A method for detecting biological tissue using the photoacoustic effect of terahertz waves and its application

Abstract

The present invention discloses a method for detecting biological tissues using the photoacoustic effect of terahertz waves and its application, comprising the following steps: designing a terahertz source to generate pulsed terahertz waves to radiate vertically to the surface of biological tissues, wherein the energy of the generated pulsed terahertz waves is in the order of uJ and the duration is in the order of ps; receiving photoacoustic signals generated by biological tissues through the photoacoustic effect of terahertz waves; distinguishing biological tissues by the difference between the received photoacoustic signals to achieve detection of different biological tissues, wherein the difference between the photoacoustic signals includes the difference in amplitude, receiving time and waveform information between the photoacoustic signals. When detecting in vitro tissues, the biological tissues are arranged between the terahertz source and the ultrasonic detector; when detecting in vivo tissues, the terahertz source and the ultrasonic detector are both arranged on the outer surface of the in vivo tissues. It is used to detect blood components and different skin tissues. Rapid and non-destructive detection of in vivo tissues is achieved by using pulsed terahertz waves.

Description

Technical Field

[0001] The invention belongs to the technical field of terahertz imaging, and relates to a method for detecting biological tissues by utilizing the photoacoustic effect of terahertz waves and an application thereof. Background Art

[0002] In recent years, terahertz waves have brought a new, label-free, non-invasive detection method to biomedical research due to their non-ionizing, wide bandwidth, and high signal-to-noise ratio characteristics. With the development of terahertz sources, especially the generation of terahertz pulses with energies up to the mJ level, research on biological tissues in the terahertz band is no longer limited to non-thermal effects. At the same time, in the diagnosis of diseases such as skin cancer, the gold standard is histopathological testing. As an invasive test, histopathological testing may cause excessive surgery, mis-cutting or incomplete cutting during the diagnosis process due to unclear tumor boundaries, resulting in treatment failure. In the detection of target tissues using terahertz technology in clinical environments, blood components may cause a great deal of interference with the reception of terahertz signals in target tumor areas such as skin, breast, and digestive tract.

[0003] Although the application of terahertz imaging technology in biomedicine has received widespread attention and recognition, there are still many shortcomings. First, in the detection of living tissue, terahertz waves are absorbed by a large number of water molecules in living cells, and the characteristic absorption peak signal of biological tissue is buried. Second, there is the problem of imaging speed. Terahertz pulse imaging can obtain higher imaging resolution, but it takes a lot of time to scan point by point through the two-dimensional sample moving stage raster type, and has high requirements for the test environment. There is still a lot of room for development in dynamic terahertz imaging. Summary of the invention

[0004] The purpose of the embodiments of the present invention is to provide a method for detecting biological tissue using the photoacoustic effect of terahertz waves and its application, so as to solve the problem that when using terahertz imaging technology for living tissue detection, terahertz waves are absorbed by a large number of water molecules in living cells, the characteristic absorption peak signals of biological tissues are buried, and different biological tissues cannot be distinguished by terahertz wave spectra, and the existing terahertz imaging system is slow, time-consuming, and has high requirements for the test environment.

[0005] The technical solution adopted in the embodiment of the present invention is: a method for detecting biological tissue using the photoacoustic effect of terahertz waves, comprising the following steps:

[0006] Design a terahertz source to generate pulsed terahertz waves and radiate them vertically onto the surface of biological tissues;

[0007] Receiving photoacoustic signals generated by biological tissues through the terahertz wave photoacoustic effect;

[0008] Biological tissues are distinguished by the differences between the received photoacoustic signals, thereby achieving detection of different biological tissues.

[0009] Another technical solution adopted by the embodiment of the present invention is: an application of a method for detecting biological tissue using the photoacoustic effect of terahertz waves, which is used to detect blood components.

[0010] Another technical solution adopted by the embodiment of the present invention is: an application of a method for detecting biological tissue using the photoacoustic effect of terahertz waves, which is used to detect different skin tissues.

[0011] The beneficial effects of the embodiments of the present invention are:

[0012] 1. By distinguishing the received photoacoustic signals, the rapid and non-destructive detection of in vivo tissues using pulsed terahertz waves is realized, solving the problem that when using terahertz imaging technology for in vivo tissue detection, terahertz waves are absorbed by a large number of water molecules in living cells, the characteristic absorption peak signals of biological tissues are buried, and different biological tissues cannot be distinguished by terahertz wave spectra;

[0013] 2. It has the characteristics of fast imaging speed, high sensitivity, excellent contrast and resolution, which solves the problems of slow speed, long time consumption and high requirements on the test environment of the existing terahertz imaging system;

[0014] 3. The photoacoustic signals of blood components and skin tissues were analyzed, and the terahertz photoacoustic effect was used to detect and distinguish different skin tissues and blood components. This provides a theoretical basis for experimental research on terahertz photoacoustic imaging of biological tissues, and is of great significance for the selection of detectors, detection methods, terahertz sources and applicable tissue types. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0016] Figure 1 These are the propagation diagrams of photoacoustic signals with six different propagation times in a thrombus, including: (a) 100ps, (b) 20ns, (c) 50ns, (d) 100ns, (e) 200ns, and (f) 400ns.

[0017] Figure 2 This is the time domain diagram of the photoacoustic signal at point A on the central surface of the thrombus when irradiated at 1.0 THz.

[0018] Figure 3 It is a diagram of the photoacoustic signal received on the section line L at different time points at 1.0 THz.

[0019] Figure 4 This is a comparison of the photoacoustic signals of thrombus, whole blood and plasma at 0.2 mm away from the irradiation plane.

[0020] Figure 5 It is a schematic diagram of different forward detection points.

[0021] Figure 6 It is the time domain diagram of the photoacoustic signal at the forward probe points A, B, C, and D (plane wave irradiation).

[0022] Figure 7 It is the time domain diagram of the photoacoustic signal at the forward probe points C, E, F, G, and H (plane wave irradiation).

[0023] Figure 8(a) is a frequency domain diagram of the photoacoustic signal at forward probe points A, B, C, and D (in the form of plane wave irradiation).

[0024] Figure 8(b) is the frequency domain diagram of the photoacoustic signal at the forward probe points C, E, F, G, and H (in the form of plane wave irradiation).

[0025] Fig. 9 It is the time domain diagram of the photoacoustic signal at the forward probe points A, B, C, and D (Gaussian distribution irradiation).

[0026] Fig.10 It is the time domain diagram of the photoacoustic signal at the forward probe points C, E, F, G, and H (Gaussian distribution irradiation).

[0027] Fig.11 It is the frequency domain diagram of the photoacoustic signal at the forward probe point (in the form of Gaussian distribution irradiation).

[0028] Fig.12 It is the maximum sound pressure detected at point A under different terahertz wave irradiation energies at 1.0 THz radiation.

[0029] Fig.13 It is the maximum sound pressure detected at point A under different terahertz wave focusing radii when radiated at 1.0 THz.

[0030] Fig.14 It is the maximum sound pressure detected at point A under different terahertz wave pulse durations when radiated at 1.0 THz.

[0031] Fig.15 is the maximum sound pressure detected at point A at different terahertz wave frequencies.

[0032] Fig.16The influence of different terahertz wave irradiation forms on the propagation of photoacoustic signals, including: (a) plane wave form, t = 500ns, (b) Gaussian distribution form, t = 500ns.

[0033] Fig.17 It is the photoacoustic signal at the center M of the irradiated surface of normal skin tissue.

[0034] Fig.18 Graphs of optical parameters of skin stratified tissues (stratum corneum, epidermis and dermis) in the terahertz band, where (a) is a graph of complex refractive index and (b) is a graph of absorption coefficient.

[0035] Fig.19 1 is a graph of optical parameters of basal cell carcinoma and normal skin in the terahertz band, where (a) is a graph of complex refractive index and (b) is a graph of absorption coefficient.

[0036] Fig. 20 It is the photoacoustic signal at the outer surface of the irradiation radius of normal skin tissue.

[0037] Fig.21 This is a diagram of the skin stratification model structure containing BCC.

[0038] Fig. 22 It is the photoacoustic signal at the center M of the irradiated surface containing different sizes of basal cell carcinoma lesions.

[0039] Fig.23 It is the photoacoustic signal (local amplification) at the center M of the irradiated surface containing different sizes of basal cell carcinoma lesions. DETAILED DESCRIPTION

[0040] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0041] Example 1

[0042] This embodiment provides a method for detecting biological tissue using the photoacoustic effect of terahertz waves, wherein a pulsed terahertz wave with energy in the uJ order and duration in the ps order is vertically irradiated onto the surface of the biological tissue, an ultrasonic detector is used to receive the photoacoustic signal generated by the photoacoustic effect of the terahertz wave on the biological tissue, and the biological tissues are distinguished by the difference in the received photoacoustic signals, thereby realizing the detection of different biological tissues.

[0043] In some embodiments, the difference between the photoacoustic signals includes differences in amplitude, reception time, peak value, and waveform information between the photoacoustic signals.

[0044] The position of the ultrasonic detector is determined according to the type of biological tissue being detected: if the biological tissue being detected is ex vivo tissue, a forward detection method is adopted, and the biological tissue is set between the terahertz source and the ultrasonic detector; if the biological tissue being detected is in vivo tissue, a backward detection method is adopted, and when the terahertz wave emitted by the terahertz source irradiates the surface of the in vivo tissue, the ultrasonic detector is set on the outer surface of the in vivo tissue.

[0045] Example 2

[0046] This embodiment provides a method for detecting biological tissue using the photoacoustic effect of terahertz waves, which is used to detect blood components and whether there is a thrombus, and distinguish different components of blood by the amplitude and reception time of all received photoacoustic signals.

[0047] 1. Generation of photoacoustic signals of thrombus under terahertz wave radiation

[0048] Photoacoustic signal simulation parameters: incident terahertz source radiation energy: 10 μJ, single pulse duration: 1 ps, thrombus absorption coefficient at 1.0 THz: 220 cm -1 , refractive index: 1.92, the thermal and acoustic parameters of thrombus are shown in Table 1.

[0049] Table 1 Thermal parameters of blood components

[0050]

[0051] Since the amplitude of the photoacoustic signal and its propagation in the thrombus are affected by the change of the non-uniform transient temperature field, when the pulse duration of the incident terahertz radiation is 1ps, the thermal diffusion effect in the thrombus has not yet occurred. The whole process can be regarded as an adiabatic process. Only the initial photoacoustic signal is generated along the incident direction within the irradiated surface. The photoacoustic signal source is generated on the irradiated surface and diffuses and decays around with the increase of time. The average attenuation of ultrasound in soft biological tissue is about 0.6dB·cm -1 MHz -1 Therefore, the attenuation of 1MHz ultrasound after propagating 5cm in soft tissue is about 3dB, and the corresponding amplitude attenuation is about 70% of the initial value. Therefore, for a thrombus with a thickness of 1mm, the absorption attenuation factor has little effect. The propagation attenuation form of the photoacoustic signal in the thrombus is mainly diffusion attenuation. Figure 1 Give specific forms of dissemination.

[0052] Figure 1 The propagation diagrams of six photoacoustic signals with different propagation times in thrombus are given. Figure 1 The photoacoustic signal at 100ps in (a) is only generated within the range of the non-uniform transient temperature field change. The photoacoustic signal amplitude at this time is 59.20kPa, which is consistent with the initial sound pressure estimation result of the thermoelastic equation. As the propagation time increases, Figure 1 (b) The initial photoacoustic signal at 20ns diffuses and decays, and spreads to the surrounding of the thrombus. The signal is not limited to the irradiated surface. The maximum value of the photoacoustic signal during the propagation process is 37.50kPa. Figure 1 (c) At 50ns, the ultrasonic wave continues to propagate in the incident direction, and the propagation speed is affected by the speed of sound in the thrombus. The propagation distance is strictly determined by the propagation time multiplied by the speed of sound in the thrombus. Figure 1 From the three result graphs (d) to (f) with time periods of 100ns, 200ns, and 400ns respectively, it can be seen that the photoacoustic signal gradually diffuses to the surrounding areas outside the irradiation radius during the propagation process, and the signal amplitude gradually decreases. The corresponding photoacoustic signal amplitudes are 26.80kPa, 26.60kPa, and 26.50kPa respectively. As the propagation time increases, the wavefront compression and waveback stretching phenomena of the sound wave occur during the propagation of the photoacoustic signal, that is, the positive and negative amplitudes of the photoacoustic signal alternate, which is in line with the propagation law of the photoacoustic signal in biological tissues.

[0053] The process of estimating the initial sound pressure using the thermoelastic equation is:

[0054] Due to the strong absorption of biological tissue in the terahertz band, its optical penetration depth is less than the terahertz wave spot radius at the irradiated surface, which meets the conditions for the generation of a planar sound source. At this time, it can be assumed that all terahertz wave energy is absorbed by biological tissue and converted into heat, causing the biological tissue temperature change to be ΔT. According to the thermoelastic law, it can be obtained:

[0055]

[0056] In the formula, E a represents the pulsed terahertz wave energy absorbed by biological tissue, V represents the volume of the terahertz absorption area, R0 is the radius of the terahertz beam or the radius of the sound source in the heated area, δ is the penetration depth of the terahertz wave, C p represents the specific heat capacity of biological tissue, and ρ represents the density of biological tissue;

[0057] Under the action of short pulse terahertz waves, biological tissues do not have enough time to undergo thermal diffusion effects. At this time, it can be regarded as an adiabatic process, resulting in a rapid increase in stress on the radiation surface. The acoustic pressure P and strain βΔT have the following functional relationship:

[0058] P=ρc 2 βΔT;

[0059] Where β is the thermal expansion coefficient, ρc 2 is the elastic modulus of biological tissue, and c is the sound velocity of biological tissue.

[0060] Substituting the calculation formula of biological tissue temperature change ΔT into the relationship between sound pressure P and strain βΔT, the sound pressure amplitude (amplitude of sound pressure P) P under the action of a short pulse can be obtained. t for:

[0061]

[0062] Where E0 is the energy density of the pulsed terahertz wave, E p It is expressed as the energy of the pulsed terahertz wave, which can be approximated as E in the absorption of terahertz waves by biological tissues. a , the penetration depth δ of the terahertz wave is equal to the inverse of the absorption coefficient α -1 .

[0063] In order to more intuitively show the generation and propagation of photoacoustic signals in thrombus, point A (0.0mm, 0.0mm) on the surface of thrombus at the center of terahertz wave irradiation is selected as the photoacoustic signal receiving and detection point, and the time domain diagram of sound pressure is drawn, as shown in Figure 2. Figure 2 As shown. Figure 2 It can be seen that the photoacoustic signal received at point A on the surface of the thrombus increases rapidly and reaches an amplitude in a very short time, causing the photoacoustic signal to rapidly decrease to the minimum value. It can be seen that there are small fluctuations in the sound wave signal during the process of returning to the initial state of the thrombus before irradiation. This is because the thrombus, as an elastic medium, has a small physical phenomenon similar to spring damping motion during the thermal expansion process.

[0064] In order to more intuitively observe the signal changes of the photoacoustic signal during the transmission process in the thrombus, a section line with a length of 1 mm was cut from the inside of the thrombus along the incident direction of the terahertz pulse and passed through the center of the thrombus. Five different propagation times of 200ps, 10ns, 20ns, 300ns and 400ns were selected, and the photoacoustic signal on the section line was plotted. Figure 3 As shown, Figure 3 The peaks of the five curves correspond to 200ps, 10ns, 20ns, 300ns and 400ns from left to right. Figure 3It can be seen that the photoacoustic signal is generated at the terahertz wave irradiated surface and propagates into the thrombus along the incident direction. The propagation law of the peak of the curve in the figure also satisfies the linear relationship between the propagation distance and time and the attenuation law of the photoacoustic signal in biological tissue. The photoacoustic signal intensity is different at different positions. The photoacoustic signal is strongest at the position close to the irradiated edge of the thrombus, and gradually weakens with the increase of the propagation distance. The photoacoustic signal amplitude is 0 at the position where the sound wave has not arrived. By observing the amplitude of the peak drop, it can be found that the sound pressure intensity decreases the most within the range where the temperature field change is not 0, and decreases exponentially with the increase of the propagation distance. At the temperature field change of 0, Figure 3 The propagation amplitude of the photoacoustic signal in the range of z>0.2mm gradually decreases with the increase of distance, and diffuses and propagates in the thrombus in the form of a plane wave. This nonlinear change is also consistent with the propagation characteristics of ultrasound in biological tissues.

[0065] Comparing the differences in photoacoustic signals of different blood components, the propagation of photoacoustic signals is affected by multiple physical parameters in biological tissues. At this time, only comparing the photoacoustic signal amplitude at the terahertz wave irradiation surface cannot effectively reflect the specific differences in the photoacoustic signal receiving end between different blood components. Different blood components are distinguished by the time domain display of the photoacoustic signal. Now, the photoacoustic signal differences of thrombus, whole blood and plasma are compared at a distance of 0.2 mm from the terahertz wave irradiation surface on the photoacoustic signal propagation path. Figure 4 As shown, Figure 4 In the figure, the peaks of the three curves are plasma, whole blood, and thrombus from high to low. Figure 4 It can be seen that the photoacoustic signals on the propagation paths of different blood components are not the same. Plasma has the strongest absorption of terahertz waves and produces the highest amplitude of photoacoustic signals, but the photoacoustic signals propagate fastest in thrombi and are first received by the detector. It can be seen that the feasibility and sensitivity of distinguishing blood components by detecting the difference in photoacoustic signals is much higher than that of thermal response methods.

[0066] 2. Generation of photoacoustic signals of thrombus under forward detection model

[0067] In the analysis of thrombus terahertz photoacoustic signals, thrombus is used as an in vitro tissue model and is suitable for the forward detection mode. In the forward detection mode, the forward receiving probe point in the thrombus is Figure 5As shown, it includes the center point A (0mm, 0mm) of the thrombus irradiated surface, the probe point B (0, 0.1mm) at a distance of 0.1mm from the thrombus surface along the terahertz wave irradiation direction, the probe point C (0, 0.2mm) at a distance of 0.2mm from the thrombus surface along the terahertz wave irradiation direction, and the probe point D (0, 0.5mm) at a distance of 0.5mm from the thrombus surface along the terahertz wave irradiation direction; along the plane wave irradiation radius direction, the probe point E (0.2mm, 0.1mm) at a distance of 0.1mm from the center of the thrombus surface, along the plane wave irradiation radius direction, the probe point F (0.2mm, 0.2mm) at a distance of 0.2mm from the center of the thrombus surface along the plane wave irradiation radius direction, the probe point G (0.2mm, 0.5mm) at a distance of 0.5mm from the center of the thrombus surface along the plane wave irradiation radius direction, and the probe point H (0.2mm, 1.0mm) at a distance of 1.0mm from the center of the thrombus surface along the plane wave irradiation radius direction.

[0068] (1) Plane wave irradiation forward photoacoustic signal

[0069] Figure 6 is the time domain propagation diagram of the photoacoustic signal at different propagation distances A, B, C and D in the irradiation direction of the terahertz beam in the form of plane wave irradiation, Figure 6 The peak values ​​of the middle curve correspond to detection points A, B, C, and D from left to right. Figure 6 It can be seen that in the forward detection model, the photoacoustic signal amplitude received at the center of the thrombus irradiated surface is the largest, and diffuses and attenuates as the photoacoustic signal propagates into the thrombus. It can be seen that for photoacoustic signal detection along the incident direction, the closer the distance to the irradiated surface, the greater the detected photoacoustic signal amplitude, and as the propagation path in the thrombus increases, the photoacoustic signal amplitude decays exponentially. Figure 6 , the photoacoustic signal differences at different detection positions can be better distinguished in the direction of the irradiation radius, such as Figure 7 As shown, Figure 7 The curve with the highest peak value corresponds to the detection points C, E, and F, the curve with the second highest peak value corresponds to the detection point G, and the curve with the lowest peak value corresponds to the detection point H. In the curves corresponding to the detection points C, E, and F, the valley values ​​correspond to F, E, and C from left to right. Figure 7It can be seen that the photoacoustic signal is relatively concentrated within the irradiated radius, and the differences in the photoacoustic signals at points C, E, and F are very small. This is because when incident in the form of a plane wave, the energy density of the terahertz wave remains constant within the irradiated range, and differences only occur when the propagation time is 0.2s to 0.6s. This is because the photoacoustic signal generated at the edge of the plane wave irradiation radius diffuses and propagates to the surface of the thrombus. Since the speed of sound in the air (340m / s) is less than the speed of sound in the thrombus (1589m / s), and the density of air is much lower than the density of the thrombus. In this case, the acoustic impedance of the photoacoustic signal propagating on the surface of the thrombus is very large, and the sound wave reflection phenomenon occurs. Figure 7 This phenomenon can be verified by probe points E and F. Due to the edge diffusion of the photoacoustic signal, the photoacoustic signal amplitude of probe point G at the edge of the irradiation radius is significantly reduced, which is different from the photoacoustic signal changes within the irradiation radius of probe points C, E, and F. For probe point H outside the irradiation radius, some tiny signals can also be received due to signal diffusion.

[0070] As shown in Figure 8(a), the frequency domain amplitude of the photoacoustic signal in biological tissue will decay rapidly with the increase of the propagation distance. Under 10μJ plane wave terahertz irradiation, the center frequency of the photoacoustic signal at the probe point A at the center of the thrombus surface is 1.0MHz, and as the photoacoustic signal propagates, its frequency spectrum tends to move to the left to the low-frequency zone as a whole. This is because the high-frequency ultrasonic wave decays rapidly in the thrombus during the propagation process. When the propagation distance is within 0.5mm, its attenuation is not obvious enough. In Figure 8(a), the peaks correspond to the probe points A, B, C, and D from top to bottom. Also in the forward propagation process, the frequency spectrum along the terahertz wave irradiation radius is shown in Figure 8(b). At the three probe points C, E, and F, since they are all within the irradiation radius, their high-frequency attenuation trends are roughly the same. Compared with the spectrum along the radius of terahertz wave Gaussian distribution, at the probe points G and H, the high-frequency components of the photoacoustic signal are significantly lower than those within the irradiated radius, and the overall spectrum also tends to move toward the low-frequency region. In Figure 8(b), the peaks correspond to the probe points C, E, F, G, and H from top to bottom. It can be seen that during the propagation of the photoacoustic signal, the proportion of the high-frequency part of the received photoacoustic signal gradually decreases.

[0071] (2) Forward photoacoustic signal in the form of Gaussian distribution irradiation

[0072] Fig. 9 is the time domain diagram of the photoacoustic signal at different propagation distances A, B, C and D in the terahertz wave irradiation direction in the form of Gaussian distribution, Fig. 9In the figure, the peaks correspond to probe points A, B, C, and D from left to right. Compared with the plane wave irradiation form, the photoacoustic signal of the Gaussian distribution irradiation form has a greater attenuation amplitude in the terahertz wave irradiation direction as the propagation time increases. When the propagation distance is 0.5mm, the signal attenuation is 1 / 3 of that at the center of the thrombus surface.

[0073] Compared with the forward probe group Fig. 9 , the differences in the amplitude and waveform of the photoacoustic signal at different detection positions can be better distinguished in the radial direction, such as Fig.10 As shown, Fig.10 In the figure, the peaks correspond to probe points C, E, F, G, and H from top to bottom. The photoacoustic signal at the central surface of the irradiated thrombus is the strongest when irradiated by terahertz waves with Gaussian distribution, and decreases exponentially along the irradiation radius. The photoacoustic signal amplitudes at points C, E, and F show a downward trend, and the corresponding photoacoustic signal amplitudes are 24.12kPa, 22.85kPa, and 18.30kPa. This is because when the incident light is in the form of Gaussian distribution, there is no obvious energy distribution perpendicular to the irradiation direction at the irradiation edge, and there is no obvious acoustic wave reflection phenomenon on the thrombus surface, which can be verified by the two curves of probe points E and F. At the edge of the irradiation radius, due to the edge diffusion of the photoacoustic signal, probe point G is distinguished from the photoacoustic signal changes within the irradiated radius of probe points C, E, and F. Its photoacoustic signal amplitude will be greatly reduced, and the signal period will also be greatly widened. For the probe point H outside the irradiation radius, some tiny signals can also be received due to the diffusion of the signal into the thrombus, but the amplitude of the received signal is smaller than that in the plane wave irradiation form, as shown in the probe point H curve.

[0074] Similarly, from the perspective of frequency domain detection of photoacoustic signals, Fig.11 The left figure is the frequency domain signal diagram of the probe points A, B, C, and D at different positions along the radiation direction of the Gaussian distributed terahertz wave in the forward detection. Fig.11 The right figure is the frequency domain signal diagram of the probe points C, E, F, G, and H at different positions along the radiation radius of the Gaussian distribution terahertz wave in the forward detection. Fig.11 In the left figure, the peak values ​​correspond to detection points A, B, C, and D from top to bottom. Fig.11 In the right figure, the peak values ​​correspond to the detection points C, E, F, G, and H from top to bottom. Fig.11As shown in the left figure, compared with the amplitude-frequency characteristics of the photoacoustic signal under the plane wave irradiation form shown in Figure 8 (a), the receiving probe points A, B, C, and D all show a certain amplitude decrease under the irradiation form of Gaussian distribution, and the attenuation waveform of the high-frequency part of the amplitude-frequency signal is better than that of the plane wave irradiation form. The center frequency at this time is also 1.0MHz. It can be seen that the center frequency of the photoacoustic signal generated by the terahertz photoacoustic effect for distinguishing thrombus depends on the optical and physical properties of the thrombus itself, and has nothing to do with the irradiation method of the light source. Similarly, in the forward propagation process, the frequency spectrum along the irradiation radius of the Gaussian distribution terahertz wave is as follows Fig.11 As shown in the right figure, at the three probe points C, E, and F within the irradiation radius of the pulsed terahertz wave, the proportion of high-frequency signals is greater than that of the plane wave irradiation form. The attenuation trend of the high-frequency components of the photoacoustic signal is roughly the same as the distance from the irradiation center within the irradiation radius. At the probe points G and H, the two irradiation methods are very different. Under the Gaussian distribution terahertz pulse irradiation, the high-frequency attenuation phenomenon is very serious.

[0075] It can be seen that no matter it is plane wave irradiation or Gaussian distribution irradiation, the center frequency of the photoacoustic signal generated by terahertz pulse irradiation on the surface of the thrombus is 1.0MHz. The main difference between the two is that along the irradiation radius, for plane wave irradiation, the photoacoustic signal measured at the probe point outside the irradiation focus radius contains higher high-frequency information than the Gaussian distribution irradiation. On the contrary, when detection is carried out within the radiation radius and the irradiation source is incident in the form of Gaussian distribution irradiation, the spectrum resolution of the photoacoustic signal at the probe points at different positions is better than that of the plane wave irradiation. The selection of the irradiation method of the terahertz source based on the tissue shape distribution of different biological tissues and the difficulty of detection at different probe point positions provides a certain reference value, that is, the terahertz pulse irradiation form can be selected according to the tissue shape distribution of different biological tissues and the difficulty of detection at different probe point positions.

[0076] Example 3

[0077] 1. Effects of different terahertz wave parameters on photoacoustic signals of thrombus

[0078] The terahertz wave irradiation energy term determines the generation and intensity change of the photoacoustic signal. The received amplitude comparison of the photoacoustic signal under different terahertz wave irradiation energies is briefly explored. p =1μJ, E p =5μJ, E p =10μJ, E p =15μJ, the other light source parameters are consistent with the thrombus thermal parameters in Example 1, when the terahertz wave radiation frequency is 1.0THz, the photoacoustic signal amplitude results under different terahertz wave energies are obtained after simulation as follows Fig.12 shown.

[0079] from Fig.12 It can be seen that the amplitude of the photoacoustic signal under different terahertz wave irradiation energies is very different. As the irradiation energy increases, the amplitude of the photoacoustic signal also increases linearly. It can be seen that the photoacoustic intensity generated by terahertz wave pulse irradiation of thrombus is largely affected by the irradiation terahertz source, which is also of great reference value for the selection of sound pressure detectors in the detection stage. The results are consistent with the theory of photoacoustic effect.

[0080] 2. Influence of terahertz wave focusing radius on photoacoustic signals

[0081] In the process of studying the interaction between terahertz waves and biological tissues, the focusing characteristics of terahertz wave pulse radiation are basic but very important parameters of terahertz sources. They are limited by the phase difference of traditional terahertz focusing lenses. On the other hand, due to the existence of the diffraction limit, the wavelength of terahertz waves is at the millimeter level, and the terahertz wave spot cannot be focused to a sub-wavelength size, which hinders the development of terahertz waves in practical applications. This simulation considers the influence of different terahertz wave focusing radii on photoacoustic signals from the perspective of different focusing radii corresponding to different irradiation energy densities under the terahertz irradiation of a single pulse of 1.0THz pulse plane wave with a single pulse energy of 10μJ. Fig.13 As shown. Fig.13 It can be seen that different terahertz wave focusing radii have a great influence on the maximum amplitude of the photoacoustic signal received at point A on the central surface of the thrombus. Different focusing radii correspond to different photoacoustic signals, and the amplitude of the photoacoustic signal decreases with the increase of the focusing radius. Fig.11 For the linear effect of pulse energy on the photoacoustic signal, the amplitude of the photoacoustic signal decreases exponentially with the increase of the focusing radius. When the focusing radius is 0.25 mm, the maximum amplitude of the received photoacoustic signal is 16 times that when the focusing radius is 1.0 mm. It can be seen that compared with different terahertz wave irradiation energies, different terahertz focusing radii have a more obvious effect on the detection of photoacoustic signals. The smaller the focused spot of the converged terahertz wave, the lower the sensitivity requirement of the ultrasonic detector of the photoacoustic signal at the receiving end.

[0082] 3. Effect of terahertz wave pulse duration on photoacoustic signals

[0083] The pulse duration of a terahertz wave is related to the way it is generated. In the method where the pump laser pumps nonlinear crystals such as LiNbO3 through optical rectification, the pulse duration of the generated terahertz wave is affected by the pulse duration of the pump light source, which is usually in the order of fs to ps. The terahertz pulse duration generated by a terahertz free electron laser is tunable according to the different time structures of the electron beam. Different terahertz durations have different effects on the photoacoustic signal. When the terahertz wave pulse duration is greater than the thermal relaxation time of biological tissue, transient sound pressure changes cannot be generated in the tissue. The photoacoustic signal generated at this time is very weak and difficult to detect. Similarly, with terahertz wave irradiation at 1.0THz and a pulse energy of 10μJ, the pulse duration of the terahertz wave is changed from 0.1ps to 10 6 ps simulation study was conducted. In order to study the correlation between the terahertz wave pulse width and the photoacoustic signal, the photoacoustic signal amplitude was measured at the center point A on the thrombus surface, and the effects of different terahertz wave pulse durations on the photoacoustic signal were compared. Fig.14 As shown. Fig.14 It can be seen that when the pulse duration is <10 3 When the terahertz wave pulse duration increases to 10 ps, ​​the photoacoustic signal slowly decreases with the increase of the terahertz wave pulse duration, and does not show a more obvious change in the photoacoustic signal amplitude. 3 ~10 4 When the pulse duration is >10 4 ps, the photoacoustic signal amplitude decreases linearly with the increase of pulse duration. The longer the pulse duration, the steeper the photoacoustic signal amplitude decreases. It can be seen that when the single pulse duration is in the order of ms, the generated photoacoustic signal will be too weak to be detected, so the single pulse duration needs to be less than the order of ns.

[0084] 4. The influence of terahertz wave radiation frequency on photoacoustic signals

[0085] According to the fingerprint spectrum characteristics of biological tissues in the terahertz band, different biological tissues are characterized by different absorption peaks when the terahertz wave irradiation frequency is different. The terahertz wave pulse irradiation condition with 10μJ energy is also used to study the influence of different terahertz wave pulse radiation on the photoacoustic signal. The optical parameters in the thrombus irradiated with different terahertz frequencies (1.0THz, 1.2THz, 1.4THz, 1.6THz, 1.8THz, 2.0THz) are characterized by absorption coefficient and complex refractive index. The absorption coefficients are μ a =220cm -1 、240cm -1、260cm -1 、290cm -1 、320cm -1 、350cm -1 Considering the difference between the refractive index parameters of biological tissues in the terahertz band and the near-infrared band, the double Debye model is used to fit the real part of the complex refractive index in the thrombus 1.92, 1.89, 1.87, 1.85, 1.82, and 1.80. The amplitude of the photoacoustic signal is studied at the center point A of the thrombus surface. The amplitude of the photoacoustic signal at different terahertz frequencies is shown in Fig.15 shown. Fig.15 The maximum amplitude curves of photoacoustic signals under different terahertz wave frequencies are given. Fig.15 It can be seen that different terahertz radiation frequencies also have a significant impact on the photoacoustic signal. Different irradiation frequencies correspond to different photoacoustic signal amplitudes, and the photoacoustic signal amplitude increases linearly with the increase in frequency. For terahertz waves with higher radiation frequencies, the photoacoustic signal amplitude is positively correlated with the absorption coefficient of thrombus to light energy.

[0086] 5. Effect of terahertz wave irradiation form on photoacoustic signal

[0087] Terahertz pulse energy can be divided into plane wave irradiation and Gaussian distribution irradiation in terms of spatial distribution. The photoacoustic signal propagation characteristics in thrombus under the two irradiation forms are analyzed. Fig.16 As shown. Fig.16 It can be obtained that at t = 500ns, the intensity distribution of the photoacoustic signal in the thrombus under different terahertz wave irradiation forms is not the same. Compared with the Gaussian distribution form, when the terahertz wave propagates in the thrombus in the form of a plane wave, it has a higher photoacoustic signal amplitude, and the photoacoustic signal waveform in the propagation process has an obvious diffusion phenomenon along the outside of the incident radius. The photoacoustic signal in the form of a Gaussian distribution has a better convergence phenomenon, and the photoacoustic signal is relatively concentrated at the center section of the terahertz wave irradiation. It can be seen that when the r-direction scale of the detection target area is smaller than the radius of the terahertz wave beam, the terahertz pulse with a Gaussian spatial distribution can eliminate the interference of the photoacoustic signal generated by non-target tissues and more accurately obtain the photoacoustic signal characteristics in the target tissue area, that is, when the r-direction scale of the detection target area is smaller than the radius of the terahertz wave beam, the Gaussian distribution irradiation form should be used, otherwise the plane wave irradiation form should be used.

[0088] Example 4

[0089] In some embodiments, this embodiment provides a method for detecting biological tissue using the photoacoustic effect of terahertz waves, which is used to detect different skin tissues, such as detecting whether the skin is normal, and distinguishing normal skin tissue from abnormal skin tissue by the received photoacoustic signal amplitude and photoacoustic signal waveform. Compared with normal skin tissue, abnormal skin, such as skin tissue containing diseased cells, has different terahertz absorption characteristics and photoacoustic effects. By irradiating skin tissue containing diseased cells with pulsed terahertz waves, photoacoustic signals are received on the skin surface, and the absorption capacity of diseased cells to terahertz waves during different growth periods is utilized to differentiate and distinguish the diseased cells by the received photoacoustic signal amplitude and photoacoustic signal waveform information.

[0090] In some embodiments, the growth period of abnormal skin tissue and skin tissue containing diseased cells is also distinguished based on the waveform information of the received photoacoustic signal.

[0091] Analysis of human skin tissue and BCC photoacoustic signals

[0092] 1. Analysis of photoacoustic signals of normal skin tissue under terahertz wave radiation

[0093] In the photoacoustic signal simulation study of normal skin tissue, the model is selected as follows Fig.17 The simulation parameters are also the terahertz wave pulse in the form of a plane wave with a single pulse energy of 10μJ, a pulse duration of 1ps, a plane wave irradiation radius of 0.5mm, and the optical parameters of the skin layered tissue are Fig.18 and Fig.19 The thermal and acoustic parameters used in the simulation are given in Table 2. Fig.18 In the figure, the real curve in (a) corresponds to the real part of the true skin, the real part of the superficial skin and the real part of the stratum corneum from top to bottom, the imaginary curve corresponds to the imaginary part of the epidermis, the imaginary part of the dermis and the imaginary part of the stratum corneum from top to bottom, and the numerical curve in (b) corresponds to the absorption coefficient of the epidermis, the absorption coefficient of the dermis and the absorption coefficient of the stratum corneum from top to bottom. Fig.19 In the figure, the real part curve in (a) corresponds to the real part of BCC and the real part of normal skin from top to bottom, and the imaginary part curve in (b) corresponds to the imaginary part of BCC and the imaginary part of normal skin from top to bottom.

[0094] Table 2 Thermal parameters of human layered skin and BCC

[0095]

[0096] Photoacoustic signal detection is performed at the center of the irradiated surface of normal skin tissue, and the obtained time domain photoacoustic signal is as follows Fig.17 As shown. Fig.17It can be seen that when the terahertz wave irradiates the stratum corneum of the skin, the waveform components of the photoacoustic signal received at the center M of the irradiated surface of the skin tissue are not unique, and the instantaneous photoacoustic signal at the irradiated surface, the photoacoustic signal of the stratum corneum and the photoacoustic signal of the epidermis are superimposed. The difference in photoacoustic signals of different skin structures can be intuitively seen in the figure, and they are marked as points S1, S2, and S3, and their photoacoustic signal amplitudes are 2.00kPa, 3.58kPa, and 10.09kPa, respectively. The ultrasonic detector quickly received the photoacoustic signal from the surface of the stratum corneum after the terahertz wave pulse duration ended. Due to the non-uniform temperature change between skin structures during the terahertz wave pulse duration, the instantaneous sound pressure generated in the lower stratum corneum and the epidermis was received by the ultrasonic detector on the skin surface after 6.4ns and 20.0ns, respectively, and rapidly decayed with the propagation time. After 100ns, only a small photoacoustic signal was received by the ultrasonic detector. The speed of sound in skin tissue is 1624m / s. The propagation distances after 0.1ns, 6.4ns and 20.0ns are 0.1624μm, 10.394μm and 32.48μm respectively. The propagation distance is determined by the speed of sound in skin tissue * propagation time. It can also be verified that the signals and waveforms received at this point come from the irradiated stratum corneum surface, the inside of the stratum corneum and the epidermis, respectively. The correctness and analyzability of the inference are.

[0097] 2. Photoacoustic signal analysis of normal skin tissue under the backward detection model

[0098] In the backward detection model, due to the complexity of the placement design of the terahertz source and the ultrasonic detector, combined with the fact that the spatial distribution of the terahertz wave pulse is in the form of a plane wave, the photoacoustic signal in the irradiated area of ​​the biological tissue can also be detected outside the beam radius. Based on this conclusion, the photoacoustic signal detection is performed on the surface of the stratum corneum of the skin at points (0.5mm, 0), (0.6mm, 0), (0.8mm, 0) and (1.0mm, 0) outside the terahertz wave irradiation radius. It can be seen that for the plane wave irradiation form, the photoacoustic signal in the skin stratified tissue can also be detected outside the irradiation radius, such as Fig. 20 As shown in Figure 20, the peak values ​​correspond to the detection points (0.5mm, 0), (0.6mm, 0), (0.8mm, 0) and (1.0mm, 0) from left to right. Fig. 20It can be seen that when the spatial distribution of terahertz waves is in the form of a plane wave, the amplitude of the photoacoustic signal at the edge of the irradiation radius is smaller than that within the irradiation radius, and the waveform remains unchanged. It can be seen that the ultrasonic detector with high sensitivity to the sound pressure amplitude response can also detect and distinguish the photoacoustic signal components inside the skin at the irradiation radius. The photoacoustic signal detected at the probe point (0.6mm, 0) in the figure is weakened compared to the probe point (0.5mm, 0). Compared with the received photoacoustic signal components, the signal difference between the stratum corneum and the epidermis increases because the frequency of the photoacoustic signal generated by the stratum corneum is higher and rapidly attenuates during the propagation of the photoacoustic signal. It can be seen that for skin tissue, a specific detection position can be selected according to the specific structural area to be analyzed. The propagation of the photoacoustic signal at the probe point positions (0.8mm, 0) and (1.0mm, 0) can more intuitively screen out the photoacoustic signal of the target area (epidermis). And the farther away from the center of the irradiated surface, the smaller the amplitude of the detected photoacoustic signal, but the more single the waveform information, the more obvious the waveform of the photoacoustic signal in the characteristic area.

[0099] 3. Photoacoustic signal analysis of BCC-containing skin tissue under terahertz wave radiation

[0100] In the simulation study of photoacoustic signals of skin tissue containing basal cell carcinoma lesions in skin cancer, the model is selected as follows Fig.21 The simulation parameters are also the plane wave terahertz wave pulse with a single pulse energy of 10 μJ, a pulse duration of 1 ps, and a plane wave irradiation radius of 0.5 mm. The optical parameters of skin tissue and basal cell carcinoma are shown in Figures 18 and Fig.19 The thermal parameters and acoustic parameters are given in Table 2. The photoacoustic signals received at the stratum corneum are used to distinguish skin tissues with different basal cell carcinoma sizes, and then characterize the degree of skin cancer lesions. The photoacoustic signals of skin tissues with different basal cell carcinoma area sizes received by the detector located on the surface of the stratum corneum are shown in Fig. 22 As shown, Fig. 22 In the figure, the peak values ​​correspond to a=50μm, 40μm, and 30μm from high to low. Fig. 22 It can be found that for skin tissue containing basal cell carcinoma lesions, the received photoacoustic signal is stronger than that of normal skin tissue ( Fig.17). As the length of the short semi-axis of the basal cell carcinoma lesion area increases, the amplitude of the photoacoustic signal received at the center M of the skin surface increases. When the short semi-axis length is 30μm, the maximum photoacoustic signal amplitude received by the skin surface at 19.32ns is 10.85kPa. Compared with the photoacoustic signal amplitude of 10.07kPa received by normal skin tissue at 20.00ns, the change is not obvious. This is because the BCC is 50μm away from the terahertz irradiation surface at this time, and a large amount of terahertz wave energy is absorbed by the epidermis, and only a small part of the terahertz wave energy is distributed in the basal cell carcinoma lesion area. It can be seen that when a=30μm, the difference in characterization by photoacoustic signals to distinguish normal skin tissue from skin tissue with skin cancer is not obvious, which also shows that it is difficult to achieve the distinction in the early stage of basal cancer cell proliferation. When the short semi-axis radius a of the basal cancer cell lesion is further increased to 40μm, the corresponding photoacoustic signal received at 17.46ns reaches an amplitude of 11.27kPa. When a is 30μm, the photoacoustic signal received at the center of the skin surface has a larger amplitude and reaches the maximum value faster than the former. Similarly, for the photoacoustic signal received when a is 50μm, the maximum amplitude is 12.14kPa at 17.05ns. Fig. 22 From the three curves in FIG, it can be seen that as the lesion area of ​​basal cell carcinoma increases, the waveform of the photoacoustic signal received at the surface of the skin stratum corneum by backward detection becomes smoother and easier to detect.

[0101] In order to distinguish the photoacoustic signal components in skin tissue containing basal cell carcinoma by backward detection, Fig. 22 The photoacoustic signals containing different sizes of basal cell carcinoma lesions received at the surface of the middle stratum corneum were locally amplified and analyzed, such as Fig.23 As shown, Fig.23 In the figure, the peaks correspond to a = 50 μm, 40 μm, and 30 μm from high to low. When the terahertz wave is radiated in the skin tissue, the tissue components within the penetration depth are not unique (in this simulation, they are the stratum corneum, epidermis, and the area containing basal cell carcinoma lesions). Fig.23 The photoacoustic signal SC0 received at the upper surface of the stratum corneum under terahertz wave irradiation is marked in the figure. As can be seen from the figure, for the photoacoustic signal curves containing different sizes of basal cell carcinoma lesions in the backward detection mode, there is no difference in the photoacoustic signal received at the upper surface of the stratum corneum, and the amplitude of the photoacoustic signal is 1.60 kPa. Fig.23They are marked as points SC1, SC2, and SC3 respectively. It can be seen from the figure that different basal cell carcinoma lesion areas affect the generation of photoacoustic signals in the epidermis, and the amplitudes are 4.19kPa, 2.96kPa, and 2.77kPa respectively. Since basal cell carcinoma lesions of different sizes have different effects on the non-uniform field changes of temperature, when the basal cell carcinoma lesion area is larger, the temperature rise in the stratum corneum is closer to the epidermis, and the less light energy is deposited in the epidermis, which is manifested as the amplitude of the photoacoustic signal decreases as the basal cell carcinoma lesion area becomes larger, SC1>SC2>SC3, and decreases in a nonlinear trend. As the basal cell carcinoma lesion area becomes larger, the photoacoustic signal in the stratum corneum has a shorter propagation time and a higher frequency, so it is easier to attenuate during detection. Regarding the influence of different sizes of basal cell carcinoma lesions on the photoacoustic signal in the epidermis, Fig.23 The points marked in the figure are E1, E2, and E3, and their amplitudes are 8.80kPa, 4.14kPa, and 3.21kPa, respectively. According to the marked points, it can be seen that the photoacoustic signal E1 in the epidermis is significantly larger than E2 and E3. This is because when the basal cancer cell lesion area is small, its proportion in the epidermis is small. At this time, the epidermis shows more normal skin tissue characteristics. As the basal cancer cell lesion area becomes larger, the amplitude of the photoacoustic signal in the epidermis decreases. In the backward detection mode, the propagation time of the epidermis photoacoustic signal received on the stratum corneum surface is shorter. The photoacoustic signal intensity is E1>E2>E3, and the decreasing trend is also nonlinear. For the photoacoustic signal containing basal cancer cell lesions, Fig.23 The points marked in the figure are B1, B2, and B3, and their amplitudes are 10.85 kPa, 11.27 kPa, and 12.14 kPa, respectively. According to the marked points, it can be seen that for the photoacoustic signal in the lesion area containing basal cancer cells, B3>B2>B1. It can be seen that when the lesion area of ​​basal cancer cells is larger, the photoacoustic signal of the lesion area received by the backward detection mode is stronger, and the proportion of the photoacoustic signal received in the stratum corneum and epidermis is smaller, and it is easier to detect basal cancer cell lesions by irradiating the skin tissue with plane terahertz waves. Here, it is only an example of the case where the abnormal skin tissue is skin tissue containing basal cancer cells. The method of this embodiment can be applied to the detection of any abnormal skin tissue that has a difference in the photoacoustic signal of terahertz waves from normal skin tissue.

[0102] The above description is only a preferred embodiment of the present invention and is not intended to limit the protection scope of the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention are included in the protection scope of the present invention.

Claims

1. A method for detecting biological tissue using the photoacoustic effect of terahertz waves, characterized in that: The following steps are involved: Design a terahertz source to generate pulsed terahertz waves and radiate them vertically onto the surface of biological tissues; Receiving photoacoustic signals generated by biological tissues through the terahertz wave photoacoustic effect; Different biological tissues can be distinguished by the difference between the received photoacoustic signals, thus realizing the detection of different biological tissues; The energy of the generated pulsed terahertz wave is in the uJ level and the duration is in the ps level; The pulsed terahertz wave is terahertz irradiation in the form of a single pulse; When designing a terahertz source, the terahertz pulse irradiation form is selected according to the tissue shape distribution of different biological tissues and the detection difficulty of different probe point positions; When detecting outside the irradiation focusing radius, the terahertz source adopts plane wave irradiation; when detecting within the radiation radius, the terahertz source adopts Gaussian distribution irradiation.

2. The method for detecting biological tissue using the photoacoustic effect of terahertz waves according to claim 1, characterized in that: The differences between the photoacoustic signals include the differences in amplitude, reception time and waveform information between the photoacoustic signals.

3. The method for detecting biological tissue using the photoacoustic effect of terahertz waves according to claim 1, characterized in that: receiving the photoacoustic signal generated by the biological tissue through the terahertz wave photoacoustic effect through an ultrasonic detector; The position of the ultrasonic detector is determined according to the type of biological tissue being detected: if the biological tissue being detected is ex vivo tissue, a forward detection method is adopted, and the biological tissue is set between the terahertz source and the ultrasonic detector; if the biological tissue being detected is in vivo tissue, a backward detection method is adopted, and both the terahertz source and the ultrasonic detector are set on the outer surface of the in vivo tissue.

4. The use of a method for detecting biological tissue using the photoacoustic effect of terahertz waves according to any one of claims 1 to 3, characterized in that: Used to detect blood components; The different components of blood are distinguished by the amplitude and reception time of all received photoacoustic signals, that is, the difference in propagation speed.

5. The use of a method for detecting biological tissue using the photoacoustic effect of terahertz waves according to any one of claims 1 to 3, characterized in that: Used to detect different skin tissues; Different skin tissues include abnormal skin tissues, which refer to skin tissues containing diseased cells; The abnormal skin tissue is skin tissue containing basal cell carcinoma cells; The normal skin and the skin tissue containing diseased cells are distinguished by the received photoacoustic signal amplitude and the difference in the photoacoustic signal waveform; The growth period of abnormal skin tissue and skin tissue containing diseased cells is distinguished based on the waveform information of the received photoacoustic signal.

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