f.sub.1,macroscopic and f.sub.2,macroscopic are employed.

(43) Similarly, mesoscopic and microscopic imaging can be combined by using different groups of excitation frequencies.

(44) Regarding further components, features and functionalities of the device shown in FIG. 2, the elucidations with reference to FIG. 1 apply accordingly.

(45) FIG. 3 shows an example of an integrated handheld device in which components of the device are integrated in a measuring head 70. The measuring head 70 comprises illumination devices 13 and detection devices 21, which are connected to the remote device casing 38 by optical fibers 12 or cables 22, respectively. The measuring head 70 can be manually moved across the object 1 for scanning the ROI in the target 4 to excite absorbers of EME and detect corresponding acoustic signals from these sources in real time. Regarding further components, features and functionalities of the handheld device shown in FIG. 3, the elucidations with reference to FIG. 1 apply accordingly.

(46) FIG. 4 shows an example of a device which is particularly adapted for endoscopic imaging, wherein the above-mentioned approach of frequency domain thermoacoustics is applied to imaging of hollow regions. In the present example, continuous-wave (CW) laser light at various wavelengths .sub.1, . . . , .sub.N is modulated at K frequencies f.sub.1, . . . , f.sub.K. The tissue can be excited using each wavelength, simultaneously modulated with the K frequencies.

(47) As apparent from exemplary implementations shown in the upper right part of FIG. 4, an illumination and detection can be combined in one catheter and/or endoscope tip to perform imaging within the hollow region, e.g. within an organ or within a vascular system. Alternatively and/or additionally, the ROI within the object can be illuminated via the surface from outside the tissue while acoustic signals are measured using a detection device in form of an optoacoustic or acoustic transducer located within the target.

(48) As apparent from another exemplary implementation shown in the lower right part of FIG. 4, an illumination, e.g. by means of fiber tip, can be arranged within the target while the acoustic sensor, e.g. an ultrasound transducer, is placed outside the tissue.

(49) Preferably, the catheter and/or endoscope transducer tip moves in the intraluminal space using a certain pattern, e.g. a spiral shape, where at each location and angle the acoustic wave generated by the optical absorber is detected with a given angular window of . The data collected across all frequencies and wavelengths is then processed using model-based or backprojection algorithms. Un-mixing methods are used to separate concentration from different biomarkers.

(50) By means of the exemplary implementations illustrated in FIG. 4 frequency-domain multi-spectral intravascular imaging and endoscopy is possible, wherein multiple wavelengths are simultaneously modulated by a group of discrete frequencies. The modulated light is then used to illuminate the tissue, either from the catheter/endoscope tip using an optoacoustic transducer or from the surface. The acoustic signal detected using a limited-view acoustic transducer is then converted to amplitude and phase information using a detection approach (such as homodyne detection). Data collected across all frequencies and wavelengths is then processed by model-based or backprojection algorithms using un-mixing of multispectral information.

(51) FIG. 5 shows an example of a diagram of detected acoustic waves in the Fourier domain, in which the amplitudes of the detected acoustic waves are plotted versus frequency.

(52) The results shown in FIG. 5 were obtained when illuminating an optical absorber with an illumination pattern consisting of a superimposed signal at multiple, in the present example four, discrete frequencies (i.e. a group of multiple frequencies).

(53) FIG. 6 shows a schematic representation of an example of a device implementing imaging based on the geometrical characteristics of the energy emitted. In this case a conditioned light beam 6, e.g. a focused or a collimated light beam, is scanned in at least two dimensions by a scanning device 7 (alternatively the target 8 can be scanned). The beam 6 generates optoacoustic contrast within the scanned target 3. The acoustic waves generated are captured by one 9 or multiple 5 acoustic detectors. While in the present example single detectors are shown, the optoacoustic signal collection system can e.g. be a conical lens, an array for acoustic detectors, an interferometric method or any other means of collecting and detecting sound waves. The graph on the right represents the illumination signal, consisting in this case of two frequencies f1 and f2, each one carrying at different wavelength 1 and 2, respectively. Correspondingly, the two wavelengths can be simultaneously emitted and their relative absorption-based ultrasonic signals separated by frequency decomposition of the detected acoustic wave.

(54) In the present example, the absorber consisted of a 350 m graphite rod which was illuminated by an intensity modulated laser of a single wavelength of 808 nm (Omicron Laserage Laserprodukte, GmbH, Germany, Model: Omicron A350). Acoustic signals are detected with a cylindrically focused single element PZT ultrasound sensor (Olympus NDT, Waltham, Mass., USA, Model: V382, central frequency: 3.5 MHz, bandwidth: 76%).

(55) In this case, the illumination pattern consisted of four different modulation frequencies at f.sub.1=3.49 MHz, f.sub.2=3.51 MHz, f.sub.3=3.48 MHz and f.sub.4=3.52 MHz. As apparent from the diagram, the amplitude of the optoacoustic signal shows clearly spectral components at each modulation frequency.

(56) Although the phase of the detected acoustic waves is not shown in the present diagram, the above elucidations regarding amplitude also apply to the phase of the detected acoustic waves the Fourier domain accordingly.

(57) Based on the values of the amplitude and/or the phase of each of the components at the distinct frequencies (f.sub.1, f.sub.2, f.sub.3, f.sub.4) of the intensity modulation of the laser light, at least one property, e.g. an absorption or absorption map, of the ROI is derived.

(58) In the following, preferred applications of the device and method according to the invention are described in more detail.

(59) A preferred application of the invention is in the biological and medical field for imaging, diagnosis, therapy, and treatment of humans and animals or part of humans and animals in-vivo, ex vivo and in vitro. However, the invention can also be applied in the industrial, environmental and geological field, for example for testing of specific properties of various materials (such as absorption, nondestructive testing, testing material deficiencies and so on).

(60) Of particular interest is the application of the present FD thermoacoustic imaging method in biological and medical imaging. Preferably, the invention can be used as a clinical diagnosis tool to image cancer, inflammations, cardiovascular diseases, skin diseases, neurodegenerative diseases, metabolic diseases, anomalies in tissue vasculature. Furthermore, the invention can be used for neurological imaging and to monitor tissue growth, for tumor staging.

(61) Since FD-MSOT enables real-time visualization of multiple biomarkers simultaneously, the invention provides further powerful applications for video-rate tracking of tissue intrinsic absorbers (hemoglobin, melanin cells) as well as exogenously applied contrast agents. Thus, FD-MSOT can be applied to determine oxygenation levels in real time and track the pathway of multiple injected agents simultaneously.

(62) The device can further be applied to determine the oxygenation levels of blood using different energy levels of the EME (such as light at different wavelengths, RF at different frequencies etc.). Particularly in the optical regime, the device can be utilized for imaging of hemodynamic processes and hematologic diseases. As blood in its oxy- and deoxygenated state have different absorption characteristics at different wavelengths, the measured opto/thermoacoustic signals can be used to determine the level of oxy and deoxy blood.

(63) The real time imaging capability of the present device and method coupled with simultaneous multispectral illumination allows for accurate tracking of physiological and molecular changes of tissue in vivo. Thus, intrinsic absorption changes at different wavelengths can be tracked, such as blood perfusion, hemoglobin, melanin, and other tissue intrinsic absorbers.

(64) Furthermore, applying extrinsic contrast agents/contrast enhancers, organ perfusion can be tracked at real time, yielding physiological and molecular information in vivo.

(65) The invention can also be applied as an endoscopic device where the detector and the illumination device are arranged so that imaging is performed within the tissue/hollow organ. Thus, at least one of the detection unit and the source unit is adapted such that it is inserted inside hollow organ or a blood vessel, for intracavity imaging such as intravascular imaging, imaging of the colon, imaging of the gastro-intestinal track, transurethral imaging and so on. Furthermore, the illumination device can be inserted within the tissue to excite tissue from within the ROI while detection of acoustic signals is performed on the surface of the tissue. Alternatively, the detector is placed within the tissue while illumination is performed on the surface of the ROI.

(66) Depending on the stimulation, i.e. modulation, frequency, the proposed invention can be used for imaging on the macroscopic, mesoscopic and microscopic scale. Using low excitation frequencies in the range of few MHz (up to 15 MHz), the device is advantageously applied to image absorbers on the macroscopic scale allowing for resolutions in the range of 100 m. Utilizing higher stimulation frequencies, the invention can be applied on the mesoscopic scale (15 MHz<f<50 MHz), combining high resolution with high penetration depths. At higher frequencies (f>50 MHz), the invention can be applied for microscopic imaging. #

(67) It is to be noted that the invention also allows for simultaneous imaging at different scales. By using different detection devices, the device can be applied for macroscopic and/or mesoscopic and/or microscopic imaging of the same sample at the same time.

(68) Particularly, the combination of mesoscoplc and microscopic imaging can be used to image skin diseases and for tumor staging.

(69) The inventive device and method can furthermore be applied in non-biological, industrial environments to screen food and drink. Using different energy levels of EME (light, RF, X-rays and so on), materials can be tested according to their absorption and or material deficiencies.

(70) Furthermore, the device can be applied in geological settings to image soil or for screening of biological plants.